舌象仪临床应用研究的方法学及报告质量评价

目的 评价舌象仪临床应用研究的随机对照试验（RCT）、病例系列研究的方法学及报告质量。方法 检索PubMed、中国期刊全文数据库（CNKI）、维普数据库（VIP）和万方数据库（Wanfang database），从建库截至2018年12月开始检索，收集应用舌象仪观察临床疾病的RCT、病例系列研究和病例对照研究，分别参考Cochrane手册5.1.0版的偏倚风险评估工具和CONSORT 2010版的声明，对纳入的RCT研究进行方法学和报告质量进行评价；根据NICE和STROBE声明第四版进行方法学的报告质量评价研究。结果 初检出相关文献567篇，最终纳入59篇文献，包括2个RCT，57个病例系列研究。50%的RCT应用Cochrane偏倚风险工具评价后显示采用的随机分配方法比较合理，没有采用分配隐藏和盲法；均采用了意向性分析，遗憾的是并没有报告失访的情况；研究也缺乏选择性报告。NICE病例系列研究质量评价结果 病例系列研究中仅14.04%符合多中心研究；59.64%的研究纳入排除标准均不明确；数据未达到预期设定目标，未进行分层分析结局。CONSORT声明2010版评价结果显示：纳入的文献均不能从题目辨别出是否是随机临床试验，多项条目报告率为0；应用STROBE声明评价后结果显示：纳入的病例系列研究均未在题目中明确标明是病例系列研究，多项条目报告率为0。结论 舌象仪临床应用的RCT和病例系列研究报告质量不高，建议在设计和报告临床病例对照和随机对照试验时分别参考CONSORT声明、STROBE声明，纠正目前研究存在的方法学问题，进一步提高临床研究质量，增强舌象仪临床应用于疾病效用证据的强度，推进中医的客观化和现代化。     

Extracellular vesicles transmitted miR-31-5p promotes sorafenib resistance by targeting MLH1 in renal cell carcinoma

Sorafenib provides survival benefits in patients with advanced renal cell carcinoma (RCC), but its use is hampered by acquired drug resistance. It is important to fully clarify the molecular mechanisms of sorafenib resistance, which can help to avoid, delay or reverse drug resistance. Extracellular vesicles (EVs) can mediate intercellular communication by delivering effector molecules between cells. Here, we studied whether EVs are involved in sorafenib resistance of RCC and its possible molecular mechanisms. Using differential centrifugation, EVs were isolated from established sorafenib-resistant RCC cells (786-0 and ACHN), and EVs derived from sorafenib-resistant cells were uptaken by sensitive parental RCC cells and thus promoted drug resistance. Elevated exogenous miR-31-5p within EVs effectively downregulated MutL homolog 1 (MLH1) expression and thus promoted sorafenib resistance in vitro. Mice experiments also confirmed that miR-31-5p could mediate drug sensitivity in vivo. In addition, low expression of MLH1 was observed in sorafenib-resistant RCC cells and upregulation of MLH1 expression restored the sensitivity of resistant cell lines to sorafenib. Finally, miR-31-5p level in circulating EVs of RCC patients with progressive disease (PD) during sorafenib therapy was higher when compared to that in the pretherapy status. In conclusion, EVs shuttled miR-31-5p can transfer resistance information from sorafenib-resistant cells to sensitive cells by directly targeting MLH1, and thus magnify the drug resistance information to the whole tumor. Furthermore, miR-31-5p and MLH1 could be promising predictive biomarkers and therapeutic targets to prevent sorafenib resistance.     

丝棉木种子化学成分及其抗肿瘤活性

目的 研究丝棉木Euonymus maackii Rupr.种子的化学成分及其抗肿瘤活性.方法 丝棉木种子95%乙醇提取物乙酸乙酯部位采用硅胶、D101、反相HPLC进行分离纯化,根据理化性质及波谱数据鉴定所得化合物的结构.MTT法测定其抗肿瘤活性.结果 从中分离得到10个化合物,分别鉴定为1β-甲基正丁酰氧基-2β-苯甲酰氧基-4α-羟基-6α-呋喃酰氧基-9β,12-二乙酰氧基-β-二氢沉香呋喃(1)、6α,9β,12-三乙酰氧基-1β,2β,8β-三苯甲酰氧基-β-二氢沉香呋喃(2)、6α,9β,12-三乙酰氧基-1β,8β-二苯甲酰氧基-2β-正己酰氧基-β-二氢沉香呋喃(3)、6α,9β,12-三乙酰氧基-1β,8β-二苯甲酰氧基-2β-正辛酰氧基-β-二氢沉香呋喃(4)、6α,9β,12-三乙酰氧基-1β,8β-二苯甲酰氧基-2β-正癸酰氧基-β-二氢沉香呋喃(5)、卫矛羰碱(6)、6α,12-二乙酸基-1β,9α-二乙酸(β-呋喃羧氧基)-4α-羟基-2β-2-甲基丁酯-β-二氢沉香呋喃(7)、6α,9β,12-三乙酰氧基-1β,8β-二苯甲酰氧基-2β-羟基-β-二氢沉香呋喃(8)、6α,12-二乙酸基-1β,9 α-二乙酸(β-呋喃羧氧基)-4α-羟基-1β-2-甲基丁酯-β-二氢沉香呋喃(9)、6α,9β,12-四乙酰氧基-1β,8β-二苯甲酰氧基-β-二氢沉香呋喃(10).化合物6对Hela细胞有明显的抑制作用,IC50为9.76 μg/mL.结论 化合物1为新化合物.化合物6有一定的抗肿瘤活性.     

