预约演示
更新于：2026-06-01
Ipragliflozin L-Proline
伊格列净L-脯氨酸盐
更新于：2026-06-01
概要
基本信息
最高研发阶段批准上市 |
最高研发阶段(中国)- |
特殊审评- |
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结构/序列
分子式C26H30FNO7S |
InChIKeyTUVGWWULBZIUBS-FVYIYGEMSA-N |
CAS号951382-34-6 |
关联
95
项与 伊格列净L-脯氨酸盐 相关的临床试验JPRN-jRCTs071190054
Program of ipragliflozin for endothelial dysfunction in chronic kidney disease and type 2 diabetes: a multicenter, randomized-controlled, open-label trial - PROCEED
开始日期2020-03-26 |
申办/合作机构- |
JPRN-jRCTs031190022
Switching sitagliptin to ipragliflozin in obese patients with type 2 diabetes mellitus who have inadequate glycemic control with sitagliptin - IPRA-SWITCH
开始日期2019-06-24 |
申办/合作机构- |
JPRN-UMIN000035555
Efficacy and Safety of SGLT2 Inhibitor Ipragliflozin in with Type 1 Diabetes patients using FGM - Efficacy and Safety of SGLT2 Inhibitor Ipragliflozin in with Type 1 Diabetes patients using FGM
开始日期2019-02-01 |
申办/合作机构- |
100 项与 伊格列净L-脯氨酸盐 相关的临床结果
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100 项与 伊格列净L-脯氨酸盐 相关的转化医学
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100 项与 伊格列净L-脯氨酸盐 相关的专利（医药）
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303
项与 伊格列净L-脯氨酸盐 相关的文献（医药）2026-08-01·INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Ipragliflozin exerts anti-fibrotic effects via a novel multi-pathway mechanism: Targeting TLR4/NF-κB /TGF-β1 cascade
Article
作者: Moustafa, Passant E ; Afifi, Nehal A ; Alsugoor, Mahdi H ; Fayed, Hany M ; Elmadani, Mevidette ; ALSuhaymi, Naif ; El Awdan, Sally A ; Ibrahim, Noha E ; Derzawy, Ahmed
Hepatic fibrogenesis represents a significant and escalating global health challenge with few effective treatments. This research explored the anti-fibrotic potential of the sodium-glucose cotransporter 2 (SGLT2) inhibitor Ipragliflozin (IPRA) in a rat model of hepatic fibrogenesis caused by thioacetamide (TAA), with a specific focus on critical pathways of inflammation, fibrosis, and oxidative stress. Groups were designated as follows: a control; a model group receiving TAA (100 mg/kg, twice weekly for 6 weeks); and two therapeutic groups receiving TAA plus either a low (3 mg/kg/day) or high (6 mg/kg/day) oral dose of Ipragliflozin during the final 4 weeks. TAA administration induced severe liver fibrosis, characterized by significant increases in serum ALT, AST, triglycerides, cholesterol, oxidative stress (↓GSH, ↓CAT, ↑MDA), and pro-inflammatory/pro-fibrotic signaling (↑TLR4, ↑IL-1β, ↑NF-κB, ↑TGF-β1). Ipragliflozin treatment, particularly at the 6 mg/kg dose, dose-dependently and significantly attenuated these changes. It restored liver function, normalized the lipid profile, reversed oxidative stress by boosting antioxidant defenses, and suppressed the core inflammatory and profibrotic TLR4/IL-1β/TGF-β1/NF-κB axis. Histopathological and immunohistochemical findings confirmed a reduction in fibrosis and inflammation. These findings highlight Ipragliflozin's promise as a multi-faceted therapeutic agent for liver fibrosis.
2026-04-01·Pharmacology Research & Perspectives
The Effects of
SGLT
2 Inhibitors on Muscle Health in Older Adults: A Systematic Review and Meta‐Analysis
Review
作者: Joongpan, Weena ; Sinchai, Pimthong ; Pathomthongtaweechai, Nutthapoom ; Boonmuen, Nittaya ; Klamsakul, Natawat ; Lapmanee, Sarawut
ABSTRACT:
Type 2 diabetes mellitus (T2DM) and obesity are growing global health concerns, particularly in older adults who are at higher risk of sarcopenia. While sodium‐glucose cotransporter 2 (SGLT2) inhibitors show promise for glycemic control and weight loss, their effects on muscle health remain unclear. We examined the effects of SGLT2 inhibitors on body weight, fat mass, and muscle mass in T2DM patients. We systematically searched the PubMed, Embase, Scopus, and Cochrane databases for relevant randomized controlled trials (RCTs). Three reviewers screened the studies, and two extracted data and assessed their quality. R software was used to evaluate heterogeneity via Cochran's
Q
and
I2
statistics. Eight RCTs (
n
= 541) were included. SGLT2 inhibitors significantly reduced body weight (standardized mean difference (SMD) = −0.85,
p
< 0.001;
I2
= 0%) and fat mass (SMD = −0.53,
p
< 0.001;
I2
= 51.1%). A small reduction in muscle mass was observed (SMD = −0.35,
p
< 0.001;
I2
= 22.9%), though substantially smaller than fat loss. Subgroup analysis confirmed that fat mass was reduced with dapagliflozin/ipragliflozin (SMD = −0.67,
p
< 0.001;
I2
= 26.4%) and empagliflozin (SMD = −0.53,
p
< 0.001;
I2
= 66.4%). SGLT2 inhibitors effectively reduce body weight primarily through fat loss in older adults. Although muscle mass declined modestly, the predominance of fat loss suggests weight reduction occurs through favorable metabolic changes. Given the slight muscle mass changes and study heterogeneity, careful monitoring in older adults is warranted, and further studies in diverse populations are needed.
2025-11-01·AACE endocrinology and diabetes
Evaluating the Comparative Effectiveness of Sodium-Glucose Transporter 2 Inhibitors (SGLT-2i) on Liver Enzymes in Patients With Nonalcoholic Fatty Liver Disease: A Comprehensive Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials
Review
作者: Khalil, Ibrahim ; Hossain, Md Imran ; Akter, Mahmuda
Objective:
This study aimed to conduct the first network meta-analysis (NMA) comparing the effectiveness of sodium-glucose transporter 2 (SGLT-2) inhibitors-dapagliflozin, empagliflozin, and ipragliflozin-in improving liver-related and metabolic outcomes in patients with nonalcoholic fatty liver disease (NAFLD), utilizing a robust Bayesian NMA framework.
Methods:
We conducted a systematic review and Bayesian NMA of randomized controlled trials (RCTs) up to December 31, 2024, following Preferred Reporting Items for Systematic Reviews and Network Meta-Analyses guidelines. Databases (PubMed, Cochrane Library, Scopus, Embase) were searched for RCTs involving NAFLD patients (with or without type 2 diabetes) treated with SGLT-2 inhibitors versus placebo/standard treatments. Outcomes included alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, fibrosis-4 score, body weight, and fasting plasma glucose. A random-effects Bayesian NMA was performed using a Markov Chain Monte Carlo method, with treatments ranked via Surface Under the Cumulative Ranking Curve (SUCRA) scores.
Results:
Eleven RCTs (805 patients) were included. Dapagliflozin led in alanine aminotransferase (mean difference [MD]: -11.35 IU/L, 95% CrI: -18.39 to -4.19, SUCRA: 84.87%), aspartate aminotransferase (MD: -7.96 IU/L, 95% CrI: -15.69 to -0.18, SUCRA: 81.70%), and body weight reduction (MD: -3.60 kg, 95% CrI: -5.92 to -1.64, SUCRA: 88.88%). Ipragliflozin excelled in gamma-glutamyl transferase (MD: -15.19 IU/L, 95% CrI: -31.25 to -2.11, SUCRA: 81.35%) and fasting plasma glucose reduction (MD: -2.20 mmol/L, 95% CrI: -9.88 to 5.30, SUCRA: 59.79%). Empagliflozin topped fibrosis-4 score reduction (MD: -0.12, 95% CrI: -0.42 to 0.13, SUCRA: 73.27%).
Conclusion:
SGLT-2 inhibitors significantly improve liver and metabolic outcomes in NAFLD, with dapagliflozin, ipragliflozin, and empagliflozin offering distinct benefits, supporting personalized treatment strategies.
22
项与 伊格列净L-脯氨酸盐 相关的新闻（医药）2026-05-07
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在现代创新药物发现与开发的漫长链条中，活性药物成分（Active Pharmaceutical Ingredient，简称 API）的物理化学性质往往决定了其最终能否成功跨越从实验室走向临床的“死亡之谷”。面对日益增加的难溶性候选分子，药物固态化学和晶体工程学扮演着至关重要的角色。API 可以以多种固态形式存在，而在药物工业中，最为核心且常见的两种改性策略便是成盐（Salt Formation）与共晶（Cocrystallization）。
本文旨在通过深度的理论剖析与工业实践总结，全面阐述在药物早期及后期开发阶段，如何科学、系统地进行盐与共晶的筛选、评价、放大以及最终的制剂转化。
固态形式的重塑：盐、共晶及其分子本质
1.盐与共晶的化学热力学界定
在分子层面上，盐和共晶的形成机制存在着根本的差异。
盐、共晶和多晶型物的示意图(doi：10.15171/apb.2016.062)
盐的形成基于经典的酸碱化学反应，其核心在于 API 与反离子之间发生了明确的质子转移。这种离子间的静电相互作用不仅极大地改变了分子的极性，更是解决可离子化 API 溶解度低下和生物利用度瓶颈的常规武器。同时，成盐还可以优化药物的熔点、纯度、化学稳定性及吸湿性等关键物理参数。
相比之下，对于那些不具备电离中心，或者受限于 pKa 无法有效成盐的弱酸弱碱类 API，共晶技术提供了一种极具潜力的替代途径。共晶并不涉及质子的转移，而是依赖于组分间（API 与共晶配体）强大的非共价相互作用，主要是氢键的定向自组装。此外，晶体工程学领域还衍生出了第三种更为复杂的固态系统——共晶盐（Salt Cocrystal），即在一个晶格网络中，同时包含了质子转移事件与组分间的氢键组装，为那些难以被传统方法驾驭的 API 提供了额外的调控空间。2.工业界的前沿应用实践
在当今的制药行业，虽然游离酸、游离碱和各类盐型药物已占据了市售药品的主导地位，但共晶技术的崛起正为新药研发注入强劲动力。多家跨国制药巨头已在临床阶段积极推进共晶项目。例如，辉瑞（Pfizer）与默克（Merck）联合研发的 SGLT2 抑制剂埃格列净（Ertugliflozin），其采用的是与焦谷氨酸形成的 1:1 共晶体。
在心血管疾病领域，诺华（Novartis）的重磅炸弹药物诺欣妥（Entresto®）则是一个极为经典的案例，它是一种含有沙库比曲（Sacubitril）和缬沙坦（Valsartan）半水三钠的共晶复合物。
诺欣妥化学结构
在日本，安斯泰来开发的依普列净 L-脯氨酸（Ipragliflozin L-proline）共晶体（Suglat®）已获批用于治疗 2 型糖尿病。这些成功案例无可辩驳地证明了盐与共晶在突破 API 理化性质瓶颈、提升成药性方面的巨大商业价值与临床意义。
探寻最优晶型的路径：多维度的筛选策略
在确认候选药物分子并将其推向深入评价之前，获取具备优异理化特性的盐或共晶形式是不可逾越的步骤。药物开发的阶段不同，其筛选的核心诉求与规模也存在显著差异。1.早期与后期筛选的目标分野
在早期药物开发阶段，主要矛盾在于时间紧迫且物料极度匮乏。此时的目标是快速锁定一种具有“可接受”或“较优”理化性质（如令人满意的结晶度、较低的吸湿性、以及能够支撑早期动物试验的溶解度和生物利用度）的固态形式。研究人员通常会在有目的性的小规模实验中展开探索：例如使用 3~5g 的原料药进行约 100 次筛选实验；若物料更为受限（不足 500mg），则必须依靠高通量筛选（High-Throughput Screening, HTS）平台，该平台能在 <1~5mg 的微量级别下运作。对于只追求最稳定、最难溶形式以评估毒理极限的情况，甚至可以使用 1g 原料药仅开展 25 次精简实验。
