Pyrimethamine/Sulfadoxine

SHANGHAI, April 26, 2024 /PRNewswire/ -- World Malaria Day is marked each year on April 25. World Health Organization (WHO) gave as the theme for World Malaria Day 2024 Accelerating the fight against malaria for a more equitable world. WHO stated that malaria not only continues to directly endanger health and cost lives, but it also perpetuates a vicious cycle of inequity. People living in the most vulnerable situations including pregnant women and children under 5 years of age continue to be disproportionately impacted. Artemisinin medicines developed with China's scientific research efforts have become a ticket for China's innovative medicines to go global. According to the WHO World Malaria Report 2023, globally in 2022, there were an estimated 249 million malaria cases and 608,000 malaria deaths. Sub-Saharan Africa accounted for more than 95% of the global malaria cases and deaths. Globally, an estimated 11.7 million malaria deaths were averted in the period 2000-2022. Among them, the average malaria mortality rate (number of deaths per 100,000 population at risk) in Africa decreased from 0.14% per 100,000 population to 0.055%, from 142.6 per 100,000 population in 2020 to 55.5 in 2022. The widespread use of artemisinin medicines is one of the key success factors. Several global multi-center phase III clinical studies and real-world data have shown that artesunate injection is effective in reducing malaria mortality rate. Self-developed Artemisinin medicines covering from prevention to severe disease treatment As a leading global R&D and production enterprise of anti-malaria drugs, anti-malaria drugs produced under the R&D and innovation of Fosun Pharma cover malaria prevention, general malaria treatment and severe malaria treatment. A total of 33 products in the anti-malaria series were approved by WHO pre-qualification (WHO PQ), which have made significant contribution to malaria prevention and treatment in countries and regions such as Africa. In 2010, Artesun®, an artesunate for injection independently developed and manufactured by Fosun Pharma, was approved by WHO PQ. Since 2011, it has been recommended by WHO as a first-line drug for the treatment of severe malaria in children and adults. At the same time, Fosun Pharma is also a supplier of anti-malaria drugs of the Global Fund, UNICEF, WHO and African governments. By the end of 2023, Fosun Pharma has supplied over 340 million doses of artesunate for injection across the world, treating more than 68 million severe malaria patients worldwide. Meanwhile, Fosun Pharma went deep into the remote areas of African villages and meet the needs of clinicians through continuous innovation. Through process optimization, it has independently developed and launched the second generation of artesunate injection (trade name: Argesun®), which is the first one-step preparation passing the WHO PQ in the world. The preparation time of the drug was reduced from 3 minutes to 1 minute, which can save the time for treating patients with