微生物与结直肠癌的发病机制、早期诊断和治疗的研究进展

结直肠癌是威胁人类健康的重大疾病之一，随着近年来微生物组学技术的发展，很多研究报道了微生物与结直肠癌发生发展的关系，发现了具核梭杆菌、脆弱拟杆菌等微生物促进结直肠癌发生的分子机制以及短链脂肪酸等细菌代谢产物抑制结直肠癌发生发展的作用。利用结直肠癌患者与健康人群之间的差异微生物，可以建立基于微生物标志物的结直肠癌诊断模型，使结直肠癌的早发现、早诊断成为可能。在结直肠癌的治疗领域，微生物可能成为抑制结直肠癌发生发展的药物靶点，并且能够影响化疗药物的疗效与不良反应。本文以微生物与结直肠癌的关系为切入点，结合近年的相关文献及自身研究，对微生物与结直肠癌的发病机制、早期诊断和治疗的研究进展作一综述。     

多囊卵巢综合征中西医研究进展

多囊卵巢综合征是一种生殖功能障碍与糖代谢异常并存的内分泌紊乱综合征。是目前青中年妇女发病率较高的内分泌系统疾病，此病可由多方面因素诱发引起下丘脑-垂体-卵巢功能轴紊乱。是育龄期妇女月经不调，不孕等疾病的主要诱因。     

基于中医体质辨识的糖尿病风险评估模型建立与验证

背景　中医体质因素在糖尿病的发生发展过程中具有重要作用，但目前糖尿病的预测预警模型仅涵盖一般人口学资料、客观检查指标、生活方式等内容。在糖尿病风险评估模型中纳入中医体质辨识内容，对有针对性地防治糖尿病的发生发展具有重要意义。目的　根据健康体检数据建立基于中医体质辨识的糖尿病风险模型并对其进行验证。方法　于2016年1月-2018年12月，以2014-2015年某省级综合性医院健康管理中心体检数据为训练集数据（n=30 951），对是否患糖尿病进行单因素和多因素Logistic回归分析，纳入有意义的影响因素指标建立糖尿病风险评估模型；以2016-2017年的健康体检数据作为测试集数据（n=24 061），采用受试者工作特征曲线（ROC）对模型进行验证。结果　训练集人群中，患有糖尿病者1 315例（4.25%），未患糖尿病者29 636例（95.75%）。多因素Logistic回归分析结果显示，logit（P）（糖尿病患病情况）=-4.632-0.198×（女）+0.864×（年龄45~59岁）+1.684×（年龄≥60岁）+0.635×（高血压）+0.149×（超重）+0.376×（肥胖）-0.531×（偏轻）-0.234×（淋巴细胞百分数偏高）+0.279×（淋巴细胞百分数偏低）+0.304×（红细胞计数异常）-0.430×（红细胞比容偏低）+0.722×（平均红细胞血红蛋白浓度异常）+0.532×（血小板分布宽度异常）+1.016×（癌胚抗原异常）-0.406×（尿酸异常）+1.341×（肌酐偏低）+0.488×（血尿素氮偏高）+0.473×（三酰甘油异常）+0.257×（总胆固醇偏高）+0.544×（高密度脂蛋白偏低）+0.290×（总蛋白异常）+0.395×（丙氨酸氨基转移酶异常）+0.362×（谷氨酰转肽酶异常）+0.993×（阴虚质）+1.016×（气虚质）+0.601×（痰湿质）。模型验证结果显示，训练集ROC曲线下面积（AUC）为0.792，95%CI为0.779~0.816（P<0.05），最佳截断值为0.405，灵敏度为0.771，特异度为0.690；测试集验证准确率达到95.69%，Kappa=0.636（P<0.001）。结论　初步构建了糖尿病风险评估模型，且此模型具有较高诊断效应。中医体质辨识作为重要的影响因素纳入糖尿病发病风险评估的模型中来，可以提高其预测能力，为糖尿病的中医药早期防治提供一定的依据。     

Myeloid dysregulation and therapeutic intervention in COVID-19

The dysregulation of myeloid cell responses is increasingly demonstrated to be a major mechanism of pathogenesis for COVID-19. The pathological cellular and cytokine signatures associated with this disease point to a critical role of a hyperactivated innate immune response in driving pathology. Unique immunopathological features of COVID-19 include myeloid-cell dominant inflammation and cytokine release syndrome (CRS) alongside lymphopenia and acute respiratory distress syndrome (ARDS), all of which correlate with severe disease. Studies suggest a range of causes mediating myeloid hyperactivation, such as aberrant innate sensing, asynchronized immune cellular responses, as well as direct viral protein/host interactions. These include the recent identification of new myeloid cell receptors that bind SARS-CoV-2, which drive myeloid cell hyperinflammatory responses independently of lung epithelial cell infection via the canonical receptor, angiotensin-converting enzyme 2 (ACE2). The spectrum and nature of myeloid cell dysregulation in COVID-19 also differs from, at least to some extent, what is observed in other infectious diseases involving myeloid cell activation. While much of the therapeutic effort has focused on preventative measures with vaccines or neutralizing antibodies that block viral infection, recent clinical trials have also targeted myeloid cells and the associated cytokines as a means to resolve CRS and severe disease, with promising but thus far modest effects. In this review, we critically examine potential mechanisms driving myeloid cell dysregulation, leading to immunopathology and severe disease, and discuss potential therapeutic strategies targeting myeloid cells as a new paradigm for COVID-19 treatment.     

