Metastatic stage vs complications at radical nephrectomy with inferior vena cava thrombectomy

BackgroundTo investigate perioperative complication rates at radical nephrectomy (RN) according to inferior vena cava thrombectomy (IVC-T) status and stage (metastatic vs non-metastatic) within kidney cancer patients.Materials and methodsWe ascertained perioperative complication rates within the National Inpatient Sample database (2016–2019). First, log-link linear Generalized Estimating Equation function (GEE) regression models (adjusted for hospital clustering and weighted for discharge disposition) tested complication rates in IVC-T patients, according to metastatic stage. Subsequently, a subgroup analysis relied on RN patients with or without IVC-T. Here, multivariable logistic regression models tested complication rates in RN patients according to IVC-T status, after propensity score matching including metastatic stage.ResultsOf 26,299 RN patients, 461 (2%) patients underwent IVC-T. Of those, 252 (55%) were non-metastatic vs 209 (45%) were metastatic. Rates of acute kidney injury (AKI), transfusion, cardiac, thromboembolic and other medical complications in non-metastatic vs metastatic patients were 40 vs 40%, 25 vs 22%, 21 vs 23%, 19 vs 14% and 38 vs 40%, respectively (all p ≥ 0.2). Metastatic stage in IVC-T patients did not predict differences in complications in log-link linear GEE regression models (all p > 0.1). However, in logistic regression models with propensity score matching, relying on the overall cohort of RN patients, IVC-T status was associated with higher complication rates (all p < 0.001): AKI (Odds ratio [OR]:2.60; 95%-CI [95%-Confidence interval: 1.97–3.44), transfusions (OR:2.40; 95%-CI: 1.72–3.36), cardiac (OR:2.27; 95%-CI: 1.49–3.47), thromboembolic (OR:9.07; 95%-CI: 5.21–16.58) and other medical complications (OR:2.01; 95%-CI: 1.52–2.66).ConclusionsThe current analyses indicate that presence of concomitant IVC-T is associated with higher complication rate at RN. Conversely, metastatic stage has no effect on recorded complication rates.     

糖尿病视网膜病变中视网膜内皮细胞功能障碍的研究进展北大核心

视网膜内皮细胞(REC)是参与糖尿病视网膜病变和许多眼部疾病的主要细胞类型之一。视网膜微血管系统有助于血-视网膜屏障的维持,这对正常的视功能至关重要。REC的改变在视网膜疾病的发生发展中起着关键作用。高血糖是糖尿病微血管损伤的重要原因,通过不同的机制导致REC功能障碍,包括向衰老表型改变、迁移和增殖能力增强、炎性凋亡等,最终导致无细胞毛细血管及病理性新生血管形成。本文对糖尿病视网膜病变中REC的功能障碍作一综述。     

携带同源重组修复相关基因突变的消化道肿瘤的临床特点

目的:探讨消化道肿瘤中同源重组修复相关基因(homologous recombination repair related gene，HRR)突变的发生情况及临床意义。方法:共92例消化道肿瘤患者，79例患者进行了血液标本HRR检测，53例患者进行了组织标本HRR检测，40例患者同时行血液和组织的HRR基因检测，收集患者基因检测结果及临床相关资料。结果:在79例患者血液标本检测中发现10例（12.6%）有临床意义HRR突变，在53例患者组织标本检测中发现9例（17.0%）有临床意义HRR突变。40例同时行血液和组织的HRR基因检测患者中常见的有临床意义HRR突变为CDK12突变4例（10.0%）、ATM突变3例（7.5%）、BRCA1突变2例（5.0%）。13例有临床意义HRR突变患者中常见共存突变为TP53突变10例（76.9%）、APC突变5例（38.5%）、PIK3CA突变4例（30.8%）。40例患者中13例患者血液和/或组织中有临床意义HRR突变，27例患者血液和组织中均无任何临床意义HRR突变且两组相比，有临床意义HRR突变组肿瘤突变负荷（tumor mutational burden，TMB）为6.17(2.24～11.52)，而未携带HRR突变组TMB为0.4(0～3.75)，差异有统计学意义（P＜0.05）。40例患者组织检测中7例HRR有临床意义的突变，33例无HRR突变，血液检测中10例HRR有临床意义的突变，30例无HRR突变，一致性检验的Kappa值为0.333（P=0.031）。结论:携带有临床意义HRR突变的消化道肿瘤患者TMB更高，血液和组织检测HRR突变有较好的一致性。     