当项目步入后期开发，筛选的维度和深度急剧增加。这一阶段不仅需要综合运用手动实验与 HTS 进行 300~400 次的大规模排查，还必须将制剂工艺的应力因素（如微粉化、高剪切共混、湿法或干法制粒）以及长期存储过程中的转晶风险纳入考量。此外，为了最大化药品的生命周期价值，围绕 API 反离子或共晶的多晶型进行全面的知识产权（IP）布局，是后期筛选中极具战略意义的一环。2.反离子与共晶配体的科学选择
无论是成盐还是共晶，配体的选择直接决定了最终晶体的命运。盐的反离子必须是能够供给或接受质子的酸性或碱性实体。共晶配体可以是与成盐所用相同的化合物（前提是环境阻断了质子交换），也可以是依靠氢键、π-π 堆积等非共价力结合的中性分子。
为了确保最终药物的安全性，配体的来源必须受到严格监管。研究人员高度依赖于“公认安全物质”（GRAS）清单以及美国食品中的可添加物质（EAFUS）数据库。从毒理学管理的角度，这些配体通常被分为三大类：
第一类：具有极高安全性、可不受限制使用的物质，它们通常是生理代谢网络中普遍存在的离子或中间产物，是首选的成盐配体。第二类：非天然存在但毒性极低、人体耐受性良好的物质。第三类：具有自身微弱药理活性，仅在特定场景下谨慎使用的物质。使用此类配体时，必须严密复查最新的毒理学文献与安全红线，并密切关注预期剂型的长期累积毒性。如反离子的最大日剂量（MDD）限制，例如对于口服途径，苯磺酸根的最大日剂量约为 160mg，而柠檬酸根则可高达 5250mg。
在物理化学预判上， pKa 差异（ΔpKa = pKa (碱) - pKa (酸)）是一个核心经验法则。当 ΔpKa < 0 时，质子转移的能量壁垒极高，体系最有可能形成共晶；当 ΔpKa > 3 时，热力学驱动力足以引发完全的质子转移，从而稳定形成盐。若该值介于 0 至 3 之间，则体系处于“连续体”的灰色地带，可能生成具有部分质子转移特征的复合物或共晶体。
在共晶设计中，超分子化学中的“合成子”概念被广泛应用。同源合成子（如羧酸形成的二聚体环状结构）与异源合成子（如磺酰胺与羧酰胺的互补配对）构成了晶格中强有力的结构节点。分子间的几何形状契合度与极性互补性极大地提高了共晶的命中率。
共晶形成中常用的典型超分子合成子（doi：10.1021/acsmedchemlett.1c00478）3.手动、自动化高通量与计算预测的交响
结晶过程受限于众多热力学与动力学变量，包括溶剂极性、混合比例、系统温度、降温或升温的梯度速率、过饱和度的演变等。著名晶体学家 Walter McCrone 曾断言，一个化合物能够被发现的多晶型数量，与其上投入的研究时间、经费及实验频次成正比。
高通量筛选（HTS）通过机械臂、自动移液与多孔板（如 96 孔板），突破了人工筛选的通量极限，仅用毫克级样品便可穷尽极其复杂的溶剂配比与孵育条件。HTS 尽管受限于某些极端工艺条件（如受限的蒸发控制或极高温模块），但若辅以精密的实验设计（DOE），仍可覆盖数百次结晶尝试，有效揭示多晶型、水合物、溶剂化物等潜在形式。
同时，计算辅助手段作为一种“预筛选”利器正崭露头角。基于晶格能量的计算、剑桥结构数据库（CSD）的大数据挖掘以及表面静电势的氢键倾向性预测，可以帮助研究人员从成百上千种候选配体中锁定“苗头（Hit）”分子。计算不仅能预测热力学稳定性，甚至能勾勒出药物在特定 pH 值水溶液中的溶解度轮廓线。尽管对盐型进行结构预测因电荷转移和远程静电相互作用更为复杂，但在某些结构已知的前提下，现代算法已经成功预测了诸如盐酸特拉唑嗪（Terazosin Hydrochloride）的无水多晶型物。4.工作流程与表征手段
一个严谨的筛选工作流程应具备闭环的验证逻辑：
①配体选择：严格基于 GRAS 清单与 pKa 导向选择目标分子。
②实验矩阵设计：覆盖宽广的 pH 范围与溶剂极性梯度，探寻任何潜在的降解风险。
③多维度表征：任何疑似的新晶型均需经历 X 射线粉末衍射（XRPD）的指纹图谱确认，热重分析（TGA）与差示扫描量热法（DSC）揭示其热力学事件与溶剂挥发特性，以及核磁共振（NMR）与离子色谱（IC）测定其化学计量比。特别是针对水合物，卡尔·费舍尔（KF）滴定法与动态水分吸附/解吸（DVS）研究至关重要。单晶 X 射线衍射虽为“金标准”，但受限于氢原子散射能力弱，常需结合固态核磁共振（ssNMR）、红外（IR）或拉曼光谱，通过键长及特征官能团振动频率的位移来佐证质子是否发生了真正的转移。
此外，在成功获得首选的盐或共晶后，启动针对该形式的衍生“多晶型物筛选”是防范后期开发风险的关键。这旨在探索其是否存在无水合物、水合物变体，并评估在制剂加工（如高湿环境）下发生歧化变回游离酸碱的风险。
从众多候选者中突围：晶型的综合评估与甄选
获得一系列具有不同化学计量比或结构的盐/共晶后，必须建立科学的决策漏斗或评估矩阵，以确定推向临床的最终先导形式。理想晶型的画像因开发策略而异，但通常需满足以下基准要求：
物理化学稳定性与结晶度：优异的结晶度赋予分子更高的化学惰性。目标形式的熔点应足够高（通常 >100°C）以耐受制剂过程中的热应力，并且在环境相对湿度（60%~75% RH）下不可发生潮解，保证储运安全。溶解行为与溶出动力学：溶解度和溶出速率是 BCSI、II 类药物逆袭的命门。对于口服固体制剂，目标水溶性通常设定在 0.1~10 mg/mL 区间；若为静脉注射剂，则需大于 10mg/mL。值得注意的是，溶解性并非越高越好，若是缓控释制剂，则可能特意追求具有缓慢溶解速率的晶型。形态学特征：优选呈板状或规则块状的晶体，尽量避免极细的针状或易断裂的棱镜状晶体，这直接关系到粉体粉碎、流动性、可压片性等下游制剂工艺顺应性。
在评估含有可电离基团的盐型时，必须深度考量其 pH-溶解度曲线。盐型的总溶解度是质子化形态与游离碱（或游离酸）饱和浓度的总和。在这个动态平衡中，随着环境 pH 跨越关键阈值（如 pHmax），占主导地位的固相会从盐型突变为游离形态，导致溶解度呈现断崖式下降或上升。
跨越放大的鸿沟：结晶工艺的工业化转化
当小试规模（克级）的最优晶型被敲定，随之而来的便是工艺放大。将烧瓶中的沉淀转化为反应釜中吨级的纯粹晶体，需要跨越动力学与热力学的多重鸿沟。
首要原则是溶剂体系的工业友好性。依据 ICH Q3C 指南，应尽量采用低毒性的 3 类溶剂，并确保 API 在预设的操作温度范围内具备可接受的浓度梯度变化。结晶的核心在于控制过饱和度的释放。工业上常用的起晶策略包括梯度降温、反溶剂滴加及减压蒸发等。为了防止不可控的爆发性成核（可能导致生成包裹杂质或形成亚稳态多晶型），通常在介稳区内精准引入目标晶型的“晶种”（添加量一般小于 5%）。这不仅有效引导了宏观形貌的演变，更能严格控制最终产品的粒径分布（PSD）。此外，还需警惕化学反应杂质，例如醇类溶剂与甲磺酸结合极易生成具有极高遗传毒性的甲磺酸酯类杂质，其残留量必须被严酷压制在 10ppm 以下。
在探讨共晶的大规模结晶时，三元相图（Ternary Phase Diagram, TPD） 是不可或缺的导航图。以 API、共晶配体（CCF）与溶剂组成的三元体系，在特定温度下描绘出各类固相（纯 API、纯 CCF、共晶体及各自混合区）与液相的平衡边界。
在咖啡因-戊二酸共晶体系的经典案例中，研究者通过构建不同温度区间的相图，精准地勾勒出了共晶的稳定操作窗口。在结晶设计空间内，不仅要确保产物的化学纯度，还要避免多晶型转化风险（例如咖啡因-戊二酸共晶中的亚稳态晶型 I 向热力学稳定态晶型 II 的相变）。通过过程分析技术（Process Analytical Technology, PAT）在线监测溶液浓度与粒子生长，研究证明采用缓慢的降温速率（0.1°C/min）辅以足够负载量的晶种，可以成功抑制亚稳态晶型的成核，并获得均一饱满的颗粒。除传统溶液结晶外，热熔挤出（HME）、喷雾干燥及高剪切制粒技术也正在成为实现共晶工业化放大的新型工程手段。
典型 HME 仪器的示意图
制剂转化中的动态演变与处方考量
在药物产品的生命周期中，纯净的原料药晶体并不能直接交予患者，必须经过复杂的单元操作（如粉碎、制粒、干燥、压片或冷冻干燥）转化为剂型。而在这些充满机械应力、热应力及湿度波动的过程中，API 的固态形式极其脆弱，常发生工艺诱导的形态转变（Process-Induced Transformations, PIT）。1.机械力与湿热环境的冲击
微粉化或研磨会引入大量机械能，不仅可能导致结晶骨架塌陷生成无定形物质，其产生的高比表面积更容易从环境中吸附水分。例如，硫酸沙丁胺醇（Albuterol Sulfate）在研磨后产生的无定形区域暴露于湿度下会迅速吸水并重新结晶，直接导致粉体结块与颗粒聚集，破坏流动性。
在湿法制粒环节，水或醇类润湿剂的加入是诱发多晶型相变或水合物形成的高危因素。苯磺酸氨氯地平（Amlodipine Besylate）在湿法制粒过程中，其无水物便会部分转化为二水合物。反之，在后续的流化床高温干燥步骤中，原本的水合物可能会失去结晶水，但在后续吸湿平衡时再度水化，导致片剂体积膨胀甚至开裂（如利塞膦酸钠的异常膨胀现象）。2.辅料相容性与微环境 pH 扰动
赋形剂绝非化学惰性的占位符。若辅料具有较强的碱性或酸性，其可能改变局部微环境的 pH 值，从而“夺取”或“捐赠”质子，导致盐型药物发生致命的歧化反应。例如，含有碱性赋形剂的处方在吸收微量水分后，会直接促使甲磺酸苯佐卡因（Benzocaine Mesylate）和甲磺酸咪康唑（Miconazole Mesylate）解离出游离碱，不仅大幅降低了药物的溶出度，还可能引发色泽变化与化学降解。
对于共晶，辅料的干预有时则是正向的。卡马西平-烟酰胺共晶体在水介质中本极易解离转化为卡马西平二水合物，但若在处方中引入微量的高分子聚合物如羟丙基甲基纤维素（HPMC），便能有效抑制晶核的异相形核，维持共晶态的高溶解优势。3.溶出测试中的沉淀风险
即便药品完好无损地被服用，在进入胃肠道或生物模拟流体（如 FaSSIF）后，过饱和度的瞬间释放也可能诱发沉淀。例如，在针对 AMG517 多种共晶体的溶解度测试中，药物一旦溶出便迅速解离，析出了溶解度极低的游离碱水合物。类似地，盐酸氟西汀-富马酸共晶在特定溶出度测试中亦会发生解离并沉淀出盐酸氟西汀，虽然在体内药代动力学（PK）研究中该共晶体依然表现出了更高的生物利用度。这警示我们在设计处方时，必须充分利用沉淀抑制剂来维系过饱和状态。
法规监管差异与知识产权博弈
在这个高度监管的行业中，监管机构对于盐与共晶的定义和分类，直接决定了药品注册申报的路径与耗费。1.FDA 与 EMA 的监管分歧
美国食品药品监督管理局（FDA）在现行法规体系下（21 CFR 314.108），将同一活性分子的不同盐型严格视作“不同的 API”。这意味着若要更换盐型，必须补充详尽的临床试验数据以证实其有效性和安全性。然而，针对共晶，FDA 的最新指南做出了关键性调整：共晶不再被视为一种独立的活性物质变体，而是被归类为与多晶型物相似的管理范畴，并被视作一种特殊形式的“溶剂化物”（其中溶剂成分是不可挥发的中性配体）。因此，不同配体的共晶（前提是配体安全可控）仅需通过生物等效性研究证明其具备可接受的吸收性能即可。
与之不同，欧洲药品管理局（EMA）则采取了更为宽泛和统一的立场。EMA 将同一分子的多晶型物、水合物、溶剂化物、盐以及共晶一视同仁，均不视为“新活性物质（New Active Substance, NAS）”。只要提供充分的交叉引用支持性安全数据及生物等效性结果，即可推进申请注册。ICH Q11 指南进一步明确，如果共晶形成物属于常见化学品，可按试剂对待；若使用了新颖且复杂的配体，则必须呈递全面的生产、表征及质控论证资料。
美国和欧洲药物共晶体的监管状况2.橙皮书与哈奇-瓦克斯曼法案的刀光剑影
为盐、共晶及其多晶型物申请专利，是创新药企构筑知识产权（IP）护城河、延长产品生命周期的核心战略。FDA 发布的《具有等效性评估的获批药品清单》（即著名的“橙皮书”，Orange Book）记录了原研药物的所有有效专利（涵盖化合物组成、制备工艺、特定盐型及多晶型）及排他期。
基于《哈奇-瓦克斯曼法案》（Hatch-Waxman Act），仿制药企业在提交简略新药申请（ANDA）以挑战原研药（上市对照药物，RLD）时，必须做出四项认证声明之一。其中最为激烈的便是“第四段认证（Paragraph IV）”：仿制药企主张橙皮书中列出的某项晶型或盐型专利无效、不可执行，或其仿制工艺使用了全然不同的避专利晶型（未构成侵权）。这往往会引发旷日持久的专利诉讼，制药史上的诸多著名战役，如围绕盐酸雷尼替丁（Ranitidine Hydrochloride）、盐酸帕罗西汀（Paroxetine Hydrochloride）等多晶型与盐型的法律对决，无一不在印证固态化学专利的巨大商业杠杆力。
穿越周期的经典工业案例解析
为了更为具象地阐释上述理论与策略在真实工业环境中的应用，我们回顾两项极具代表性的新药研发案例。1.茚地那韦（Indinavir）：早期盐型切换力挽狂澜
由默克（Merck）公司开发的硫酸茚地那韦（Indinavir Sulfate），是一款被批准用于治疗成人 HIV-1 感染与艾滋病（AIDS）的关键蛋白酶抑制剂。
在研发初期，原计划使用的是茚地那韦的游离碱水合物。然而，该游离碱呈现出极其严重的 pH 依赖性：在胃肠道天然生理 pH（7~7.5）环境下，其水溶解度仅为微乎其微的 0.02 mg/mL，导致口服吸收率极差。
研究人员果断决定进行盐型筛选。分子的解离常数（ pKa）表明，唯有强酸性的反离子才能诱导完全的质子转移并攻克溶解度难关。但棘手的是，茚地那韦在酸性溶液中化学稳定性极差，容易发生水解降解。经过严密筛选，研究团队最终锁定了一种结晶态的硫酸乙醇溶剂化物。该盐型的水溶性飙升至 >500 mg/mL，且水溶液呈酸性（pH < 3）。但该盐型又带来了极强的吸湿性与高湿转晶风险。为了保护这一脆弱但具有救命疗效的晶型，制剂团队量身定制了极为严苛的“干法制粒”工艺，并控制环境相对湿度维持在 <30%，最终实现了长达 2 年以上的保质期。后续临床数据显示，该硫酸盐形式在空腹状态下的血药暴露量显著优于游离碱，成功推向市场。2.阿托伐他汀（Atorvastatin）：后期临床的华丽转身
辉瑞公司（原华纳-兰伯特公司）研发的降脂神药阿托伐他汀钙（Atorvastatin Calcium），属于典型的 BCS II 类分子（高渗透性、低溶解度）。
阿托伐他汀钙化学结构
在 I 期与 II 期临床试验中，药企使用的是其半钙盐对映体的“无定形”粉末。无定形结构以其高能态赋予了药物极佳的溶解度和早期优异的药效表现。
然而，当项目进入需要大规模生产的阶段时，无定形物质的工艺灾难显现：极差的粉末流动性、无法顺利过滤与干燥、以及对热、光照、氧气与水分的极度敏感，使其在大生产中步履维艰。面对这一困局，辉瑞在 III 期临床试验期间进行了战略性转向，成功分离出并转而放大生产了一种结晶体的“三水合物”结构（即著名的晶型 I）。
晶型 I 展现出了压倒性的工业制造优势：更高的化学纯度、无与伦比的固态化学稳定性、优良的干燥过滤性能以及狭窄的粒度分布。尽管理论上无定形和结晶三水合物在吸收率上存在差异，但严格的生物等效性人体试验证明，二者的吸收程度高度一致。这一华丽的晶型切换不仅拯救了产品的工艺链，更为辉瑞赢得了极其强大的专利保护网。辉瑞相继为晶型 I、II、IV 等多达数十种晶型申请了涵盖物质组成及晶型专利的《橙皮书》列名，其中某关键多晶型专利的保护期一直延续至 2016 年 7 月。凭借精准的晶型生命周期管理与专利策略，阿托伐他汀一举成为制药史上最畅销的重磅炸弹药物之一，年销售额连续7年超过100亿美元。
立普妥历年销售额（图源：摩熵医药）
结语
从小试管内配体的氢键组装与质子夺取，到巨型反应釜中晶核的生长与析出；从微观晶格的粉碎研磨，再到法规与专利权杖下的市场角逐——盐与共晶的开发是一项融合了化学热力学、物理药剂学、化学工程学以及法规科学的系统性跨界工程。
在药物生命周期的管理中，通过不断的筛选验证、精密的相图指导放大以及严密的剂型保护，不仅可以化解早期药物因水溶性低下而夭折的风险，更能在产品上市后迭代出更优良的疗效、更低的副作用与更高的患者依从性。盐与共晶作为晶体工程学中最锋利的长矛，将继续在现代药用固体材料的探索之路上开疆拓土。
#创新药#活性药物成分#药物固态化学#晶体工程学
注：本文不构成任何投资意见和建议，以官方/公司公告为准；以上内容仅代表作者观点，如有不科学之处，请在下方留言指正。任何文章转载需要得到授权。
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长效DPP-4抑制剂的研发——奥格列汀，治疗2型糖尿病
点点点，赞和分享都在这儿！
2026-04-11
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截至04月11日15点59分，近期共有 526 本期刊发布了 1043 篇文章，其中糖尿病相关的文章共 331 篇，覆盖 36 个领域的内容。中国专家参与发表的文章有 84 篇。今日，影响因子最高的文章刊登在 Journal of the American Medical Association (IF: 55.000) 期刊上。
今日头条
Headlines
01 Irish journal of medical science IF: 01.600 2型糖尿病患者心房颤动消融：心房快速性心律失常复发及不良心血管事件的长期随访研究
Ardıç, Mustafa Lütfullah, Cetin, Abdullah Eren, Ozdemir, Hasan Burak, Koca, Fadime, Sumbul, Hilmi Erdem, Koc, Mevlut, etc.
一项最新发表的研究显示，2型糖尿病（T2DM）是接受冷冻球囊消融（CBA）治疗心房颤动（AF）患者心房快速性心律失常复发及不良心血管事件的重要独立危险因素。
研究回顾性分析了2013年至2023年间接受CBA治疗的748例阵发性AF患者，其中26%患有T2DM。
结果显示，T2DM组患者心房快速性心律失常复发率（24% vs. 15%，P=0.004）和心血管事件发生率（33% vs. 9%，P=0.045）均显著高于非T2DM组。多因素分析发现，左心房直径（LAd）和T2DM独立预测心房快速性心律失常复发，而男性性别、T2DM、CHA₂DS₂-VASc评分及尿酸水平则独立预测心血管事件。
研究结论指出，T2DM是影响CBA治疗AF长期效果的关键因素，综合管理T2DM对改善CBA治疗结局至关重要。该研究由Mustafa Lütfullah Ardıç等学者完成，为糖尿病患者AF治疗提供了新的风险管控方向。
本文由 韩玉莲 编辑
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Irish journal of medical science | Ahead of Print.
10.1007/s11845-026-04380-5
02 Neuroepidemiology IF: 04.000 中国舟山群岛农民工与当地居民缺血性卒中的流行病学模式：一项横断面研究
Li, Ling, Xu, Yiwei, Liu, Jingjing, Dong, Jiaoxuan, He, Songbin, Dai, Fangyu, etc.
在线发表的中国舟山群岛横断面研究，分析了农民工与当地居民缺血性卒中的流行病学模式及临床特征差异。舟山群岛作为城市化群岛，农民工群体心血管疾病风险受关注，本研究旨在明确其缺血性卒中特点。
研究纳入1006例缺血性卒中患者，其中452例为农民工，554例为当地居民。团队收集临床及影像学数据，采用t检验/非参数检验、卡方检验、二元logistic回归等方法对比两组患者特征，统计显著性设定为P<0.05。
结果显示，与当地居民相比，农民工患者体重指数更高，超重/肥胖比例显著升高；糖尿病和房颤发病率更低。实验室指标中，农民工淋巴细胞、尿酸、叶酸及维生素B12水平更低。影像学方面，两组病因分类无差异，但农民工基底节梗死发生率更高（P<0.05）。
结论指出，农民工缺血性卒中临床特征与当地居民不同，表现为更高BMI、超重/肥胖比例及基底节梗死发生率，更低糖尿病和房颤发病率。提示城市化群岛环境中需针对农民工开展针对性预防性医疗干预。
本文由 韩玉莲 编辑
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Neuroepidemiology | Ahead of Print.
10.1159/000551939
03 Frontiers in endocrinology IF: 04.600 温度和湿度对糖尿病患者舌色的依赖型交互作用：定量分析及中医视角
Zhang, Bingnan, Zhang, Naijin, Ren, Huixia, Li, Yonghui, Du, Haiyan, Ren, Tingjing, etc.
