预见习在精神病学教学中的作用研究

目的探讨预见习在精神病教学中的作用。方法选取120名本科学生,随机分为预见习组(n=60)和对照组(n=60)。预见习组在学习精神病学理论课程前一学期开始实施带教老师带领学生预见习、见习、实习全程教学,对比两组学生实践操作、理论知识成绩和学生满意度。结果干预后,导师制预见习组实践操作和理论知识成绩显著高于对照组(P<0.05)。导师制预见习组学生满意度显著高于对照组(P<0.05)。结论预见习教学有助于学生全面发展,提高精神病学教学水平。     

Unexpected Return for Follow-up During the First Year of Multidisciplinary Care May Be Predictive of Rapid Deterioration of Renal Function

Multidisciplinary predialysis education and team care (MDC) may slow the decline in renal function in patients with chronic kidney disease (CKD). However, associations between unexpected return during MDC and progression of renal dysfunction have not been characterized in patients with CKD. Our study aimed to determine the association between exacerbation of renal dysfunction and the frequency of unexpected return during follow-up.A total of 437 patients with CKD receiving multidisciplinary care between January 2009 and June 2013 at the Shin-Kong Wu Ho-Su Memorial Hospital were included in this retrospective observational cohort study, and multiple imputations were performed for missing data. The predictor was the frequency of unexpected return for follow-up during the first year after entering MDC. Main outcome was monthly declines in estimated glomerular filtration rates (eGFR). Moreover, the demographic data, comorbidities, history of medication, and routine laboratory data for patients with CKD were collected.Among all patients, 59.7% were male, the mean age at initiation of MDC was 69.4 ± 13.2 years, and the duration of follow-up was 21.4 ± 3.3 months. The subjects were divided into 2 groups according to frequencies of follow-up (≤4 and > 4 visits) during the 1st year of MDC. The patients with CKD were regularly followed up every 3 months as a part of MDC in our hospital, and patients who returned for more than 4 follow-up visits were included in the unexpected return group. In crude regression analyses, unexpected return was significantly associated with higher monthly declines of eGFR (β = 0.092, 95% confidence interval, 0.014–0.170). This association remained after adjustments for multiple variables, and subgroup analyses of unexpected return showed that male gender, older age, CKD stage 1 to 3, hypertension, history of coronary artery disease, and use of renin–angiotensin system blockade were significantly associated with declines in renal function.In conclusion, unexpected return for follow-up during the 1st year of MDC was significantly associated with the deterioration of renal function.     

8周基础军训对入伍新兵红细胞及其相关指标的影响

目的探讨8周基础军训(basic military training,BMT)对入伍新兵血像中红细胞及其相关指标的影响,为指导科学的军事训练提供参考。方法数据来自新疆边防部队2015年度入伍的50名男性新兵,分别在BMT前后测定并记录受试新兵的红细胞计数、血红蛋白浓度及血清铁蛋白等。结果经过8周的BMT,新兵血液中血红蛋白浓度、红细胞计数及血清铁蛋白均显著下降(P0.05,P0.01)。结论 8周BMT可能导致入伍新兵发生运动性贫血,铁缺乏可能是其主要原因。     

以医院登记为基础的20万例恶性肿瘤患者生存报告

背景与目的：恶性肿瘤是全球重大的公共健康问题，患者生存率是评价恶性肿瘤诊治水平的重要指标。通过描述以医院登记为基础的20万例恶性肿瘤患者的生存情况，以真实世界数据从一个侧面反映我国恶性肿瘤的治疗效果。方法：纳入2008年1月1日—2017年12月31日之间在复旦大学附属肿瘤医院确诊为恶性肿瘤并接受住院治疗的患者共计202 542例。通过患者复诊病史资料、电话随访及死因数据链接等方式收集生存随访信息，随访统计时间截至2019年11月30日。应用寿命表法估计各个病种1年、3年和5年总生存率（overall survival，OS），以性别、年龄组、首次治疗时间分层。采用Kaplan-Meier生存曲线绘制各病种的总体生存曲线。结果：患者总体的1年、3年、5年OS分别为89.8%、77.4%和71.0%；男性患者5年OS为58.8%，女性患者为78.7%。在常见的恶性肿瘤中，甲状腺癌患者的5年OS最高，为98.6%；胰腺癌患者最低，为11.4%。2013—2017年首次治疗的乳腺癌、肺癌和肾癌患者5年OS分别为90.0%、55.9%和80.7%，显著高于2008—2012年首次治疗患者，其他肿瘤未见显著上升。结论：大部分恶性肿瘤患者经规范诊治可以获得较为理想的预后，女性生存情况显著优于男性，乳腺癌和肺癌患者的生存改善可能归功于新的临床治疗和早诊手段。     

