IL-1β

前言十年来，中国生物医药产业实现了飞跃发展。现阶段，全球临床在研管线接近1.5万个，其中34.0%的项目已在中国展开临床试验，中国在研管线数量仅次于美国（41.7%），位居全球第二。而生物医药研发属于重资金投入行业，受国际环境影响，投资大幅下降成为当前中国生物医药产业面临的突出问题。众多Biotech企业处境艰难，融资被停、现金流紧张、项目削减等都是不得不面对的难题。2023年，一级市场政府引导基金和国资背景基金的数量持续增加，运作模式日趋完善，已逐渐步入规范化高质量发展阶段，成为中国医药行业度过“低谷”期的重要支撑力量。同时，在新形势下，国内医药行业对资源整合提出新要求。一方面，Biopharma（大药企）加速通过并购新公司来补充或重构具备核心竞争力的新业务线；另一方面，越来越多未盈利的Biotech（初创型生物医药企业）在IPO阶段性收紧后冷静思考并重新定位，被并购案例逐渐增多。如华润双鹤收购华润紫竹、中国通用集团并购整合重药控股、新天药业收购汇伦医药、迈瑞医疗收购惠泰医疗等大型交易案例。《2023年度中国生物医药投融资蓝皮书》 通过详实的数据调研及分析，力求全面、客观反映中国生物医药投融资聚焦领域以及投融资企业研发最新发展趋势；同时，为应对错综的国际环境，紧随国家 “源头创新”支持政策，推动资本市场正确导向回暖、创新成果不断落地，为我国生物医药产业创新发展贡献力量。《2023年度中国生物医药投融资蓝皮书》 重磅发布《2023年度中国生物医药投融资蓝皮书》（以下简称《蓝皮书》）于2024年4月初正式对外发布。蓝皮书由中国医药企业管理协会投融资服务专委会发起，药渡集团撰写，联合财数科技、国投招商投资、富煜亚洲、三生制药、泱深生物等多家科技企业及投资机构共同发布。蓝皮书共分为八大部分，分别为中国生物医药企业二级市场融资情况、一级市场融资情况、中国创新药临床在研情况分析、中国医药上市公司研发投入及管线布局、中国CRO/CDMO融资情况、中国疫苗企业融资情况、中国IVD企业融资情况、投资公司重点关注的治疗领域分析。以下为《蓝皮书》重点内容摘录：012023年度生物医药企业二级/一级市场融资情况《蓝皮书》数据显示，2023年，二级市场对生物医药企业的投融资热度降温，总计29家中国生物医药公司在中国大陆、香港、美国完成IPO。其中： A股上市21家，募资223.56亿人民币（含科创版4家，募资80.83亿元）；H股上市5家， 募资285.82亿港元; 美股上市3家，募资2.27亿美元。总体来看，2023年IPO金额较2022年下滑了约36%，IPO数量下滑约49%，医药板块IPO热度处于持续降低的阶段。A股上市数量和金额与2022年相比出现明显下滑：2022年49家IPO融资合计749亿人民币，2023年21家IPO融资合计223.56亿人民币。港股上市数量出现略微下滑，但上市募集金额有明显提高。港股市场从2022年8家上市下滑到2023年的5家上市；但2023年的IPO金额达到285.82亿港元，比2022年的36.38亿港元提高约6倍，增加的金额主要来自京东健康的IPO募集，单个IPO上市募集了264.57亿港元。美股3家企业上市，总募集2.27亿美元，对比2021年有8家成功在美国IPO募集共计10.65亿美元（2022年没有医药企业成功在美国上市），从数量上和IPO金额上较2021年仍有一定差距。2023年中国生物医药企业一级市场共发生376起融资事件，融资高峰发生在1月，融资规模105亿元。从融资额来看，除47家未披露融资金额外，剩余252家生物医药企业总融资额为547亿5891万人民币，其中170家生物医药研发企业累计176起融资事件的融资额占比为59.69%。由下图可知，医药研发型企业仍是投资热门，其次为CDMO类企业。图1 2023年生物医药行业各轮次企业类型融资金额占比数据来源：药渡咨询团队整理02中国创新药中国1类临床阶段在研新药统计 据药渡数据库统计，中国1类临床在研新药产品共计2817个，与2022年（2104个）、2021年（1586个）相比增长明显；肿瘤领域在研个数仍保持绝对领先，免疫系统、神经系统疾病领域成为后起之秀，其中免疫系统疾病领域项目增幅超95%。图2 中国1类新药数量历年对比数据来源：药渡咨询团队整理《蓝皮书》总结了2023年度生物医药企业投融资项目TOP10靶点和治疗领域，并针对投融资公司重点关注的靶点及治疗领域进行综合分析。图3 融资额TOP10治疗领域临床在研品种分布数据来源：药渡咨询团队整理在融资额TOP10靶点涉及的中国1类在研品种中，EGFR靶点在研品种数量最多（86个），其次为HER2靶点（65个），CD19、VEGF、MET及BCMA靶点的在研品种数量均超过20个，融资额前十大靶点涉及的临床在研项目主要集中在临床Ⅰ期，占比达56.45%。03中国上市医药公司研发投入TOP100 2017-2023年，中国医药上市企业研发投入持续上升；2023年研发投入TOP100企业研发投入保持相对稳定，融资紧缩尚未明显影响到企业的研发投入及相关支出。TOP20的中国上市医药企业主要可分为两种类型，一类为大型综合医药企业，如恒瑞医药、复星医药、石药集团等，另一类创新型新药研发Biotech企业，如百济神州、再鼎医药、君实生物等。百济神州近年来的研发投入始终显著高于其他医药研发型企业，自2018年的45.97亿元增长至2022年的111.52亿元；2023年Q1-Q2，百济神州研发费用为58.82亿元，仍位于第一位。表4-1 2023年中国TOP100生物医药企业研发投入（节选）数据来源：财数科技，药渡咨询团队整理    TOP100生物医药企业产品管线治疗领域聚集在抗肿瘤领域。其中，20家代表性企业产品管线肿瘤领域品种占比高达54.71%，其次为内分泌及代谢疾病领域，占比约为9.12%。04展望 在医药行业参与者的共同努力下，截至2024年3月初，A股已有245家生物医药公司公布2023年业绩，超半数（130家）公司年报业绩预喜，预计2023年医药生物行业净利润实现翻倍增长的企业超50家。