本研究通过对1711名糖尿病患者的多中心回顾性研究，首次量化验证了温度和相对湿度（以11月-次年4月为冷季、5-10月为热季） 对舌色的影响。
研究将参与者分为无糖尿病、单纯糖尿病、糖尿病合并高血压、糖尿病合并冠心病、糖尿病合并高血压和冠心病五组，采用TFDA-1舌诊仪采集舌色RGB数据（5个部位×3色，共30个指标），并通过多元线性回归分析发现：糖尿病患者舌色与温湿度存在显著交互作用，其中糖尿病合并高血压和冠心病的患者在高温高湿季节（7-8月） 舌色显著变红（P<0.0001），而无糖尿病组全年舌色稳定。
进一步主成分分析显示，舌体中部R值 对温湿度最敏感，且与并发症数量呈剂量反应关系（P<0.05）。
这些结果为中医“天人相应”理论提供了现代科学支持，提示舌色可作为高温高湿环境下糖尿病心血管代谢风险的动态生物标志物。
本文由 韩玉莲 编辑
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Frontiers in endocrinology | Volume 17, Issue
10.3389/fendo.2026.1772207
中国发表（84）
China
Chin J Integr Med IF: 02.500Ahead of Print.No.01Mechanisms of Tianma Gouteng Yin in Treating Hypertension-Associated Vascular Cognitive Impairment: Insights from Experiments, Network Pharmacology, and Molecular Docking天麻钩藤饮治疗高血压相关血管性认知障碍的机制：实验、网络药理学和分子对接的见解DOI: 10.1007/s11655-026-4039-6
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Free radical biology & medicine IF: 08.200Ahead of Print.No.09Echinacoside Improves Antioxidant Responses and Angiogenesis Through Parkin-MFN2-Mediated Mitophagy to Promote Diabetic Wound Healing松果菊苷通过Parkin-MFN2介导的线粒体自噬改善抗氧化反应和血管生成以促进糖尿病创面愈合DOI: 10.1016/j.freeradbiomed.2026.04.012
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Biomedical materials IF: 03.700Ahead of Print.No.11Multifunctional eutectogel for co-delivery of baicalein and metformin to promote diabetic wound healing多功能共晶凝胶用于黄芩素和二甲双胍的共递送以促进糖尿病伤口愈合DOI: 10.1088/1748-605X/ae5e13
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Int J Oral Sci IF: 12.200Volume 18, Issue 1No.21The structure and function of taste G protein-coupled receptors and their implications in diseases味觉G蛋白偶联受体的结构、功能及其在疾病中的意义DOI: 10.1038/s41368-026-00436-5
J Int Med Res IF: 01.500Volume 54, Issue 4No.22Association between cardiometabolic index and high-sensitivity C-reactive protein: A cross-sectional study from National Health and Nutrition Examination Survey 2015 to 2018心脏代谢指数与高敏C反应蛋白的关联：基于2015-2018年美国国家健康与营养检查调查的横断面研究DOI: 10.1177/03000605261436654
Environmental pollution IF: 07.300Ahead of Print.No.23Gender-Specific Association between Household Cooking Oil Fume exposure and Small Airway Dysfunction in China: a national cross-sectional study中国家庭烹饪油烟暴露与小气道功能障碍的性别特异性关联：一项全国性横断面研究DOI: 10.1016/j.envpol.2026.128094
IF: 03.700Ahead of Print.No.24FTO-mediated m6A demethylation inhibits bladder cancer progression via decreasing EMG1 and reducing ribosome biosynthesisFTO介导的m6A去甲基化通过降低EMG1和减少核糖体生物合成抑制膀胱癌进展DOI: 10.1016/j.bbamcr.2026.120147
JCTS IF: 01.500Ahead of Print.No.25de Winter-like anterior electrocardiographic changes coexisting with inferior ST-elevation myocardial infarction: a case report and literature insight类似De Winter型前壁心电图改变并存下壁ST段抬高型心肌梗死：病例报告及文献解读DOI: 10.1186/s13019-026-04031-x
BMC pregnancy and childbirth IF: 02.700Ahead of Print.No.26Association between maternal thyroid function and adverse outcomes of pregnant women and offspring: evidence from an umbrella review孕妇甲状腺功能与孕妇及后代不良结局的关联：来自总览综述的证据DOI: 10.1186/s12884-026-09024-1
Phytomedicine IF: 08.300Ahead of Print.No.27Amygdalin alleviates MAFLD via inhibiting cytoplasmic calcium ion overload-induced liver sinusoidal endothelial cell defenestration苦杏仁苷通过抑制细胞质钙离子超载诱导的肝血窦内皮细胞窗孔缺失来缓解代谢功能障碍相关脂肪性肝病DOI: 10.1016/j.phymed.2026.158135
Food chemistry IF: 09.800Ahead of Print.No.28Deciphering the molecular mechanism of DPP-IV inhibition by quinoa-derived peptides: Insights from kinetics, spectroscopy, and in silico perspectives破译藜麦来源肽对DPP-IV抑制的分子机制：来自动力学、光谱学和计算机模拟视角的见解DOI: 10.1016/j.foodchem.2026.149169
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Medicine IF: 01.400Volume 105, Issue 15No.30Visceral adipose tissue and risk of kidney stones: Evidence from NHANES 2011-2018 and Mendelian randomization analysis内脏脂肪组织与肾结石风险：来自NHANES 2011-2018的数据及孟德尔随机化分析的证据DOI: 10.1097/MD.0000000000048216
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Medicine IF: 01.400Volume 105, Issue 15No.33Celiac disease increases the risk of pulmonary arterial hypertension: A multivariable Mendelian randomization and mediation analysis乳糜泻增加肺动脉高压风险：一项多变量孟德尔随机化与中介分析DOI: 10.1097/MD.0000000000048334
Medicine IF: 01.400Volume 105, Issue 15No.34Association between urinary cadmium exposure and metabolic syndrome and the mediating role of thyroid dysfunction: NHANES 2007 to 2012尿镉暴露与代谢综合征的关联及甲状腺功能障碍的中介作用：2007-2012年NHANES研究DOI: 10.1097/MD.0000000000048230
Medicine IF: 01.400Volume 105, Issue 15No.35Diabetes, obesity, hyperlipidemia, and sudden sensorineural hearing loss: A bidirectional and multivariable Mendelian randomization study糖尿病、肥胖、高脂血症与突发性感音神经性听力损失：一项双向多变量孟德尔随机化研究DOI: 10.1097/MD.0000000000048255
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Medicine IF: 01.400Volume 105, Issue 15No.37Urinary bladder obstruction caused by fungal balls: Unusual computed tomography findings - a case report真菌球导致的膀胱梗阻：不寻常的CT表现——病例报告DOI: 10.1097/MD.0000000000048244
Medicine IF: 01.400Volume 105, Issue 15No.38Association between serum dehydroepiandrosterone sulfate and type 2 diabetes in US adults with adiposity as a mediator血清脱氢表雄酮硫酸盐与美国成年人2型糖尿病的关联（以肥胖为中介）DOI: 10.1097/MD.0000000000048280
Medicine IF: 01.400Volume 105, Issue 15No.39Association between the endothelial activation and stress index and cardiometabolic multimorbidity: Results from the NHANES 2003 to 2020内皮激活和应激指数与心脏代谢共病的关联：来自美国国家健康与营养检查调查2003-2020的结果DOI: 10.1097/MD.0000000000048226
Journal of robotic surgery IF: 03.000Volume 20, Issue 1No.40Robotic versus laparoscopic surgery for rectal cancer in overweight and obese patients: pathological outcomes, complications, and trial sequential analysis超重和肥胖患者直肠癌的机器人手术与腹腔镜手术：病理结果、并发症及试验序贯分析DOI: 10.1007/s11701-026-03394-6
Singapore Medical Journal IF: 01.900Ahead of Print.No.41Metabolic dysfunction-associated steatotic liver disease in Asia: implications on management亚洲代谢功能障碍相关脂肪性肝病：对管理的影响DOI: 10.4103/singaporemedj.SMJ-2025-167
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The FASEB journal : IF: 04.200Volume 40, Issue 8No.43BGP-15 Mitigates Oxidative Stress and Mitochondrial Dysfunction in In Vitro Matured Oocytes From Type 1 Diabetic MiceBGP-15缓解1型糖尿病小鼠体外成熟卵母细胞中的氧化应激和线粒体功能障碍DOI: 10.1096/fj.202505013RR
Ophthalmology and therapy IF: 03.200Ahead of Print.No.44Efficacy, Durability, and Safety of Faricimab for Diabetic Macular Edema: 1-Year Results from the China RHINE SubpopulationFaricimab治疗糖尿病黄斑水肿的有效性、持久性及安全性：中国RHINE亚组的1年结果DOI: 10.1007/s40123-026-01378-1
J Bioenerg Biomembr IF: 03.000Volume 58, Issue 1No.45USF1 transcriptionally activates TRIM55 to promote diabetic cardiomyopathy progression by enhancing HSPB1 protein degradationUSF1通过转录激活TRIM55促进糖尿病心肌病进展（增强HSPB1蛋白降解）DOI: 10.1007/s10863-026-10107-z
The FASEB journal : IF: 04.200Volume 40, Issue 8No.46CTNNB1 Genetic Variation and Its Interaction With DLK1 in Type 2 Diabetes MellitusCTNNB1基因变异及其与DLK1在2型糖尿病中的相互作用DOI: 10.1096/fj.202600107R
Renal failure IF: 03.000Volume 48, Issue 1No.47Resveratrol inhibits renal ischemia and reperfusion injury in diabetes via reducing oxidative stress, inflammation, and apoptosis白藜芦醇通过降低氧化应激、炎症和凋亡抑制糖尿病肾缺血再灌注损伤DOI: 10.1080/0886022X.2026.2652103
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Frontiers in public health IF: 03.400Volume 14, Issue No.49High rate of marginal vitamin A deficiency in children aged 0-6 years in Quanzhou, China: a cross-sectional study中国泉州0-6岁儿童维生素A边缘性缺乏高患病率：一项横断面研究DOI: 10.3389/fpubh.2026.1727761
Frontiers in nutrition IF: 05.100Volume 13, Issue No.50CT-assessed abdominal visceral adiposity and MASLD: a sex-stratified cross-sectional analysis性别分层及非线性分析：腹部脂肪分布与代谢功能障碍相关脂肪性肝病（MASLD）的关联DOI: 10.3389/fnut.2026.1750470
Frontiers in endocrinology IF: 04.600Volume 17, Issue No.51The impact of bariatric surgery on male sexual function: a systematic review and meta-analysis减重手术对男性性功能的影响：一项系统综述与荟萃分析DOI: 10.3389/fendo.2026.1798050
Renal failure IF: 03.000Volume 48, Issue 1No.52Emerging roles of ATP citrate lyase in kidney diseases: from pathogenic driver to therapeutic target三磷酸腺苷柠檬酸裂合酶在肾脏疾病中的新兴作用：从致病驱动因素到治疗靶点DOI: 10.1080/0886022X.2026.2652826
J Health Popul Nutr IF: 02.800Ahead of Print.No.53Obesity, physical activity, and gene-environment interactions: a natural experiment framework肥胖、体力活动与基因-环境相互作用：一种自然实验框架DOI: 10.1186/s41043-026-01312-y
Frontiers in nutrition IF: 05.100Volume 13, Issue No.54Associations between lipid-derived indices and cardiovascular-kidney-metabolic syndrome progression among Chinese middle-aged and elderly adults: a longitudinal study脂质衍生指标与心血管-肾脏-代谢综合征患者心血管疾病风险的关系：一项回顾性队列研究DOI: 10.3389/fnut.2026.1742974
Frontiers in pediatrics IF: 02.000Volume 14, Issue No.55Risk factors for necrotizing enterocolitis in preterm infants: a 1:1 matched case-control study早产儿坏死性小肠结肠炎的危险因素：一项回顾性队列研究DOI: 10.3389/fped.2026.1807022
Frontiers in endocrinology IF: 04.600Volume 17, Issue No.56The effect of continuous glucose monitoring on neonatal outcomes in pregnant women with diabetes合并糖尿病的妊娠中持续葡萄糖监测：随机对照试验的系统综述与荟萃分析DOI: 10.3389/fendo.2026.1815133
China CDC weekly IF: 02.900Volume 8, Issue 10No.57Association Between Longitudinal Serum Ferritin and Gestational Diabetes Mellitus - Beijing, Shanxi, and Shandong PLADs, China, 2021-2024中国人群中孕早期和孕中期血清铁蛋白与妊娠糖尿病的关联：一项多中心前瞻性队列研究DOI: 10.46234/ccdcw2026.044
BMC pregnancy and childbirth IF: 02.700Ahead of Print.No.58Association of mid-pregnancy remnant cholesterol levels with adverse pregnancy outcomes in women with gestational diabetes mellitus妊娠期糖尿病女性妊娠中期残余胆固醇水平与不良妊娠结局的关联DOI: 10.1186/s12884-026-09031-2
Journal of pregnancy IF: 02.200Volume 2026, Issue 1No.59A Qualitative Study on TPB-Based Factors for Breastfeeding Cessation in Women With Gestational Diabetes Mellitus in the Early Postpartum Period一项基于计划行为理论（TPB）的妊娠期糖尿病女性产后早期母乳喂养中断因素的定性研究DOI: 10.1155/jp/5369691
Front Cell Dev Biol IF: 04.300Volume 14, Issue No.60ChatGPT-5 versus other mainstream large language models in core diabetic retinopathy patient queries五种主流大语言模型在糖尿病视网膜病变健康教育和患者分诊中的比较分析DOI: 10.3389/fcell.2026.1754221
Materials today bio IF: 10.200Volume 38, Issue No.61Glucose modulates macrophage polarization via glycating adsorbed albumin on titanium葡萄糖通过钛表面糖化吸附白蛋白调节巨噬细胞极化DOI: 10.1016/j.mtbio.2026.103047
Frontiers in pharmacology IF: 04.800Volume 17, Issue No.62The influence of tranexamic acid on intraoperative blood transfusion in short-segment PLIF and analysis of influencing factors of the transfusion: a retrospective case study氨甲环酸减少短节段腰椎椎间孔融合术中失血和输血：一项回顾性研究DOI: 10.3389/fphar.2026.1736382
Frontiers in endocrinology IF: 04.600Volume 17, Issue No.63Helicobacter pylori infection is independently associated with triglyceride levels: a propensity score-matched cross-sectional study幽门螺杆菌感染与甘油三酯水平独立相关：一项倾向评分匹配的横断面研究DOI: 10.3389/fendo.2026.1792530
Frontiers in endocrinology IF: 04.600Volume 17, Issue No.64Prevalence, risk factors, and early prediction of cognitive impairment in patients with diabetes mellitus: a systematic review and meta-analysis糖尿病患者认知障碍的系统综述与荟萃分析DOI: 10.3389/fendo.2026.1757367
Frontiers in endocrinology IF: 04.600Volume 17, Issue No.65Temperature and humidity-dependent interaction effects on tongue color in diabetic patients: a quantitative analysis and TCM perspective温度和湿度对糖尿病患者舌色的依赖型交互作用：定量分析及中医视角DOI: 10.3389/fendo.2026.1772207
Frontiers in endocrinology IF: 04.600Volume 17, Issue No.66Efficacy and safety of different anti-VEGF agents combined with pars plana vitrectomy in proliferative diabetic retinopathy: a systematic review and network meta-analysis of randomized controlled trials抗血管内皮生长因子药物联合经扁平部玻璃体切割术治疗增殖性糖尿病视网膜病变的有效性和安全性：一项网络荟萃分析DOI: 10.3389/fendo.2026.1772351
Frontiers in endocrinology IF: 04.600Volume 17, Issue No.67Cross-sectional analysis of the association between physical activity and metabolic syndrome in the elderly社区居住老年人中体力活动与代谢综合征的关联：一项横断面研究DOI: 10.3389/fendo.2026.1799367
Frontiers in endocrinology IF: 04.600Volume 17, Issue No.68Real-world performance of open-source large language models in diabetes diagnosis临床糖尿病诊断中的开源大语言模型：亚分型、并发症及提示策略的综合评估DOI: 10.3389/fendo.2026.1747468
Frontiers in endocrinology IF: 04.600Volume 17, Issue No.69Epigenetic dichotomy in florid vs. gliotic proliferative diabetic retinopathy: hypomethylation of EGLN1 and MMP9 drives divergent pathogenic pathways in angiogenesis and fibrosis增殖性糖尿病视网膜病变亚型（旺炽型vs纤维增生型）表观遗传特征的差异甲基化模式DOI: 10.3389/fendo.2026.1664104
