Dysautonomia, Familial

Scientists have written a review to discuss emerging research and evidence of the roles of alternative splicing defects in major neurodegenerative diseases. They also summarize the latest advances in RNA-based therapeutic strategies to target these disorders. Alternative splicing, a clever way a cell generates many different variations of messenger RNAs -- single-stranded RNAs involved in protein synthesis -- and proteins from the same stretch of DNA, plays an important role in molecular biology. Progressing rapidly, the field of alternative splicing is a complex topic and the scientific literature on it is already extensive. David Nikom, a student in the UC Riverside Neuroscience Graduate Program, and his advisor, Sika Zheng, an associate professor of biomedical sciences in the UCR School of Medicine and director of the Center for RNA Biology and Medicine, have written a review in Nature Reviews Neuroscience to discuss emerging research and evidence of the roles of alternative splicing defects in major neurodegenerative diseases. They also summarize the latest advances in RNA-based therapeutic strategies to target these disorders. According to them, the topic of alternative splicing in neurodegenerative disease is particularly relevant in view of the increasing frequency of neurodegenerative disease worldwide and the urgent need for novel approaches for their treatment and management. They argue that since aberrant splicing dysregulation occurs commonly in neurodegenerative disease, the promise of using RNA therapies is important to understand and well-suited for a review. Titled "Alternative Splicing in Neurodegenerative Disease and the Promise of RNA Therapies," their review aims at providing comprehensive, all-inclusive knowledge for a scientific audience interested in the topic. It synthesizes knowledge and discoveries from decades of research made by many labs worldwide on Alzheimer's disease, Parkinson's disease, Huntington's disease, ALS, frontal temporal dementia, etc. The work is supported by grants to Zheng from the National Institutes of Health. In the following Q&A, Zheng and Nikom unpack key aspects of the review. Q: What is alternative splicing dysregulation? Once the DNA of a gene is transcribed into a pre-messenger RNA (RNA before it is spliced), only a small fraction of the pre-messenger RNA makes into the final messenger RNA, or mRNA, transcript that encodes protein. Alternative splicing is a process by which a cell can select which of those protein-coding parts to include in the resulting RNA or protein. Alternative splicing dysregulation is when this process goes wrong in some way. The cell chooses to include the wrong protein-coding parts or exclude some correct parts. This can cause all sorts of problems with the resulting protein: it could be shorter than it is supposed to be which would disrupt its normal function in the cell, or it could result in the protein not being produced at all. Q: What role does alternative splicing play in molecular biology? Alternative splicing greatly expands the diversity of the proteins that can be made from a single gene. This is important because multicellular organisms make so many different types of cells that compose the diverse tissue types of their body. But each cell only has the same genetic code. To produce the dazzling complexity of multicellular life, cells depend on alternative splicing to give them the flexibility to make large families of similar proteins with different tissue-specific and developmental stage-specific functions. For example, certain alternative splicing networks are only activated during embryonic development and get shut down when the organism matures. Q: Briefly, how does it contribute to the molecular pathology of a wide range of neurodegenerative diseases? Certain organs rely on alternative splicing to generate cellular diversity more than others. We don't know why for sure, but the brain has more alternative splicing going on than any other organ in the