钙离子通道蛋白TRPV6及其相关疾病的研究进展

瞬时受体电位亚家族V成员6 (Transient Receptor Potential Channel Subfamily V Member 6, TRPV6) 是一种钙离子高度选择性离子通道，在多种组织中均有表达，控制细胞顶端钙离子的进入，在维持钙稳态中发挥重要作用。TRPV6功能异常会影响体内钙稳态，进而引发新生儿骨骼发育异常、甲状旁腺功能亢进、骨与软骨代谢异常、肾结石和高尿钙症、 以及炎症性肠病和慢性胰腺炎等多种疾病。近年来研究也表明，TRPV6的上调与多种肿瘤的侵袭性增加有关，具有作为肿瘤检测的标志物以及治疗靶点的潜力。本综述将聚焦于TRPV6与其在相关疾病中发挥的作用，旨在为TRPV6作为药物靶点实现临床转化提供理论依据。     

Video-assisted thoracoscopic surgery for thoracic empyema in patients on maintenance hemodialysis

Thoracic empyema in uremic patients on maintenance hemodialysis is a challenging situation. The clinical characteristics are rarely reported, and the surgical outcomes remain unclear. We report our experience with video-assisted thoracoscopic surgery in these patients during 10-year period of time. Between 2005 and 2015, we retrospectively reviewed the clinical characteristics, bacteriological studies, and thoracoscopic surgical results of 23 empyema patients undergoing maintenance hemodialysis. The mean patient age was 67.1 ± 12.9 years. All patients had additional preexisting systemic diseases. The mean duration of hemodialysis was 34.7 ± 25.8 months. The infections causing empyema were pneumonia in 11 (47.8%), blood stream infection in 8 (34.8%), and uremic pleuritis in 4 (17.4%). Among the 22 identified microorganisms, the most common pathogen was methicillin-resistant Staphylococcus aureus (31.8%). After thoracoscopic surgery, 8 patients (34.8%) required additional procedures for complications, including 2 patients who required repeated thoracoscopy for hemothorax and 6 (26.1%) patients who required open drainage for residual empyema. The mean hospital stay was 62.4 days, and 6 patients (26.1%) died in the hospital. Univariate and multivariate analyses revealed that maintenance hemodialysis longer than 5 years was a significant factor associated with in-hospital mortality (odds ratio: 14.8, 95% confidence interval 1.5–151.6; p < 0.0001). While surgical management of thoracic empyema in uremic patients undergoing maintenance hemodialysis is associated with high rates of complication and mortality, thoracoscopic surgery is feasible, especially for patients undergoing hemodialysis for less than 5 years.     

生化汤加味促进剖宫产后子宫复旧随机对照试验的系统评价及Meta分析＊

目的 对生化汤加味促进剖宫产后子宫复旧的有效性与安全性进行系统评价，为其在临床应用提供循证医学证据。方法 检索中国生物医学文献数据库（CBM）、中国知网（CNKI）、万方资源数据库（WanFang）、维普期刊数据库（VIP）、Cochrane Library、PubMed、Web of Science等，检索时限为建库至2020年7月，选择生化汤加味促进剖宫产后子宫复旧的随机对照试验（RCT），采用Cochrane系统评价员手册提供的偏倚风险评估工具进行文献质量评价，应用RevMan5.3软件进行Meta分析。结果 共纳入12篇RCT文献，共计1804例剖宫产产妇；Meta分析结果显示，生化汤加味联合缩宫素组在产后第1、3、5天子宫底高度［MD = -0.75，95%CI（-1.35， -0.15），P < 0.00001；MD = -1.92，95%CI（-3.13， -0.72），P < 0.00001；MD = -1.92，95%CI（-3.79， -0.06），P < 0.00001］低于单用缩宫素组，联合用药组血性恶露时间［MD = -1.52，95%CI（-2.71，-0.34），P < 0.00001］和产后恶露持续时间［MD = -4.47，95%CI（-6.20，-2.75），P < 0.00001］均短于单用缩宫素组。结论 生化汤加味联合缩宫素与单用缩宫素比较，更能促进产后子宫复旧；不良反应少，报道的仅有4例出现轻微腹泻，安全性较高；但由于纳入文献质量较低，上述结论尚需更多的随机对照临床研究加以证实。     

肝细胞癌TACE术后病灶存活或复发18F-FDGPET/CT和增强CT诊断价值Meta分析

目的采用Meta分析方法评价¹⁸F-脱氧葡萄糖正电子发射计算机体层摄影(¹⁸F-FDG PET/CT)和增强CT(CECT)诊断经导管肝动脉化疗栓塞术(TACE)术后存活或复发病灶的临床价值。方法根据PRISMA报告规范开展Meta分析。检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方和维普数据库中¹⁸F-FDG PET/CT和CECT诊断TACE术后存活或复发病灶的临床研究,时间至2019-04。由2位研究人员独立筛选文献、提取资料,根据诊断准确性研究质量评价工具-2(QUADAS-2)评价纳入研究的偏倚风险后,采用Stata 12.0软件进行Meta分析,计算其汇总敏感度(Sen)和特异度(Spe),绘制受试者工作特征曲线(SROC)并计算曲线下面积(AUC)。结果共纳入10篇¹⁸F-FDG PET/CT及13篇CECT诊断TACE术后存活或复发病灶的原始研究,分别包括322例患者的467个病灶和748例患者的943个病灶。Meta分析显示,¹⁸F-FDG PET/CT诊断TACE术后存活或复发病灶的Sen=0.92(95%CI为0.87~0.94)、Spe=0.95(95%CI为0.82~0.99)、AUC=0.97(95%CI为0.93~0.99);CECT诊断TACE术后存活或复发病灶的Sen=0.72(95%CI为0.66~0.78)、Spe=0.99(95%CI为0.93~1.00)、AUC=0.87(95%CI为0.83~0.89)。此外,CECT诊断TACE术后存活或复发Sen(Z=2.34,P=0.02)和AUC(Z=2.21,P=0.03)值低于¹⁸F-FDG PET/CT,差异有统计学意义。结论相比于CECT,¹⁸F-FDG PET/CT对TACE术后存活或复发病灶具有较高诊断效能,可视为TACE术后存活或复发病灶有效的影像学诊断方法。     

Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.