Front Bioeng Biotechnol IF: 04.800Volume 14, Issue No.70Hydroxypropyl methylcellulose stearoxy ether hydrogel loaded with aloe vera peel-derived extracellular vesicle mimetics promotes wound healing in diabetic mice芦荟皮来源细胞外囊泡模拟物通过Sangeose 60L水凝胶递送促进糖尿病伤口愈合DOI: 10.3389/fbioe.2026.1768930
Ophthalmology science IF: 04.600Volume 6, Issue 5No.71Using OCT Angiography to Predict Diabetic Retinopathy Progression and Vision Decline in a Multiethnic CohortOCT血管造影预测糖尿病视网膜病变进展及视力下降的多中心研究DOI: 10.1016/j.xops.2026.101111
Frontiers in immunology IF: 05.900Volume 17, Issue No.72Recent advances in the positive role of Clostridium in autoimmune diseases: as a crucial regulator of restoring immune-metabolic equilibrium有益梭菌及其代谢物在自身免疫性疾病中的作用：综合综述DOI: 10.3389/fimmu.2026.1730351
Frontiers in medicine IF: 03.000Volume 13, Issue No.73Longitudinal associations between treatment adherence patterns and blood pressure control among rural hypertensive patients in Central China: a real-world retrospective cohort study现实世界基层医疗环境中血压控制的时间趋势及预测因素：一项纵向队列研究DOI: 10.3389/fmed.2026.1791265
Chemistry & biodiversity IF: 02.500Volume 23, Issue 4No.74Rapid Identification of Chemical Components and Prediction of Medicinal Value for Blachia Siamensis Leaves暹罗黑面神叶的化学成分快速鉴定及药用价值预测DOI: 10.1002/cbdv.202503300
Zhonghua Wei Zhong Bing Ji Jiu Yi XueVolume 38, Issue 3No.75[Predictive value of the modified Nutrition Risk in Critically Ill Score for intensive care unit mortality risk in septic patients]改良型重症患者营养风险评分（mNUTRIC）对脓毒症患者ICU死亡率风险的预测价值DOI: 10.3760/cma.j.cn121430-20250716-00390
Front Cell Dev Biol IF: 04.300Volume 14, Issue No.76MicroRNA, MicroRNA-lncRNA and MicroRNA-Circular RNA axes, and exosomal MicroRNAs: driving exercise-induced cardioprotection in heart failure运动诱导心脏保护中的非编码RNA：机制、生物标志物及治疗潜力DOI: 10.3389/fcell.2026.1767057
Current opinion in physiology IF: 01.900Volume 46, Issue No.77Caveolin in extracellular vesicles: orchestrating interorgan communication in diabetes-associated cardiovascular disease(☆)窝蛋白在小细胞囊泡中：调控糖尿病相关心血管疾病中的器官间通讯DOI: 10.1016/j.cophys.2025.100862
Journal of oral microbiology IF: 05.500Volume 18, Issue 1No.78Association between oral microbial shifts and polycystic ovary syndrome: a systematic review多囊卵巢综合征中的口腔微生物群失调：系统综述与荟萃分析DOI: 10.1080/20002297.2026.2650921
Frontiers in immunology IF: 05.900Volume 17, Issue No.79Role of Treg cells in diabetes mellitus and association with traditional Chinese medicine: a literature review调节性T细胞（Tregs）在糖尿病及其并发症中的作用：综述DOI: 10.3389/fimmu.2026.1763798
J Cell Mol Med IF: 04.200Volume 30, Issue 7No.80Exploration of the Potential Mechanism of Metal Ion Transport-Related Genes in Myocardial Infarction Based on Transcriptomics基于转录组学探索心肌梗死中金属离子转运相关基因的潜在机制DOI: 10.1111/jcmm.71134
Frontiers in endocrinology IF: 04.600Volume 17, Issue No.81The diagnostic value of immune-inflammatory markers for diabetic kidney disease in type 2 diabetic patients: a meta-analysis2型糖尿病患者免疫炎症标志物对糖尿病肾病的诊断价值：一项荟萃分析DOI: 10.3389/fendo.2026.1811189
Zhonghua Wei Zhong Bing Ji Jiu Yi XueVolume 38, Issue 3No.82[Risk factors for critical illness-related corticosteroid insufficiency in sepsis and construction of nomogram prediction model]脓毒症中危重病相关皮质类固醇功能不全的危险因素及列线图预测模型的构建DOI: 10.3760/cma.j.cn121430-20250616-00587
Frontiers in endocrinology IF: 04.600Volume 17, Issue No.83Clinical efficacy of combining fenofibrate with statins in patients with diabetes and hyperlipidemia: a meta-analysis非诺贝特与他汀类药物联合治疗糖尿病合并高脂血症患者的Meta分析DOI: 10.3389/fendo.2026.1694928
Journal of diabetes research IF: 03.400Volume 2026, Issue 1No.84Effectiveness of Wearable Devices for Diabetes Management: An Overview of Systematic Reviews and Meta-Analyses可穿戴设备用于糖尿病管理的有效性：系统综述和荟萃分析概述DOI: 10.1155/jdr/1464982
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BMC medical imaging IF: 03.200Ahead of Print.No.02Automated MRI-based brain volumetric analysis in women with polycystic ovary syndrome多囊卵巢综合征女性的基于MRI的大脑体积自动分析DOI: 10.1186/s12880-026-02336-w
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J Nutr Biochem IF: 04.900Ahead of Print.No.04Small litter size attenuates adverse hepatic effects induced by a high-sucrose diet小窝产仔数减少可减轻高蔗糖饮食诱导的肝脏不良影响DOI: 10.1016/j.jnutbio.2026.110372
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BMC medicine IF: 08.300Volume 24, Issue 1No.12Interventions to prevent and treat multiple long-term conditions and their consequences across the life course: concepts and definitions干预措施预防和治疗生命全程中的多种长期疾病及其后果：概念和定义DOI: 10.1186/s12916-026-04838-4
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J Expo Sci Environ Epidemiol IF: 04.700Ahead of Print.No.17Bisphenol S and female reproductive toxicity: a scoping review of human studies双酚S与女性生殖毒性：人类研究的范围综述DOI: 10.1038/s41370-026-00868-5
Pediatric research IF: 03.100Ahead of Print.No.18Antibodies to mannose-binding lectin and factor XI Inhibit Shiga toxin-induced kidney injury additively in a murine model针对甘露聚糖结合凝集素和XI因子的抗体在小鼠模型中对志贺毒素诱导的肾损伤具有叠加抑制作用DOI: 10.1038/s41390-025-04535-7
Scientific reports IF: 03.900Ahead of Print.No.19Comparison of biochemical oxidative stress markers of glucose tolerance tests performed for葡萄糖耐量试验的生化氧化应激标志物比较DOI: 10.1038/s41598-026-45946-8
Nature communications IF: 15.700Ahead of Print.No.20Pervasive non-triplet alternative splicing drives functional isoform diversity普遍的非三联体选择性剪接驱动功能性异构体多样性DOI: 10.1038/s41467-026-71615-5
Nature communications IF: 15.700Volume 17, Issue 1No.21Exposome-wide patterns predict brain health in aging全暴露组模式预测衰老中的大脑健康DOI: 10.1038/s41467-026-71271-9
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Clin Microbiol Infect IF: 08.500Ahead of Print.No.29Pharmacokinetic and Pharmacodynamic Evaluations of Oral Moxifloxacin for Enterococcus faecalis Endocarditis口服莫西沙星对粪肠球菌心内膜炎的药代动力学和药效学评估DOI: 10.1016/j.cmi.2026.04.001
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Biochem Biophys Res Commun IF: 02.200Ahead of Print.No.31ADAMDEC1 is not a driver of intestinal fibrosis but a marker of the inflammation-stromal niche in Crohn's diseaseADAMDEC1不是肠道纤维化的驱动因素，而是克罗恩病中炎症-基质微环境的标志物DOI: 10.1016/j.bbrc.2026.153749
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BMC medicine IF: 08.300Volume 24, Issue 1No.35Why hyperinsulinemia is detrimental to weight loss: insights from type 1 diabetes高胰岛素血症为何不利于减肥：来自1型糖尿病的见解DOI: 10.1186/s12916-026-04849-1
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J Laparoendosc Adv Surg Tech A IF: 01.100Ahead of Print.No.37Hiatal Hernia Following a Sleeve Gastrectomy袖状胃切除术后的食管裂孔疝DOI: 10.1177/10926429261420529
Surg Obes Relat Dis IF: 03.800Ahead of Print.No.38International expert consensus on definitions and management of weight recurrence and suboptimal response after metabolic and bariatric surgery: a Delphi study国际专家共识：代谢与减重手术后体重复发及反应不佳的定义与管理——一项德尔菲研究DOI: 10.1016/j.soard.2026.03.006
Sleep health IF: 03.400Ahead of Print.No.39Objective prediction of siesta based on machine learning and association with obesity基于机器学习的午睡客观预测及其与肥胖的关联DOI: 10.1016/j.sleh.2026.02.007
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BMJ case reports IF: 00.500Volume 19, Issue 4No.41Awake video laryngoscopy and tracheal intubation in a super morbidly obese critically ill patient with a physiologically difficult airway清醒视频喉镜检查与气管插管在超级病态肥胖重症患者（伴生理困难气道）中的应用DOI: 10.1136/bcr-2025-269211
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Neuroscience letters IF: 02.000Ahead of Print.No.44The exposure to the air pollutant fine particulate matter (PM(2.5)) slightly enhances high-fat diet-induced anxiety-like behavior and impairs brain redox balance in female rats空气污染物细颗粒物(PM2.5)暴露略微增强高脂饮食诱导的雌性大鼠焦虑样行为并损害脑氧化还原平衡DOI: 10.1016/j.neulet.2026.138599
J Am Pharm Assoc (2003)Ahead of Print.No.45Real-world weight impact upon tirzepatide discontinuation at a single-center endocrinology clinic in patients with overweight or obesity单中心内分泌诊所中超重或肥胖患者停用替尔泊肽后的真实体重影响DOI: 10.1016/j.japh.2026.103112
Clinical nutrition ESPEN IF: 02.600Ahead of Print.No.46Indirect relationship between alexithymia and binge eating disorder in the context of obesity肥胖背景下述情障碍与暴饮暴食障碍的间接关系DOI: 10.1016/j.clnesp.2026.103274
Brain research bulletin IF: 03.700Ahead of Print.No.47Exposure to a High-Fat Diet Compromises Gut Health, Behavior, and HPA Axis Function, with Partial Reversal When Limited to Adolescence暴露于高脂饮食会损害肠道健康、行为和HPA轴功能，青春期限制暴露后部分逆转DOI: 10.1016/j.brainresbull.2026.111883
The American journal of surgery IF: 02.700Ahead of Print.No.48Patient perspectives on access to bariatric surgical care in the Deep South: A qualitative study美国南部地区患者获取减重手术护理的观点：一项定性研究DOI: 10.1016/j.amjsurg.2026.116973
Nutrition IF: 03.000Ahead of Print.No.49The effect of ultra-processed food reduction in an attempt to control abdominal pain after Roux-Y gastric bypass: A retrospective cohort study减少超加工食品以控制Roux-Y胃旁路术后腹痛的效果：一项回顾性队列研究DOI: 10.1016/j.nut.2026.113182
Atención primaria IF: 01.600Ahead of Print.No.50[Anti-obesity drugs and potential changes in the epidemiology of this condition and in cardiovascular risk factors]抗肥胖药物及该疾病流行病学和心血管危险因素的潜在变化DOI: 10.1016/j.aprim.2026.103496
Chemosphere IF: 08.100Ahead of Print.No.51Exposure to lead on children's intellectual functioning: A target trial with multimedia biomarkers in Mexico City儿童智力功能的铅暴露：墨西哥城采用多介质生物标志物的目标试验DOI: 10.1016/j.chemosphere.2026.144932
BMJ case reports IF: 00.500Volume 19, Issue 4No.52Leydig cell ovarian tumour: a rare cause of hyperandrogenism卵巢间质细胞瘤：高雄激素血症的罕见原因DOI: 10.1136/bcr-2025-268251
Clin Exp Nephrol IF: 01.700Ahead of Print.No.53Effects of individual sodium-glucose cotransporter-2 inhibitors on all-cause mortality in patients with diabetic kidney disease个体化钠-葡萄糖协同转运蛋白2抑制剂对糖尿病肾病患者全因死亡率的影响DOI: 10.1007/s10157-026-02865-2
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Hypertension Research IF: 04.600Ahead of Print.No.58The effects of glucagon-like peptide-1 receptor agonists on sympathetic neuron activity胰高血糖素样肽-1受体激动剂对交感神经元活动的影响DOI: 10.1038/s41440-026-02633-5
Clinical nutrition ESPEN IF: 02.600Ahead of Print.No.59The Impact of Malnutrition and Probable Sarcopenia on Mortality in Older Patients with Type 2 Diabetes营养不良和可能的肌少症对老年2型糖尿病患者死亡率的影响DOI: 10.1016/j.clnesp.2026.103273
Scientific reports IF: 03.900Ahead of Print.No.60Metabolic determinants of torque teno virus load across the diabetes spectrum: insights from a cross-sectional analysis跨糖尿病谱的转矩骨病毒载量的代谢决定因素：来自横断面分析的见解DOI: 10.1038/s41598-026-47810-1
Obes Res Clin Pract IF: 02.300Ahead of Print.No.61Bariatric surgery reverses blunted blood pressure reactivity to cold-induced stress in patients with severe obesity减重手术逆转严重肥胖患者对冷诱导应激的血压反应迟钝DOI: 10.1016/j.orcp.2026.03.005
Clinical nutrition ESPEN IF: 02.600Ahead of Print.No.62TRIGLYCERIDE-RELATED LIPID CHANGES IN ADULTS WITH CYSTIC FIBROSIS TREATED WITH ELEXACAFTOR/TEZACAFTOR/IVACAFTOR: A REAL-WORLD CROSS-SECTIONAL STUDY使用依伐卡托/泰泽卡托/依伐卡托治疗的囊性纤维化成人患者的甘油三酯相关脂质变化：一项真实世界横断面研究DOI: 10.1016/j.clnesp.2026.103275
Arch Gerontol Geriatr IF: 03.800Ahead of Print.No.63Efficacy of telephone-based health counseling with wearable device-Smartphone monitoring in older adults with metabolic syndrome: A randomized controlled trial基于可穿戴设备（智能手机监测）的电话健康咨询对代谢综合征老年患者的有效性：一项随机对照试验DOI: 10.1016/j.archger.2026.106232
Pediatric neurology IF: 02.100Ahead of Print.No.64Caring for Gender Diverse Youth With Duchenne Muscular Dystrophy: A Multisite Case Series关怀性别多样化杜氏肌营养不良症青年：多中心病例系列研究DOI: 10.1016/j.pediatrneurol.2026.03.018
EClinicalMedicine IF: 10.000Ahead of Print.No.65Weight trajectories and obesity onset between 17 and 60 years of age, and cause-specific mortality: the Obesity and Disease Development Sweden (ODDS) pooled cohort study成年男性和女性的体重增加轨迹与死亡率：ODDS队列研究DOI: 10.1016/j.eclinm.2026.103870
Int Arch Allergy Immunol IF: 01.800Ahead of Print.No.66Bioinformatics Analysis and Animal Experiments Revealed the Potential Role of IGFBP3 in Allergic Rhinitis生物信息学分析和动物实验揭示IGFBP3在过敏性鼻炎中的潜在作用DOI: 10.1159/000551921
Journal of medicinal food IF: 02.000Ahead of Print.No.67Coffee Berry Pulp Extract Improves Hepatic Lipid Metabolism and Reduces Triglyceride Levels in High-Fat, High-Fructose Diet-Fed Mice咖啡浆果提取物改善高脂高果糖饮食喂养小鼠的肝脏脂质代谢并降低甘油三酯水平DOI: 10.1177/1096620X261441411
Dermatology IF: 02.700Ahead of Print.No.68Efficacy of Gabapentin Combined with Standard-dose Antihistamines versus Antihistamine Monotherapy in Prurigo Nodularis: A Prospective Monocentric Real-world Observational Study加巴喷丁联合标准剂量抗组胺药与抗组胺药单药治疗结节性痒疹的有效性：一项前瞻性单中心真实世界观察性研究DOI: 10.1159/000551865
