麦芽4个化学部位通过多巴胺D2受体对产后缺乳模型大鼠催乳作用研究

目的基于多巴胺D2受体(DRD2),考察小剂量麦芽4个化学部位的催乳作用,初步探讨小剂量麦芽生物碱对产后缺乳模型大鼠泌乳素(PRL)分泌的调节机制。方法采用ig甲磺酸溴隐亭方法制备缺乳大鼠模型,造模成功后,各给药组均ig给予相应的药物,应用ELISA法检测各组大鼠血清PRL、雌二醇(E_2)、孕酮(P)水平;HE染色观察各组大鼠乳腺组织病理改变;采用实时荧光定量PCR(qRT-PCR)法检测各组大鼠脑垂体中泌乳素受体及DRD2 mRNA表达。结果与对照组比较,模型组大鼠血清中PRL、P及E_2水平、脑垂体PRL mRNA表达水平显著降低;脑垂体DRD2 mRNA表达水平显著升高。与模型组比较,麦芽总生物碱组大鼠乳腺小叶体积明显增加,导管明显扩张,且导管及腺泡内含有大量乳汁。麦芽总生物碱明显增加模型大鼠血清中PRL、P、E_2水平及脑垂体PRL mRNA表达水平,降低脑垂体DRD2 mRNA表达水平。结论麦芽催乳的主要药效物质为总生物碱,其作用机制可能与促进PRL分泌,增加脑垂体PRL受体、降低DRD2 mRNA表达水平有关。     

Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study

ABSTRACT

Objectives: Limited evidence has suggested that cefoperazone-sulbactam causes coagulation disorders and bleeding.

Methods: The authors conducted a retrospective study to compare patients receiving cefoperazone-sulbactam versus those treated with cefoperazone-tazobactam or ceftazidime. Propensity-score matching was used to explore whether treatment with cefoperazone-sulbactam increased the risk of prothrombin time (PT) prolongation, coagulation disorders, and bleeding, or decreased platelets (PLT).

Results: The cohort included 23,242 patients. Among patients receiving cefoperazone-sulbactam, the risk of PT prolongation, coagulation disorders, decreased PLT, and bleeding was 5.3%, 9.2%, 15.7%, and 4.2%, respectively. Propensity-score matching analyses suggested that cefoperazone-sulbactam increased the risk of PT prolongation (aOR 2.26, 95% CI 1.61–3.18), coagulation disorders (aOR 1.81, 95% CI 1.43–2.30), and decreased PLT (aOR 1.46, 95% CI 1.25–1.72), but not increase bleeding (aOR 1.05, 95% CI 0.79–1.40) compared with ceftazidime. Patients receiving cefoperazone-sulbactam had higher risk of PT prolongation (aOR 1.53, 95% CI 1.11–2.10), coagulation disorders (aOR 1.53, 95% CI 1.21–1.95), but not decreased PLT (aOR 0.93, 95% CI 0.81–1.07) or bleeding (aOR 1.11, 95% CI 0.87–1.42), compared with those receiving cefoperazone-tazobactam.

Conclusion: Cefoperazone-sulbactam may be associated with a higher risk of PT prolongation and coagulation disorders compared with cefoperazone-tazobactam and ceftazidime.     

左金丸抗幽门螺杆菌感染的分子网络调控机制研究

目的基于网络药理学和生物信息学方法探究左金丸抗幽门螺杆菌(Hp)感染的分子网络调控机制。方法通过中药系统药理学数据库和分析平台(TCMSP)检索左金丸化学成分,筛选并预测其入血活性成分和作用靶点,检索疾病数据库中与Hp感染相关的作用靶点,构建左金丸成分靶点与疾病靶点的交互网络,获得左金丸抗Hp的特征性基因;通过DAVID6.8数据库对上述特征性基因进行GO功能富集和KEGG通路富集分析;利用Cytohubba筛选出左金丸抗Hp感染的关键靶点。结果通过TCMSP筛选、预测得到左金丸32个入血活性成分和197个作用靶点。GO分析共得到199条富集结果,其中生物过程包含炎症反应、RNA信号转录、信号传导等152条,细胞组分包含细胞核、细胞外基质、蛋白复合物等19条,分子功能包含细胞因子活性、DNA结合、ATP结合等28条。KEGG分析结果显示,Jak-STAT信号通路、T细胞受体信号通路、细胞周期信号通路、Wnt信号通路等65条通路与左金丸抗Hp感染密切相关。经Cytohubba筛选得到CXCL8、IL10、IL4、VEGFA、MMP9等10个关键基因。结论左金丸抗Hp感染具有多成分、多靶点、多通路协同作用的特点,可为其活性成分研究和抗Hp药效及机制研究提供依据。     

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high‐risk Chinese individuals