severe malaria. Meanwhile, the concentration of Argesun® was standardized for intravenous and intramuscular injections, which makes it more convenient and safer for clinical purposes. Artemisinin-based combination therapies (ACTs) are recognized by WHO as the best available treatment. However, in recent years, drug resistance to these therapies has also begun to emerge in Plasmodium falciparum, which is becoming a major threat to malaria control. The global multicenter Phase III clinical trial project led by Fosun Pharma for a triple artemisinin combination drug (Artemether-Lumefantrine-Amodiaquine fixed-dose formulation) against malaria in Africa and Southeast Asia has also received attention from all parties, and the Japan-based Global Health Innovative Technology Fund (GHIT Fund) announced in December 2023 that it will invest approximately US$3.3 million (approximately 500 million yen[1]), to accelerate the development and commercialization of this new drug. This drug candidate should have a significant public health benefit as it is expected to play an important role in the fight against artemisinin partial resistance (ART-R) which is now observed widely in the Greater Mekong Subregion (GMS) of Southeast Asia[2] and to some extent in several African countries, including Rwanda and Uganda. Further improving the accessibility of second generation of Artesunate for injection to benefit remote areas of Africa From April 21 to 27, the 8th Multilateral Initiative on Malaria (MIM) Pan-African Malaria Conference was held in Kigali-Rwanda. As one of the main sponsors of the conference, Fosun Pharma showcased its full range of antimalarial products and successfully hosted the academic symposium "Improving antimalarial treatment for severe P. falciparum malaria" on April 23. The symposium introduced the recent trends in the global and particularly African burden of severe malaria and the latest treatment and clinical management strategies to over 300 malaria researchers, clinicians, malaria control officials, and NGO representatives from Africa and around the world. The session was co-chaired by Professor Olugbenga A Mokuolu from Nigeria (Co-Chair of RBM Case Management Working Group; Strategic Adviser on Malaria Elimination to the Honorable Minister of Health Nigeria) and Professor Marielle Bouyou Akotet from the Université des Sciences de la Santé Gabon. Professor Arjen Dondorp and Professor Joel Tarning from the University of Oxford, and Dr. Samwel Gesase from the National Institute for Medical Research in Tanzania, respectively, presented the important contributions of injectable artesunate in the treatment of severe malaria patients from the epidemiological, clinical pharmacological, and pharmacoeconomic perspectives. They also highlighted the clinical advantages of Fosun Pharma's second-generation of artesunate injection with one-step preparation in the management of severe malaria. The 1.5 hours scientific session was ended by an introduction of the post-discharge malaria chemoprevention, PDMC by