PloS one IF: 02.600Volume 21, Issue 4No.69Examining the mediating effects of metabolic syndrome components on the relationship between dairy product consumption and nonalcoholic fatty liver disease in Korean adults韩国成年人中代谢综合征组分对乳制品摄入与非酒精性脂肪肝关系的中介作用研究DOI: 10.1371/journal.pone.0346774
J Neurosurg Pediatr IF: 02.100Ahead of Print.No.70Endoscopic disconnection of hypothalamic hamartoma: an already outdated story?内镜下下丘脑错构瘤切断术：是否已过时？DOI: 10.3171/2025.11.PEDS25377
Wiadomo?ci LekarskieVolume 79, Issue 3No.71The gut-brain axis and its role in obesity-induced homeostatic dysregulation肠脑轴及其在肥胖诱导的体内平衡失调中的作用DOI: 10.36740/WLek/218289
Wiadomo?ci LekarskieVolume 79, Issue 3No.72Body mass index as a determinant of surgical outcomes in total hip arthroplasty体重指数作为全髋关节置换术手术结果的决定因素DOI: 10.36740/WLek/218174
Hepatology : IF: 15.800Ahead of Print.No.73Genetic risk of steatotic liver disease: Pathogenesis, prognosis, and implications for treatment脂肪性肝病的遗传风险：发病机制、预后及治疗意义DOI: 10.1097/HEP.0000000000001758
JMIR formative research IF: 02.100Volume 10, Issue No.74Evaluating an Incentive-Based mHealth App for Physical Activity Promotion Using the Obesity-Related Behavioral Intervention Trial Model: Small Cohort Study基于激励的移动健康应用促进体力活动：使用与肥胖相关的行为干预试验模型的小队列研究DOI: 10.2196/85484
J Paediatr Child Health IF: 01.400Ahead of Print.No.75Effects of Probiotic and Synbiotic Supplementation on Metabolic and Hepatic Outcomes in Children and Adolescents With Obesity, Including Those With Obesity-Related Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis益生菌和益生元补充剂对患有肥胖症（包括患有与肥胖相关的代谢功能障碍相关脂肪性肝病的儿童和青少年）的代谢和肝脏结局的影响：一项系统综述和荟萃分析DOI: 10.1111/jpc.70344
PloS one IF: 02.600Volume 21, Issue 4No.76Association of visceral fat and plasmacytoid dendritic cell-derived interferon alpha with SARS-CoV-2 infection内脏脂肪与浆细胞样树突状细胞衍生的干扰素α和SARS-CoV-2感染的关联DOI: 10.1371/journal.pone.0344870
PLOS global public health IF: 02.500Volume 6, Issue 4No.77Prevalence and factors associated with obesity in Rwanda: Evidence from the 2022 NCD STEPS Survey卢旺达肥胖患病率及相关因素：来自2022年非传染性疾病阶梯式调查的证据DOI: 10.1371/journal.pgph.0004736
Respiration IF: 03.800Ahead of Print.No.78Sex comparison in clinical presentation, response, and remission in severe type-2 asthma patients treated with biologics: a real-world analysis from the "Southern Italy Network on Severe Asthma Therapy"生物制剂治疗重度2型哮喘患者的临床表型、反应和缓解情况的性别差异：来自“意大利南部重度哮喘治疗网络”的真实世界分析DOI: 10.1159/000550911
Respiration IF: 03.800Ahead of Print.No.79Paediatric long-term home respiratory support: Recommendations of the Swiss Society of Paediatric Pulmonology儿科长期家庭呼吸支持：瑞士儿科肺科学会的建议DOI: 10.1159/000550985
American journal of nephrology IF: 03.200Ahead of Print.No.80Potentially modifiable factors associated with longitudinal health-related quality of life in the National Unified Renal Translational Research Enterprise CKD (NURTuRE-CKD) cohort国家统一肾脏转化研究企业慢性肾脏病（NURTuRE-CKD）队列中与纵向健康相关生活质量相关的潜在可调节因素DOI: 10.1159/000551177
Medicina IF: 00.600Volume 86, Issue 2No.81[REMI-ICAR: Argentine multicenter registry of hospitalization due to heart failure in medical clinic services]REMI-ICAR：阿根廷内科门诊心力衰竭住院患者多中心登记研究https://pubmed.ncbi.nlm.nih.gov/41961598
Journal of neurosurgery. Spine IF: 03.100Ahead of Print.No.82Diabetes as a significant risk factor for postoperative dysphagia following cervical spine surgery糖尿病是颈椎手术后吞咽困难的重要危险因素DOI: 10.3171/2025.11.SPINE25838
Wiadomo?ci LekarskieVolume 79, Issue 3No.83Obesity as an interdisciplinary medical and social problem: Therapeutic opportunities肥胖作为一个跨学科的医学和社会问题：治疗机会DOI: 10.36740/WLek/218280
Wiadomo?ci LekarskieVolume 79, Issue 3No.84Lifestyle, diet, and physical activity in the prevention and rehabilitation of chronic diseases: A review生活方式、饮食和体力活动在慢性病预防与康复中的作用：综述DOI: 10.36740/WLek/217892
Wiadomo?ci LekarskieVolume 79, Issue 3No.85Clinico-epidemiological spectrum of constipation patients at a tertiary care center in Ajman, UAE - a descriptive 5 year data analysis阿联酋阿治曼某三级医疗中心便秘患者的临床流行病学特征——一项为期5年的描述性数据分析DOI: 10.36740/WLek/218273
Wiadomo?ci LekarskieVolume 79, Issue 3No.86Clinico-epidemiological spectrum of chronic liver disease patients at a tertiary care center in Ajman, UAE - a descriptive 5 year data analysis阿联酋阿治曼一家三级医疗机构慢性肝病患者的临床流行病学特征——5年描述性数据分析DOI: 10.36740/WLek/218412
Swiss Med WklyVolume 156, Issue No.87Effect of implementing measures to reduce resource utilisation in medical wards (CopAIN project): a single-centre interrupted time-series analysis实施减少医疗病房资源利用措施（CopAIN项目）的效果：一项单中心中断时间序列分析DOI: 10.57187/4539
Plast Reconstr Surg IF: 03.400Ahead of Print.No.88Mini Free Flaps for Diabetic Foot Reconstruction用于糖尿病足重建的小型游离皮瓣DOI: 10.1097/PRS.0000000000012628
The Journal of urology IF: 06.800Ahead of Print.No.89Generalized Sensory Sensitivity in Patients with Urinary Urgency - a LURN II Urinary Urgency Phenotyping Study尿急迫患者的广义感觉敏感性——LURN II尿急迫表型研究DOI: 10.1097/JU.0000000000005061
JBJS case connectorVolume 16, Issue 2No.90Differentiating Infective Bursitis and Prosthetic Joint Infection in a Patient With Medial Knee Pain After Total Knee Arthroplasty: A Case Report全膝关节置换术后内侧膝痛患者感染性滑囊炎与假体关节感染的鉴别：一例报告DOI: e25.00515
Science advances IF: 12.500Volume 12, Issue 15No.91Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity组成型AMPK激活通过抑制HNF4α活性预防肝细胞癌发展DOI: 10.1126/sciadv.aea8017
Crit Rev Clin Lab Sci IF: 05.500Ahead of Print.No.92Glycation and disease: a systematic review of the analytical methods and applications of advanced glycation end products (AGEs) as biomarkers of disease糖基化与疾病：晚期糖基化终产物（AGEs）作为疾病生物标志物的分析方法与应用系统综述DOI: 10.1080/10408363.2026.2651310
PloS one IF: 02.600Volume 21, Issue 4No.93Predicted meta-omics: A potential solution to multi-omics data scarcity in microbiome studies预测元组学：解决微生物组研究中多组学数据稀缺的潜在方案DOI: 10.1371/journal.pone.0345919
PloS one IF: 02.600Volume 21, Issue 4No.94Exploring barriers and enablers to diabetes self-care practice in Ethiopia, 2025: A qualitative systematic review埃塞俄比亚2025年糖尿病自我护理实践的障碍与促进因素：一项定性系统综述DOI: 10.1371/journal.pone.0346867
PloS one IF: 02.600Volume 21, Issue 4No.95WHO five moments for medication safety among diabetic patients in Saudi Arabia沙特阿拉伯糖尿病患者用药安全的WHO五时刻模型DOI: 10.1371/journal.pone.0346935
PloS one IF: 02.600Volume 21, Issue 4No.96Risk factors for spontaneous abortion following hepatitis E vaccination during and shortly before pregnancy: Further analysis from a cluster-randomized trial妊娠期间及孕前短期内接种戊型肝炎疫苗后自发性流产的危险因素：来自整群随机试验的进一步分析DOI: 10.1371/journal.pone.0345974
Kidney & Blood Pressure Research IF: 02.100Ahead of Print.No.97New Anticomplement Drugs in Nephrology - Mechanism and Indication肾脏病学中的新型抗补体药物——作用机制与适应症DOI: 10.1159/000551965
European thyroid journal IF: 04.300Ahead of Print.No.98Thyroid hormone therapy in a population cohort over two decades indicates persistent overtreatment二十年间人群队列中的甲状腺激素治疗表明持续过度治疗DOI: 10.1530/ETJ-25-0259
ESC Heart Failure IF: 03.700Ahead of Print.No.99An integrated Biobank in the Swedish Heart Failure Registry - clinomics, proteomics, transcriptomics and genomics瑞典心力衰竭登记处（SwedeHF）中的综合生物库——临床组学、蛋白质组学、转录组学和基因组学DOI: 10.1093/eschf/xvag092
Medicina IF: 00.600Volume 86, Issue 2No.100[Pulmonary cryptococcosis in a non-HIV patient]非HIV患者的肺隐球菌病https://pubmed.ncbi.nlm.nih.gov/41961617
EJHF IF: 10.800Ahead of Print.No.101Kidney Failure Risk Equation and Risk of Kidney and Cardiovascular Outcomes in Patients with Heart Failure with Reduced Ejection Fraction: Insights from PARADIGM-HF射血分数降低的心力衰竭患者的肾衰竭风险方程及肾脏和心血管结局风险：来自PARADIGM-HF研究的见解DOI: 10.1093/ejhf/xuag079
IEEE J Biomed Health Inform IF: 06.800Ahead of Print.No.102Lesion Learning Network with Relation Aware Transformer for Diabetic Retinopathy Grading带有关系感知Transformer的病变学习网络用于糖尿病视网膜病变分级DOI: 10.1109/JBHI.2026.3682783
Journal of neurosurgery IF: 03.600Ahead of Print.No.103Glucagon-like peptide-1 receptor agonists in patients with moyamoya disease and type 2 diabetes mellitus胰高血糖素样肽-1受体激动剂在烟雾病合并2型糖尿病患者中的应用DOI: 10.3171/2025.12.JNS251072
Reproduction & fertility IF: 03.400Ahead of Print.No.104Interconnection between Polycystic Ovary Syndrome, Immune Disorders, and Reproductive Outcomes多囊卵巢综合征、免疫失调与生殖结局的相互联系DOI: 10.1530/RAF-25-0186
The Lancet Digital Health IF: 24.100Ahead of Print.No.105ChatGPT for obesity management: a review of evidence, potential challenges, and clinical implicationsChatGPT在肥胖管理中的应用、挑战与未来方向综述DOI: 10.1016/j.landig.2026.100980
Fish physiology and biochemistry IF: 02.500Volume 52, Issue 2No.106Low temperatures impact on the expression of growth genes and miRNAs in Nile tilapia (Oreochromis niloticus)低温对尼罗罗非鱼生长基因和微小RNA表达的影响DOI: 10.1007/s10695-026-01679-z
Clin Hemorheol MicrocircAhead of Print.No.107A comprehensive review of GLP-1 and aerobic training in cardiovascular disease managementGLP-1和有氧运动在心血管疾病管理中的综合综述DOI: 10.1177/13860291251414840
International endodontic journal IF: 07.100Ahead of Print.No.108Foetal Development and Placental Health in Response to Apical Periodontitis Induced in Pregnant Wistar Rats妊娠Wistar大鼠诱导根尖周炎后胎儿发育及胎盘健康DOI: 10.1111/iej.70155
Sports medicine IF: 09.400Ahead of Print.No.109Instrumented Mouthguards in Women's Rugby League: Quantifying the Incidence and Probability of Head Acceleration Events at Group and Individual Levels女子橄榄球联盟中仪器化护齿套：量化群体和个体层面的头部加速事件发生率与概率DOI: 10.1007/s40279-026-02420-9
Molecular diversity IF: 03.800Ahead of Print.No.110Transdermal self-assembled Xanthine/hybrid needle nanofibers for management of abdominal obesity via phosphodiesterase 4B suppression经皮自组装黄嘌呤/杂化针状纳米纤维通过抑制磷酸二酯酶4B用于管理腹型肥胖DOI: 10.1007/s11030-026-11512-7
European journal of nutrition IF: 04.300Volume 65, Issue 3No.111The swift study: dietary profiles of night shift workers characterised by overweight and obesity快速研究：以超重和肥胖为特征的夜班工作者饮食特征DOI: 10.1007/s00394-026-03917-9
Indian journal of pediatrics IF: 02.000Ahead of Print.No.112Smartphone Applications-Based Intervention to Reduce Body Mass Index and Improve Health-Related Behavior Among Children with Overweight/Obesity: A Pilot Clinical Trial - Authors' Reply基于智能手机应用的干预措施降低超重/肥胖儿童体重指数并改善健康相关行为：一项试点临床试验——作者回复DOI: 10.1007/s12098-026-06117-9
Journal of robotic surgery IF: 03.000Volume 20, Issue 1No.113Trends and comparative study of robotic-assisted benign hysterectomy among morbidly obese patients in united States美国病态肥胖患者中机器人辅助良性子宫切除术的趋势与比较研究DOI: 10.1007/s11701-025-02991-1
Nutrición hospitalaria IF: 01.100Ahead of Print.No.114Longitudinal analysis of weight regain after Roux-en-Y gastric bypass ‒ The role of the MTCH2 gene polymorphism and dietary factorsRoux-en-Y减重手术后体重反弹的纵向分析——MTCH2基因多态性与饮食因素的作用DOI: 10.20960/nh.06238
Int J Gynaecol Obstet IF: 02.400Ahead of Print.No.115Influence of maternal body mass index on the accuracy of clinical and sonographic fetal weight estimation母体体重指数对临床和超声胎儿体重估计准确性的影响DOI: 10.1002/ijgo.71012
ANZ journal of surgery IF: 01.600Ahead of Print.No.116Re: How to Do an Emergency Robotic Hartmann's Procedure in a Morbidly Obese Patient如何在病态肥胖患者中进行紧急机器人哈特曼手术DOI: 10.1111/ans.70681
JAMA IF: 55.000Ahead of Print.No.117Triple Agonist Reduces Hemoglobin A1C and Weight in Patients With Type 2 Diabetes三重激动剂可降低2型糖尿病患者的糖化血红蛋白和体重DOI: 10.1001/jama.2026.2107
Mol Cell Pediatr IF: 03.400Volume 13, Issue 1No.118The conundrum in diagnosing Maturity-Onset Diabetes of the Young (MODY) in a large German pedigree with early-onset diabetes and a novel HNF1A variant在具有早发性糖尿病的大型德国家系中诊断年轻发病的成人型糖尿病（MODY）的难题及新型HNF1A变异DOI: 10.1186/s40348-026-00229-0
Current diabetes report IF: 06.400Volume 26, Issue 1No.119Correction: Glucagon-Like Peptide-1 and Dual Incretin Agonists in Type 2 Diabetes with Peripheral Artery Disease: A Systematic Review and Meta-Analysis of Vascular, Cardiovascular, Metabolic, and Mortality Outcomes修正：胰高血糖素样肽-1和双重肠促胰素激动剂在合并外周动脉疾病的2型糖尿病中的应用：血管、心血管、代谢和死亡率结局的系统综述与荟萃分析DOI: 10.1007/s11892-026-01622-9
Acta diabetologica IF: 02.900Ahead of Print.No.120Diabetes mellitus and risk of endometrial cancer: an updated systematic review and meta-analysis糖尿病与子宫内膜癌风险：更新的系统综述与荟萃分析DOI: 10.1007/s00592-026-02681-w
Osteoporosis international IF: 05.400Ahead of Print.No.121Romosozumab versus teriparatide and risk of all-cause mortality in patients with osteoporosis: a real-world propensity score-matched cohort study罗莫佐单抗与特立帕肽在骨质疏松症患者中的全因死亡率风险比较：一项真实世界倾向评分匹配队列研究DOI: 10.1007/s00198-026-07968-w
Osteoporosis international IF: 05.400Ahead of Print.No.122Adjusting fracture probability according to duration of diabetes: the Manitoba BMD Registry根据糖尿病病程调整骨折概率：曼尼托巴骨密度登记处DOI: 10.1007/s00198-026-08001-w
