Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

Neoadjuvant chemotherapy increases the 5-year overall survival of patients with resectable cervical cancer: A systematic review and meta-analysis

Cervical cancer is a global health challenge in women. Neoadjuvant chemotherapy (NACT) is a recent prospect for alternative cervical cancer treatments. This study investigated the efficacy of NACT against resectable cervical cancer based on the medium and long-term survival of patients with the disease. We searched through PubMed, Web of Science, EBSCO and Cochrane Library for relevant reports published by June 2020. The primary outcomes were 3-year and 5-year progression-free survival (PFS) and overall survival (OS) of patients with resectable cervical cancer. Overall, 22 publications encompassing 5627 patients fulfilled the inclusion criteria. We found NACT not to affect both 3-year PFS and OS as well as 5-year PFS of patients with resectable cervical cancer. However, NACT significantly improves the 5-year OS of patients with resectable cervical cancer (HR = 0.83, 95% CI: 0.73–0.94, p = 0.013). Subgroup analysis (RCTs, non-RCTs, NACT + surgery + AT vs. surgery + AT, NACT + surgery + AT vs. CCRT/RT/CRT) further revealed NACT had no significant effect on 5-year PFS of patients with resectable cervical cancer, converse to the 5-year OS subgroup analysis, which validated the beneficial effect of NACT in patients with resectable cervical cancer. In addition, the effect of NACT was most significant in the non-RCTs subgroup (p = 0.012). NACT may improve the long-term prognosis of patients with resectable cervical cancer. However, further large-scale multicenter studies are needed to validate this finding.     

基于基因表达谱相似性的四物汤重定位及抗乳腺癌有效成分群辨识＊

目的 发现四物汤的新药理作用并辨识其有效成分群。方法 于GEO和Cmap数据库获取四物汤和1309个小分子药物的基因表达谱，计算差异表达基因及四物汤与1309个小分子药物的基因表达谱间的相似性，相似性较高的小分子药物的药理作用为四物汤的新药理作用。相似性较高的小分子药物的靶点作为四物汤发挥新药理作用的靶标，利用分子对接技术辨识四物汤的有效成分群。结果 四物汤具有抗乳腺癌的作用，其有效成分群为荭草苷、芍药苷和半乳糖醛酸等，并通过文献调研验证了辨识结果的可靠性。结论 本研究将为扩大四物汤的临床应用范围及质量控制奠定基础，为乳腺癌的治疗提供新方法。     

杜仲叶提取物所含四种主要成分体外抗非酒精性脂肪肝活性研究＊

目的 研究杜仲叶所含4种主要成分体外抗非酒精性脂肪肝（Non-alcoholic fatty liver disease，NAFLD）活性。方法 首先用UPLC-MS检测杜仲叶提取物中绿原酸、杜仲苷、京尼平苷酸、车叶草苷含量；以HepG2细胞为载体，建立NAFLD细胞模型，设正常组、模型组、绿原酸组、杜仲苷组、京尼平苷酸组、车叶草苷组；油红O染色检测细胞内脂质；微量法检测细胞内甘油三酯（Triglyceride，TG）、胆固醇（Total cholesterol，TC）、高密度脂蛋白（High-density lipoprotein cholesterol，HDL-C）、低密度脂蛋白（Low-density lipoprotein cholesterol，LDL-C）含量；微量法检测细胞培养液中谷草转氨酶（Aspartate aminotransferase，AST）、谷丙转氨酶（Alanine aminotransferase，ALT）含量。结果 杜仲叶提取物主要含绿原酸、杜仲苷、京尼平苷酸和车叶草苷，其中京尼平苷酸的含量最高；杜仲叶提取物所含四种主要成分可明显降低细胞内TG、TC、LDL-C含量，其中京尼平苷酸效果最为显著；绿原酸、杜仲苷，京尼平苷酸可显著降低细胞培养液中AST、ALT含量，其中京尼平苷酸效果最好。结论 杜仲叶提取物所含四种主要成分可不同程度降低HepG2细胞内脂质含量，其中京尼平苷酸效果较好。     

经颅直流电刺激对精神分裂症伴迟发性运动障碍患者空间 工作记忆的影响

目的 探讨经颅直流电刺激（tDCS）对精神分裂症伴迟发性运动障碍（TD）患者空间工作记 忆的影响。方法 选取2017 年6 月至2018 年1 月来源于苏州市广济医院、苏州市社会福利总院、太仓市 精神卫生中心、南充市第六人民医院四家精神专科医院的38 例住院精神分裂症伴TD 患者，随机分为试 验组（21 例）和对照组（17 例）。研究期间，两组患者均接受常规药物治疗，试验组予以tDCS 治疗，采用的 电流为2 mA，刺激部位为左侧背外侧前额叶皮质及对侧眶上缘；对照组相应地予以伪tDCS 治疗。在基 线期、治疗15 次结束后及2 周后进行随访，采用剑桥神经心理自动化成套测试（CANTAB）中的空间工作 记忆（SWM）模块分别对两组患者进行认知测评。结果 在完成15 次治疗后，试验组SWM 指标分析中 的总错误数［31.00（28.50，49.00）］、平均第一次响应时间（4 盒子）［3 289.500（1 871.750，5 018.000）ms］、 平均第一次响应时间（6 盒子）［2 862.500（2 128.500，4 672.250）ms］、平均第一次响应时间（8 盒子） ［3 328.500（2 611.250，5 120.750）ms］与对照组比较，差异无统计学意义（P＞ 0.05）；试验组SWM 指标分 析中的策略分［19.00（17.00，20.00）］低于对照组［21.00（19.50，23.00）］，差异有统计学意义（P ＜ 0.05）。 在2 周后的随访中，两组的SWM 各指标比较，差异均无统计学意义（P＞ 0.05）。结论 tDCS 可能对精神 分裂症患者使用策略的能力有即刻改善效应。     

Safety and feasibility of laparoscopic living donor right hepatectomy for adult liver transplantation: a meta-analysis

BackgroundLaparoscopic living donor right hepatectomy (LDRH) was a controversial topic due to its unknown safety and feasibility.MethodsPubMed, EMBASE and Cochrane Library databases were searched for studies comparing LDRH with open living donor right hepatectomy (ODRH), which were published between the date of database establishment and June 2020. Revman5.3 was used for statistical analysis.ResultsFourteen studies were included. For the donors, there was no significant difference in warm ischemic time, hospital stay, graft weight, hepatic arterial anomalies (HAA), hepatic vein anomalies (HVA), portal vein anomalies (PVA), biliary anomalies, bleeding, wound infection, severe complication rate and readmission rate. The estimated blood loss, incidence of complication, intra-abdominal fluid rate in the LDRH group were significantly lower than those in the ODRH group, while the operation time, time to remove liver in the LDRH group were significantly higher than those in the ODRH group. For the recipients, there was no significant difference in complication rate, bleeding, HAA, PVA, biliary anomalies, graft failure and mortality. The HVA rate in the LDRH group was significantly higher than that in the ODRH group.ConclusionLDRH is safe and feasible for adult living donor liver transplantation compared with ODRH and it can reduce intraoperative bleeding and postoperative complication in donors, which requires further verification by more multi-center comparative studies with large sample and high quality.