Professor Kamija Phiri from Kamuzu University of Health Sciences Malawi. The attendees highly appreciated the academic professionalism of Fosun Pharma's symposium on severe malaria and recognized Fosun Pharma's commitment to affordable innovation in bringing a new generation of artesunate injection with one-step preparation to Africa. The experts agreed that " artesunate injection is currently the most effective drug for the treatment of severe malaria. The new generation of artesunate injection with one-step preparation will further enhance the convenience of clinical use and reduce the clinical cost of severe malaria treatment, benefiting critically ill children with malaria in remote areas of Africa where medical conditions are poor." From treatment to prevention, effectively reducing the incidence of severe malaria in children According to the WHO, children under 5 years old are still the most vulnerable population to malaria infection. in 2022, an estimated 4 out of 5 malaria-related deaths in the African Region were among children under 5 years of age. Inequities in access to education and financial resources further exacerbates risk: children under 5 years of age from the poorest households in sub-Saharan Africa are 5 times more likely to be infected with malaria than those from the wealthiest households. To improve this situation, Fosun Pharma, in collaboration with the National Malaria Control Program in Africa, continued to carry out the "Promoting Malaria Prevention Knowledge among Children Program" in 14 malaria-prone countries in Africa, targeting at the community level, in order to raise the awareness of malaria prevention among the local population in Africa, and to help reduce the incidence rate of malaria and interrupt the transmission of malaria in the community. In August 2018, Fosun Pharma's SPAQ-CO® Disp (co-packed sulfadoxine-pyrimethamine dispersible tablets and amodiaquine dispersible tablets), for the prevention of malaria in children, was approved by WHO PQ . By the end of 2023, more than 258 million children in Africa had benefited from the "Seasonal Malaria Chemoprevention Program", for which SPAQ-CO® Disp is used as the core drug, effectively reducing the incidence of malaria in children under five years old in Africa. Promoting the localization of pharmaceutical production and helping to enhance the healthcare capacity of developing countries Based in China and with a global presence, Fosun Pharma has always been committed to providing high-quality medical solutions to patients worldwide. It actively expands its business in emerging markets, including Africa, India and Southeast Asia, to improve the accessibility of medicines in developing countries. By the end of 2023, Fosun Pharma had established five regional distribution centers in emerging markets. The overseas commercialization team consists of approximately 1,000 people, dedicated to enhancing the accessibility of pharmaceutical products. To achieve localized pharmaceutical manufacturing and supply in Africa