Endocrine connections IF: 02.800Ahead of Print.No.123Mapping Transition of Care for Rare Endocrine Conditions: Findings from a Cross-Sectional Survey by the Endo-ERN ToC Working Group罕见内分泌疾病的护理过渡映射：Endo-ERN护理过渡工作组横断面调查结果DOI: 10.1530/EC-25-0798
Invest Ophthalmol Vis Sci IF: 04.700Volume 67, Issue 4No.124Age-Specific Increases in the Prevalence and Treatment Burden of Neovascular Age-Related Macular Degeneration in a Super-Aged Society超老龄化社会中新生血管性年龄相关性黄斑变性的患病率和治疗负担的年龄特异性增加DOI: 10.1167/iovs.67.4.19
Int J Low Extrem Wounds IF: 01.500Ahead of Print.No.125Assessment of the Comprehensive Score for Financial Toxicity (COST) among People with Diabetic Foot Ulcers at a Tertiary Care Centre in South India南印度三级医疗中心糖尿病足溃疡患者财务毒性综合评分（COST）评估DOI: 10.1177/15347346261441107
J Am Coll Surg IF: 03.400Ahead of Print.No.126Increasing Use of Wearable Devices for Health or Activity Tracking Among Adults with Chronic Diseases in the US美国慢性病成年人群中用于健康或活动追踪的可穿戴设备使用量增加DOI: 10.1097/XCS.0000000000001746
Int J Gynaecol Obstet IF: 02.400Ahead of Print.No.127Polycystic ovarian syndrome and perinatal outcomes: A population-based pooled cross-sectional study多囊卵巢综合征与围产期结局：一项基于人群的汇总横断面研究DOI: 10.1002/ijgo.71006
Curr Opin Endocrinol Diabetes Obes IF: 02.700Ahead of Print.No.128Parathyroid hormone assays in 2026: second versus third generation, standardization, and clinical interpretation2026年甲状旁腺激素检测：第二代与第三代、标准化及临床解读DOI: 10.1097/MED.0000000000000960
Diabetes therapy IF: 02.600Ahead of Print.No.129Tirzepatide as an Add-on for Participants with Inadequate Glycemic Control Using Basal Insulin: Pooled Subgroup Analysis of SURPASS-5 and -6替尔泊肽作为基础胰岛素治疗血糖控制不佳参与者的附加治疗：SURPASS-5和-6研究的合并亚组分析DOI: 10.1007/s13300-026-01859-3
European journal of pain IF: 03.400Volume 30, Issue 4No.130Postoperative Pain Management After Lumbar Discectomy. A Systematic Review With Meta-Analyses and Trial Sequential Analyses腰椎间盘切除术后的术后疼痛管理：一项系统综述、荟萃分析及试验序贯分析DOI: 10.1002/ejp.70261
BioMed research international IF: 02.300Volume 2026, Issue 1No.131Bacteria Associated With Urinary Tract Infections, Antimicrobial Resistance Profiles, and Associated Factors Among Diabetes Mellitus Patients at Debre Tabor Comprehensive Specialized Hospital, Northwest Ethiopia埃塞俄比亚西北部德布雷塔布尔综合专科医院糖尿病患者尿路感染相关细菌、抗菌药物耐药谱及相关因素DOI: 10.1155/bmri/6664132
Eur J Ophthalmol IF: 01.400Ahead of Print.No.132The impact of polycystic ovarian syndrome on ocular health多囊卵巢综合征对眼部健康的影响DOI: 10.1177/11206721261436102
Nutrición hospitalaria IF: 01.100Ahead of Print.No.133Effects of betaine-containing nutrients on homocysteine levels and glucose-lipid metabolism in overweight and obese patients with hyperhomocysteinemia甜菜碱类营养物质对伴有高同型半胱氨酸血症的超重和肥胖患者的同型半胱氨酸水平及糖脂代谢的影响DOI: 10.20960/nh.05892
Nutrición hospitalaria IF: 01.100Ahead of Print.No.134[Triglycerides glucose index in Madrid university students]马德里大学生甘油三酯葡萄糖指数DOI: 10.20960/nh.06225
Med Lett Drugs Ther IF: 01.400Volume 68, Issue 1752No.135In brief: Rybelsus R2 rebranded as Ozempic简要介绍：Rybelsus R2重命名为OzempicDOI: 10.58347/tml.2026.1752f
Am J Phys Med Rehabil IF: 02.400Ahead of Print.No.136Semaglutide-Associated Sequential Unilateral Transient Osteoporosis of The Hip: A Case Report司美格鲁肽相关序贯单侧髋部暂时性骨质疏松症：一例报告DOI: 10.1097/PHM.0000000000003003
Diabetes therapy IF: 02.600Ahead of Print.No.137Fixed-Dose Combination Therapy as a Strategy to Improve Antidiabetic Medication Adherence in People with Type 2 Diabetes: A Narrative Review固定剂量联合疗法作为提高2型糖尿病患者抗糖尿病药物依从性的策略：一项叙述性综述DOI: 10.1007/s13300-026-01863-7
Infectious diseases and therapy IF: 05.300Ahead of Print.No.138Burden of Respiratory Syncytial Virus in Older ADults in Nagasaki, Japan (Nagasaki ROAD): Preliminary Results (April 2024-March 2025) of a Prospective, Multicenter, Epidemiological Study日本长崎地区老年人群呼吸道合胞病毒（RSV）负担（Nagasaki ROAD研究）：2024年4月-2025年3月前瞻性多中心流行病学研究初步结果DOI: 10.1007/s40121-026-01312-9
Journal of obesity IF: 03.900Volume 2026, Issue 1No.139Expression Analysis of Selected microRNAs in Diabetes Mellitus Visceral Fat Tissues糖尿病内脏脂肪组织中选定微小RNA的表达分析DOI: 10.1155/jobe/3230015
Clin J Am Soc Nephrol IF: 07.100Ahead of Print.No.140Expanding Evidence for Glucagon-Like Peptide-1 Receptor Agonists in Those with Diabetes and Kidney Disease胰高血糖素样肽-1受体激动剂在糖尿病和肾病患者中的证据扩展DOI: 10.2215/CJN.0000001072
JAMA Network Open IF: 09.700Volume 9, Issue 4No.141Risk Prediction Model for Taxane-Induced Peripheral Neuropathy in Early-Stage Cancer早期癌症中紫杉醇诱导的周围神经病变风险预测模型DOI: 10.1001/jamanetworkopen.2026.4901
Eur J Appl Physiol IF: 02.700Ahead of Print.No.142Hyperlactatemia and pulmonary gas exchange at rest and during exercise: lessons from patients on metformin高乳酸血症与静息及运动时的肺气体交换：二甲双胍治疗患者的启示DOI: 10.1007/s00421-026-06213-w
JAMA IF: 55.000Ahead of Print.No.143PCSK9 Inhibitors in Diabetes, Tirzepatide's Cardiorenal Effects, Shingles Vaccine, and More From ACC糖尿病中的PCSK9抑制剂、替尔泊肽的心脏肾脏影响、带状疱疹疫苗及ACC其他相关内容DOI: 10.1001/jama.2026.2399
Acta diabetologica IF: 02.900Ahead of Print.No.144The silent side effect of metformin: understanding Vitamin B12 deficiency in Type 2 Diabetes二甲双胍的隐性副作用：认识2型糖尿病中的维生素B12缺乏症DOI: 10.1007/s00592-026-02684-7
J Interv Cardiol IF: 01.700Volume 2026, Issue 1, Page 5898802-5898802No.145Gentamicin–Collagen Sponge Use in the Implant Pocket for the Prevention of Cardiac Implantable Electronic Device Infections庆大霉素-胶原海绵用于植入袋预防心脏植入式电子设备感染DOI: 10.1155/joic/9922994
Int J Hepatol IF: 01.400Volume 2026, Issue No.146Natriuretic Effect of Dapagliflozin in Cirrhosis With Ascites: A Randomized, Placebo-Controlled Crossover Trial达格列净对肝硬化腹水患者尿钠排泄及临床结局的影响：一项随机、双盲、安慰剂对照交叉试验DOI: 10.1155/ijh/9503323
Public health nursing IF: 01.300Ahead of Print.No.147Enhancing Community-Based Nursing Decision Support: Machine Learning Models for Diabetes Risk Prediction Using Home Health Nursing Notes增强基于社区的护理决策支持：利用家庭健康护理记录进行糖尿病风险预测的机器学习模型DOI: 10.1111/phn.70122
Bioinformation IF: 01.900Volume 22, Issue 1No.148Obesity and periodontal diseases: A review肥胖与牙周疾病：综述DOI: 10.6026/973206300220392
Bioinformation IF: 01.900Volume 22, Issue 1No.149Smoking and its impact on eating behavior: A review吸烟及其对进食行为的影响：综述DOI: 10.6026/973206300220132
J Health Dispar Res PractVolume 10, Issue 2No.150Investigation of the Cultural Context of Sugars Consumption Behavior in Low-Income Mexican-American Women美国墨西哥裔美国母亲的食品采购、制备及呈现行为与糖消费研究：焦点小组研究https://pubmed.ncbi.nlm.nih.gov/41960351
Research squareVolume 2026, Issue No.151Metabolic Adaptations to Caloric Restriction: Time- and Group-Dependent Metabolomic Signatures from the CALERIE™ Trial热量限制调节健康成年人的血浆代谢组：来自CALERIE试验的纵向代谢组学分析DOI: 10.21203/rs.3.rs-9237764/v1
J Coll Med S AfrVolume 4, Issue 1No.152A unique case report of bilateral spontaneous cerebrospinal fluid leak from bilateral sphenoid sinus skull base defects双侧蝶窦颅底缺损致双侧自发性脑脊液漏的独特病例报告DOI: 10.4102/jcmsa.v4i1.271
Frontiers in pediatrics IF: 02.000Volume 14, Issue No.153Impact of pediatric obesity on abdominal surgery outcome: a narrative review儿童肥胖与腹部手术：围手术期并发症及管理策略的叙事性综述DOI: 10.3389/fped.2026.1780811
Curēus IF: 01.300Volume 18, Issue 3No.154Impact of Pre-pregnancy BMI and Gestational Weight Gain on Fetomaternal Outcomes: A Cross-Sectional Analytical Study孕前体重指数和孕期增重对母婴结局的影响DOI: 10.7759/cureus.104941
Osteoarthr Cartil Open IF: 02.800Volume 8, Issue 2No.155Implementing a guideline-based model of care for hip and knee osteoarthritis in Finland (FIN-OA): Protocol for a benchmarking-controlled trial芬兰国家骨关节炎实施（FIN-OA）试验：基层医疗中基于指南的髋膝关节骨关节炎护理模式的混合3型基准对照试验方案DOI: 10.1016/j.ocarto.2026.100782
Surgery in practice and science IF: 00.600Volume 25, Issue No.156Comment on "Associations between obesity and lymph node metastasis and early recurrence in pancreatic head cancer: A single-center retrospective cohort study"对“胰头癌中肥胖与淋巴结转移及早期复发的关联：单中心回顾性队列研究”的评论DOI: 10.1016/j.sipas.2026.100342
bioRxivVolume 2026, Issue No.157Cognitive reappraisal of food and emotion cues involves common and unique neural contributions参考文献列表DOI: 10.64898/2026.03.09.710570
bioRxivVolume 2026, Issue No.158Adrβ2 in skeletal muscle cells is required for exercise-induced Pgc1α but not for metabolic benefits of exercise on diet-induced obesity骨骼肌中的Adrβ2对于运动在饮食诱导肥胖中的代谢益处并非必需DOI: 10.64898/2026.03.27.714812
bioRxivVolume 2026, Issue No.159Hypothalamus amyloid levels are associated with early sex-dependent alterations in energy homeostasis in TgF344-AD rats下丘脑淀粉样蛋白水平与TgF344-AD大鼠早期能量稳态的性别依赖性改变相关DOI: 10.64898/2026.03.08.710398
bioRxivVolume 2026, Issue No.160Diet quality shapes development and feeding circuits in poison frog tadpoles饮食质量影响箭毒蛙蝌蚪的发育与摄食回路DOI: 10.64898/2026.03.28.714959
bioRxivVolume 2026, Issue No.161Spontaneous Pregravid Obesity Reshapes Fetal Immune Ontogeny in a Nonhuman Primate Model自发性孕前肥胖在非人灵长类模型中重塑胎儿免疫发育DOI: 10.64898/2026.03.27.714880
J Indian Assoc Pediatr SurgVolume 31, Issue 2No.162Chemoport Placement in Children Who are Overweight or Obese: A Practical Approach儿童超重或肥胖时的Chemoport放置：一种实用方法DOI: 10.4103/jiaps.jiaps_379_25
J Hum Reprod Sci IF: 01.100Volume 19, Issue 1No.163Psychological Morbidity (Stress, Anxiety and Depression) and Fertility Quality of Life amongst Infertile Women with and without Polycystic Ovary Syndrome (PCOS): A Cross-sectional Study多囊卵巢综合征（PCOS）有无的不孕女性心理疾病（压力、焦虑和抑郁）与生育生活质量：一项横断面研究DOI: 10.4103/jhrs.jhrs_241_25
Frontiers in medicine IF: 03.000Volume 13, Issue No.164The effect of iron treatment on fetal fraction according to gestational weeks in maternal anemia非侵入性产前检测中母体血液学参数和铁补充对胎儿分数的影响：一项队列研究DOI: 10.3389/fmed.2026.1772334
HSS journal : IF: 01.300Ahead of Print.No.165Preoperative GLP-1 Receptor Agonist Use Is Not Associated With Complications in Non-Obese Patients Undergoing Total Shoulder Arthroplasty: A Propensity Score Matched Large Database Analysis围手术期使用胰高血糖素样肽-1受体激动剂与非肥胖患者全肩关节置换术后并发症增加无关DOI: 10.1177/15563316261439127
Addiction IF: 05.300Ahead of Print.No.166A genetically informed cross-lagged twin study of the longitudinal association between addiction-related behaviors and obesity基于遗传学的交叉滞后双胞胎研究：成瘾相关行为与肥胖的纵向关联DOI: 10.1111/add.70407
Obesity reviews IF: 07.400Ahead of Print.No.167How Does the Ultra-Processed Food Industry Drive Consumption Through Product Design and Marketing? Mapping a Complex Commercial System According to Expert Mental Models and Evidence Review超加工食品行业如何通过产品设计和营销推动消费？基于专家心智模型与证据综述的复杂商业系统解析DOI: 10.1111/obr.70135
Diabetes & metabolism journal IF: 08.500Ahead of Print.No.168Obesity Transitions by Age, Period, and Cohort: A Population-Based Application of the Lancet Commission Framework in the United States and Korea不同年龄、时期和队列的肥胖转变：美国和韩国基于人群的《柳叶刀》委员会框架应用DOI: 10.4093/dmj.2025.0918
International journal of cancer IF: 04.700Ahead of Print.No.169At what age should people with obesity start colorectal cancer screening?肥胖人群应从什么年龄开始结直肠癌筛查？DOI: 10.1002/ijc.70448
Annals of African medicine IF: 00.600Ahead of Print.No.170The Impact of Competency-based Medical Education-mandated Yoga Training on First-Year Medical Students: A Quasi-experimental Study基于能力的医学教育要求的瑜伽训练对一年级医学生的影响：一项类实验研究DOI: 10.4103/aam.aam_869_25
J Integr Complement Med IF: 01.700Ahead of Print.No.171Osteopathic Visceral Manipulation on Functional Constipation in Obese Adults: A Randomized Controlled Clinical Trial整骨内脏手法对肥胖成人功能性便秘的随机对照临床试验DOI: 10.1177/27683605261427696
Lipids in health and disease IF: 04.200Ahead of Print.No.172Serum metabolite patterns of adipose tissue distribution and body composition subphenotypes血清代谢物模式与脂肪组织分布及身体成分亚型DOI: 10.1186/s12944-026-02944-z
Int J Behav Nutr Phys Act IF: 05.500Ahead of Print.No.173Socioeconomic inequalities in exposure to neighbourhood environments for physical activity: a systematic review体力活动相关社区环境暴露的社会经济不平等：一项系统综述DOI: 10.1186/s12966-026-01912-1
bioRxivVolume 2026, Issue No.174Empagliflozin preserves cardiac function and modulates metabolism in a mouse model of Duchenne muscular dystrophy恩格列净在杜氏肌营养不良症小鼠模型中维持心脏功能并调节代谢DOI: 10.64898/2026.03.11.710889
Curēus IF: 01.300Volume 18, Issue 3No.175Lacunar Pontine Infarct Presenting as Ipsilateral Lower Motor Neuron Facial Palsy: A Case Report腔隙性脑桥梗死表现为同侧下运动神经元面瘫：一例报告DOI: 10.7759/cureus.104930
Shoulder & elbow IF: 01.100Ahead of Print.No.176Perioperative testosterone therapy linked to higher 5-year risk of periprosthetic joint infection without increased 90-day major complications or revision rates in total shoulder arthroplasty围手术期睾酮治疗与初次肩关节置换术后5年假体周围关节感染风险增加相关但90天并发症无增加DOI: 10.1177/17585732261437972