基于网络药理学与分子对接技术的金花清感颗粒防治新型冠状病毒肺炎的潜在药效物质研究

目的探究金花清感颗粒防治新型冠状病毒肺炎(COVID-19)的潜在物质基础。方法采用中药系统药理学分析平台(TCMSP)检索金花清感颗粒中11味药材所含化学成分与作用靶点。借助Uniprot数据库查询靶点对应基因,采用Cytoscape软件构建"药材-成分-靶点"网络,运用DAVID对相关靶点进行GO功能与KEGG通路富集分析。通过分子对接评价"药材-成分-靶点"网络中核心成分与新型冠状病毒(SARS-CoV-2)3CL水解酶及血管紧张素转化酶Ⅱ(ACE2)的结合作用。结果金花清感颗粒"药材-成分-靶点"网络包含154个化合物和276个相关靶点,关键靶点涉及PTGS2、HSP90AB1、HSP90AA1、PTGS1、NCOA2等。GO功能富集分析得到278个条目,主要涉及ATP结合、转录因子活化、细胞凋亡进程调控等。KEGG通路富集得到127条信号通路,涉及TNF、PI3K/Akt及HIF-1等与肺损伤保护相关通路。分子对接显示金花清感颗粒中芒柄花黄素、豆甾醇、β-谷甾醇、脱水淫羊藿素等核心成分与SARS-CoV-2 3CL水解酶及ACE2的亲和作用较好。结论金花清感颗粒可能通过多成分结合SARS-CoV-2 3CL水解酶及ACE2作用于PTGS2、HSP90AB1、HSP90AA1、PTGS1、NCOA2等靶点调节相关信号通路,从而防治COVID-19。     

肺腺癌对一代EGFR-TKIs原发耐药的危险因素分析

目的:分析对一代表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs)原发耐药的EGFR突变肺腺癌患者的临床特征,为预测肺腺癌患者是否对一代EGFR-TKIs原发耐药提供依据。方法:收集2014年01月至2019年04月于本院住院,一线使用一代EGFR-TKIs且随访时间超过6个月的EGFR敏感突变(19Del/21L858R)肺腺癌患者,根据疗效纳入原发性耐药组(NR=40)和敏感组(NS=237),比较两组患者的临床、影像特征及实验室指标之间的差异,分析对一代EGFR-TKIs原发耐药的危险因素。结果:EGFR敏感突变患者的原发性耐药发生率为14.4%。原发性耐药组与敏感组患者相比,二者在吸烟指数(P=0.004)及淋巴结转移(P=0.03)的差异有统计学意义。血清神经元特异性烯醇化酶(neuron specific enolase,NSE)≥10.725 ng/mL、肿瘤直径≥3.55 cm的患者更易对一代EGFR-TKIs耐药(P<0.05),各因素AUC值分别为0.615、0.716。联合NSE+肿瘤直径两项指标时AUC为0.735(95%CI:0.665~0.804),联合NSE+肿瘤直径+吸烟指数三项指标时AUC为0.751(95%CI:0.679~0.822),均优于单项指标。多因素Logistics回归分析证实,血清NSE浓度、肿瘤直径及吸烟指数是预测EGFR敏感突变患者对一代EGFR-TKI原发耐药的独立影响因素(P<0.05)。结论:吸烟指数≥400、病灶直径≥3.55 cm、血清NSE浓度≥10.725 ng/mL的患者更易对一代EGFR-TKIs原发耐药。单因素对预测EGFR突变患者是否对一代EGFR-TKIs原发耐药准确性较低,综合上述三项指标预测效果更好。     

Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).     

针刺辅助治疗难治性肠易激综合征临床试验方案关键点设计的思考＊

肠易激综合征（Irritable bowel syndrome，IBS）是临床常见病、多发病，其治疗方法丰富，但部分患者疗效欠佳，发展成难治性IBS。目前国内外关于针灸治疗难治性IBS的临床随机对照试验尚不多见。本文立足试验方案设计的“PICOS”原则，从研究对象及诊断标准、干预措施、对照措施、结局指标四个方面入手，重点探讨针刺辅助治疗难治性肠易激综合征临床试验设计的关键要点。从选择特色优势病种、明确诊断标准、制定符合临床实际的干预方案、运用符合目标的安慰针刺、结合研究设计和目的选定结局指标几个角度，阐述试验相关环节设计的原因和思考。     

灯盏乙素介入IP3R-Ca2+途径抑制β淀粉样蛋白诱导的神经细胞凋亡

目的：观察灯盏乙素（Scu）对β淀粉样蛋白（Aβ）诱导的细胞模型中1，4，5-三磷酸肌醇受体（IP₃R）-Ca²⁺途径的影响，探讨其在阿尔茨海默病（AD）病程中可能发挥的积极作用。方法：选用神经母细胞瘤细胞分为对照组、Scu处理组、Aβ处理组、Aβ+Scu （高、中、低）处理组及Aβ+IP₃R拮抗剂组，用CCK-8法筛选药物浓度并检测各组细胞生存率；用酶联免疫吸附法检测各组细胞中1，4，5-三磷酸肌醇（IP₃）的含量；用蛋白印迹和实时荧光定量聚合酶链反应方法检测各组细胞IP₃R和凋亡相关因子Caspase-3、Bcl-2、Bax的蛋白及mRNA的表达水平；用激光共聚焦显微镜观察各组细胞内Ca²⁺浓度的变化；用AnnexinV/PI双染法测定各组细胞的凋亡率。结果：与对照组和Scu处理组相比，Aβ处理组细胞存活率下降，IP₃含量升高，IP₃R、Bax和Caspase-3的蛋白及mRNA表达上调，Bcl-2蛋白及mRNA的表达下调，细胞胞浆内Ca²⁺浓度及细胞凋亡率升高；Aβ+Scu处理组细胞中各检测指标的变化与Aβ处理组的结果正好相反，IP₃R通道下游指标的变化与Aβ+IP₃R拮抗剂组基本一致。结论：Scu能够下调通路蛋白IP₃、IP₃R的表达，抑制Aβ介导的Ca²⁺内流所致的细胞凋亡，可能通过对IP₃R-Ca²⁺途径的调控来影响AD病程。