and to enhance the accessibility and affordability of pharmaceutical and healthcare products in the African region, Fosun Pharma's Cote d'Ivoire park project was initiated in November 2022. The project is planned to be carried out in three phases, with the first phase expected to be completed in 2024. Upon completion of the project, the production capacity of the park will be expanded to 5 billion tablets per year and include a warehouse with a storage capacity of 10,000 pallets, which is expected to bring nearly 1,000 job opportunities to the Greater Bassam area and effectively promote the development of the pharmaceutical industry in Cote d'Ivoire. About Fosun Pharma Founded in 1994, Shanghai Fosun Pharmaceutical (Group) Co., Ltd.* ("Fosun Pharma"; stock code: 600196. SH, 02196. HK) is a global innovation-driven pharmaceutical and healthcare industry group. Fosun Pharma directly operates businesses including pharmaceuticals, medical devices, medical diagnosis, and healthcare services. As a shareholder of Sinopharm Co., Ltd., Fosun Pharma expands its areas in the pharmaceutical distribution and retail business. Fosun Pharma is patient-centered and clinical needs-oriented. The company continuously enriches its innovative product pipeline through independent research and development, cooperative development, license-in, and in-depth incubation. Fosun Pharma improves the research and clinical development capabilities of FIC (First-in-class) and BIC (Best-in-class) new drugs as well as accelerates the R&D and launch of innovative technologies and products. Fosun Pharma's innovative products mainly covered core therapeutic areas such as tumors (solid tumors and hematologic tumors), immunology, central nervous system, and chronic diseases (liver disease/metabolism/kidney disease). Guided by the 4IN strategy (Innovation, Internationalization, Intelligentization, and Integration), Fosun Pharma will uphold the development model of "Innovation Transformation, Integrated Operation and Steady Growth", with the mission of creating shareholder values through strengthening its independent R&D and external cooperation and enriching its product pipelines, as well as promoting the global networks and enhancing operational efficiency. Fosun Pharma will actively promote the digital and physical business layout in the pharmaceutical and healthcare industry and is committed to becoming a first-class enterprise in the global pharmaceutical and healthcare markets. For more information, please visit our official website: SOURCE Fosun Pharma

01月05日的《热心肠日报》，我们解读了 10 篇文献，关注：免疫治疗，微生物酶，菌群-肠-脑轴，生命早期，拟杆菌，肠道血管系统，胆石症，营养不良，内镜。 Science：菌群依赖性T细胞反应，促进免疫治疗引发的结肠炎 Science——[56.9] ① 给野生型小鼠定植野外小鼠菌群（WildR），WildR小鼠接受抗CTLA-4抗体免疫治疗时易发结肠炎，而SPF小鼠不会，表明CTLA-4阻断治疗引发的结肠炎依赖于肠道菌群组成；② 这种肠道炎症的驱动因素是：产IFNγ的CD4+ T细胞的无限制活化，以及由识别抗体Fc段的Fcγ受体介导的肠道RORγt+ pTreg耗竭；③ 使用缺少Fc段的抗CTLA-4纳米抗体（单域抗体），可以在WildR小鼠中有效激活抗肿瘤免疫而不诱导结肠炎。 【主编评语】 免疫检查点抑制剂（如抗CTLA-4抗体）可以激活抗肿瘤免疫，但也可能诱发免疫相关不良事件（irAE），包括结肠炎。然而，非遗传操纵或辅助干预（如DSS）的实验室小鼠在接受免疫检查点阻断治疗后，对肠道炎症具有高度抵抗力，因此对肠道irAE的机制理解一直受到阻碍。