Mol Nutr Food Res IF: 04.200Volume 70, Issue 7No.177Ellagic Acid Reduces Inulin's Adverse Effects: A Combined Approach to Enhance Therapeutic Potential in Nonalcoholic Steatohepatitis鞣花酸减轻菊粉的不良反应：联合方法增强非酒精性脂肪性肝炎的治疗潜力DOI: 10.1002/mnfr.70456
Journal of medicine and lifeVolume 19, Issue 2No.178Epigenetic alterations in preeclampsia: a systematic review of current mechanisms and biomarker potential子痫前期中的表观遗传失调：2022-2025年分子与临床特征的系统综述与荟萃分析DOI: 10.25122/jml-2026-0009
Acta Obstet Gynecol Scand IF: 03.100Ahead of Print.No.179Perinatal and long-term implications of diagnosing gestational diabetes mellitus using only fasting and one-hour post-load glucose concentrations: Secondary analysis of the GEMS trial and its five-year follow-up仅用空腹和1小时负荷后血糖诊断妊娠糖尿病的围产期及长期影响：GEMS试验及其五年随访的二次分析DOI: 10.1111/aogs.70191
Bioinformation IF: 01.900Volume 22, Issue 1No.180A case of takayasu arteritis presenting with multiple cerebral infarcts: Diagnostic and therapeutic challenges一例以多发脑梗死为表现的Takayasu动脉炎：诊断与治疗挑战DOI: 10.6026/973206300220071
Bioinformation IF: 01.900Volume 22, Issue 1No.181The impact of obesity, smoking and diabetes on the susceptibility to postoperative spinal infections: A risk-based approach肥胖、吸烟和糖尿病对术后脊柱感染风险的影响DOI: 10.6026/973206300220409
Bioinformation IF: 01.900Volume 22, Issue 1No.182Clinicopathological and microbiological profile of osteomyelitis at a teaching hospital in India: A retrospective study印度某教学医院骨髓炎的临床病理和微生物学特征回顾性研究DOI: 10.6026/973206300220443
Bioinformation IF: 01.900Volume 22, Issue 1No.183Fitness assessment to promote exercise for diabetes and hypertension用于促进糖尿病和高血压患者运动的体质评估DOI: 10.6026/973206300220142
Bioinformation IF: 01.900Volume 22, Issue 1No.184Sarcopenia with postoperative outcomes in patients undergoing pancreaticoduodenectomy胰十二指肠切除术后患者的肌少症及其术后结局DOI: 10.6026/973206300220066
Bioinformation IF: 01.900Volume 22, Issue 1No.185Early thiamine therapy in Rogers syndrome: Systematic review of hematologic, auditory and glycemic outcomes罗杰斯综合征早期硫胺素治疗：血液学、听觉和血糖结局的系统综述DOI: 10.6026/973206300220026
Bioinformation IF: 01.900Volume 22, Issue 1No.186Periodontal severity and metabolic syndrome: A cross-sectional study from a tertiary care hospital in India印度一家三级医疗机构牙周炎严重程度与代谢综合征的横断面研究DOI: 10.6026/973206300220477
Bioinformation IF: 01.900Volume 22, Issue 1No.187Treatment outcomes and clinical characteristics in diabetic versus non-diabetic sinonasal tuberculosis糖尿病与非糖尿病患者鼻窦结核的治疗结局及临床特征对比DOI: 10.6026/973206300220206
Frontiers in public health IF: 03.400Volume 14, Issue No.188Impact of a brief diabetes education on teachers' diabetes-related knowledge, attitude, and confidence: a nonrandomized school-based intervention study标准化糖尿病教育课程对教师1型糖尿病管理知识态度和信心的短期影响DOI: 10.3389/fpubh.2026.1747185
Research squareVolume 2026, Issue No.189Abdominal Waist Circumference and Subcutaneous Adipose Tissue Thickness Predicts Development of Post-Transplant Diabetes Mellitus肾移植后糖尿病风险预测中腹部皮下脂肪厚度和腰围的应用：一项回顾性队列研究DOI: 10.21203/rs.3.rs-8543193/v1
Research squareVolume 2026, Issue No.190Risk Factors for Hepatocellular Carcinoma: Findings from a Case-Control Study in Vietnam越南人群肝细胞癌的风险因素DOI: 10.21203/rs.3.rs-8383243/v1
Research squareVolume 2026, Issue No.191Epidemiological and Multi-Omics Investigation of Phytosterol Intake and Type 2 Diabetes Risk植物甾醇摄入与2型糖尿病风险的流行病学及多组学研究DOI: 10.21203/rs.3.rs-9222420/v1
South Afr J HIV Med IF: 02.300Volume 27, Issue 1No.192Cardiovascular risk profiles in people living with HIV taking antiretroviral therapy in rural Lesotho: Findings from the PRECARIF study莱索托农村地区接受抗逆转录病毒治疗的HIV感染者心血管疾病风险特征：PRECARIF研究结果DOI: 10.4102/sajhivmed.v27i1.1779
Case Rep Obstet Gynecol IF: 00.600Volume 2026, Issue No.193Intrauterine Tampon Identified on CT as an Intrauterine Foreign Body Associated With Bilateral Leg Edema: A Case ReportCT显示宫内棉条为宫内异物并伴双侧腿部水肿：一例报告DOI: 10.1155/crog/1505612
Bioimpacts IF: 02.200Volume 16, Issue No.194Three-dimensional bioprinted hydrogels for the management of diabetic wounds: A review3D打印技术在糖尿病伤口愈合中的应用进展：综合综述DOI: 10.34172/bi.32751
Curēus IF: 01.300Volume 18, Issue 3No.195Incidence of Sepsis After Transrectal Ultrasound-Guided Prostate Biopsy in Dubai Tertiary Care Hospitals: A Multicenter Cohort Study迪拜三家三级医院经直肠超声引导前列腺穿刺活检术后脓毒症发生率：一项多中心队列研究DOI: 10.7759/cureus.104933
Curēus IF: 01.300Volume 18, Issue 3No.196Health-Seeking Behavior for Noncommunicable Diseases in Rural and Urban Areas of Ernakulam District, Kerala: A Cross-Sectional Study喀拉拉邦厄纳库拉姆地区城乡居民非传染性疾病就医行为比较研究DOI: 10.7759/cureus.104899
Int J Breast Cancer IF: 03.000Volume 2026, Issue No.197Modifiable and Nonmodifiable Risk Factors for Breast Cancer: A Comprehensive Scoping Review乳腺癌风险因素：综合综述DOI: 10.1155/ijbc/8689986
Case reports in endocrinology IF: 00.900Volume 2026, Issue No.198A Rare Primary Adrenal Malignancy Manifesting as a Hemorrhagic Mass: Case Report and Literature Review罕见原发性肾上腺恶性肿瘤表现为出血性肿块：病例报告及文献综述DOI: 10.1155/crie/1260707
Curēus IF: 01.300Volume 18, Issue 4No.199Assessing Functional Outcomes and Complications After Turndown Flap With Flexor Hallucis Longus Augmentation in Chronic Achilles Tendon Ruptures腓肠肌下翻瓣联合拇长屈肌增强治疗慢性跟腱断裂的回顾性病例系列研究DOI: 10.7759/cureus.106610
ACG case reports journal IF: 00.500Volume 13, Issue 4No.200Semaglutide-Induced Symptomatic Remission in Ulcerative Colitis司美格鲁肽诱导溃疡性结肠炎的症状缓解DOI: 10.14309/crj.0000000000002070
bioRxivVolume 2026, Issue No.201Deletion of endothelial KLF4 as a model for preeclampsia内皮KLF4缺失诱导小鼠子痫前期DOI: 10.64898/2026.03.30.715448
bioRxivVolume 2026, Issue No.202Synthetic Immunological Niche Reveals Early Immune Dysregulation and Stratifies Therapeutic Response in Type 1 Diabetes工程化免疫微环境揭示1型糖尿病中阶段特异性免疫失调及预测治疗效果DOI: 10.64898/2026.03.06.710219
bioRxivVolume 2026, Issue No.203Exploring Links between Brain Image-Derived Phenotypes and Accelerometer-Measured Physical Activity in the UK Biobank体力活动与脑成像：英国生物样本库中功能连接性和灰质体积的综合分析DOI: 10.64898/2026.03.10.710798
bioRxivVolume 2026, Issue No.204Serum proteomics reveals distinct phenotypic signatures to IL-6 blockade between two immunotherapies血清蛋白质组学揭示两种免疫疗法在IL-6阻断时的不同表型特征DOI: 10.64898/2026.03.27.712461
bioRxivVolume 2026, Issue No.205Aberrant immune regulation and enrichment of stem-like CD8 (+) T cells in the pancreatic lymph node during type 1 diabetes development1型糖尿病发展过程中胰腺淋巴结中异常免疫调节及类干细胞样CD8(+)T细胞的富集DOI: 10.1101/2025.05.23.655848
Kidney international reports IF: 05.700Volume 11, Issue 5No.206Response to the Letter to the Editor Entitled "Beyond Access: How Homelessness Shapes Kidney Trajectories in Diabetes"对题为‘超越获取：无家可归如何影响糖尿病患者肾脏轨迹’的信件的回应DOI: 10.1016/j.ekir.2026.106381
Imaging Neurosci (Camb)Volume 4, Issue No.207Retinal nerve fibre layer thickness reflects characteristics of brain grey and white matter视网膜神经纤维层厚度反映大脑灰白质特征DOI: 10.1162/IMAG.a.1174
JMA journal IF: 01.800Volume 9, Issue 2No.208Melioidosis Presenting as Parapharyngeal Abscess类鼻疽表现为咽旁脓肿DOI: 10.31662/jmaj.2025-0546
Frontiers in medicine IF: 03.000Volume 13, Issue No.209Acupuncture in the treatment of inflammation-related ocular degenerations: a systematic review针灸治疗炎症相关眼部退行性病变：一项系统综述DOI: 10.3389/fmed.2026.1749297
HSS journal : IF: 01.300Ahead of Print.No.210The Outpatient Surge in Total Hip Arthroplasty: National Trends in Volume Migration, Demographic Disparities, and Comorbidity Profiles (2019-2022)全髋关节置换术在住院与门诊环境中的比例：全国趋势、人口统计学和合并症（2019-2022）DOI: 10.1177/15563316261431234
Journal of medicine and lifeVolume 19, Issue 2No.211Correlations between Psoriasis Area and Severity Index (PASI), body mass index (BMI), smoking, and alcohol consumption in patients with psoriasis - a Romanian study银屑病患者中银屑病面积和严重程度指数（PASI）、体重指数（BMI）、吸烟和饮酒之间的相关性——一项罗马尼亚研究DOI: 10.25122/jml-2026-0013
Journal of materials chemistry IF: 05.700Ahead of Print.No.212H(2)O(2) responsive rhodamine-based probe for monitoring early-stage diabetes diagnosis对H₂O₂响应的若丹明基探针用于早期糖尿病诊断监测DOI: 10.1039/d5tb02687c
Nuclear medicine communications IF: 01.300Ahead of Print.No.213Pilot feasibility study investigating 68Ga-NODAGA-RGD PET-computed tomography molecular angiogenesis imaging in patients with peripheral arterial diseases: can it be of potential clinical value?初步可行性研究：68Ga-NODAGA-RGD PET-CT分子血管生成成像在外周动脉疾病患者中的潜在临床价值探讨DOI: 10.1097/MNM.0000000000002160
British journal of nutrition IF: 03.000Ahead of Print.No.214Cardiometabolic health effects of dietary counselling on a high-quality, fibre-rich diet in adults with type 2 diabetes: A randomised controlled trial饮食咨询对成年2型糖尿病患者高质量高纤维饮食的心脏代谢健康影响：一项随机对照试验DOI: 10.1017/S0007114526107041
Stroke IF: 08.900Ahead of Print.No.215Cost-Effectiveness of Prehospital Delay Reduction Versus Primary Stroke Prevention in US Adults With Type 2 Diabetes美国2型糖尿病成年人减少院前延误与一级卒中预防的成本效益比较DOI: 10.1161/STROKEAHA.126.055187
Prim Health Care Res Dev IF: 01.700Volume 27, Issue No.216From silos to synergy: assessing tuberculosis basic management units readiness for integrated diabetes mellitus care across different districts of Pakistan从孤立到协同：评估巴基斯坦不同地区结核病基层管理单位开展糖尿病综合管理的准备情况DOI: 10.1017/S146342362610111X
Public health nutrition IF: 03.000Ahead of Print.No.217Dietary Knowledge and Perceptions in UK Pakistani/Bangladeshi Communities: A Survey on Low-Carbohydrate and Intermittent Fasting diets for Diabetes Prevention and Management英国巴基斯坦/孟加拉裔社区的饮食知识与认知：关于低碳水化合物和间歇性禁食饮食对糖尿病预防和管理的调查DOI: 10.1017/S136898002610250X
Chemistry & biodiversity IF: 02.500Volume 23, Issue 4No.218Capparis Spinosa and Glutamine Reduce Oxidative Stress via Nrf2/Ho-1 Pathway in Diabetic Wound Healing刺山柑与谷氨酰胺通过Nrf2/HO-1通路减轻糖尿病创面愈合中的氧化应激DOI: 10.1002/cbdv.71196
Sci Diabetes Self Manag Care IF: 02.200Ahead of Print.No.219Transition to Virtual Diabetes Self-Management Education Delivery in the Setting of Health Care Disruption for Adults With Diabetes and Their Support Persons医疗保健中断背景下，成年糖尿病患者及其支持者向虚拟糖尿病自我管理教育交付的转变DOI: 10.1177/26350106261432172
Annals of African medicine IF: 00.600Ahead of Print.No.220Role of Renal Doppler and Shearwave Elastography in Diabetic Nephropathy肾多普勒超声和剪切波弹性成像在糖尿病肾病中的作用DOI: 10.4103/aam.aam_877_25
Diabetes, obesity & metabolism IF: 05.700Ahead of Print.No.221Biological Context and Endpoint Alignment Are Critical for Interpreting Population-Based Validation of Cluster-Based MASLD Subtypes生物学背景和终点对齐对解释基于人群的聚类代谢相关脂肪性肝病（MASLD）亚型验证至关重要DOI: 10.1111/dom.70627
Ethnicity & health IF: 02.000Ahead of Print.No.222Overcoming barriers to blood glucose monitoring: the mediating role of social cognitive theory components in black/African American men with type 2 diabetes克服血糖监测障碍：社会认知理论组成部分在黑人/非裔美国2型糖尿病男性中的中介作用DOI: 10.1080/13557858.2026.2655624
Am J Surg Pathol IF: 04.200Ahead of Print.No.223Segmental Atrophy of the Liver: An Increasingly Recognized Pseudotumor With Distinct Clinicopathologic and Imaging Features肝脏节段性萎缩：一种日益被认识的具有独特临床病理和影像学特征的假瘤DOI: 10.1097/PAS.0000000000002543
Curēus IF: 01.300Volume 18, Issue 3No.224Human Insulin-Like Growth Factor II mRNA-Binding Protein 3 (IMP3) and p16 Expression in Squamous Cell Carcinoma of the Head and Neck人乳头瘤病毒(HPV)状态及p16INK4a、IMP3在头颈部鳞状细胞癌(HNSCC)中的表达DOI: 10.7759/cureus.104895
Genes & diseases IF: 09.400Volume 13, Issue 4No.225FOXA2 in islet biology: Orchestrating pancreatic development and glucose homeostasisFOXA2在胰腺胰岛生物学中的作用：调控发育、功能与疾病DOI: 10.1016/j.gendis.2025.101972
Pediatric diabetes IF: 05.600Volume 2026, Issue No.226Achieving Glycemic Targets in and out-of-School: Real-World Data From 1341 Italian Children Using the MiniMed 780G System During Auto Mode意大利1341名儿童使用MiniMed 780G自动模式系统在学校内外实现血糖目标的真实世界数据DOI: 10.1155/pedi/1653728
bioRxivVolume 2026, Issue No.227Desynchrony between events triggers a compensatory delay during C. elegans development秀丽隐杆线虫发育过程中事件不同步触发补偿性延迟DOI: 10.1101/2024.03.31.587169
bioRxivVolume 2026, Issue No.228Profiling Peripheral Blood with an Optimized, Multiplexed, Single-cell Multiome Approach Supports an Insulin-driven Asthma Subtype采用优化的多重单细胞多组学方法分析外周血支持胰岛素驱动的哮喘亚型DOI: 10.64898/2026.03.27.714744
bioRxivVolume 2026, Issue No.229Sex and breeding stage differences in neurogenomic profiles reflect hormone signaling in a socially polyandrous shorebird社会性一妻多夫制滨鸟中神经基因组谱的性别和繁殖阶段差异反映激素信号DOI: 10.64898/2026.03.10.710941
bioRxivVolume 2026, Issue No.230A high-resolution mass spectrometry-based method for quantifying insulin-stimulated glucose uptake in mice following an intraperitoneal injection of tracer腹腔注射示踪剂后基于高分辨率质谱的小鼠胰岛素刺激葡萄糖摄取定量方法DOI: 10.64898/2026.03.31.714892
bioRxivVolume 2026, Issue No.231Biosensor Cell Array Reveals Temporal GABA Secretion Dynamics from Pancreatic Islets生物传感器细胞阵列揭示胰岛GABA分泌的时间动态DOI: 10.64898/2026.03.31.715660
