骨肉瘤差异表达基因的生物信息学分析及关键基因筛选

目的筛选成骨型骨肉瘤与正常成骨细胞的差异表达基因, 寻找成骨型骨肉瘤发生、发展的关键基因。方法从Gene Expression Omnibus(GEO)数据库获得正常成骨细胞和骨肉瘤组织的基因表达数据集GSE33382, 采用R语言的limma包筛选正常成骨细胞和成骨型骨肉瘤的差异表达基因, 对差异表达基因进行京都基因与基因组百科全书(KEGG)通路富集分析。采用String数据库构建蛋白交互网络, 应用Cytoscape软件的分子复合物检测(MCODE)插件筛选互作网络中的网络模块, 应用Cytoscape软件中的BiNGO模块对MCODE筛选得到的前3个主要模块所包含的差异表达基因进行基因本体(GO)富集分析。采用MCC算法筛选蛋白互作网络中前10个关键基因。从GEO数据库获得骨肉瘤的基因表达和生存数据集GSE39055, 采用Kaplan-Meier法进行生存分析。选取2005年1月至2015年12月福建医科大学附属第一医院收治的48例成骨型骨肉瘤患者的资料进行验证, 采用免疫组化法测定骨肉瘤组织中STC2蛋白的表达, 结合患者的临床资料进行生存分析。结果从GSE33382数据集...     

外周血单个核细胞内人类免疫缺陷病毒DNA和RNA定量对病毒转录活性的区分

目的基于人类免疫缺陷病毒Ⅰ型(HIV-1)感染者外周血单个核细胞(PBMCs)中HIV-1总DNA和RNA定量检测结果对感染细胞内病毒的转录活性进行区分。方法采集2017年10月至2018年12月于哈尔滨医科大学附属第四医院感染科就诊的HIV-1感染者血液样本,分离PBMCs细胞,采用PCR荧光探针法对PBMCs细胞内HIV-1总DNA和RNA进行定量检测,并计算两者比值(Ratio)。根据Ratio值筛选出HIV-1转录活跃组样本和相对非活跃组样本,另外选择健康人PBMCs样本作为对照组。对3组样本进行基因转录组表达谱检测以及人口特征差异性检验,并对基因表达谱检测结果进行主成分分析以验证对3组样本病毒转录活性区分的准确性。结果从60例感染HIV-1患者的PBMCs样本中筛选出HIV-1转录活跃组样本(10例)和相对非活跃组样本(11例),另外选择6例健康人PBMCs样本作为对照组。其中转录活跃组样本Ratio值为165.2~738.93,平均为(339.27±189.68);相对非活跃组Ratio值为4.67~42.39,平均为(17.65±11.78)。转录活跃组和相对非活跃组样本间的CD4+T细胞计数(P=0.049)和Ratio值(P<0.001)差异均具有统计学意义;3组样本年龄(P=0.989)和性别(P=0.650)分布差异无统计学意义。对3组样本的PBMCs基因表达谱主成分分析结果显示:对照组与HIV-1感染者(包括转录活跃组和相对非活跃组)间区分明显。转录活跃组和相对非活跃组间有部分样本重合,同时结果也显示当HIV-1感染者的CD4+T淋巴细胞计数与健康人无显著差异时,其细胞内的基因表达与健康人接近。结论基于HIV-1总DNA和RNA定量检测结果及两者间比值可以较好地区分PBMCs内病毒转录活性。HIV-1感染细胞内部病毒的不同转录激活状况可导致其基因表达谱的异质性。     

Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The anti liver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the anti hepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an anti hepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an anti hepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group".     

盐酸利托君治疗晚期先兆流产保胎患者的临床疗效及不良反应发生率分析

目的分析盐酸利托君治疗晚期先兆流产保胎患者的临床疗效及不良反应发生率。方法选取2019年6—12月本院收治的行硫酸镁保胎治疗的35例晚期先兆流产患者作为对照组,另选取2020年1—7月本院收治的行盐酸利托君保胎治疗的35例晚期先兆流产患者作为研究组,比较两组治疗情况、保胎成功率、不良反应发生率、新生儿Apgar评分。结果研究组宫缩消失时间、止血时间、腹痛缓解时间、腰痛缓解时间、起效时间均短于对照组,且延长孕期时间长于对照组(P<0.05);研究组保胎成功33例(94.29%),对照组保胎成功26例(74.29%),差异有统计学意义(P<0.05);研究组不良反应发生率为22.86%,低于对照组的20.00%,但差异无统计学意义;研究组Apgar评分高于对照组,差异有统计学意义(P<0.05)。结论盐酸利托君治疗晚期先兆流产保胎患者,可尽快改善患者临床症状,有助于提高保胎成功率,改善母婴结局,且无明显不良症状,安全性较高,值得临床推广。     

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.     

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。