Tocilizumab en el tratamiento del rechazo humoral crónico activo resistente a terapia estándar

IntroductionThere is no consensus on the most appropriate treatment for chronic active antibody-mediated rejection (cAMR). Recent studies suggest that treatment with tocilizumab (TCZ) may stabilize graft function, decrease the intensity of donor-specific HLA antibodies (DSAs) and reduce inflammation of microcirculation.Patients and methodsObservational study with renal allograft recipients diagnosed with cAMR (n = 5) who had not submitted a response to traditional treatment based on the combination of plasma replacements, immunoglobulins, and rituximab. Patients were told to be treated with TCZ as compassionate use in six doses per month (8 mg/kg/month). Renal function, proteinuria, and the intensity of DSAs were monitored during follow-up.ResultsFive patients, average age 60 ± 13 years, three male and two retrasplants (cPRA average 55%) with preformed DSAs. Treatment with TCZ was initiated within 47 ± 52 days of biopsy. In two cases treatment was discontinued after the first dose, by severe bicitopenia with cytomegalovirus viremia and by graft failure, respectively. In the three patients who completed treatment, no stability of renal function (serum creatinine from 1.73 ± 0.70 to 2.04 ± 0.52 mg/dL, e-FGR 4 6 ± 15 to 36 ± 16 mL/min), showed increased proteinuria (3.2 ± 4.0 to 6.9 ± 11.0 g/g) and the intensity of DSAs maintain stable. No changes were observed in the degree of inflammation of microcirculation (g + pt 4.2 ± 0.8 vs. 4.3 ± 1.0) or in the degree of transplant glomerulopathy (cg 1.2 ± 0.4 vs. 1.8 ± 1.0).ConclusionsTCZ therapy does not appear to be effective in modifying the natural history of chronic active antibody-mediated rejection, does not improve the degree of inflammation of microcirculation and does not reduces the intensity of DSAs.     

主动脉出口血压对左心室血流特性的影响

采用Mimics对心脏进行三维重构，用3-matic进行模型优化以及模型误差分析，对左心室室壁运动做速度分布假设，基于UDF宏文件对左心室室壁运动编写程序，将血液视为非牛顿流体，采用动网格技术研究不同血压对左心室血液流动的影响。模拟发现当左心室收缩时，压力梯度明显，内部压力减小。当左心室舒张时，内部压力逐渐增高。二尖瓣口处的速率先增大后减小。血压升高，左心室内剪切应力持续增大，极易破坏红细胞结构，产生溶血现象，导致心脏功能紊乱。     

Bayesian consensus clustering for multivariate longitudinal data

In clinical and epidemiological studies, there is a growing interest in studying the heterogeneity among patients based on longitudinal characteristics to identify subtypes of the study population. Compared to clustering a single longitudinal marker, simultaneously clustering multiple longitudinal markers allow additional information to be incorporated into the clustering process, which reveals co-existing longitudinal patterns and generates deeper biological insight. In the current study, we propose a Bayesian consensus clustering (BCC) model for multivariate longitudinal data. Instead of arriving at a single overall clustering, the proposed model allows each marker to follow marker-specific local clustering and these local clusterings are aggregated to find a global (consensus) clustering. To estimate the posterior distribution of model parameters, a Gibbs sampling algorithm is proposed. We apply our proposed model to the primary biliary cirrhosis study to identify patient subtypes that may be associated with their prognosis. We also perform simulation studies to compare the clustering performance between the proposed model and existing models under several scenarios. The results demonstrate that the proposed BCC model serves as a useful tool for clustering multivariate longitudinal data.     

衰减伪影对冠心病患者门控心肌灌注显像图像质量及灌注结果的影响

目的探讨衰减伪影对冠心病患者门控心肌灌注显像(GMPI)图像质量及灌注结果的影响。资料与方法回顾性分析2020年3月—2021年3月在郑州大学第一附属医院核医学科经冠状动脉造影证实且于造影前后1周行GMPI的99例冠心病患者的图像,定性及半定量分析衰减校正前后GMPI图像结果,比较衰减校正前后左心室各壁段平均放射性计数及灌注结果的差异,进一步分析衰减校正前后灌注结果不一致部分的受检者的节段性室壁运动及增厚情况。结果与衰减校正前比较,衰减校正后左心室间隔、下后壁及侧壁的平均放射性计数较高(Z=-7.302、-8.014、-3.991,P均<0.001),心尖部较低(Z=-8.021,P<0.001)。其中女性衰减校正后前壁平均放射性计数减低(Z=-2.314,P=0.021)。男性衰减校正前后下后壁放射性计数差值明显高于女性(t=-8.408,P<0.05)。衰减校正后44%(44/99)的左前降支及37%(37/99)的右冠状动脉分支供血区域显像结果发生改变,结合超声心动图及GMPI结果显示其中85%(35/41)的左前降支及81%(29/36)的右冠状动脉分支供血区域室壁运动及室壁增厚率均正常。结论衰减伪影对GMPI的图像质量和灌注结果有较大影响,结合室壁运动和增厚情况等有助于鉴别衰减伪影,提高诊断准确度与特异度。     