展望 2024 年，随着拖累行业的负面影响（如疫情、带量采购、医疗腐败、同质化研发等）的消退，以及国家医疗改革得卓有成效，医药行业有望实现业绩复苏驱动下的估值修复。中国医药产业格局深度调整、全面重塑之后，必将迎来新的发展机遇。扫描下方二维码，并回复“蓝皮书”，获得蓝皮书完整pdf下载链接：药渡咨询“依托强大的药渡数据库核心资源，利用“数据”链接“资源”，通过对药物数据深度挖掘和洞鉴，形成专业化咨询系统服务体系，提供涉及商业尽调、行业研究、赛道评估、战略规划、产品上市策略、IPO行业顾问、专利FTO评估等全方位全产业链深度咨询服务，已为国内外500+药研企业、投资机构，政府机构，科技园区提供专业深度咨询服务，在国内医药咨询行业位列一线”《不可成药靶点临床进展—PROTAC的巨大潜力课件》《TGF-β&PD-L1：全球及中国临床在研药物浅析》《抗痛风药物竞争格局及潜力靶点分析—URAT1、IL-1β课件》《外泌体：极具潜力的再生医学技术及药物递送工具》《2023年创新医疗器械全景分析报告》《胆管癌潜力靶点及品种分析FGFR2、TP53、IDH1/2、SMAD4课件》《冷肿瘤转热——TIL疗法的巨大潜力-PPT课件》咨询详细服务&获取免费报告，联系以下二维码：

TARA-002 demonstrated a complete response rate of 43% at three months in BCG-Unresponsive/Experienced patients in ongoing NMIBC programTARA-002 demonstrated a complete response rate of 63% at three months in CIS-only patients in ongoing NMIBC programTARA-002 demonstrated a favorable safety and tolerability profile with no Grade 3 or greater treatment-related adverse eventsPreliminary data from six-month evaluable patients in ADVANCED-2 trial of TARA-002 in NMIBC expected in 2H 2024 NEW YORK, April 05, 2024 (GLOBE NEWSWIRE) -- Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, today announced positive data from three-month evaluable carcinoma in situ (CIS) patients treated across its ongoing clinical program of TARA-002, the Company’s investigational cell-based therapy, in high-risk Non-Muscle Invasive Bladder Cancer (NMIBC), including Bacillus Calmette-Guérin (BCG)-Unresponsive, BCG-Experienced and BCG-Naïve patient populations. “These promising three-month results support the continued development of TARA-002 for patients with NMIBC for whom there are currently limited treatment options,” said Timothy Lyon, M.D., Associate Professor of Urology and the Urology Residency Program Director at Mayo Clinic in Florida, and TARA-002 study investigator. “Given our understanding that up to half of patients treated with intravesical immune therapies that do not initially respond can be salvaged with repeat induction, there is reason to believe that the promising three-month response rates shared today could be further improved through reinduction with TARA-002. This encouraging anti-tumor activity coupled with a favorable safety profile and mode of administration that is both convenient and familiar to urologists indicates that, if confirmed in future studies, TARA-002 could potentially play a meaningful role in NMIBC treatment in the future.” Enrollment continues in the Company’s ADVANCED-2 Phase 2 clinical trial of TARA-002 in patients with high-grade NMIBC with BCG-Unresponsive CIS and BCG-Naïve CIS. The ADVANCED-2 trial design incorporates both reinduction and