肿瘤坏死因子-α-308基因对导管相关性脓毒症患者病情的影响

目的探究肿瘤坏死因子-α(Tumornecrosis factor-α,TNF-α)-308基因对导管相关性脓毒症(Catheter related sepsis,CRS)患者病情的影响,旨在为临床治疗CRS提供科学依据。方法选取2017年7月-2018年10月于浙江大学医学院附属杭州市第一人民医院接受治疗的86例CRS患者为研究对象,按照是否并发多器官功能障碍综合征将患者分为试验组和对照组,对照组共48例,未并发多器官功能障碍综合征,试验组共38例,并发多器官功能障碍综合征,分析两组患者TNF-α-308基因多态性差异,使用多因素Logistic回归分析CRS患者并发多器官功能障碍综合征的危险因素。结果试验组GA基因型频率34.21%、AA基因型频率50.00%、高G等位基因频率18.42%均高于对照组,GG基因型频率52.63%、A等位基因频率28.95%均低于对照组,差异均具有统计学意义(P<0.05);多因素Logistic回归分析结果显示,低GG基因型频率、低G等位基因频率、高GA基因型频率、高AA基因型频率、高A等位基因频率是CRS患者并发多器官功能障碍综合征的危险因素(P<0.05)。结论TNF-α-308基因与CRS患者病情密切相关,GG基因型频率和G等位基因频率降低,GA基因型频率、AA基因型频率、A等位基因频率升高会加重患者的病情,增加多器官功能障碍综合征的发生风险,临床上应该加以重视。     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

依维莫司联合全反式维甲酸逆转急性早幼粒细胞白血病细胞耐药的研究

目的探讨依维莫司联合全反式维甲酸(简称维甲酸)逆转急性早幼粒细胞白血病(APL)细胞株NB4-R1耐药的作用。方法应用CD11b染色流式细胞术及硝基四唑氮蓝(NBT)还原实验检测两药联合应用对细胞分化的影响, 流式细胞术检测细胞周期情况, Annexin V/PI双染色检测细胞凋亡情况, 蛋白质印迹法检测自噬相关蛋白微管结合蛋白轻链3(LC3)、Beclin 1及早幼粒白血病-维甲酸受体融合蛋白(PML-RARα)、磷酸化核糖体S6激酶(P-P70S6K)、磷酸化4E结合蛋白1(P-4E-BP1) 等表达水平。结果与维甲酸组比较, 联用组能诱导耐药细胞株NB4-R1细胞的分化, 并将细胞增殖阻止在G ₁期而对细胞凋亡无明显影响。100 nmol/L依维莫司组、1μmol/L维甲酸组、联用组、对照组NB4-R1细胞培养48 h后分化百分率分别为(2.29±0.57)%、(17.06±2.65)%、(54.47±4.91)%、(2.54±0.53)%; 处于G ₁期的细胞百分率分别为(35.20±11.97)%、(33.54±6.25)%、(53.70±8.73)%、(27.40±6.01)%; 四组细胞凋亡细胞百分率分别为(2.30±0.14)%、(2.25±0.21)%、(2.40±0.28)%、(1.95±0.07)%。与维甲酸组比较, 联用组mTOR信号通路下游的P70S6K、4E-BP1分子磷酸化水平下降, LC3-II和Beclin 1的表达上调, 且能部分降解融合蛋白PML-RARα。 结论依维莫司联合维甲酸能诱导NB4-R1细胞分化, 且能阻滞细胞周期而不致细胞凋亡, 其机制可能与依维莫司联合维甲酸抑制mTOR信号通路激活自噬作用从而降解PML-RARα蛋白有关。     

Anatomical structures at risk using different approaches for sacrospinous ligament fixation

For 50 years now, sacrospinous ligament fixation (SSLF) has been used to treat pelvic organ prolapse consequent on altered integrity of the pelvic myofascial structures. It is usually performed vaginally, but it has recently been performed laparoscopically through either an anterior or a posterior approach, with the broad ligament as a landmark to differentiate the two. In the present study, these two laparoscopic approaches were assessed using Thiel-embalmed cadavers. The anterior and posterior approaches were compared in terms of the closest distance to anatomical structures at risk, including pelvic viscera, the obturator nerve, and vascular structures. The posterior approach was more often closer to the investigated vessels and the rectum. The obturator nerve and the ureter were close to both the anterior and posterior approaches. The urinary bladder was closer using the anterior approach. From an anatomical standpoint, therefore, the anterior laparoscopic approach for SSLF is more likely to cause injury to the urinary bladder, whereas the posterior approach is more prone to causing rectal and vessel injuries. This study illustrates, from a basic science perspective, the importance of combining fascia research, novel endoscopic or minimally invasive surgical exposures informed by anatomy, and contemporary trends in gynecology in order to improve patient outcomes. Clin. Anat. 33:522–529, 2020. © 2019 Wiley Periodicals, Inc.     

