芫根调节免疫功能的小肠转录组学研究

利用生物信息学技术初步探索芫根调控肠道免疫功能的分子生物学机制。方法 选择雄性SPF级BALB/c小鼠18只，随机分为3组，每组6只。SC1组小鼠每只每次灌胃芫根提取液150 μL，SC2组小鼠每只每次灌胃绞碎芫根原浆悬液150 μL，NC组小鼠每只每次灌胃生理盐水150 μL，连续7 d每日灌胃一次。分别取每组小鼠小肠组织样品提取RNA，总RNA的质检合格后，进行转录组测序。按GO功能和KEGG信号通路对差异表达基因聚类分析揭示差异表达高度富集的免疫相关通路。从免疫角度分析芫根灌胃小鼠小肠组织的基因表达变化情况。结果 转录组测序共检测到27733条 mRNA的表达，SC1组与NC组比较，显著差异表达基因1635个，其中上调差异表达基因1236个，下调差异表达基因399个；SC2组与NC组比较，显著差异表达基因2872个，其中上调差异表达基因2233个，下调差异表达基因639个（P＜0.05）。按GO功能和KEGG信号通路聚类分析显示差异表达基因在白介素分泌、干扰素反应、T细胞受体信号通路及维生素和脂肪消化吸收等途径的富集度在两个芫根组中均居于前20位（P＜0.01），肠黏膜趋化因子CCL20和巨噬细胞极化标志物CD274等免疫蛋白编码基因差异表达显著且同属于上述多个免疫通路。结论 芫根灌胃小鼠小肠的差异表达基因在白介素分泌、干扰素反应、T细胞受体信号通路、营养物质消化吸收等途径高度富集，提示芫根对肠道免疫系统及肠黏膜功能的调节，其中CD274的表达上调和CCL20的表达下调提示诱导M1型巨噬细胞极化和T细胞活化可能是芫根调控免疫和维护肠道正常结构功能的重要途径。     

基于苗药五藤膏外敷对CIA大鼠炎性骨破坏的影响探讨苗医外治就近驱邪的作用＊

目的 通过研究明确苗药五藤膏外敷缓解胶原诱导性关节炎（CIA）大鼠关节局部炎症和骨破坏的机制，证实苗医外治就近驱邪的作用。方法 将70只Wistar大鼠随机分为空白组、模型组、苗药五藤膏高、中、低剂量组、扶他林组及IL-17阻断组，每组10只。除空白组外，其余6组均构建CIA模型，并给予相应的外敷治疗。观察大鼠一般情况，HE染色进行病理学分析，TRAP染色检测OC生成，ELISA检测各炎症因子的含量，RT-PCR和WB分别检测RANKL的基因及蛋白表达。结果 苗药五藤膏能改善CIA大鼠破骨细胞浸润及关节病理性结构，并降低RANKL蛋白、基因表达以及TNF-α、IL-1、IL-6、IL-17含量。结论 苗药五藤膏外敷剂对CIA大鼠的治疗机制可能与降低致炎因子的分泌，抑制RANKL及OC的表达相关。     

Contemporary Management of Ischemic Mitral Regurgitation at Coronary Artery Bypass Grafting

BackgroundRecent guidelines for the treatment of moderate or severe ischemic mitral regurgitation (IMR) in patients undergoing coronary artery bypass grafting (CABG) have changed. This study assessed the real-world impact of changing guidelines on the management of IMR during CABG over time. We hypothesized that the utilization of mitral valve repair for IMR would decrease over time, whereas mitral valve replacement for severe IMR would increase.MethodsPatients undergoing CABG in a statewide collaborative database (2011-2020) were stratified by severity of IMR. Trends in mitral valve repair or replacement were evaluated. To account for differences of the patients, propensity score–matched analyses were used to compare patients with and without mitral intervention.ResultsA total of 11,676 patients met inclusion criteria, including 1355 (11.6%) with moderate IMR and 390 (3.3%) with severe IMR. The proportion of patients undergoing mitral intervention for moderate IMR decreased over time (2011, 17.7%; 2020, 7.5%; P_trend = .001), whereas mitral replacement for severe IMR remained stable (2011, 11.1%; 2020, 13.3%; P_trend = .14). Major morbidity was higher for patients with moderate IMR who underwent mitral intervention (29.1% vs 19.9%; P = .005). In a propensity analysis of 249 well-matched pairs, there was no difference in major morbidity (29.3% with mitral intervention vs 23.7% without; P = .16) or operative mortality (1.2% vs 2.4%; P = .5).ConclusionsConsistent with recent guideline updates, patients with moderate IMR were less likely to undergo mitral repair. However, the rate of replacement for severe IMR did not change. Mitral intervention during CABG did not increase operative mortality or morbidity.     