maintenance dosing. The Company expects to share preliminary results from a pre-planned risk-benefit analysis of the ADVANCED-2 trial in ten patients, who are six-month evaluable in the second half of 2024. “We are highly encouraged by these early results observed in these three-month evaluable patients across our ADVANCED-1 and ADVANCED-2 clinical trials, which clearly demonstrate TARA-002’s activity in both BCG-Unresponsive and BCG-Naïve patients. We look forward to sharing data from post-reinduction, six-month evaluable patients in our ADVANCED-2 trial in the second half of 2024,” said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. Overview of Three-Month Evaluable Data Data reported today highlight the potential of TARA-002 in patients with NMIBC. Data were derived from three-month evaluable NMIBC patients with CIS pooled across the Company’s ADVANCED-1 Phase 1a, Phase 1b-expansion and ADVANCED-2 Phase 2 trials of TARA-002 in patients with high-risk NMIBC, including BCG-Unresponsive, BCG-Experienced and BCG-Naïve patients. The overall three-month complete response (CR) rate prior to reinduction for 16 evaluable patients treated across the three trials with varying BCG status was 38% (6/16), with a CR rate of 63% (5/8) in CIS-only patients and 13% (1/8) in patients with CIS +Ta/T1. The Company believes that reinduction and planned enhancements to dosing and administration will lead to an increased CR rate at six months in patients who did not achieve a CR at three months, as reinduction with other immune agents in NMIBC patients with CIS has demonstrated a 30%-50% salvage rate. The Company plans to explore additional dosing cohorts, which may prove effective in patients who might benefit. Three Month Evaluable Patients # Patients# of CRsCR % BCG-Unresponsive/ ExperiencedCIS-only6350% CIS +Ta/T11--% 7343% BCG-Naïve CIS-only22100% CIS +Ta/T17114% 9333% 16638% By Stage of Disease at Baseline CIS-only8563% CIS +Ta/T18113% 16638% By Study Phase 1a3133% Phase 1b-EXP8338% Phase 2 Naïve5240% 16638% The majority of reported adverse events were Grades 1 and 2 across all dose levels, and treatment emergent adverse events (TEAEs), as assessed by study investigators, were in line with typical responses to bacterial immunopotentiation, and included fatigue, headache, fever, and chills. The most common urinary symptoms were urinary urgency, urinary frequency, urinary tract pain/burning, incomplete emptying, and bladder spasm. Most bladder irritations resolved soon after administration or in a few hours to a few days. “TARA-002 is a broad spectrum