Neuroendocrine,epigenetic, and intergenerational effects of general anesthetics

The progress of modern medicine would be impossible without the use of general anesthetics (GAs). Despite advancements in refining anesthesia approaches, the effects of GAs are not fully reversible upon GA withdrawal. Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly. Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research, but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects. The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents, which are far more extensively studied than any other species. Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated. Specifically, we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities (somatic effects), but also epigenetic reprogramming of germ cells (germ cell effects). The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring, who may be affected even at levels of anesthesia that are not harmful to the exposed parents. The large number of patients who require general anesthesia, the even larger number of their future unexposed offspring whose health may be affected, and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs. In this mini review, we discuss emerging experimental findings on neuroendocrine, epigenetic, and intergenerational effects of GAs.     

Association between de novo lipogenesis susceptibility genes and coronary artery disease

Background and aimsCoronary artery disease (CAD) is the principal cause of death in individuals with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to use genetic epidemiology to study the association between de novo lipogenesis (DNL), one of the major pathways leading to NAFLD, and CAD risk.Methods and resultsDNL susceptibility genes were used as instruments and selected using three approaches: 1) genes that are associated with both high serum triglycerides and low sex hormone-binding globulin, both downstream consequences of DNL (unbiased approach), 2) genes that have a known role in DNL (biased approach), and 3) genes that have been associated with serum fatty acids, used as a proxy of DNL. Gene-CAD effect estimates were retrieved from the meta-analysis of CARDIoGRAM and the UK Biobank (～76014 cases and ～264785 controls). Effect estimates were clustered using a fixed-effects meta-analysis. Twenty-two DNL susceptibility genes were identified by the unbiased approach, nine genes by the biased approach and seven genes were associated with plasma fatty acids. Clustering of genes selected in the unbiased and biased approach showed a statistically significant association with CAD (OR:1.016, 95%CI:1.012; 1.020 and OR:1.013, 95%CI:1.007; 1.020, respectively), while clustering of fatty acid genes did not (OR:1.004, 95%CI:0.996–1.011). Subsequent exclusion of potential influential outliers did reveal a statistically significant association (OR:1.009, 95%CI:1.000; 1.018).ConclusionsDNL susceptibility genes are associated with an increased risk of CAD. These findings suggest that DNL may be involved in the pathogenesis of CAD and favor further development of strategies that target NAFLD through DNL.     

对血清蛋白白球比值参考范围的修改及其临床应用

目的探讨血清蛋白白球比值(A／G)的参考范围和A／G在计算过程中产生的误差对临床应用的影响。方法①选取健康查体人员统计其A／G参考范围；②从理论上分析A／G计算误差的存在。结果①以统计结果的2s置信区间作为A／G的参考范围是1.1～2.2；②A／G计算值的误差会远大于相应总蛋白和白蛋白的测定误差。结论A／G较合适的参考范围为1.1～2.2,并且在临床应用中仍可根据实际情况降低其范围的下限。     

股骨转子间骨折GAMMA钉治疗临床分析

目的：评价GAMMA钉治疗股骨转子间骨折的效果。方法：对32例股骨转子间骨折采用GAMMA钉治疗。结果：经6～18月随访，所有病例均获骨性愈合，下肢功能及关节活动良好。其中1例为粉碎性骨折内固定后出现髋内翻，按X线评分标准90％病人满意。结论：GAMMA钉治疗股骨转子间骨折效果满意。     

伽玛刀治疗颅底良性脑膜瘤临床研究

目的探讨伽玛刀放射外科治疗良性颅底脑膜瘤中长期疗效和不良反应。方法选取了1998-2003年治疗的获得完全随访资料的颅底脑膜瘤患者166例,全组患者肿瘤体积0.42- 43.4cm3,平均(7.2±3.9)cm3,给予周边剂量平均(12.4±2.6)Gy,中心剂量平均(27.9±5.9)Gy,其中12例患者采用肿瘤体积分割二阶段治疗。对治疗前后的影像学改变、KPS评分和神经功能缺损评估。结果平均随访期为(55.4±18.2)个月(36-96个月)。总体控制率为95.2%(158/166);KPS评分得到显著提高,神经症状总体满意率为94.5%(157/166),主要副作用是放射性脑水肿11例(6.6%),有5例(3%)患者出现新的神经缺损。结论伽玛刀放射外科可以作为有手术禁忌或拒绝手术治疗体积较小脑膜瘤患者的首选性治疗,也可以作为颅底较大脑膜瘤开颅术后的辅助性治疗,能够较长期控制肿瘤复发,提高或保持患者的生存质量。     

星形胶质细胞瘤伽玛刀治疗的疗效与影响因素

目的分析星形胶质细胞瘤伽玛刀(γ-刀)治疗的疗效与影响因素.方法回顾性分析48例星形胶质细胞瘤病人的γ-刀治疗结果.以性别、有无普通放疗经过、有无化疗经过、边缘剂量、病灶的平均直径、病变的病理等级、影像学上有无相对较清楚的边界为治疗结果影响因素,判定标准以病灶缩小为有效,采用logistic回归模型,确定多因素条件下治疗结果的影响因素.结果有效32例(66.7%),logistic回归模型分析表明:病理等级和病灶平均直径为与肿瘤控制有关的影响因素.结论γ-刀对星形胶质细胞瘤的治疗有一定的意义.     

Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B

Abstract The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic, patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.     

伽玛刀治疗垂体大腺瘤临床分析(附30例报告)

目的 研究伽玛刀治疗垂体大腺瘤的效果及影响疗效的因素。方法 30例垂体大腺瘤病人用1．0T磁共振定位，Gamma-plan计划系统规划，等剂量曲线45％～60％(平均49．7％)，周边剂量12～35Gy(平均22.9Gy)，中心剂量24～70Gy(平均45．4Gy)．Leksell伽玛刀实施放射外科治疗。分析治疗后垂体大腺瘤病例，总结其疗效和影响疗效的因素。结果 随访12～60个月，平均28个月，肿瘤完全消失6例(20％)，肿瘤缩小19例(63．3％)，无变化5例(16．7％)；19／20(95．5％)功能性垂体腺瘤内分泌症状改善，临床症状好转，1例过早绝经(年龄36岁)；5／10(50％)无功能性垂体腺瘤体积缩小．症状改善。结论 伽玛刀对于垂体大腺瘤仍是一种有效的治疗方法，其疗神与腺瘤的举类型、体积、照射剂量、剂量体剂、MRI信号特征密切相姜。