慢性疼痛中枢调控网络的研究现状与思考＊

慢性疼痛是一种复杂的身心疾病，包括躯体痛觉异常、认知障碍、负性情绪等多个方面的改变，同时伴随着神经系统的功能以及结构的改变。本文将对慢性疼痛与下行疼痛调节通路、疼痛情感-认知调控网络以及中脑边缘奖赏网络的相关性，以及针刺镇痛的中枢机制相关研究文献进行综述，旨在探讨下行疼痛调节通路、疼痛情感-认知调控网络以及中脑边缘奖赏网络在慢痛发生机制中的作用，为临床治疗慢性疼痛类疾病提供更优势的治疗方案。     

预测年轻乳腺癌患者生存率列线图的建立和验证

目的:构建预测年轻乳腺癌患者生存情况的列线图，以期帮助临床诊疗。方法:收集SEER数据库中5 525例年轻乳腺癌患者的临床信息，通过单因素Log-rank检验和多因素Cox生存分析筛选出独立预后因素,用于构建预测患者3、5年总生存率(overall survival,OS)和癌症特异性生存率（cancer special survival,CSS)的列线图，将我院就诊的147例年轻乳腺癌患者作为验证集进行外部验证。结果:单因素和多因素分析结果显示，种族、病理类型、组织学分级、T分期、N分期、M分期、ER状态、HER-2状态、手术方式是与患者OS和CSS相关的独立危险因素，将这些因素纳入并建立预测患者OS和CSS的列线图模型。内部和外部验证结果显示模型具有良好的预测性能。基于建立的OS和CSS列线图模型对患者进行了风险分层，能够准确地将年轻乳腺癌患者分成预后有显著差异的三个风险亚组。结论:本研究构建的预测模型能较为准确的预测年轻乳腺癌患者的预后情况，为临床的诊疗提供科学依据。     

基于TCGA数据库挖掘甲状腺乳头状癌淋巴结转移相关的突变基因及其机制探讨北大核心

目的:挖掘并筛选与甲状腺乳头状癌(papillary thyroid carcinoma,PTC)淋巴结转移相关的突变基因及其潜在的机制。方法:从TCGA数据库获得377例PTC患者的测序数据及完整的临床资料,并分为淋巴结转移组(LM,n=212)与无淋巴结转移组(NLM,n=165)。利用R语言(v3.6.2)对转移组特有的突变基因进行富集分析。采用String在线软件绘制蛋白互作网络,Cytoscape软件筛选网络中的核心基因。在UALCAN网站上验证基因表达量与淋巴结转移之间的关系。利用荧光实时定量PCR测定候选基因在细胞系中mRNA的表达量。结果:一共筛选出1197个仅在LM组发生突变的基因,它们主要富集在黏着连接、细胞黏附分子(cell adhesion molecules,CAMs)通路。CAMs通路的核心基因ITGB1与VCAN的表达量与淋巴结转移相关。与正常甲状腺细胞系相比,VCAN基因在PTC细胞系TPC-1和B-CPAP中mRNA的表达量较高,尤其是B-CPAP细胞系。结论:CAMs通路可能是PTC淋巴结转移相关机制之一,其中VCAN基因可能是潜在的分子标志物。     

Registries,Databases and Repositories for Developing Artificial Intelligence in Cancer Care

Modern artificial intelligence techniques have solved some previously intractable problems and produced impressive results in selected medical domains. One of their drawbacks is that they often need very large amounts of data. Pre-existing datasets in the form of national cancer registries, image/genetic depositories and clinical datasets already exist and have been used for research. In theory, the combination of healthcare Big Data with modern, data-hungry artificial intelligence techniques should offer significant opportunities for artificial intelligence development, but this has not yet happened. Here we discuss some of the structural reasons for this, barriers preventing artificial intelligence from making full use of existing datasets, and make suggestions as to enable progress. To do this, we use the framework of the 6Vs of Big Data and the FAIR criteria for data sharing and availability (Findability, Accessibility, Interoperability, and Reuse). We share our experience in navigating these barriers through The Brain Tumour Data Accelerator, a Brain Tumour Charity-supported initiative to integrate fragmented patient data into an enriched dataset. We conclude with some comments as to the limits of such approaches.     

Transhiatal lower mediastinal lymph node dissection for esophagogastric junction carcinoma by interconnecting four body cavities

BackgroundDue to the limited number of landmark structures, it is difficult to standardize the surgical procedures for advanced esophagogastric junction cancer such as Ivor Lewis esophagectomy that require transhiatal lower mediastinal lymph node dissection (TH-LMND). We demonstrate an easily reproducible procedure for TH-LMND, wherein four body cavities, namely, the abdominal cavity, infracardiac bursa (ICB), and left and right thoracic cavities are interconnected.MethodsFirst, the dissection between the right crus and the esophagus was used to connect the abdominal cavity to the ICB — a lower mediastinal cavity separated from the omental bursa during embryonic development [1,2]. Second, the right thoracic cavity was opened with the shortest distance by dissecting the cranial side of the ICB. The right pulmonary ligament was dissected from the right lung. Third, the dissection to the contralateral side while exposing the aorta and the pericardium connected the left and right thoracic cavities. Then, the left pulmonary ligament was dissected from the left lung. The dissected tissues, including the lymph nodes, were subsequently peeled from the esophagus.ResultsBetween April 2018 and August 2021, 14 patients underwent laparoscopic or robotic TH-LMND via the procedure above. The median time required to complete the dissection was 75 min. None of the procedures were converted to open surgery, and none of the patients experienced intraoperative complications such as pericardial injury, lung injury, or massive bleeding.ConclusionThe surgical concept of interconnecting four body cavities made the procedure more accessible and reproducible while achieving en bloc TH-LMND.     