immunopotentiator with a similar mechanism of action as the standard of care, BCG. Because TARA-002 is an inactivated bacteria, there are no special dosing and administration protocol requirements, which makes it ideal for administration in the community urology practice setting,” said Gautam Jayram, MD., Director, Advanced Therapeutics Center, Urology Associates PC in Nashville and TARA-002 study investigator. “I am encouraged by the early three-month data in a challenging disease state and look forward to continued participation in the TARA-002 clinical program.” NMIBC Clinical Program The ADVANCED-1 expansion trial is evaluating intravesical TARA-002 at the 40KE1 dose in up to 12 NMIBC patients with CIS and CIS +Ta/T1, including BCG-Unresponsive, BCG-Naïve, and BCG-Experienced patient populations. The primary endpoint is safety and complete response (CR) rate at the preliminary three-month assessment timepoint. The Phase 2 open-label ADVANCED-2 trial is assessing intravesical TARA-002 in at least 102 NMIBC patients with CIS (± Ta/T1) who are BCG-Unresponsive (n=75-100) and BCG-Naïve (n=27). The BCG-Unresponsive cohort has been designed to be registrational aligned with the FDA’s 2018 BCG-Unresponsive Non-muscle Invasive Bladder Cancer: Developing Drugs and Biologics for Treatment Guidance for Industry. Trial subjects receive an induction course of six weekly intravesical instillations, followed by either reinduction (if eligible) or maintenance for up to 24 months. Two additional exploratory cohorts will be added to the ADVANCED-2 trial assessing higher dosing at an 80KE dose (Cohort C) and systemic priming prior to initiation of intravesical administration (Cohort D). In addition, the Company intends to initiate a proof-of-concept study of TARA-002 in combination with pembrolizumab in NMIBC patients with CIS to assess the potential synergistic effects of the combination regimen. About TARA-002 TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of lymphatic malformations (LMs), for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil® in Japan and approved in Taiwan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432. When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a pro-inflammatory response with release of cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, IL-1b, IL-6, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF) and natural killer cells. TARA-002 also directly kills tumor cells and triggers a host immune response by inducing immunogenic cell death, which further enhances the antitumor immune response. About Non-Muscle