肠内肠外联合营养支持治疗肝细胞癌患者围术期临床研究*

目的 探讨采用肠内肠外联合营养支持对于肝细胞癌（HCC）患者肝叶切除术围手术期的影响。方法 2015年1月~2017年12月在本院行肝叶切除术治疗的HCC患者130例, 在术后根据营养支持方案的不同分为对照组65例和试验组65例, 分别给予肠外营养支持和肠内肠外联合营养支持, 观察术后恢复情况。结果 术后2w, 观察组患者血清白蛋白水平为（41.4±2.9）g/L, 前白蛋白水平为（260.8±12.5）mg/L, Child-Pugh评分为（5.7±1.7）, 与对照组的（34.6±2.5）g/L、（233.3±2.4）mg/L和（6.6±1.5）比, 差异显著（P<0.05）;两组肝功能指标比较, 无显著性差异（P>0.05）;术后, 试验组排便时间为（3.3±1.5）d, 显著早于对照组的【（4.3±1.2）d, P<0.05】, 但住院花费为（53696.3±16754.4）元, 显著多于对照组的（50780.6±13632.7）元（P<0.05）;试验组术后胆瘘、感染和肝功能不全发生率为26.2%, 与对照组的32.2%比, 差异无统计学意义（P>0.05）。结论 在HCC患者接受肝叶切除术的围术期, 采用肠内肠外联合营养支持治疗可以早期促进胃肠运动, 加速康复, 有利于术后恢复。     

中医分时辨治与盐酸氟西汀比较治疗糖尿病合并抑郁症的Meta分析＊

目的 系统评价中医分时辨治糖尿病合并抑郁症的效果。方法 计算机检索中国期刊全文数据库（CNKI）、维普中文科技期刊全文数据库（VIP）、万方数据库（Wanfang Data），中国生物医学文献数据库（CBM），搜集国内有关中医分时辨治相关的随机病例对照研究，检索时限均从2010年1月1日到至2020年12月20日。由2名独立研究者对文献资料进行提取，并评价纳入研究的偏倚风险后，采用RevMan5.3软件进行研究合并Meta分析。结果 共纳入10个相关研究，包括1008名研究对象。Meta分析结果显示：与盐酸氟西汀相比较，中医分时辨治糖尿病合并抑郁症在降低汉密尔顿抑郁量表（HAMD）［MD=-0.61， 95%CI （-3.68， 2.46）， P<0.00001］与汉密尔顿焦虑量表（HAMA）［MD=-0.21， 95%CI （-3.49， 3.08）， P<0.00001］评分没有统计学意义，但对空腹血糖（FPG）［MD=-0.80， 95%CI （-0.94， -0.65）， P<0.00001］、餐后2 h血糖（2HPG）［MD=-0.74， 95%CI （-1.02， -0.46）， P<0.00001］、糖化血红蛋白（HbA1c）［MD=-0.21， 95%CI （-0.38， -0.04）， P=0.02］、总胆固醇（TG）［MD=-0.48， 95%CI （-0.61， -0.36）， P<0.00001］、总甘油三酯（TC）［MD=-0.47， 95%CI （-0.62， -0.32）， P<0.00001］水平下降明显。结论 当前的证据表明，中医分时辨治方法治疗糖尿病合并抑郁症相对于西药盐酸氟在降低抑郁症状方面没有明显优势，但在降低血糖与血脂水平方面有较高的临床价值，这可能与分时辨治的药物有关，但同时结论受研究数量和质量的影响，更多高质量临床研究仍需开展，对上述结论予以确认。     

Application of neuroendoscopic surgical techniques in the assessment and treatment of cerebral ventricular infection

Cerebral ventricular infection(CVI) is one of the most dangerous complications in neurosurgery because of its high mortality and disability rates. Few studies have examined the application of neuroendoscopic surgical techniques(NESTs) to assess and treat CVI. This multicenter, retrospective study was conducted using clinical data of 32 patients with CVI who were assessed and treated by NESTs in China. The patients included 20 men and 12 women with a mean age of 42.97 years. NESTs were used to obliterate intraventricular debris and pus, fenestrate or incise the intraventricular compartment and reconstruct cerebrospinal fluid circulation, and remove artificial material. Intraventricular irrigation with antibiotic saline was applied after neuroendoscopic surgery(NES). Secondary hydrocephalus was treated by endoscopic third ventriculostomy or a ventriculoperitoneal shunt. Neuroendoscopic findings of CVI were used to classify patients into Grade I(n = 3), Grade II(n = 13), Grade III(n = 10), and Grade IV(n = 6) CVI. The three patients with grade I CVI underwent one NES,the 23 patients with grade II/III CVI underwent two NESs, and patients with grade IV CVI underwent two(n = 3) or three(n = 3) NESs.The imaging features and grades of neuroendoscopy results were positively related to the number of neurosurgical endoscopic procedures.Two patients died of multiple organ failure and the other 30 patients fully recovered. Among the 26 patients with secondary hydrocephalus,18 received ventriculoperitoneal shunt and 8 underwent endoscopic third ventriculostomy. There were no recurrences of CVI during the 6-to 76-month follow-up after NES. Application of NESTs is an innovative method to assess and treat CVI, and its neuroendoscopic classification provides an objective, comprehensive assessment of CVI. The study trial was approved by the Institutional Review Board of Beijing Shijitan Hospital, Capital Medical University, China.