婚姻状态对原发性中枢神经系统淋巴瘤患者预后的影响：一项倾向性评分匹配研究

背景 原发性中枢神经系统淋巴瘤（PCNSL）的预后较差，明确其预后危险因素是改善其预后的关键。生物-心理-社会医学模式提示社会心理因素的重要性。婚姻是重要的社会心理因素之一，但婚姻状态对PNSCL患者预后的影响尚不明确。 目的 探究婚姻状态对PCNSL患者总生存（OS）和癌因生存（CSS）的影响。 方法 于2020年，提取2000—2016年美国"监测、流行病学和结果"数据库的3 993例PCNSL患者的病例资料，包括社会人口学资料（婚姻状态、确诊年龄、种族、性别和确诊年份）、临床病理资料（病理类型、肿瘤位置）、治疗资料（手术、放疗和化疗）及结局资料（生存信息和随访时间）。依据婚姻状态将患者分为已婚和非已婚两组，其中非已婚包括单身、离异和丧偶。采用倾向性评分匹配均衡基线资料，采用Kaplan-Meier分析（Log-rank检验）、Cox回归评估婚姻状态对患者OS和CSS的影响。 结果 倾向性评分匹配后，已婚组和非已婚组患者基线资料比较，差异均无统计学意义（P>0.05）。将患者按婚姻状态分为已婚和非已婚组：Log-rank检验结果显示，与已婚患者相比，非已婚患者的OS和CSS更差（P<0.05）；倾向性评分匹配后，校正确诊年龄、种族、性别、确诊年份、病理类型、肿瘤位置、手术、放疗和化疗因素后，多因素Cox回归分析结果显示，非已婚患者的OS风险是已婚患者的1.24倍〔95%CI（1.14，1.36），P<0.001〕，非已婚患者的CSS风险是已婚患者的1.22倍〔95%CI（1.11，1.33），P<0.001〕。将患者按婚姻状态分为已婚、单身、离异、丧偶组：Log-rank检验结果显示，与已婚患者相比，丧偶患者的OS和CSS预后更差（P<0.05）；校正确诊年龄、种族、性别、确诊年份、病理类型、肿瘤位置、手术、放疗和化疗因素后，多因素Cox回归结果显示，单身患者OS和CSS风险分别是已婚患者的1.14倍〔95%CI（1.03，1.27），P=0.013〕和1.15倍〔95%CI（1.03，1.29），P=0.012〕，离异患者OS和CSS风险分别是已婚患者的1.23倍〔95%CI（1.07，1.41），P=0.004〕和1.22倍〔95%CI（1.05，1.41），P=0.009〕，丧偶患者OS和CSS风险分别是已婚患者的1.37倍〔95%CI（1.21，1.54），P<0.001〕和1.28倍〔95%CI（1.12，1.46），P=0.013〕。 结论 婚姻状态影响PCNSL患者OS和CSS，与已婚相比，单身、离异和丧偶患者的预后更差，这提示在临床管理和决策中，除了传统的肿瘤生物学特征，还应关注婚姻状态对PCNSL患者预后的影响。     

段迎喜“升脾”学术思想探微

脾胃之气的充足和清气的正常升发对人体生命活动具有决定意义,饮食、劳倦、情志、外感对脾胃的损伤往往影响中焦脾胃清阳的生成及升发,脾胃病以本虚为主,多由虚致实,虚实兼有,病机关键为升降失常,脾气不升。肝对人体气机具有升宣调畅作用,脾气的升清有赖于肝气升发促进。在补中益气的同时,要补肝益气。同时,肾精气充盈,元气方能充沛,肾阳又主气化,肾精不封、肾气不固者必致肾气下陷。治疗须温肾壮阳、升阳举陷。脾胃中气不足,气机郁滞而化火,并脾之清气下流而生泄泻,相火乘其土位更加耗伤中焦清阳之气。段老师特别注重脾气生长、升发,只有清阳升发,脾气上升,元气才能充沛,阴火才会收敛潜藏。治疗时运用辛甘之药以补益中气,借升阳风药以助肝胆之用,补其中而升其阳,升浮变通,使生长之气健旺。段老师善于运用甘温之品,温补中气,升发清阳。