Invasive Bladder Cancer (NMIBC) Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle. About Protara Therapeutics, Inc. Protara is a clinical-stage biotechnology company committed to advancing transformative therapies for people with cancer and rare diseases. Protara’s portfolio includes its lead candidate, TARA-002, an investigational cell-based therapy in development for the treatment of non-muscle invasive bladder cancer (NMIBC) and lymphatic malformations (LMs). The Company is evaluating TARA-002 in an ongoing Phase 2 trial in NMIBC patients with carcinoma in situ (CIS) who are unresponsive or naïve to treatment with Bacillus Calmette-Guérin (BCG), as well as a Phase 2 trial in pediatric patients with LMs. Additionally, Protara is developing IV Choline Chloride, an investigational phospholipid substrate replacement for patients on parenteral nutrition who are otherwise unable to meet their choline needs via oral or enteral routes. For more information, visit www.protaratx.com. References 1. Klinische Einheit, or KE, is a German term indicating a specified weight of dried cells in a vial. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Protara may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “designed,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words or expressions referencing future events, conditions or circumstances that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such forward-looking statements include but are not limited to, statements regarding Protara’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: Protara’s business strategy, including its development plans for its product candidates and plans regarding the timing or outcome of existing or future clinical trials; statements related to expectations regarding interactions with the FDA; Protara’s financial position; statements regarding the anticipated safety or efficacy of Protara’s product candidates; and Protara’s outlook for the remainder of the year. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Factors that contribute to the uncertain nature of the forward-looking statements include: risks that Protara’s financial guidance may not be as expected, as well as risks and uncertainties associated with: Protara’s development programs, including the initiation and completion of non-clinical studies and clinical trials and the timing of required filings with the FDA and other regulatory agencies; general market conditions; changes in the competitive landscape; changes in Protara’s strategic and commercial plans; Protara’s ability to obtain sufficient financing