Identification of deleterious variants in hereditary breast and ovarian cancer (HBOC) susceptibility genes allows for increased clinical surveillance and early detection, and could predict the response to poly (ADP‐ribose) polymerase (PARP) inhibitor in patients with advanced ovarian carcinomas. To determine the prevalence and clinical prediction factors for HBOC syndrome, 882 selected individuals underwent multigene panel testing for HBOC risk assessment during the period from January 2015 to March 2018. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) of individuals. Twenty‐six of 176 mutations could not be retrieved in related public databases and were considered to be novel. Among patients with ovarian cancer, 115 deleterious mutations were identified in 429 patients (48.6%) with significant enrichment for a family history of breast or ovarian cancer syndrome (P < .05). In the breast cancer subgroup, 31 deleterious mutations were identified in 261 patients. Besides BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%), the most frequently occurring genes, an additional 12 deleterious mutations (38.7%) were found in seven other susceptibility genes. Higher mutation incidence (57.9%) was observed in subjects with histories of breast and ovarian cancer. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of a multigene panel in carrying out risk assessment.     

Experimental animal models of pancreatic carcinogenesis and metastasis

Pancreatic cancer is a lethal disease characterized by early metastasis, local invasion, and resistance to conventional therapies. To understand its etiology and eventually make prevention of it possible and effective, appropriate carcinogenesis models will certainly help us understand the effects of environmental and genetic elements on pancreatic carcinogenesis. The development of new treatment strategies to control cancer metastasis is of immediate urgency. Fulfillment of this task relies on our knowledge of the cellular and molecular biology of pancreatic cancer metastasis and the availability of biologically and clinically relevant model systems. Many of the existing pancreatic cancer carcinogenesis and metastasis animal models are described in this review. The advantages and disadvantages of each model and their clinical implications are discussed, and special attention is focused on experimental therapeutic strategies targeting pancreatic cancer metastasis.     

肝肾胰联合移植手术的麻醉及围术期管理

目的探讨肝、肾、胰联合移植手术的麻醉及围术期管理方法。方法肝肾胰联合移植患者1例，行充分术前准备，改善肝功能，减轻尿毒症症状，控制血糖水平，使患者各脏器功能处于最佳状态。选用异氟烷、咪唑安定、芬太尼和维库溴铵行静脉吸入复合麻醉，维持合适麻醉深度和充分供氧。行桡动脉和颈内静脉穿刺置管，用于监测血压和维持静脉通道；选用食管超声多普勒行血流动力学监测；定时检测肝、肾功能指标、凝血参数、动脉血气、血糖浓度以及血、尿淀粉酶等生化参数，根据上述检测结果调整治疗。结果术中循环稳定，血气结果正常。术毕时血糖浓度较术前升高。患者肝脏及胰腺功能在术后1周恢复正常。肾脏功能恢复不良，予以二次肾移植术，两次手术期间行血液透析。肾功能于二次肾移植术后第3天恢复正常。目前患者各脏器功能正常。结论肝胰肾联合移植麻醉及管理的重点是充分术前准备，选择静吸复合麻醉，兼顾各脏器功能，维持血流动力学和内环境稳态的平衡。     

影响重型肝炎预后的因素分析

目的研究重型肝炎的各种预后因素的重要性。方法选择2000年1月至2004年12月我院收治的重型肝炎患者358例,分为好转治愈组和恶化死亡组,将两组的临床资料进行单因素和多因素分析。结果两组之间在凝血酶原活动度、肝性脑病、总胆红素和天冬氨酸氨基转移酶/丙氨酸氨基转移酶等方面有显著性差异(P<0.05)。结论凝血酶原活动度、肝性脑病、总胆红素和天冬氨酸氨基转移酶/丙氨酸氨基转移酶比值等可以作为判断重型肝炎预后的指标,对指导临床有一定价值。     

新生儿硬肿症脂质过氧化物变化的观察

为探讨脂质过氧化损伤及自由基在新生儿硬肿症发病机理中的作用，将观察对象分为疾病组和对照组，疾病组于入院时，对照组于出生后１周内取静脉血检测血浆脂质过氧化物及红细胞超氧化物歧化酶含量。     

脑前循环系统动脉瘤的外科治疗

本文报告113例脑前循环系统动脉管其中包括颈内动脉后交通动脉瘤75例.前交通动脉瘤17例,大脑中动脉瘤10例,人脑前动脉-胼周动脉瘤3例,颈内动脉-眼动脉瘤2例,颈内动脉海绵窦段动脉瘤1例.多发动脉瘤5例.共118个动脉瘤在显微镜下直视手术,动脉瘤直接夹闭术108例.孤立或包裹术5例:5例多发动脉瘤行同期手术3例,分期手术2例.术中发生动脉瘤破裂18次.Hunt和HessⅠ～Ⅱ级病人中有例行早期手术.全组术后死亡率为7.9%.着重讨论手术时机.术中动脉瘤破裂处理及多发动脉瘤的治疗.