Aging attenuates the ovarian circadian rhythm

ObjectiveTo study the effect of aging on ovarian circadian rhythm.DesignHuman and animal study.SettingUniversity hospital and research laboratory.Patients/animalsHuman granulosa cells were obtained by follicular aspiration from women undergoing in vitro fertilization (IVF), and ovarian and liver tissues were obtained from female C57BL/6 mice.Intervention(s)None.Main outcome measure(s)Expression of circadian genes in young and older human granulosa cells and circadian rhythm in ovaries and livers of young and older mice.Result(s)All examined circadian clock genes in human granulosa cells showed a downward trend in expression with aging, and their mRNA expression levels were negatively correlated with age (P < 0.05). Older patients (≥ 40 years of age) had significantly reduced serum anti-Müllerian hormone (AMH) levels. Except for Rev-erbα, all other examined circadian clock genes were positively correlated with the level of AMH (P < 0.05). The circadian rhythm in the ovaries of older mice (8 months) was changed significantly relative to that in ovaries of young mice (12 weeks), although the circadian rhythm in the livers of older mice was basically consistent with that of young mice.Conclusion(s)Lower ovarian reserve in older women is partially due to ovarian circadian dysrhythmia as a result of aging.Electronic supplementary materialThe online version of this article (10.1007/s10815-020-01943-y) contains supplementary material, which is available to authorized users.     

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。     

针刺治疗慢性疼痛的功能磁共振研究述评＊

目的基于针刺治疗慢性疼痛的功能磁共振(Functional magnetic resonance imaging,fMRI)文献进行述评,为针刺治疗慢性疼痛的机制研究提供思路和借鉴。方法对近10年针刺治疗慢性疼痛的fMRI研究进行回顾,依据病种选择、样本量计算、试验设计、研究结果四方面内容进行述评,分析并总结当前研究现状。结果偏头痛、膝骨关节炎和下腰痛是目前研究中涉及频次最高的3个病种。受试者的疾病亚型、年龄段、利手习惯及fMRI禁忌症在研究中基本都保证了一致性和规范性。但多数研究仍存在样本量计算方式不明确的问题。对照组设置主要包括标准对照、无效对照和安慰对照。针刺效应因素在各研究间存在较大差异。研究中结局指标包括疾病特异性量表、疼痛评分及心理、精神状态的评估。fMRI设计以静息态和单一任务态设计为主,多任务fMRI研究相对较少。研究证实针刺可调节疼痛处理网络的功能连接,有效建立心理物理疼痛稳态。结论运用fMRI探讨针刺治疗慢性疼痛作用机制的研究成果丰硕,未来可通过扩大病种的选择,完善质量控制,关注针刺效应影响因素,丰富数据处理手段,借鉴多学科任务设计方式等方式,促进针刺疗慢性疼痛机制研究的进一步发展。     

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.     

基于网络药理学和临床试验探讨前列消汤对ⅢA型前列腺炎IL-17与Foxp3表达影响研究＊

目的 基于网络药理学进行前列消汤治疗慢性前列腺炎的预测，同时采用临床试验进行验证，证明前列消汤对ⅢA型前列腺炎患者的临床疗效及对前列腺液（Expressed Prostatic Secretion， EPS）中白细胞介素17（interleukin 17， IL-17）及双头叉转录因子p3（Forkhead box p3， Foxp3）表达的影响。方法 采用网络信息学分析方法，筛选出前列消汤在ⅢA型前列腺炎治疗中发挥疗效的主要作用靶点，采用临床随机非盲法，将符合纳入标准的80例ⅢA型前列腺炎湿热下注证患者随机分为观察组和对照组各40例，观察组口服自拟前列消汤，对照组口服银花泌炎灵片。观察治疗前后两组的症状及证候评分情况、前列腺按摩液以及其IL17、Foxp3表达的差异。取40例正常男性前列腺液为正常对照。结果 网络药理学分析结果提示IL17信号通路为前列消汤治疗慢性前列腺炎的重要通路之一，临床试验结果提示经治疗后观察组有效率达89.19%，较对照组的73.68%为优（P < 0.05）。两组患者服药后的临床表现、前列腺按摩液WBC、症状及证候评分均存在明显改善。观察组和对照组IL-17水平较治疗前下降，Foxp3表达较治疗前升高（P < 0.05）。观察组对降低IL-17表达和提升Foxp3表达上较对照组差异更大（P < 0.05）。观察组治疗后与正常组IL-17和Foxp3水平比较差异较小（P > 0.05）。结论 网络药理学能一定程度上预测中药作用于疾病的相应靶点，前列消汤对ⅢA型前列腺炎湿热下注证患者的临床症状有明显改善作用，并能降低IL-17表达，对Foxp3表达有提升作用，在总有效率和对细胞因子的影响上较银花泌炎灵片组明显。     

Fibroblast growth factor receptors in cancer: genetic alterations,diagnostics, therapeutic targets and mechanisms of resistance

Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5–10% of all human cancers, although this frequency increases to 10–30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment of FGFR3-mutated urothelial carcinoma and FGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.Subject terms: Cancer, Cancer