to fund its strategic plans and commercialization efforts; having to use cash in ways or on timing other than expected; the impact of market volatility on cash reserves; failure to attract and retain management and key personnel; the impact of general U.S. and foreign, economic, industry, market, regulatory, political or public health conditions; and the risks and uncertainties associated with Protara’s business and financial condition in general, including the risks and uncertainties described more fully under the caption “Risk Factors” and elsewhere in Protara's filings and reports with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. Protara undertakes no obligation to update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise, except as required by law. Company Contact: Justine O'MalleyProtara TherapeuticsJustine.OMalley@protaratx.com646-817-2836

本期话题：后生元，昼夜节律，生命早期，早产儿，肠脑轴，母乳喂养，嗜酸性胃肠道疾病，环保胃肠病学，EnteroBiotix，嘉亨医药，菊乐股份，Onego Bio，盒马 该篇日报由R·AI辅助创作生成，人工审核校对。 中农Cell子刊：后生元在人类与动物营养和健康中的作用机制（综述） Cell Metabolism——[29] ① 中国农业大学曹志军及团队在Cell Metabolism发表最新综述，从宿主抗氧化活性调节、免疫调控、肠道微生物群修饰和增强上皮屏障功能等方面总结了后生元对机体健康发育的影响；② 提出三种新型后生元制剂的研发思路，包括利用非细菌微生物，识别并区分健康与患病个体肠道菌群的差异性和评估不同生产工艺对后生元制剂功效的影响；③ 后生元制剂在宿主体内潜在的作用机制包括提高抗氧化性能、免疫反应调节、菌群调节和增强肠上皮屏障功能等；④ 后生元制剂对宿主的各种作用是相互联系并达到帮助宿主维持体内稳态的最终结果。 【原文信息】 Unlocking the power of postbiotics: A revolutionary approach to nutrition for humans and animals 2024-04-02 , doi: 10.1016/j.cmet.2024.03.004 Cell子刊：肠道菌群的节律性在生命早期就开始发展 Cell Host and Microbe——[30.3] ① 本研究通过随机对照干预试验，探讨了婴儿配方奶与母乳喂养对婴儿肠道微生物群落发展的影响；② 在婴儿出生后的第一年纵向采集婴儿的粪便样本，发现配方奶和母乳喂养的婴儿之间的粪便细菌群落相似，但随着年龄的增长有所不同，但配方奶和母乳喂养的婴儿的代谢物组成有很大差异；③ 与含有B. longum和B. breve或安慰剂的配方奶相比，含有低聚半乳糖（GOS）的婴儿配方奶可以维持高水平的双歧杆菌；④ 婴儿肠道中存在细菌节律性，且细菌多样性、特定菌群和功能通路的节律性随年龄增加而增强，并在母乳喂养和添加GOS的配方奶喂养后最强，即微生物群落的节律性在生命早期就开始发展，并受饮食影响；⑤ 实验还证实了肠道主要菌群的昼夜节律可以在体外连续培养模型中得以维持。 【原文信息】 Diurnal rhythmicity of infant fecal microbiota and metabolites: A randomized controlled interventional trial with infant formula 2024-04-02 , doi: 10.1016/j.chom.2024.02.015 Cell子刊：早产儿肠穿孔或与脑损伤相关 Cell Stem Cell——[23.9] ① 研究基于回顾性人群阵列发现早产儿中次脑室区回声性增强（SVE）与肠穿孔相关，肠穿孔后出现的SVE与2岁时认知或运动障碍显著相关；② 构建的新生鼠肠穿孔模型中，小鼠也表现出SVE类似症状；③ 肠穿孔会介导小鼠多纤毛FoxJ1+室管膜细胞中NLRP3炎症体的激活以及室管膜边界的丧失；④ 基于体内冠状脑组织空间转录组测序和体外LPS刺激室管膜细胞模拟肠穿孔，发现炎症环境导致室管膜NF-κB信号传导和与睫状体维持相关的基因表达丢失；⑤ 组装的炎症小体被激活，导致IL-1β的成熟和细胞焦亡发生，最终导致乳酸脱氢酶LDH释放和细胞死亡。 