body. Scientists speculate this might be due to the brain's unique complexity, rapid evolution, or the extraordinary diversity of cell types it contains. What we do know is that there are a lot of brain-specific alternative splicing events that consistently go wrong in neurological diseases. These include neurodevelopmental disorders, like autism spectrum disorder, or neurodegenerative diseases, like Alzheimer's Disease or ALS. The best understood example we have so far has to do with dysregulated alternative splicing in ALS. Scientists found these erroneous splicing events lead to production of aberrant proteins or reduction of normal proteins, which ultimately affect neuronal health and function. Some other neurodegenerative diseases with dysregulated alternative splicing include frontotemporal dementia, Parkinson's disease, Familial dysautonomia, Huntington's disease, spinal muscular atrophy, and Duchenne muscular dystrophy. Q: Does alternative splicing play a role in other diseases? Alternative splicing has been linked to about 15% of human genetic diseases and cancers. Mutations in the components that regulate alternative splicing are causative for many diseases, both common and rare. Myotonic dystrophy, myelodysplastic syndromes (bone marrow cancers), retinal degenerative disorders like retinitis pigmentosa, and progeria (rare premature aging syndrome) are prominent examples of diseases caused by splicing defects. Q: You conclude the review with the latest advances in RNA-based therapeutic strategies developed to target the underlying splicing mechanisms. What are some of these advances? A good example of targeting underlying splicing mechanisms to treat diseases is with a disease called spinal muscular atrophy, a major genetic disease of children and infants. Humans carry two near identical copies of the Survival Motor Neuron gene: SMN1 and SMN2 which are essential for the survival of all animal cells. Patients with Spinal Muscular Atrophy have loss of SMN1; SMN2 is the only source of the SMN protein in patients. The critical difference between SMN1 and SMN2 is splicing of exon 7, a small fragment of protein-coding sequence within the SMN gene. Unlike SMN1 exon 7, SMN2 exon 7 is usually not included in most tissues. The exon 7-skipped transcript generated by SMN2 produces a partially functional and unstable protein. The first therapeutic approval for SMA targets the SMN2 pre-mRNA and binds to a region that is accessed by the splicing machinery to remove exon 7. This ultimately leads to blocking of the removal of exon 7 and promotes the formation of functional SMN protein. By promoting splicing of exon 7, this drug (Spinraza) increased SMN expression in the cell from the SMN2 gene, compensating for the loss of SMN1, and preventing the loss of cells in the central nervous system. This story is a textbook example of a splicing mechanism that can be targeted to treat an otherwise fatal disease in children. The hope is to understand many more splicing mechanisms and find new ways to target them to treat other diseases. Some of the latest advances:

DUBLIN, June 15, 2023 /PRNewswire/ -- Endo International plc (OTC: ENDPQ) announced today that one of its operating companies, Par Pharmaceutical, Inc., has begun shipping dexlansoprazole 30 mg capsules, a generic version of Takeda's Dexilant®. This additional dosage strength rounds out the product family, now with both 30 mg and 60 mg delayed-release capsules. "We're proud to provide this high-quality, affordable generic medication to appropriate patients," said Scott Sims, Senior Vice President and General Manager, Injectable Solutions & Generics at Endo. "The dexlansoprazole product family strengthens our portfolio and our reputation as a reliable supplier." Dexlansoprazole is a proton pump inhibitor with a novel delivery system approved for the treatment of erosive esophagitis and heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (GERD). According to IQVIA™, Dexilant® 30 mg sales were approximately $45 million for the 12 months ended April 30, 2023. Dexilant® is a registered trademark of Takeda Pharmaceuticals U.S.A., Inc. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS Dexlansoprazole delayed-release capsules are contraindicated in patients with known hypersensitivity to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis and urticaria. PPIs, including dexlansoprazole delayed-release capsules, are contraindicated with rilpivirine-containing products. WARNINGS AND PRECAUTIONS Dexlansoprazole Delayed-Release Capsules, 60 mg, contain FD&C Yellow #5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow #5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. Presence of Gastric Malignancy: In adults, symptomatic response to therapy with dexlansoprazole does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy. Acute Tubulointerstitial Nephritis (TIN): TIN has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms, from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (eg, malaise, nausea, anorexia). Discontinue dexlansoprazole and evaluate patients with suspected acute TIN. Clostridium difficile-Associated Diarrhea: Published observational studies suggest that PPI therapy like dexlansoprazole may be associated with an increased risk of Clostridium difficile-associated diarrhea, especially in hospitalized patients. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Bone Fracture: Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the conditions being treated. Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs. Discontinue dexlansoprazole delayed-release capsules at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. Cutaneous and Systemic Lupus Erythematosus (CLE and SLE): CLE and SLE have been reported in patients taking PPIs. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. SLE is less commonly reported than CLE in patients receiving PPIs. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported. Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving dexlansoprazole delayed-release capsules, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Cyanocobalamin (Vitamin B12) Deficiency: Daily treatment with any acid-suppressing medications over a long period of time (eg, longer than three years) may lead to malabsorption of cyanocobalamin (Vitamin B12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. Hypomagnesemia and Mineral Metabolism: Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (eg, diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically. Interactions with Investigations for Neuroendocrine Tumors: Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop dexlansoprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. Interaction with Methotrexate: Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients. Fundic Gland Polyps: PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated. Risk of Heart Valve Thickening in Pediatric Patients Less Than Two Years of Age: Dexlansoprazole is not recommended in pediatric patients less than two years of age. ADVERSE REACTIONS Adults (≥2%): diarrhea, abdominal pain, nausea, upper respiratory tract infection, vomiting, and flatulence. Patients 12 to 17 years of age (≥5%): headache, abdominal pain, diarrhea, nasopharyngitis, and oropharyngeal pain. USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause adverse effects on fetal bone growth and development. Pediatrics: Based on data with lansoprazole, dexlansoprazole is not effective in patients with symptomatic GERD 1 month to less than 1 year of age and nonclinical studies have demonstrated adverse effects in juvenile rats. INDICATIONS AND USAGE Healing of Erosive Esophagitis (EE): Dexlansoprazole delayed-release capsules are indicated in patients 12 years of age and older for healing of all grades of EE for up to eight weeks. Maintenance of Healed Erosive Esophagitis and Relief of Heartburn: Dexlansoprazole delayed-release capsules are indicated in patients 12 years of age and older to maintain healing of EE and relief of heartburn for up to six months