丹参酮生物合成相关SmERF108转录因子的鉴定及其靶基因分析＊

目的 鉴定与丹参酮合成相关转录因子AP2/ERF家族中SmERF108转录因子，并分析转录因子SmERF108的靶基因。方法 利用生物信息学在线分析平台如NCBI、PFAM等分析SmERF108的序列特征；MEGA-X软件用于构建SmERF108与不同功能转录因子的系统进化树；拟南芥原生质体转化法鉴定SmERF108蛋白的亚细胞定位；通过实时荧光定量PCR（Real-time qPCR）对SmERF108基因在丹参不同器官和组织差异表达进行检测；利用酵母体系对SmERF108的转录激活活性进行探究并用酵母单杂技术确定其靶基因。结果 SmERF108具有典型的AP2/ERF保守结构域，属于ERF-B3亚组，系统进化树和保守基序分析显示SmERF108与丹参中SmERF128、青蒿中AaERF2亲缘关系较近且保守基序分布一致；亚细胞定位显示SmERF108蛋白定位于细胞核；SmERF108基因在周皮中表达最高，且呈现周皮（R1）>韧皮部（R2）>木质部（R3）的规律；酵母自激活验证SmERF108具有转录激活活性，同时酵母单杂交确认其能与关键酶基因SmCPS1启动子结合。结论 鉴定到丹参中一个新转录因子SmERF108，生物信息学分析及差异表达分析预测与丹参酮合成相关，分子互作初步证实靶基因为SmCPS1二萜环化酶。     

Contemporary Epidemiology of and Risk Factors Associated with Removal of a Pathologically Normal Appendix in Children with Suspected Appendicitis

BackgroundThe goal of this study was to characterize contemporary performance benchmarks and risk factors associated with negative appendectomy (NA) in children with suspected appendicitis.MethodsA multicenter retrospective cohort analysis of children undergoing appendectomy for suspected appendicitis was performed using data from the 2016–2021 NSQIP-Pediatric Appendectomy Targeted Public Use Files. Multivariable regression was used to evaluate the influence of year, age, sex, and WBC count on NA rate, and to generate rate estimates for NA based on different combinations of demographic characteristics and WBC profiles.Results100,322 patients were included from 140 hospitals. The overall NA rate was 2.4%, and rates decreased significantly during the study period (2016: 3.1% vs. 2021: 2.3%, p < 0.001). In adjusted analyses, the highest risk for NA was associated with a normal WBC (<9000/mm³; OR 5.31 [95% CI: 4.87–5.80]), followed by female sex (OR 1.55 [95% CI: 1.42–1.68]) and age <5 years (OR 1.64 [95% CI 1.39, 1.94]). Model-estimated risk for NA varied significantly across demographic and WBC strata, with a 14.4-fold range in rates between subgroups with the lowest and highest predicted risk (males 13–17 years with elevated WBC [1.1%] vs. females 3–4 years with normal WBC [15.8%]).ConclusionsContemporary NA rates have decreased over time, however NA risk remains high in children without a leukocytosis, particularly for girls and children <5 years of age. These data provide contemporary performance benchmarks for NA in children with suspected appendicitis and identify high-risk populations where further efforts to mitigate NA risk should be targeted.Level of EvidenceIII.     

Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer

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Pan-cancer proteomic map of 949 human cell lines

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