【原文信息】 Subventricular zone stem cell niche injury is associated with intestinal perforation in preterm infants and predicts future motor impairment 2024-03-26 , doi: 10.1016/j.stem.2024.03.001 母亲患牙周病，胎儿早产的机率较高 Microbiome——[15.5] ① 研究发现口腔菌群通过血清转移到胎盘，并通过激活免疫信号通路诱导胎盘血管病理，从而解释了患有牙周病女性出现妊娠并发症的风险较高；② 对130例足月分娩、早产（PT）和并发子痫前期（PTPE）分娩期间的唾液、菌斑、血清和胎盘样本进行全基因组测序，在胎盘发现420种微生物类群；③ 胎盘微生物是妊娠并发症最大的鉴别因素，超过高血压、BMI、吸烟和孕妇年龄；④ 使用机器学习算法基于微生物数据集预测PTPE和PT的误差率分别为4.05%和8.6%（分类学）以及6.21%和7.38%（功能）；⑤ PTPE和PT组TLR9显著上调，TLR7下调，并且胎盘微生物基因与这些TLR之间存在密集的相关网络；⑥ 70-82%的胎盘微生物可追溯至血清，进而追溯至唾液和龈下微生物群，而PTPE和PT组的口腔和血清微生物组在编码铁运输、外泌体、粘附、群体感应、脂多糖、生物膜和类固醇降解的基因显著富集。 【原文信息】 Placental TLR recognition of salivary and subgingival microbiota is associated with pregnancy complications 2024-03-26 , doi: 10.1186/s40168-024-01761-9 早期生活压力与肠道菌群：童年经历对健康的影响 Brain Behavior and Immunity——[15.1] ① 本研究在广泛的人群基础上探讨了早期生活压力（ELS）与儿童肠道菌群之间的关系，发现ELS中的社会经济压力与肠道菌群多样性降低有关；② 纳入2004名儿童中从出生到10岁进行了前瞻性测量，研究了整体ELS，以及五种不同ELS领域的独特影响，包括生活事件、环境风险、父母风险、人际风险和直接受害；③ 尽管整体ELS与肠道菌群之间未发现显著关联，但与社会经济压力相关的环境风险（包括金融困难和母亲教育水平低）与α多样性降低、β多样性以及色氨酸生物合成等功能途径的变化显著相关；④ 这些关联在一定程度上受整体饮食质量、促炎饮食、纤维摄入和身体质量指数的影响；⑤ 综上，社会经济压力与一般人群中菌群多样性低相关，并且这种关联部分地可以通过较差的饮食和较高的BMI来解释，改变饮食或能减轻社会经济逆境对菌群及相关健康后果的负面影响。 【原文信息】  Early-life stress and the gut microbiome: A comprehensive population-based investigation 2024-02-23 , doi: 10.1016/j.bbi.2024.02.024 极早产儿喂养中添加人乳基营养强化剂是否有效？ EClinicalMedicine——[15.1] ① 本研究旨在探讨对极低出生体重婴儿纯母乳喂养时添加人乳基营养强化剂（HMBF）相比牛乳基营养强化剂（BMBF）是否能降低坏死性小肠结肠炎（NEC）、败血症和死亡率的综合结果；② 在瑞典24个新生儿中心进行的多中心随机对照试验中，228名极早产婴儿被随机分配到HMBF组和BMBF组；③ HMBF组中有41名（35.7%）婴儿出现NEC、败血症或死亡，而BMBF组有39名（34.5%）；④ 两组之间的不良事件发生率没有显著差异；⑤ 研究结果表明，与BMBF相比，HMBF的补充并未降低NEC、败血症或死亡的综合发生率，因此不支持将HMBF作为一种预防极早产儿仅喂人乳时发生NEC、败血症或死亡的营养策略进行常规补充。 【原文信息】 Effect of human milk-based fortification in extremely preterm infants fed exclusively with breast milk: a randomised controlled trial 2024-01-02 , doi: 10.1016/j.eclinm.2023.102375 JAMA子刊：纯母乳喂养3个月或能降低儿童白血病风险 JAMA Network Open——[13.8] ① 一项基于人口的队列研究发现，较长时间的纯母乳喂养与儿童期B细胞前体急性淋巴细胞性白血病（BCP-ALL）的风险降低有关，与病例对照研究结论一致，建议未来研究应关注潜在的生物机制；② 纳入309,473名儿童，在1,679,635人年的随访中，332名儿童（0.1%）在1至14岁时被诊断出患有癌症其中124名（37.3%）被诊断为血液肿瘤（81名为ALL，其中74名为B细胞前体ALL)，44名（13.3%）为中枢神经系统肿瘤，80名（24.1%）为实体肿瘤，84名（25.3%）为其他和未特指的恶性肿瘤；③ 与纯母乳喂养少于3个月相比，纯母乳喂养3个月以上或更长时间的儿童，其血液癌症的风险显著降低（AHR为0.66），尤其是BCP-ALL（AHR为0.62）；④ 纯母乳喂养对中枢神经系统肿瘤（AHR为0.96）和实体瘤（AHR为0.87）的风险并无显著影响。 【原文信息】 Exclusive Breastfeeding Duration and Risk of Childhood Cancers 2024-03-26 , doi: 10.1001/jamanetworkopen.2024.3115 JAMA子刊：为什么与家人一起吃饭很重要？ JAMA Pediatrics——[26.1] ① 本文强调了家庭共餐的重要性，发现每周至少3-4次与家人共餐对父母和孩子都有益处；② 家庭共餐可以降低孩子超重、肥胖、饮食失调、药物滥用、青少年怀孕、抑郁的风险，同时提高自尊和学业表现；③ 家庭共餐有助于家庭成员摄入更多水果和蔬菜，减少油炸食品和含糖饮料的摄入；④ 共餐时应避免手机、电视和电脑等干扰，促进交流，增强家庭凝聚力和孩子的安全感；⑤ 父母应决定用餐时间和食物种类，而孩子决定吃什么和吃多少，避免以食物作为奖励或惩罚；⑥ 饭菜不必花哨，提供至少1种水果和蔬菜，并让孩子参与食物的计划、准备和清理，形式不必拘泥于晚餐，最重要的是要享受和家人在一起的时光！ 