Prolyl and lysyl hydroxylases in collagen synthesis

Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra‐ and extracellular modifications are needed to make functional collagen molecules, intracellular post‐translational modifications of proline and lysine residues having key roles in this. In this article, we provide a review on the enzymes responsible for the proline and lysine modifications, that is collagen prolyl 4‐hydroxylases, 3‐hydroxylases and lysyl hydroxylases, and discuss their biological functions and involvement in diseases.     

PCI术后病人的体力活动水平及其影响因素分析研究

目的:探讨经皮冠状动脉介入(PCI)术后病人的体力活动水平及其影响因素。方法:选择常州市三级甲等综合医院心内科接受PCI治疗的冠心病病人,收集资料,分析PCI术后冠心病病人体力活动动机、体力活动和自我效能现状;冠心病病人自我效能、体力活动动机与体力活动的相关性,并分析影响PCI术后病人体力活动水平的相关危险因素。结果:共发放调查问卷400份,回收400份,有效率为94.75%(379/400);379例冠心病病人术后每周体力活动为(3570.85±314.19)MET-min,以低、中强度为主;冠心病病人术后自我效能总分、体力活动动机总分与体力活动呈正相关(P<0.05);体质指数(BMI)、PCI次数≥2次、年龄、PCI支架数量≥3枚、自我效能、体力活动动机是影响PCI术后冠心病病人体力活动水平的高危因素(OR>1且P<0.05)。结论:PCI术后病人体力活动水平处于较低的水平,PCI次数、BMI、年龄、PCI支架数量、自我效能、体力活动动机是影响PCI术后冠心病病人体力活动水平的高危因素,临床需针对各高危因素制定相应的干预措施,提高病人体力活动水平。     

Atrial fibrillation after cardiac surgery: A systematic review and meta-analysis

ObjectiveNew-onset postoperative atrial fibrillation (POAF) after cardiac surgery is common, with rates up to 60%. POAF has been associated with early and late stroke, but its association with other cardiovascular outcomes is less known. The objective was to perform a meta-analysis of the studies reporting the association of POAF with perioperative and long-term outcomes in patients with cardiac surgery.MethodsWe performed a systematic review and a meta-analysis of studies that presented outcomes for cardiac surgery on the basis of the presence or absence of POAF. MEDLINE, EMBASE, and the Cochrane Library were assessed; 57 studies (246,340 patients) were selected. Perioperative mortality was the primary outcome. Inverse variance method and random model were performed. Leave-one-out analysis, subgroup analyses, and metaregression were conducted.ResultsPOAF was associated with perioperative mortality (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.58-2.33), perioperative stroke (OR, 2.17; 95% CI, 1.90-2.49), perioperative myocardial infarction (OR, 1.28; 95% CI, 1.06-1.54), perioperative acute renal failure (OR, 2.74; 95% CI, 2.42-3.11), hospital (standardized mean difference, 0.80; 95% CI, 0.53-1.07) and intensive care unit stay (standardized mean difference, 0.55; 95% CI, 0.24-0.86), long-term mortality (incidence rate ratio [IRR], 1.54; 95% CI, 1.40-1.69), long-term stroke (IRR, 1.33; 95% CI, 1.21-1.46), and longstanding persistent atrial fibrillation (IRR, 4.73; 95% CI, 3.36-6.66).ConclusionsThe results suggest that POAF after cardiac surgery is associated with an increased occurrence of most short- and long-term cardiovascular adverse events. However, the causality of this association remains to be established.     

我国家庭医生签约服务政策执行的制约因素与优化路径：基于史密斯政策执行过程模型

深化家庭医生签约服务是深化医药卫生体制改革、强化基层医疗卫生服务、实现"健康中国"战略目标的重要选择，也是当前更好维护人民群众健康的重要途径。为有效推进签约服务工作，国家陆续推出各项政策，全国各地也在积极进行实践探索，成效明显。但是，签约服务仍面临诸多问题，其中"执行难"是签约服务深度推进的一大困境。通过史密斯政策执行过程模型，结合签约服务政策执行过程，发现签约服务仍存在法治性不足、政策执行人员水平不高、激励不足、政策环境影响等诸多制约因素。因此，需要从法律和制度方面进行顶层设计、提升执行人员素质和职业认同、建立医患互信、优化政策执行环境等角度进行政策创新，探索家庭医生签约服务可持续发展的路径。     

Deepm5C: A deep-learning-based hybrid framework for identifying human RNA N5-methylcytosine sites using a stacking strategy

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