in adults and 16 weeks in patients 12 to 17 years of age. Treatment of Symptomatic Non-Erosive Gastroesophageal Reflux Disease: Dexlansoprazole delayed-release capsules are indicated in patients 12 years of age and older for the treatment of heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (GERD) for four weeks. Please click for Full Prescribing Information. About Endo Endo (OTC: ENDPQ) is a specialty pharmaceutical company committed to helping everyone we serve live their best life through the delivery of quality, life-enhancing therapies. Our decades of proven success come from passionate team members around the globe collaborating to bring treatments forward. Together, we boldly transform insights into treatments benefiting those who need them, when they need them. Learn more at or connect with us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements Certain information in this press release may be considered "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 and any applicable Canadian securities legislation including, but not limited to, the statements by Mr. Sims, any statements relating to product launch, commercialization, sales, supply or distribution, and any statements that refer to expected, estimated or anticipated future results or that do not relate solely to historical facts. Statements including words or phrases such as "believe," "expect," "anticipate," "intend," "estimate," "plan," "will," "may," "look forward," "intend," "guidance," "future," "potential" or similar expressions are forward-looking statements. All forward-looking statements in this communication reflect the Company's current views as of the date of this communication about its plans, intentions, expectations, strategies and prospects, which are based on the information currently available to it and on assumptions it has made. Actual results may differ materially and adversely from current expectations based on a number of factors, including, among other things, the outcome of the Company's contingency planning and restructuring activities; the timing, impact or results of any pending or future litigation, investigations, proceedings or claims, including opioid, tax and antitrust related matters; any actual or contingent liabilities; settlement discussions or negotiations; the Company's liquidity, financial performance, cash position and operations; the risks and uncertainties associated with chapter 11 proceedings; the time, terms and ability to confirm a sale of the Company's businesses under Section 363 of the U.S. Bankruptcy Code; the risk that the Company's chapter 11 cases may be converted to cases under chapter 7 of the Bankruptcy Code; the adequacy of the capital resources of the Company's businesses and the difficulty in forecasting the liquidity requirements of the operations of the Company's businesses; the unpredictability of the Company's financial results; the Company's ability to discharge claims in chapter 11 proceedings; negotiations with the holders of the Company's indebtedness and its trade creditors and other significant creditors; the risks and uncertainties with performing under the terms of the restructuring support agreement and any other arrangement with lenders or creditors while in chapter 11 proceedings; the performance, including the approval, introduction, and consumer and physician acceptance of new products and the continuing acceptance of currently marketed products; and the Company's ability to obtain and successfully manufacture, maintain and distribute a sufficient supply of products to meet market demand in a timely manner. The Company expressly disclaims any intent or obligation to update these forward-looking statements, except as required to do so by law. Additional information concerning risk factors, including those referenced above, can be found in press releases issued by the Company, as well as the Company's public periodic filings with the U.S. Securities and Exchange Commission and with securities regulators in Canada, including the discussion under the heading "Risk Factors" in the Company's most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q or other filings with the U.S. Securities and Exchange Commission. SOURCE Endo International plc