Science最新发表的一项研究发现，CTLA-4阻断引发的小鼠结肠炎依赖于肠道菌群组成，揭示了该小鼠模型中T细胞驱动的肠道炎症机制，并基于这一发现提供了开发具有较低肠道炎症毒性的新型CTLA-4抑制剂的新策略。（@mildbreeze） 【原文信息】 Microbiota-dependent activation of CD4+ T cells induces CTLA-4 blockade–associated colitis via Fcγ receptors 2024-01-04, doi: 10.1126/science.adh8342 江晓芳等Nature子刊：鉴定肝肠循环重要代谢物胆红素的菌群酶 Nature Microbiology——[28.3] ① 基于胆红素结合后的UnaG荧光激发试验，鉴定出一系列具备胆红素还原酶的肠道细菌，它们均属于厚壁菌门的梭状芽胞杆菌纲；② 通过比较基因组学从亲缘性靠近、胆红素还原酶有无的菌株间鉴定胆红素还原酶基因，基于关键残基同源比对确定胆红素还原酶bilR基因；③ 异源表达确定BilR的胆红素还原酶活，基于关键残基鉴定绘制bilR的进化分支谱；④ 人宏基因组数据集显示bilR在健康成年人中广泛存在，但在新生儿和炎症性肠病患者中发现率下降。 【主编评语】 近期发表在Nature Microbiology的这份工作，由美国国立卫生研究院国家图书馆江晓芳和团队完成。他们针对影响宿主健康的肝肠循环中重要代谢物胆红素的菌群来源胆红素还原酶进行了鉴定，填补了宿主胆红素转化的一块空白。基于荧光报告实验和比较基因组学，他们从厚壁菌门的梭状芽胞杆菌纲细菌中鉴定出胆红素还原酶bilR基因，随后根据该基因的关键残基绘制了bilR基因的进化分支谱。基于bilR基因序列在人宏基因组的流行度，发现新生儿和炎症性肠病（IBD）患者bilR基因的发现率降低，为胆红素和黄疸的因果提供证据，以及为IBD患者的肝肠循环紊乱提供证据。（@Johnson） 【原文信息】 BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen 2024-01-03, doi: 10.1038/s41564-023-01549-x Nature子刊：肠道菌群通过维生素B12调节宿主神经系统功能 Nature Cell Biology——[21.3] ① 肠道菌群通过产生维生素B12调节秀丽隐杆线虫的兴奋性信号；② 维生素B12通过蛋氨酸/s-腺苷甲硫氨酸（Met/SAM）循环和肠内胆碱氧化途径之间的代谢串扰，降低神经系统中的胆碱能信号；③ 维生素B12驱动代谢重新布线，并减少游离胆碱的可用性，游离胆碱被神经元用于合成乙酰胆碱；④ 维生素B12对胆碱能信号传导的抑制作用被高亲和胆碱转运体CHO-1的突变所阻断。 【主编评语】 肠道菌群的变化与自闭症、焦虑、抑郁、精神分裂症等神经系统疾病有关，然而，目前尚不清楚肠道菌群的不平衡是否导致了神经系统疾病，或者肠道菌群组成的破坏是否是神经系统疾病的结果。近期发表于Nature Cell Biology上的文章，利用秀丽隐杆线虫的细菌饮食来确定调节宿主神经功能和行为的肠道菌群。结果表明，在肠道中定植的菌群通过产生维生素B12引起秀丽隐杆线虫行为的持续变化，维生素B12通过蛋氨酸（Met）/s-腺苷蛋氨酸（SAM）循环和胆碱氧化途径之间的代谢串扰减少兴奋性胆碱能信号。（@RZN） 【原文信息】 Vitamin B12 produced by gut bacteria modulates cholinergic signalling 2024-01-02, doi: 10.1038/s41556-023-01299-2 社交焦虑症相关肠道菌群让小鼠“社恐” PNAS——[11.1] ① 与健康对照组相比，社交焦虑症（SAD）患者的肠道微生物群的组成不同；② 将SAD患者的菌群移植到小鼠，小鼠在评估抑郁和一般焦虑样行为的测试中表现出正常行为，但它们对社会恐惧（SAD的一种模型）的敏感性特别高；③ SAD菌群移植降低循环应激激素和外周免疫，改变神经炎症标志物，损害血脑屏障功能；④ SAD菌群移植到小鼠后，纹状体末端床核中神经元催产素的减少以及杏仁核内侧和额前皮质中催产素相关基因的表达，都与社交恐惧的增加有关。 【主编评语】 社交焦虑症（SAD）是一种致残性精神障碍，其特征是在社交环境中产生强烈的恐惧或焦虑以及回避。越来越多的研究显示，肠道微生物群已成为大脑和行为的关键调节因子，尤其是与社会功能相关的调节因子。此外，越来越多的数据支持免疫功能和催产素信号在社会反应中的作用。PNAS近期发表的文章，发现将SAD患者的菌群移植到小鼠中，小鼠对社会恐惧的敏感性特别高，这提示肠道菌群或是治疗SAD的潜在靶点。（@章台柳） 【原文信息】 Social anxiety disorder-associated gut microbiota increases social fear 2023-12-26, doi: 10.1073/pnas.2308706120 Nature子刊：婴儿肠道利用人乳低聚糖的菌群鉴定 Nature Communications——[16.6] ① 从母乳喂养的婴儿中分离出多氏拟杆菌（Bacteroides dorei），发现多糖利用位点（PUL）33使多氏拟杆菌能够利用唾液酸化人乳低聚糖（HMOs）；② 利用CRISPR-Cas12敲除4个PUL33基因（GH20、GH33、SusD和SusC）等实验，确定了GH33是PUL33中唾液酸化HMOs利用的关键基因；③ 本实验为进一步研究其他HMOs利用系统开辟了道路，这将更好地了解婴儿肠道中HMOs的利用。 【主编评语】 母乳中的人乳低聚糖（HMOs）不能被婴儿消化，而是作为肠道细菌的营养物质。虽然绝大多数HMO利用研究集中在双歧杆菌属上，但最近的研究表明还有其他HMO利用者，主要是拟杆菌属，但它们的利用机制还不清楚。近期Nature Communications发表的一项研究对此做了相关探索。（@注册营养师陈彬林） 【原文信息】 CRISPR-Cas-based identification of a sialylated human milk oligosaccharides utilization cluster in the infant gut commensal Bacteroides dorei 2024-01-02, doi: 10.1038/s41467-023-44437-y Cell子刊：机器学习通过阴道微生物组特征进行早产预测 Cell Reports Medicine——[14.3] ① 利用9项阴道微生物组研究数据，包括1268名孕妇的3578个样本，构建机器学习模型来预测早产（PTB，<37周）或早期早产（ePTB，<32周）；② 预测模型在两个独立的未发表数据集上进行了验证，这两个数据集包括148名孕妇的331个样本；③ 表现最好的模型在预测PTB和ePTB的AUROC曲线分别是0.69和0.87；④ 阿尔法多样性、VALENCIA 群落状态类型和组成是性能最好的模型中的重要特征。 【主编评语】 每年，11%的婴儿出现早产，对健康产生重大影响，而阴道微生物群落是早产的危险因素。