bioRxivVolume 2026, Issue No.232Functional genomics reveals mediators of beta cell survival in ER stress and type 2 diabetes risk胰腺β细胞应激反应的单细胞多组学分析鉴定2型糖尿病风险机制DOI: 10.64898/2026.03.30.715154
bioRxivVolume 2026, Issue No.233Sleeve gastrectomy protects lean mice from future obesity减重手术减轻高脂饮食诱导小鼠的代谢恶化DOI: 10.64898/2026.03.09.710623
Frontiers in endocrinology IF: 04.600Volume 17, Issue No.234Correction: Intrinsic, pro-apoptotic effects of IGFBP-3 on breast cancer cells are reversible: involvement of PKA, Rho, and ceramide更正：IGFBP-3对乳腺癌细胞的内在促凋亡作用具有可逆性：涉及PKA、Rho和神经酰胺DOI: 10.3389/fendo.2026.1810747
Annals of African medicine IF: 00.600Ahead of Print.No.235Association of Serum Leptin with Insulin Resistance in Obese and Nonobese Patients with Type 2 Diabetes Mellitus: A Case-control Study from Eastern India血清瘦素与肥胖和非肥胖2型糖尿病患者胰岛素抵抗的关联：来自印度东部的病例-对照研究DOI: 10.4103/aam.aam_65_26
Bioinformation IF: 01.900Volume 22, Issue 1No.236Linking diabetic retinopathy with lipid abnormalities糖尿病视网膜病变与脂质异常的关联DOI: 10.6026/973206300220128
Bioinformation IF: 01.900Volume 22, Issue 1No.237The prevalence of anemia among type 2 diabetes mellitus with respect to renal function at a tertiary care hospital: A case-control study三级护理医院中2型糖尿病患者贫血患病率与肾功能的关系：一项病例对照研究DOI: 10.6026/973206300220353
Mayo Clinic proceedings. Digital healthVolume 4, Issue 2No.238Patients' Perspectives on Telemedicine for Type 2 Diabetes in Primary Care: Systematic Review and Thematic Synthesis2型糖尿病患者在基层医疗中使用远程医疗的观点：系统综述与主题综合分析DOI: 10.1016/j.mcpdig.2025.100333
bioRxivVolume 2026, Issue No.239Pharmacologic DPP-4 inhibition promotes CD8⁺ T cell metabolic fitness to enhance anti-tumor activity药理DPP-4抑制促进CD8⁺ T细胞代谢适应性以增强抗肿瘤活性DOI: 10.64898/2026.03.31.715681
BMC public health IF: 03.600Ahead of Print.No.240Incidence and predictors of diabetic ketoacidosis among adults with type 1 diabetes in Northwest, Ethiopia, 2023: a retrospective cohort study2023年埃塞俄比亚西北部1型糖尿病成人患者糖尿病酮症酸中毒的发病率及预测因素：一项回顾性队列研究DOI: 10.1186/s12889-026-27281-9
Bioimpacts IF: 02.200Volume 16, Issue No.241Moroccan virgin olive oil triterpenes: HPLC-DAD-ELSD profiling and computational investigation of anti-diabetic potential摩洛哥初榨橄榄油三萜类化合物：HPLC-DAD-ELSD分析及抗糖尿病潜力的计算研究DOI: 10.34172/bi.31007
Curēus IF: 01.300Volume 18, Issue 3No.242Successful Pregnancy Post-Kidney Transplant: A Case Report肾移植术后成功妊娠病例报告DOI: 10.7759/cureus.104884
J Chin Med Assoc IF: 02.400Ahead of Print.No.243Beyond disease treatment and prevention: From geroscience and molecular hallmarks to gerotherapeutics and precision geromedicine超越疾病治疗与预防：从衰老科学与分子特征到衰老治疗与精准衰老医学DOI: 10.1097/JCMA.0000000000001374
Trials IF: 02.000Ahead of Print.No.244Applying a hypothetical strategy to the intercurrent event of non-adherence with the parametric g-formula: a post hoc secondary analysis of the MET-PREVENT randomised controlled trial应用参数化g公式处理不依从偶发事件的假设性策略：对MET-PREVENT随机对照试验的事后二次分析DOI: 10.1186/s13063-026-09708-1
Cardiology in the Young IF: 00.900Ahead of Print.No.245Obesity prevalence and risk factors in surgically repaired CHD手术修复的先天性心脏病患儿肥胖患病率及危险因素DOI: 10.1017/S1047951126111718
213
Diabetes Mellitus(DM)
糖尿病
118
Obesity
肥胖症
49
Insulin
胰岛素
20
Type 2 diabetes mellitus(T2DM)
2型糖尿病
15
Metabolic Syndrome
代谢综合征
14
Diabetic Retinopathy
糖尿病视网膜病
13
Gestational Diabetes Mellitus(GDM)
妊娠糖尿病
9
Metformin
二甲双胍
6
Glucagon-Like Peptide-1 Receptor Agonists(GLP-1RA)
胰高血糖素样肽-1受体激动剂
6
Diabetic Kidney Disease(DKD)
糖尿病肾脏病
5
Diabetic Foot
糖尿病足
3
Hypoglycemic Agents
降糖药
3
Semaglutide
司美格鲁肽
3
Tirzepatide
替尔泊肽
2
Dipeptidyl-Peptidase IV Inhibitors(DPP-4i)
二肽基肽酶-4抑制剂
2
Sitagliptin
西他列汀
2
Type 1 diabetes mellitus(T1DM)
1型糖尿病
2
Diabetic acidosis
糖尿病性酸中毒
2
Diabetic Cardiomyopathies
糖尿病心肌病
2
Dapagliflozin
达格列净
2
Empagliflozin
恩格列净
2
Gabapentin
加巴喷丁
1
Pregabalin
普瑞巴林
1
Diabetic Peripheral Neuropathy(PDN)
糖尿病周围神经病变
1
gamma-Aminobutyric Acid(GABA)
γ-氨基丁酸
1
Ipragliflozin
依格列净
1
Luseogliflozin
鲁格列净
1
Tofogliflozin
托格列净
1
Diabetes Complications
糖尿病并发症
1
Saxagliptin
沙格列汀
1
Linagliptin
利格列汀
1
Alogliptin
阿格列汀
1
Sodium-Glucose Transporter 2 Inhibitors(SGLT-2i)
钠-葡萄糖协同转运蛋白2抑制剂
1
Canagliflozin
卡格列净
1
Exenatide
艾塞那肽
1
Liraglutide
利拉鲁肽
编辑：韩玉莲
审校：韩玉莲
2026-03-11
·商业新知
纵观全球创新药发展史，First-in-Class（首创药物）往往享有极高的市场先发优势。然而，在SGLT-2抑制剂这一拥挤的百亿美金赛道中，欧唐静（英文通用名：empagliflozin，恩格列净）却生动演绎了一场“后发先至”的经典商业反超战。2013年12月31日，恩格列净 率先于哥伦比亚获批，随后在2014年相继拿下欧盟与美国的上市许可。截至2024年，作为后来者的 恩格列净，其全球年销售额已强势突破131.5亿美元，正式跻身全球标志性重磅炸弹药物的超级俱乐部。恩格列净 是如何打破达格列净与卡格列净的先发壁垒的？其底层逻辑又为当下的创新药立项与生命周期管理带来了哪些启示？我们需要从人类对抗糖尿病的漫长历史中去寻找答案。一、靶点溯源：从“甜尿”到代谢科学的演进糖尿病，这一以长期高血糖为显著特征的代谢性疾病，其典型临床表现为“三多一少”（多食、多饮、多尿及体重下降）。在病理学分类上，主要分为因自身免疫导致胰岛B细胞受损、胰岛素绝对缺乏的1型糖尿病（胰岛素依赖型），以及因胰岛素抵抗或分泌进行性不足引发的2型糖尿病。根据国际糖尿病联盟（IDF）的统计，2021年全球20-79岁成年糖尿病患者已达5.37亿，其中2型糖尿病占比高达90%，且预计到2045年全球患者规模将攀升至7.83亿。人类对这一疾病的认知历经了数千年的探索：•上古时期的症状观察：早在公元前1550年的古埃及莎草纸文献中，便记录了一种具有“多尿”特征的贵族疾病，这是人类迄今发现最早的糖尿病史料。•中外古典医学的共识：公元前400年，中国《黄帝内经》详述了“消渴”病的症状 ；古印度医学（公元5-6世纪）与中国隋唐时期的甄立言（《古今录验方》）则不约而同地发现了患者尿液“甜如蜜”的核心病征。•现代病理学的曙光：17世纪，英国医生Thomas Willis首次使用拉丁文“mellitus”（极甜）来描述该病 ；1815年，法国化学家确证尿液中的甜味物质为葡萄糖。•胰岛素时代的开启：1869年Paul Langerhans发现胰岛 ，直至1920年Banting与Macleod成功提取胰岛素，人类终于掌握了干预糖尿病的利器，两人因此荣获1923年诺贝尔奖。然而，面对占据绝对主力的2型糖尿病患者，单纯的胰岛素补充疗法因“胰岛素抵抗”机制的存在而显得捉襟见。肘寻找口服降糖新靶点，成为了现代制药工业的百年命题。二、药物迭代：2型糖尿病治疗药物的百年变迁在SGLT-2抑制剂大放异彩之前，2型糖尿病的临床治疗经历了多次重要的靶点迭代，每一次都伴随着偶然的发现与艰难的机制探索：双胍类（二甲双胍）：源自天然牧草山羊豆中的山羊豆碱。1957年首次应用于临床后，二甲双胍曾因同类药物（苯乙双胍等）引发的致死性乳酸性酸中毒风波而一度被冷落。直至历时30年的具有里程碑意义的UKPDS（英国糖尿病前瞻性研究）证实了其在降糖的同时兼具心血管保护作用，FDA才于1995年批准其上市，奠定了其一线用药的霸主地位。磺酰脲类：发现源自二战期间磺胺类抗菌药（2254PR化合物）导致的低血糖副作用。经历第一代的高不良反应后，发展至第三代（如1995年上市的格列美脲），具备了刺激胰岛素分泌与增敏的双重机制。噻唑烷二酮类（TZDs）：日本三共制药基于抗氧化理念研发的曲格列酮（1995年）开启了PPARγ激动剂时代。但该类药物饱受安全性困扰，曲格列酮因肝毒性退市，罗格列酮被FDA黑框警告提示心衰风险，吡格列酮则因隐瞒膀胱癌风险致使礼来遭到巨额罚单。肠促胰素类（GLP-1与DPP-4）：科学家发现口服葡萄糖比静脉注射能引发更强烈的胰岛素分泌（肠促胰素效应）。人体Langerhans细胞分泌的GLP-1能稳定血糖，但半衰期极短 。由此诞生了抑制GLP-1降解的DPP-4抑制剂（如2006年获批的西格列汀）和直接补充作用的GLP-1受体激动剂。正是在不断追求更优效、更安全的降糖机制的驱动下，科学家的目光转向了人体的排泄器官——肾脏。三、SGLT-2抑制剂的结构破局：从根皮苷到恩格列净肾脏近端肾小球的钠葡萄糖转运蛋白-2（SGLT-2）负责了人体约90%的葡萄糖重吸收。阻断这一通道，就能让过量的葡萄糖随尿液直接排出，这是一种完全独立于胰岛素的降糖路径。1. 先导化合物的发现与困境SGLT-2抑制剂的灵感源泉，是1835年法国化学家从苹果树皮中提取的根皮苷。1886年其降糖作用被发现，但根皮苷作为药物存在两大致命缺陷：第一，选择性差。它不仅抑制肾脏的SGLT-2，还会抑制小肠内负责吸收葡萄糖的SGLT1，从而引发严重的胃肠道不良反应；第二，极度不稳定。其分子结构中的O-糖苷键在肠道中极易被水解酶切断，降解为无活性的根皮素和葡萄糖。根皮苷化学结构2. 构效关系（SAR）的突破与First-in-Class的诞生早期的结构改造中，田边三菱制药尝试合成的T-1095因未能克服O-糖苷不稳定性而在临床二期折戟。百时美施贵宝（BMS）随后提出缩短连接基的策略，成功解决了高选择性问题。最终的破局之法，是将易水解的O-苷键巧妙替换为极其稳定的C-C键（C-苷）。基于这一底层逻辑，两款具有开创意义的SGLT-2抑制剂率先完成了临床转化并相继问世：达格列净（Dapagliflozin/Farxiga）：由BMS与阿斯利康联合开发。它在A环上引入了氯原子，R基团设定为甲氧基。作为全球首个获批（2012年于澳大利亚和欧盟）的SGLT-2抑制剂，达格列净率先推开了这一全新降糖机制的大门。达格列净化学结构卡格列净（Canagliflozin/Invokana）：由田边三菱与强生公司联合开发。采用了A环为苯环、B环为苯基噻吩的母核结构，并引入了甲基与氟苯基。它于2013年3月成为首个登陆美国FDA的SGLT-2抑制剂，2016年达销售峰值14.13亿美元，一度在北美市场独领风骚。卡格列净化学结构3. 恩格列净的精妙设计勃林格殷格翰（BI）在此基础上进行了更深入的结构优化。恩格列净的分子设计在保留核心骨架的同时，精细调节了基团，赋予了其极佳的药代动力学特征。2009年9月，恩格列净正式步入临床试验阶段，2011年1月，勃林格殷格翰与礼来强强联手，共同推进恩格列净的全球研发进程。恩格列净化学结构四、核心临床数据解构：坚实的降糖基本盘恩格列净 的上市基石，建立在三项严谨且大规模的关键3期临床试验之上（Trial 1245.20、1245.23、1245.19），不仅验证了其单药疗效，更确立了其作为联用方案的黄金地位。恩格列净三项关键性3期临床试验核心数据对比分析上述数据充分证明，恩格列净不仅能够独立或协同其他经典降糖药物产生强效的降糖作用，还能凭借其独特的渗透性利尿机制与能量排泄机制，额外带来减轻体重、降低血压的“溢出红利”。然而，这仅仅是它问鼎王座的序曲。FDA于2014年8月1日正式批准欧唐静用于2型糖尿病患者的血糖控制。五、循证医学重塑市场格局：跨越圈层的“三大战役”如果仅作为一款降糖药，恩格列净由于上市时间晚于达格列净和卡格列净，在早期市场争夺中处于绝对劣势。恩格列净的真正突围，源自其在心血管与肾脏适应证上的前瞻性战略布局，彻底改变了SGLT-2抑制剂的用药格局。战役一：EMPA-REG OUTCOME —— 降糖药跨界心血管的“历史性拐点”长期以来，学术界普遍悲观地认为“单纯降糖无法改善糖尿病患者的大血管预后”。•试验设计：EMPA-REG OUTCOME研究历时多年，纳入7064例确诊心血管疾病的2型糖尿病患者，中位随访时间长达3.1年。•震撼结果：恩格列净组心血管死亡相对风险大幅降低38%，任何原因死亡风险降低32%，因心衰住院发生率降低35%。•商业意义：2016年12月，FDA依据此结果批准其用于降低心血管死亡风险。这是全球医学史上极具划时代意义的突破，凭借这一关键适应证，恩格列净销量在2017年迅速实现对卡格列净与达格列净的反超，确立了绝对的领先优势。而同期，卡格列净因被FDA标注下肢截肢的黑框警告，遭遇重创，逐渐淡出核心竞争圈。战役二：EMPEROR 项目 —— 攻克心力衰竭的“不治之症”心力衰竭分为射血分数降低（HFrEF）和射血分数保留（HFpEF）两种类型，后者长期处于无特效药的学术荒漠地带。•EMPEROR-Reduced（针对HFrEF）：纳入3730例患者，证实恩格列净可显著降低心血管死亡或心衰恶化住院的复合终点发生率（19.4% vs 安慰剂组24.7%），且无论患者是否伴有糖尿病。•EMPEROR-Preserved（针对HFpEF）：纳入5988例患者。该试验更是成为了业界首个在HFpEF领域取得阳性结果的大型临床试验，具备极其重要的里程碑意义。•基于此，FDA分别于2021年8月及2022年2月，全线批准恩格列净用于两型心力衰竭患者。这直接推动了其百亿美元销售额的第二增长曲线。战役三：EMPA-KIDNEY —— 筑牢慢性肾病（CKD）防线•试验概况：纳入6609名慢性肾脏病患者，恩格列净组肾脏疾病进展或心血管死亡的复合终点发生率为13.1%，显著优于安慰剂组的16.9%。•适应证获批：2023年9月21日，FDA批准其用于降低CKD成人患者的eGFR持续下降及终末期肾病等风险。•至此，恩格列净完美构筑了“糖-心-肾”共治的超宽护城河。恩格列净研发现状图源：摩熵医药数据库六、商业权谋与王座加冕：后来居上的市场逻辑医药市场的较量从来都不是纸面数据的单纯比拼，而是临床证据、监管决策、处方习惯与市场推广的多维综合博弈。恩格列净的逆袭，教科书般地展示了“First-in-disease（最佳疾病获益）”如何从战略层面击溃“First-in-class（同类首创）”。截至2025年，全球SGLT-2抑制剂市场规模估值已达178亿美元，并预计在未来十年持续扩张。在这片蓝海中，各方势力的沉浮令人唏嘘。1. 竞争对手的滑铁卢：卡格列净的黑框之痛曾在美国市场风头无两的卡格列净（Invokana），因安全性问题惨遭滑铁卢。FDA在评估CANVAS-R试验时发现，该药会导致下肢截肢（主要为脚趾和中足）的风险显著增加（发生率7.5/1000，远超安慰剂组的4.2/1000）。2017年5月，FDA对其发出了极其严厉的“黑框警告”。尽管强生等后续补充了心肾保护数据，并于2020年促使FDA撤销警告 ，但医学界的处方信心已然溃败，其全球销售额从2016年的巅峰断崖式下跌，彻底退出第一梯队。卡格列净全球销售额图源：摩熵医药数据库2. 双雄对决：恩格列净与达格列净的交锋分化卡格列净退场后，市场演变为恩格列净（Jardiance）与达格列净（Farxiga）的双雄争霸。恩格列净背靠礼来与勃林格殷格翰，凭借核心适应证的时间差优势步步为营：它于2016年率先斩获“降低心血管死亡风险”适应证，比达格列净早了整整三年 ；在攻克射血分数保留型心衰（HFpEF）的战役中，恩格列净于2022年2月率先获批，再次领先达格列净一年多。此外，真实世界处方分化显示，达格列净在降低心房颤动风险上受部分电生理医生青睐，但恩格列净在降低心血管死亡硬终点和改善心脏泵血效能上表现更佳，斩获了更广泛的内分泌与心肾专家的处方转化。3. 财务底座与远景扩张强大的临床护城河带来了巨额回报。恩格列净2024年全球销售额突破131.5亿美元。恩格列净历年销售图源：摩熵医药数据库在2025年总规模约178亿美元的SGLT-2抑制剂全球市场中，恩格列净凭借广泛的处方信任，以高达55.3%的市占率稳居霸主地位。业绩方面，2025年上半年勃林格殷格翰端恩格列净销售额达43亿欧元，礼来亦在25年第一季度因其获得3.7亿美元一次性收益。得益于完善的专利布局以及新适应症的拓展，预计恩格列净在未来数年内将继续维持其市场主导地位。七、SGLT-2抑制剂的最新进展根据摩熵医药数据库最新统计，截至2026年3月初，全球SGLT-2抑制剂赛道依然保持极高的研发热度。全球范围内处于研发或上市阶段的SGLT-2抑制剂共计99款。其中，已获批上市达42款，NDA申请阶段1款，处于三期临床的有19款，一二期临床共计28款，临床前研究8款。全球在研的SGLT-2抑制剂阶段分布恩格列净获批之后，全球相继涌现了多款创新型SGLT-2抑制剂，包括日本的伊格列净、鲁格列净；美国的艾托格列净、索格列净；以及中国恒瑞医药的脯氨酸恒格列净（2022年1月上市）和四环医药的加格列净（2024年1月上市）等。这标志着该领域的竞争已步入微创新的差异化时代。八、结语欧唐静的成功，是医药产业战略与执行力完美结合的典范：① 疗效与安全性是永恒的底色：卡格列净虽顶着美国First-in-Class的光环，却因截肢黑框警告折戟沉沙，这警示产业界：分子特性的底层安全性决定了药物的最终生命周期上限。② 顶层试验设计的“降维打击”：恩格列净虽上市较晚，但在关键的适应证拓展上（尤其是心血管预后及HFpEF），凭借极具魄力和前瞻性的大型随机双盲临床试验设计，实现了差异化占位。赢得首批上市只是第一步，依靠坚实的循证医学数据不断重塑疾病治疗指南，才是Best-in-Class加冕销售王座的核心密码。正如这段长达千年的医学探索史所昭示的：科学的突破永远属于那些不满足于现状、勇于在未知领域寻找更高确定性的探路者。恩格列净百亿美金突围密码的背后，是一部精准医疗战略指导下的大型临床循证史诗。
100 项与 伊格列净L-脯氨酸盐 相关的药物交易
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| 适应症 | 国家/地区 | 公司 | 日期 |
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| 1型糖尿病 | 日本 | - | 2014-01-17 |
| 2型糖尿病 | 日本 | - | 2014-01-17 |
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
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| 肝功能不全 | 临床1期 | 美国 | 2010-05-01 |
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| 研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
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N/A | HbA1c | BMI | visceral fat area ... 更多 | 103 | 網網鏇構壓壓簾鏇願積(餘鹹積糧選膚鬱憲簾觸) = 窪製選鏇範顧顧壓廠膚 齋餘糧壓膚顧夢鑰遞鬱 (膚糧鏇簾淵構窪齋壓願 ) | 积极 | 2022-09-20 | ||
Metformin 1000 mg | 網網鏇構壓壓簾鏇願積(餘鹹積糧選膚鬱憲簾觸) = 製繭衊醖製齋膚窪襯蓋 齋餘糧壓膚顧夢鑰遞鬱 (膚糧鏇簾淵構窪齋壓願 ) | ||||||
N/A | 2型糖尿病 一线 | 11,412 | (Treatment-naïve patients) | 製鏇顧淵醖繭遞鬱艱製(築齋築鑰醖衊簾選蓋選) = 鹹糧糧鹹膚衊簾餘觸積 糧衊夢壓顧積鹽窪選艱 (夢獵糧願願積壓鏇積夢 ) 更多 | - | 2021-10-01 | |
(Non-naïve patients) | 製鏇顧淵醖繭遞鬱艱製(築齋築鑰醖衊簾選蓋選) = 鹹製獵醖壓廠鹹範糧鹹 糧衊夢壓顧積鹽窪選艱 (夢獵糧願願積壓鏇積夢 ) 更多 | ||||||
临床3期 | - | 廠襯鑰鬱築淵壓糧衊齋(憲壓衊襯齋願鏇衊壓築) = 網構簾淵憲獵觸艱網憲 壓餘網鏇窪齋簾鏇艱鏇 (淵壓鹽鹹獵襯淵鏇夢構 ) | - | 2021-05-25 | |||
N/A | 11,412 | Ipragliflozin in patients aged <65 years | 選顧蓋醖繭鹽壓鹽願窪(鑰廠廠鬱餘鏇簾遞廠糧) = 壓鹽鏇遞糧範餘鹽觸觸 鬱憲積餘壓積糧選膚構 (願壓糧膚膚鑰鹽鹽築艱 ) 更多 | - | 2021-03-17 | ||
Ipragliflozin in patients aged ≥65 years | 選顧蓋醖繭鹽壓鹽願窪(鑰廠廠鬱餘鏇簾遞廠糧) = 簾遞鏇鑰蓋憲鑰餘淵憲 鬱憲積餘壓積糧選膚構 (願壓糧膚膚鑰鹽鹽築艱 ) 更多 | ||||||
临床4期 | 2型糖尿病 二线 | - | 淵糧廠夢憲築鬱製鏇壓(糧艱獵選窪淵憲齋鑰衊) = 鏇鏇淵壓鬱鑰選鑰構構 餘糧襯鹽餘範鹽膚遞築 (憲範範淵鹽壓製觸襯鑰 ) 更多 | - | 2020-06-01 | ||
Sitagliptin | 淵糧廠夢憲築鬱製鏇壓(糧艱獵選窪淵憲齋鑰衊) = 範蓋製鬱遞獵鬱範獵觸 餘糧襯鹽餘範鹽膚遞築 (憲範範淵鹽壓製觸襯鑰 ) 更多 | ||||||
N/A | - | 膚餘淵製積餘觸憲鏇鏇(蓋膚餘鑰憲壓淵網製積) = 鹽醖簾網膚窪遞鬱醖壓 遞鑰廠艱遞襯壓構憲醖 (齋艱衊蓋憲製鹽鹽廠鑰 ) 更多 | - | 2019-12-01 | |||
Placebo | 膚餘淵製積餘觸憲鏇鏇(蓋膚餘鑰憲壓淵網製積) = 夢壓糧網網衊窪襯蓋鏇 遞鑰廠艱遞襯壓構憲醖 (齋艱衊蓋憲製鹽鹽廠鑰 ) 更多 | ||||||
N/A | 11,412 | (Non-elderly patients) | 獵顧廠觸願鹽膚願遞壓(製衊淵網衊壓醖襯製遞) = 鬱網壓淵觸顧觸糧構範 糧遞繭範鹽淵繭憲衊遞 (夢壓鏇簾願襯糧選網顧 ) 更多 | - | 2019-11-01 | ||
(Elderly patients) | 獵顧廠觸願鹽膚願遞壓(製衊淵網衊壓醖襯製遞) = 觸構範簾觸獵艱鹽壓鹽 糧遞繭範鹽淵繭憲衊遞 (夢壓鏇簾願襯糧選網顧 ) 更多 | ||||||
临床3期 | 175 | insulin+ipragliflozin | 齋鑰齋衊範壓築醖蓋齋(蓋顧夢鏇遞糧壓蓋製蓋): difference = -3.8 (95% CI, -6.2 ~ -1.5) 更多 | 积极 | 2019-10-01 | ||
insulin+Placebo | |||||||
N/A | insulin | α1microglobulin (α1MG) | glutamic pyruvic transaminase (GPT) | 103 | 顧繭鹽醖積觸鬱鑰襯繭(壓膚顧鏇襯鑰鹽膚製顧) = 觸鏇艱網衊窪齋衊憲範 蓋衊鏇繭鏇窪膚製範積 (觸襯襯遞鑰鬱衊窪膚夢 ) 更多 | 积极 | 2019-09-17 | ||
顧繭鹽醖積觸鬱鑰襯繭(壓膚顧鏇襯鑰鹽膚製顧) = 觸憲蓋簾遞醖鏇壓獵膚 蓋衊鏇繭鏇窪膚製範積 (觸襯襯遞鑰鬱衊窪膚夢 ) 更多 | |||||||
N/A | 2型糖尿病 一线 visceral fat area | bone-specific alkaline phosphatase (BAP) | tartrate-resistant acid phosphatase-5b (TRACP-5b) | 103 | 齋選夢廠衊網築襯鏇鹹(範鑰糧憲積願窪簾顧壓) = 顧繭選積簾鏇鏇餘襯襯 膚餘鬱獵鹽觸餘衊鑰鬱 (鏇遞選選窪積願獵齋膚 ) 更多 | 不佳 | 2018-10-05 | ||
齋選夢廠衊網築襯鏇鹹(範鑰糧憲積願窪簾顧壓) = 積憲製鬱鹽廠蓋網夢夢 膚餘鬱獵鹽觸餘衊鑰鬱 (鏇遞選選窪積願獵齋膚 ) 更多 |
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