＊ 补充基金信息（立项部门，项目类型，课题名称，负责人信息）

病机是认识疾病病变的关键，抓住核心病机演变发展的规律，是中医临床诊疗的主旨和核心。病机兼化理论由中国中医科学院胡镜清研究员提出，用以从病机层面理解疑难复杂疾病病证关系和把握其演变规律，在明确疾病基本矛盾的同时，兼顾疾病的复杂性和多变性。文章通过构建新型冠状病毒肺炎病机兼化框架，揭示其病机演化规律，认为新冠肺炎属于“湿毒疫”范畴，湿毒始终是本病的病变核心，初期寒化，进展期热化，恢复期虚化是本病病机的传变方式。知本病之机，可未病先防，知病机传变，可截断扭转，有利于临床上增强对疾病发生发展趋势的预见性。     

气机逆乱是脓毒症MODS的根本病机

脓毒症是机体对于感染导致失调的宿主反应所引发的危及生命的器官功能障碍或衰竭。多器官功能障碍综合征(MODS)是脓毒症的严重并发症,也是脓毒症高死亡率的主要原因。本文从中医气机升降出入角度讨论MODS发生,认为脓毒症时外邪引起的脏腑气机升降出入失常,即气机逆乱是MODS发生的根本病机,且其具有始于肺、困于中焦,后期气血皆乱的特点。临床应重视调理气机,升降相宜,初期重在治肺,宜调气降气,尤重视恢复中焦气机,后期调气不忘治血。     

Evidence-based pathogenesis and treatment of ulcerative colitis: A causal role for colonic epithelial hydrogen peroxide

In this comprehensive evidence-based analysis of ulcerative colitis (UC), a causal role is identified for colonic epithelial hydrogen peroxide (H₂O₂) in both the pathogenesis and relapse of this debilitating inflammatory bowel disease. Studies have shown that H₂O₂ production is significantly increased in the non-inflamed colonic epithelium of individuals with UC. H₂O₂ is a powerful neutrophilic chemotactic agent that can diffuse through colonic epithelial cell membranes creating an interstitial chemotactic molecular “trail” that attracts adjacent intravascular neutrophils into the colonic epithelium leading to mucosal inflammation and UC. A novel therapy aimed at removing the inappropriate H₂O₂ mediated chemotactic signal has been highly effective in achieving complete histologic resolution of colitis in patients experiencing refractory disease with at least one (biopsy-proven) histologic remission lasting 14 years to date. The evidence implies that therapeutic intervention to prevent the re-establishment of a pathologic H₂O₂ mediated chemotactic signaling gradient will indefinitely preclude neutrophilic migration into the colonic epithelium constituting a functional cure for this disease. Cumulative data indicate that individuals with UC have normal immune systems and current treatment guidelines calling for the suppression of the immune response based on the belief that UC is caused by an underlying immune dysfunction are not supported by the evidence and may cause serious adverse effects. It is the aim of this paper to present experimental and clinical evidence that identifies H₂O₂ produced by the colonic epithelium as the causal agent in the pathogenesis of UC. A detailed explanation of a novel therapeutic intervention to normalize colonic H₂O₂, its rationale, components, and formulation is also provided.     

颅内动脉夹层的发病机制、影像学特点和自然病程

颅内动脉夹层相比颅外动脉夹层较少见，且临床表现缺乏特异性，既可以表现为缺血性 事件，也可以表现为出血性事件，多发生于年轻人。由于夹层发生部位、形成时机以及病变严重程度 不同，临床表现各种各样，影像学对于确诊动脉夹层至关重要。颅内动脉夹层易复发，且死亡率较高， 除无症状或症状轻微的患者给予保守治疗或随访观察外，对于症状较重或进展性动脉夹层患者，应 给予积极治疗，包括血管内治疗。     

Ethnic differences in genetic polymorphism associated with irritable bowel syndrome

Genetic polymorphism is associated with irritable bowel syndrome(IBS) in terms of susceptibility and clinical manifestations. Previous studies have shown that genetic polymorphism might play a key role in the onset and progression of IBS by modulating components of its pathogenesis such as the gut-brain axis,gastrointestinal motility, inflammatory activity, and immune status. Although underlying pathophysiological mechanisms have not been fully clarified, the potential ethnic differences that are present in worldwide genetic studies of IBS deserve attention. This review surveyed numerous studies focusing on IBSassociated single nucleotide polymorphisms, and investigated the ethnic disparities revealed by them. The results demonstrate the need for more attention on ethnic factors in IBS-related genetic studies. Taking ethnic backgrounds into accounts and placing emphasis on disparities potentially ascribed to ethnicity could help lay a solid and generalized foundation for transcultural, multi-ethnic,or secondary analyses in IBS, for example, a meta-analysis. Broader genetic studies considering ethnic factors are greatly needed to obtain a better understanding of the pathophysiological mechanisms of IBS and to improve the prevention, intervention, and treatment of this disease.