Cell Reports Medicine近期发表的文章，利用机器学习开发出基于阴道微生物组来预测早产的模型，或可更好地了解和预防早产。（@章台柳） 【原文信息】 Microbiome preterm birth DREAM challenge: Crowdsourcing machine learning approaches to advance preterm birth research 2023-12-21, doi: 10.1016/j.xcrm.2023.101350 关于肠道血管系统新功能、新机制的新见解（综述） Journal of Experimental Medicine——[15.3] ① 肠道脉管系统具备维持上皮细胞稳态、应对菌群诱导的炎症及招募特异性免疫细胞等新功能；② 与淋巴系统交互依绒毛-隐窝轴而建，通过血管内皮生长因子VEGFA依赖和非依赖性方式促进营养吸收；③ 上皮和成纤维细胞产生VEGFA，通过血管内皮细胞“窗孔”转运养分；④ 隐窝通过Apelin信号促进内皮细胞迁移和血管生成；⑤ 高内皮微静脉通过粘附分子MADCAM1等的表达招募肠道特异性免疫细胞；⑥ 肠道血管通过TNF信号、通透性调节等机制抵御菌群诱导的炎症。 【主编评语】 过去100年来人们一直在研究肠道血管系统及其在吸收和分配摄入的物质方面的重要作用。Journal of experimental Medicine发表的综述对肠道血管系统特异性新功能和机制进行了总结，包括维持肠上皮细胞功能、应对微生物引起的炎症压力、招募肠道特异性免疫细胞以及与其他器官的互作。（@好雨） 【原文信息】 Mechanisms and functions of intestinal vascular specialization 2023-12-05, doi: 10.1084/jem.20222008 吉大第一医院：降脂药与胆石症间有何关联？ Small——[13.3] ① 利用英国生物银行数据，探究血脂与胆石症风险间的关系，发现血清HDL-C和LDL-C和胆石症风险呈线性负相关，而血清TC和TG和胆石症则存在显著的非线性关系；② 采用六种孟德尔随机化模型分别估算血脂和胆石症风险，发现血清HDL-C、LDL-C和TC的下降会升高胆石症风险；③ 磁共振分析支持也证实血清TC降低和TG水平升高是胆石症的独立因果危险因素；④ 通过探究11个脂代谢相关靶点和胆石症关系，HMGCR降脂靶点所代表的他汀类药物可降低胆石症风险。 【主编评语】 胆石症是一种常见的肝胆疾病，先前的研究已经探讨了血脂和脂质修饰靶点在胆石症发展中的作用。然而，调查结果不一致，需要进一步调查。近日，吉大一院吕国悦及团队在Gut发表最新研究，发现血清胆固醇和甘油三酯是胆石症的独立风险因素，且影响方向相反，胆固醇越高，患胆石症的风险越低，而甘油三酯越高，患胆石症的风险越高。此外，研究证明使用HMGCR降脂靶点所代表的他汀类药物可降低胆石症风险，值得关注。（@九卿臣） 【原文信息】 Novel insights into causal effects of serum lipids and lipid-modifying targets on cholelithiasis 2023-11-09, doi: 10.1136/gutjnl-2023-330784 疟疾药物或可成为终结营养不良恶性循环的关键？ EBioMedicine——[11.1] ① 使用患者类器官来源的十二指肠上皮细胞与人肠道内皮细胞在体外构建肠道器官芯片模型，通过灌注营养缺乏培养基模拟肠道营养不良；② 磺胺多辛-乙胺嘧啶（SP）干预可显著减轻营养不良引起肠道功能障碍，如绒毛损伤、屏障功能损伤、粘液分泌减少等；③ SP干预逆转营养不良对肠道多种代谢过程（如脂肪酸和胆汁酸代谢）和生物途径的抑制作用，促进肠道吸收；④ SP干预可减少营养不良诱导的炎症因子（如IL-8、TNF-α等）分泌和对免疫细胞的募集。 【主编评语】 磺胺多辛-乙胺嘧啶（SP）抗疟疾疗法已被认为有可能增加撒哈拉以南非洲孕妇婴儿的出生体重，而不受疟疾感染的影响。近日，哈佛大学研究人员在EBioMedicine发表最新研究，通过构建肠道器官芯片模型，发现SP可能通过预防肠道功能障碍和抑制肠道炎症来增加出生体重，改善营养不良，值得关注。（@九卿臣） 【原文信息】 Direct therapeutic effect of sulfadoxine-pyrimethamine on nutritional deficiency-induced enteric dysfunction in a human Intestine Chip 2023-12-14, doi: 10.1016/j.ebiom.2023.104921 2022年度十大内窥镜主题（综述） Gastrointestinal Endoscopy——[7.7] ① 美国胃肠内窥镜学会的10名编辑委员会成员列出了2022年度胃肠道内窥镜中10个最重要的主题领域；② 每位编委会成员被要求在纳入候选主题名单时考虑3个标准——重要性、新颖性和对临床实践的全球影响；③ 这10个确定的领域共同代表了以下内镜领域的进展：人工智能、内镜粘膜下剥离、Barrett食管、介入性超声内镜（EUS）、内镜切除技术、胰胆内镜、急性胰腺炎管理、内镜环境可持续性、NordICC试验和螺旋肠镜检查。 【主编评语】 近期Gastrointestinal Endoscopy通过对本刊和其他高影响力医学和胃肠病学期刊在2022年发表的原创文章进行系统的文献检索，确定了2022年度胃肠道内窥镜中10个最重要的主题领域。（@注册营养师陈彬林） 【原文信息】 The 2022 top 10 list of endoscopy topics in medical publishing: an annual review by the American Society for Gastrointestinal Endoscopy Editorial Board 2023-11-16, doi: 10.1016/j.gie.2023.08.021 感谢本期日报的创作者：mildbreeze，熙子，RZN，章台柳，注册营养师陈彬林，YANG WEI，九卿臣，鹿刺刺 点击阅读过去10天的日报： 01-04 | 傅静远等Nature突破：在遗传互作层面揭示血型与肠菌的密切关系 01-03 | 初波/朱书/柴人杰/顾伟等Nature子刊：肠菌代谢物促大肠癌的新机制 01-02 | 双重作用：65分综述深度探讨肠炎中的一类免疫细胞 01-01 | 12月，最值得看的40篇肠道健康文献！ 2023-12-31 | 26页综述详解：浆果的健康作用和食品价值 2023-12-30 | 多吃还是少吃？10文聚焦食欲调控的奥秘 2023-12-29 | 22页《自然·综述》讲透自闭症与胃肠道的关系 2023-12-28 | 65分综述详解：母亲菌群如何影响孩子免疫发育？ 2023-12-27 | Cell子刊揭秘：肠道衰老，源头在哪？ 2023-12-26 | 《自然·综述》年度回顾：炎症性肠病疗法的新进展