【原文信息】 Eating Family Meals Together at Home 2024-03-25 , doi: 10.1001/jamapediatrics.2023.6669 JAMA：嗜酸性粒细胞性胃肠道疾病临床现状（观点） JAMA——[120.7] ① 本文介绍了嗜酸性粒细胞性胃肠道疾病（EGIDs），揭示了其患病率、临床特征、诊断标准及治疗方法；② 嗜酸细胞性食管炎（EoE）是EGIDs中最常见的类型，北美和欧洲患病率约为0.0344%，婴幼儿常表现出呕吐、腹痛和喂食困难等非特异性反应，青年和成年患者常表现为吞咽困难和胃灼热，其与食物暴露、过敏性疾病以及遗传因素相关，可通过饮食调整和药物治疗（布地奈德或dupilumab单抗）缓解症状；③ 非EoE的EGIDs较少见，临床需使用肠镜进行多次活检确认，其临床表现多样，目前尚无FDA批准的药物，治疗主要依赖于饮食调整和局部皮质类固醇或质子泵抑制剂；④ 近期的一项临床试验显示氨基酸要素膳饮食干预能可使所有入组患者达到完全组织学缓解，但其长期影响仍需进一步研究；⑤ 针对EGIDs的未来研究方向包括dupilumab临床试验、长期要素膳效果、针对炎症级联和细胞信号通路的新药物临床试验等。 【原文信息】 Eosinophilic Gastrointestinal Disease 2024-03-25 , doi: 10.1001/jama.2024.2143 Lancet子刊：胃肠健康与环境保护：如何实现可持续发展？（综述） Lancet Gastroenterology & Hepatology——[35.7] ① 通过探讨胃肠病学实践中如何在保证临床效果的同时，减少对环境的影响，提出了一系列可持续的策略；② 避免不必要的内镜检查是减少内镜手术碳足迹的最有效方法，并对于一次性使用的内镜及其配件的使用提出了改革建议；③ 研究还涵盖了胃肠病学实践的其他方面，如诊所管理、虚拟护理和会议等，强调了数字化医疗在环保方面的潜力；④ 通过深入分析，提出了一条实现胃肠科医疗可持续发展的道路，强调了患者护理与环境管理并重的综合策略。 【原文信息】 Ecogastroenterology: cultivating sustainable clinical excellence in an environmentally conscious landscape 2024-03-27 , doi: 10.1016/S2468-1253(23)00414-4 EnteroBiotix启动活菌药EBX-102-02治疗IBS 2期临床研究 ① 4月3日，EnteroBiotix公司宣布，启动在研管线EBX-102-02治疗肠易激综合征（IBS）的2期临床试验TrIuMPH研究；② TrIuMPH研究是一项多中心、随机、双盲、安慰剂对照试验，将在英国招募60名便秘型IBS患者；③ TrIuMPH研究主要评价终点为评估EBX-102-02的安全性和耐受性，次要和探索性终点包括评估其初步疗效和潜在生物标志物；④ 在研管线EBX-102-02是一种含有高丰度菌群的活菌药，据信可以重塑肠道菌群，未来将以白色无味的胶囊形式供患者使用。 【原文信息】 EnteroBiotix Initiates Phase 2 Study of EBX-102-02 in Patients with Irritable Bowel Syndrome (IBS) 2024-04-03 , Enterobiotix 嘉亨医药「二甲双胍恩格列净片(I)」上市许可申请获受理 ① 4月3日，嘉亨医药二甲双胍恩格列净片（I）提交的上市许可申请，获得国家药品监督管理局受理；② 二甲双胍恩格列净片（I）适用于2型糖尿病成人患者，用于改善血糖控制，该药物由盐酸二甲双胍和恩格列净复配而成；③ 二甲双胍恩格列净片（I）具有良好的降糖效果，无严重不良反应，且与原研参比制剂生物等效性一致；④ 二甲双胍恩格列净片（I）为医保乙类品种，将进一步丰富嘉亨医药在糖尿病治疗领域的产品管线，产品上市后将会为广大糖尿病患者提供更多的治疗选择。 【原文信息】 喜讯丨二甲双胍恩格列净片(Ⅰ)提交上市许可申请并获得受理 2024-04-03 , 嘉亨医药 「菊乐股份」第四次冲击IPO审核中止 ① 近日，菊乐股份首次公开发行股票（IPO）审核因财务资料过期再次中止；② 这是自2023年3月以来菊乐股份第三次因同样原因中止上市审核；③ 菊乐股份成立于1985年，是西南地区龙头乳企，入选农业产业化国家重点龙头企业；④ 菊乐股份此次IPO计划募资13.63亿元，此前，菊乐股份曾于2017年12月、2019年8月、2020年6月三次披露招股书，并在2017年、2019年提交上市申请后撤回，本次为菊乐股份第四次冲击IPO。 【原文信息】 菊乐食品IPO审核再中止 2024-04-03 , FoodTalks食品资讯 精准发酵蛋白开发商Onego Bio获得3700万欧元融资 ① 4月2日，芬兰生物技术公司Onego Bio宣布完成了3700万欧元（约合人民币2.88亿元）的A轮融资，投资方包括NordicNinja VC领投和芬兰政府基金等；② Onego Bio公司计划利用这笔资金继续扩大和优化生产工艺，以及为产品向FDA提交上市申请做准备；③ Onego Bio公司利用精密发酵技术生产鸡蛋蛋白质，其表达系统采用的是一株从芬兰VTT研究机构授权获得的里氏木霉；④ 未来，Onego Bio公司将首先在北美市场推出产品，随后在欧洲、南美和亚洲进行布局。 【原文信息】 Onego Bio raises €37m for precision-fermented egg proteins 2024-04-02 , FoodBev 盒马上线宠物系列食品 ① 4月1日，盒马官方宣布上线宠物系列商品；② 此次新增商品包括40余款，涵盖主食、零食、营养补剂及洗护用品等；③ 此举是继上海推出“洗猫洗狗”服务后，盒马进一步拓展宠物市场的行动；④ 此外，盒马还一并推出“不爱吃包退”服务，若宠物对特定商品口味或口感不满意，用户可通过盒马App退货退款。 【原文信息】 盒马加码宠物商品，上线“不爱吃包退”服务 2024-04-02 , FoodDaily 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