明治中国参加上海市营养创新健康论坛并进行科普展示与学术交流 上海 2023年3月28日 /美通社/ -- 2023年2月10日，以上海市卫生健康委员会作为指导单位，由上海市疾病预防控制中心、上海君石生命科学研究院作为主办单位的“上海市营养创新健康论坛”（以下简称“论坛”）顺利举办。明治（中国）投资有限公司（以下简称“明治中国”或“明治”）作为上海市营养创新平台第二批成员单位，参加了本次论坛并进行了营养创新技术的科普展示和学术交流。在本次论坛的“营养创新奖颁奖”环节，明治中国荣获了上海市营养创新平台办公室颁发的第一届“营养创新奖”。 明治中国的明治佰乐益优LG21风味发酵乳荣获上海市营养创新平台办公室颁发的第一届“营养创新奖”以及LG21乳酸菌的筛选过程 明治中国的明治佰乐益优LG21风味发酵乳荣获上海市营养创新平台办公室颁发的第一届“营养创新奖”以及相关荣誉证书 在论坛的“营养创新技术的科普展示”区域，明治作为“营养创新奖”的获奖单位，带来了旗下“创新的酸奶”明治佰乐益优，包含明治佰乐益优LG21风味发酵乳、明治佰乐益优R-1风味酸乳。该系列酸奶强调含有 “特别的乳酸菌”，且明治还展示了科研成果以及相关成果产品化的过程。在论坛的学术交流环节，明治中国乳酸菌研究中心主任、医学博士大津俊广，以《产品营养化转型：基于循证的功能性食品开发及科普活动介绍“以添加了在胃里工作的LG21乳酸菌的酸奶为例”》为题进行发言。 在上海市营养创新健康论坛上，明治中国乳酸菌研究中心主任、医学博士大津俊广，以《产品营养化转型：基于循证的功能性食品开发及科普活动介绍“以添加了在胃里工作的LG21乳酸菌的酸奶为例”》为题进行演讲 明治 70余年乳酸菌研究的集大成：严格精选“在胃里工作的LG21乳酸菌”并产品化 于《“健康中国2030”规划纲要》的引领下，食品行业的前沿技术与趋势以营养、健康为“风向标”。2022年发布的《中国居民膳食指南（2022）》中，乳制品每日建议摄入量较往年大幅增长。明治根据中国本土的市场需求，用自身强大的乳制品研发能力为中国消费者带来营养、安全、美味的乳制品，并不断开发牛奶、酸奶品类的新产品。 在众多乳制品中，酸奶是其中一种深受大家喜爱的营养乳制品，而且酸奶的发酵过程使用了乳酸菌，对膳食健康起到了更加精准的促进作用。拥有百年以上乳制品制造经验的明治，不仅掌握着先进的食品生产技术，还具备乳酸菌研发的独特优势。 本次论坛中，明治展示的明星产品“明治佰乐益优系列酸奶”就是凝聚了明治70余年乳酸菌科研经验的成果。其中包括两款产品，元气加持的明治佰乐益优R-1风味酸乳和挑战胃酸的明治佰乐益优LG21风味发酵乳。在日本，明治在2000年发售的日本同品牌产品“明治 プロビオヨーグルト LG21”使用了LG21乳酸菌，这款产品在日本热销20年以上，并且在日本开拓了“功能性酸奶”的市场，以及“根据不同健康需求，选择合适的乳酸菌”的酸奶购买与饮用习惯。 LG21乳酸菌可以说是产学合作的典型成果。添加了LG21乳酸菌的明治佰乐益优LG21风味发酵乳，是明治基于不同乳酸菌的特点，通过产学研合作，从商品策划到产品化形成完整的、自有技术的营养创新闭环。 1997年，日本明治集团与日本东海大学医学部古贺泰裕教授、高木敦司教授的LG21乳酸菌共同研究正式开始。LG21乳酸菌在成功商品化之前历经了层层考验，从当时明治的菌种库中拥有2500多株乳酸菌菌株中被选出。筛选方法的具体描述在伊藤喜久治主编的《益生菌与生物源素 -- 科学依据与今后的开发展望》一书中有详细记载，主要包括如下三个阶段： 第一阶段，根据菌株的特性，从明治的菌株库中筛选出200多种极具潜力的乳酸杆菌。 第二阶段，以“对于人工胃液的耐受性”、“对人体胃上皮细胞株MKN45的附着性”等条件为基准进行精选，共有3种菌株在这一轮中表现优异。 第三阶段，以“在酸奶中的存活性”“美味”等条件开展层层严选，最终选定LG21乳酸菌。 格氏乳杆菌OLL2716菌株的筛选过程与特点 日渐增多的现代健康问题以及乳酸菌的更多可能性 目前在中国，胃部健康已经逐步成为一个社会化的健康课题。生活压力以及不规律的饮食、幽门螺旋杆菌的交叉感染和耐药性的增加都是胃部健康的主要议题，这也是白领人群正面临的各种胃部健康烦恼。而幽门螺旋杆菌感染是胃炎、消化性溃疡的主要原因，也是胃癌的高危因素。在中国，幽门螺旋杆菌平均感染率已达到一半以上（56%） [1] 。在亚洲人群中，患有功能性消化不良（FD）的人群中，幽门螺旋杆菌的感染率约60% [2] 。 近年来也有研究关注着乳酸菌所拥有的多种多样的健康提升效果。针对胃部健康问题，小小的乳酸菌，蕴藏着巨大的可能性。2009年，日本东海大学的高木教授领导研究小组将格氏乳杆菌OLL2716菌株与除菌疗法联用探究其对于幽门螺旋杆菌的除菌效果 [3] 。结果表明，与仅以通常方法进行除菌治疗（三联疗法）的幽门螺旋杆菌感染者组对比，联合OLL2716菌株与三联疗法同时进行治疗的幽门螺旋杆菌感染者的除菌成功率要高出10个点左右。 此外，格氏乳杆菌OLL2716菌株对于功能性消化不良（FD）的4种主要症状，主要表现为上腹部疼痛、上腹部烧灼感、餐后上腹部饱胀感和早饱感，也有一定的改善作用。Ohtsu T等人的研究结果表明 [4] ，未感染幽门螺旋杆菌的功能性消化不良（FD）患者在接受不同酸奶干预后结果不同。与食用安慰剂酸奶组对比，含格氏乳杆菌OLL2716菌株的酸奶摄入组对胃部症状整体效果来看有着良好改善的倾向，且摄取12周后，含格氏乳杆菌OLL2716菌株摄入组FD的4种主要症状清除率显著更高，是安慰剂酸奶组的两倍。由此可见，对于幽门螺旋杆菌的根除和对于功能性消化不良（FD）的4种主要症状改善，格氏乳杆菌OLL2716菌株都有其明显的功能价值。 格氏乳杆菌OLL2716菌株与功能性消化不良以及幽门螺旋杆菌根除率的关系 明治在乳酸菌教育方面“双管齐下”，落实丰富多样的科普创新 明治中国重视并不断探索实践的膳食营养科普，兼顾了以科学循证为支撑的“可信性”，以及易于理解、寓教于乐的“趣味性”。明治致力于与学术界的专家与科研机构合作，以“营养健康”为基础，以消费者的健康需求为导向，坚持探索具备各种功能价值的乳酸菌。为实现乳酸菌功能的有效传播，明治中国开展了“系列科普漫画与科普网站”、“科普快闪活动”与“营养师职场健康知识公益沙龙”等贴合消费者兴趣的多样创新活动，将科学知识与趣味内容结合。在酸奶以及乳酸菌的科普上，明治不仅“严谨”而且“活泼”，始终站在消费者的角度，助力消费者更好地选择合适自己的乳酸菌。 明治中国作为上海市营养创新平台的成员单位，将持续贯彻该平台科学发展、创新融合、共建共享的目标，发挥成员单位优势，参与良性互动、密切协作，贡献于推进上海营养创新工作发展，助力健康上海目标实现，为提高中国消费者做出更多贡献。 与此同时，明治也将继续扎根于中国，秉承“创享健康新理念”，作为“食品和健康”的专家，为消费者“健康的饮食生活”做出贡献。并且通过开发面向不同年龄段的产品线，来向世界传递“美味、快乐、健康、安心”的理念，为《健康中国2030行动》和《“健康中国2030”规划纲要》《国民营养计划（2017-2030年）》的实现作出积极贡献。 [1]参考文献：崔璨璨,李长锋,张斌.幽门螺旋杆菌感染治疗方案的研究现状和进展[J].吉林大学学报（医学版）,2017,43(6):1287-1290.DOI:10.13481/j.1671-587x.20170642. [2] 参考文献：中华医学会消化病学分会胃肠动力学组,中华医学会消化病学分会胃肠功能性疾病协作组.中国功能性消化不良专家共识意见(2015年,上海)[J].中华消化杂志,2016,36(4):217-229.DOI:10.3760/cma.j.issn.0254-1432.2016.04.001. [3] Deguchi R, Nakaminami H, Rimbara E, et al. Effect of pretreatment with Lactobacillus gasseri OLL2716 on first-line Helicobacter pylori eradication therapy. J Gastroenterol Hepatol. 2012;27(5):888-892. doi:10.1111/j.1440-1746.2011.06985.x [4] Ohtsu, T., Takagi, A., Uemura, N., Inoue, K., Sekino, H., Kawashima, A., Uchida, M., & Koga, Y. (2017). The Ameliorating Effect of Lactobacillus gasseri OLL2716 on Functional Dyspepsia in Helicobacter pylori-Uninfected Individuals: A Randomized Controlled Study. Digestion, 96(2), 92–102.