Report of a National Conference on Donation after Cardiac Death

A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care. This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues. When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States.     

Development of the New Lung Allocation System in the United States

This article reviews the development of the new U.S. lung allocation system that took effect in spring 2005. In 1998, the Health Resources and Services Administration of the U.S. Department of Health and Human Services published the Organ Procurement and Transplantation Network (OPTN) Final Rule. Under the rule, which became effective in 2000, the OPTN had to demonstrate that existing allocation policies met certain conditions or change the policies to meet a range of criteria, including broader geographic sharing of organs, reducing the use of waiting time as an allocation criterion and creating equitable organ allocation systems using objective medical criteria and medical urgency to allocate donor organs for transplant. This mandate resulted in reviews of all organ allocation policies, and led to the creation of the Lung Allocation Subcommittee of the OPTN Thoracic Organ Transplantation Committee. This paper reviews the deliberations of the Subcommittee in identifying priorities for a new lung allocation system, the analyses undertaken by the OPTN and the Scientific Registry for Transplant Recipients and the evolution of a new lung allocation system that ranks candidates for lungs based on a Lung Allocation Score, incorporating waiting list and posttransplant survival probabilities.     

A Comparison Between Recipients Receiving Matched Kidney and Those Receiving Mismatched Kidney from the Same Cadaver Donor

The optimal allocation of cadaveric kidneys for transplantation with reference to human leukocyte antigen (HLA) match and sharing these organs to a distant center remains controversial. The current analysis was performed using the United Network for Organ Sharing (UNOS) database for cadaveric kidney transplants (Tx) between 1988 and 1997. The graft survivals of zero-mismatch (matched) kidneys with the mate (mismatched) kidneys were compared. There were 2385 donors and 4770 Tx. Significant differences in recipient demographics between matched and mismatched Tx were: fewer African-American race (AA) in the matched group (9.0% vs. 21.9%), higher number of previous Tx (25.5% vs. 14.8%) and elevated mean cold ischemia time (24.0 vs. 22.2 h). Post-Tx dialysis requirements were similar (22.8% vs. 24.1%, p = 0.62) and matched kidneys had to travel more distance (920 vs. 232 miles). Using a Cox model, the matched group had a decreased relative hazard of graft failure of 23.0% (p = 0.0002) or 35% (p < 0.0001) with and without censoring for death. There was significantly better graft survival in the matched recipients in all pairs except AA (matched) and non-AA (mismatched). For older donors (> or = 50 years, n = 1508), the matched grafts survival was marginally significant (p =0.05). Matched kidneys have improved survival compared with the mismatched kidneys despite the longer distance traveled. The benefit of mismatched transplants was predominantly seen in non-AA.     

谷氨酰胺肠外营养对创伤后多器官衰竭患者的营养作用

目的探讨补充谷氨酰胺(Gln)的肠外营养在严重创伤后多器官衰竭(MOF)患者治疗中的作用。方法采用随机对照方法,将60例MOF患者分为Gln组和对照组,每组30例。Gln组给予Gln1.5ml/kg联合常规治疗[热量104～125kJ/(kg·d),其中脂肪供热40%,氮供给量为0.2～0.25g/(kg·d)的完全胃肠外营养(TPN)支持];对照组仅给予常规治疗,连续7d。对照分析营养指标、免疫指标、并发症及临床结果。结果所有患者营养指标(血清白蛋白、前清蛋白、转铁蛋白)和免疫指标(IgG、IgA、IgM)明显减低,处于负氮平衡。第8天时,Gln组营养指标明显高于治疗前及对照组(P<0.05),负氮平衡得到纠正(P<0.05),而对照组仅血清白蛋白、转铁蛋白较治疗前增高(P<0.05),仍处于负氮平衡(P>0.05)。Gln组免疫指标明显高于治疗前及对照组(P<0.01),而对照组仅IgG高于治疗前(P<0.01)。对照组14例(46.7%)出现了血清胆红素、丙氨酸转氨酶和血糖的升高,而Gln组仅4例(13.3%)增高(P<0.05),至14d时对照组病死率为36.7%,而Gln组仅为10%,两者相比差异有显著性(P<0.05)。结论应用Gln的肠外营养能够明显纠正MOF患者的营养代谢障碍,纠正负氮平衡,增强免疫功能,降低并发症及病死率。