Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

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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.     

Immediate effects of rhythmic joint mobilization of the temporomandibular joint on pain,mouth opening and electromyographic activity in patients with temporomandibular disorders

BackgroundRhythmic joint mobilizations (RJM) of the temporomandibular joint (TMJ) are employed to relieve pain and improve function in patients with temporomandibular disorders (TMD). However, the evidence on the immediate effects of RJM in patients with TMD is scarce. The aim of this study was to assess the immediate clinical and functional effects of RJM in patients with TMD.Materials and methodsThis was a one-group quasi-experimental before and after study. Thirty-eight patients with TMD were assessed by means of pain intensity (visual analogue score, VAS), pressure pain threshold (PPT, measured through pressure algometry on the masseter and temporal muscles), mouth opening (MO, measured with a ruler), and surface electromyographic activity of the masseter and temporal muscles (asymmetry index, AI). Measurements were performed before and after a single, 1-min session of RJM of each TMJ. All statistical analyses were performed using the SPSS version 20.0 statistical package.ResultsA statistical significant difference was found in pain intensity, PPT and MO after the intervention (p < 0.05). No difference was found in the AI. A large effect size was observed for pain intensity, PPT of the left and right masseter muscles and MO (d = 0.85–1.13), whereas for the left and right temporal muscles the effect size was moderate (d = 0.62) and small, respectively (d = 0.49).ConclusionIn this sample of patients with TMD, a single session of RJM of the TMJ seemed to be effective in reducing pain intensity, increasing PPT and improving MO immediately after the intervention, without differences in the AI.     

基于文本挖掘和生物医学数据库的新型冠状病毒肺炎药物发现

目的 基于文本挖掘技术和生物医学数据库对新型冠状病毒肺炎（COVID-19）相关文献进行数据挖掘分析，探究COVID-19及其主要症状发热、咳嗽、呼吸障碍相关基因靶点，筛选潜在有效的化学药和中药。方法 使用GenCLiP 3网站获取COVID-19和其主要症状咳嗽、发热、呼吸障碍共4个关键词的共有靶点，在METASCAPE数据库中对其进行基因本体（GO）和通路富集分析，再利用String数据库和Cytoscape软件构建共有靶点的蛋白质相互作用网络，筛选获得核心基因，运用DGIdb数据库、SymMap数据库针对核心基因进行中西医治疗药物预测。结果 获得COVID-19及其主要症状共有基因靶点28个，其中有IL2、IL1B、CCL2等核心基因16个，使用DGIdb数据库筛选获得与16个关键靶点相互作用的化学药包括沙利度胺、来氟米特、环孢素等28种，中药包括虎杖、黄芪、芦荟等70味。结论 COVID-19及其主要症状的病理机制可能和CD4、KNG1、VEGFA等28个共有基因相关，可能通过介导TNF、IL-17等信号通路参与COVID-19病理过程。潜在有效药物可能通过作用相关靶点通路起到治疗COVID-19的作用。     

肥胖型PCOS患者的生物学特征和临床特征

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是一种内分泌代谢紊乱综合征,临床表现高度异质性。肥胖是PCOS异质性临床表现之一,超过50%的PCOS患者超重或肥胖。肥胖型PCOS主要表现为高雄激素血症、中心型肥胖和糖脂代谢紊乱,非肥胖型PCOS主要表现为黄体生成激素（luteinizing hormone,LH）水平异常升高。尽管肥胖型和非肥胖型PCOS均存在内分泌代谢异常,然而肥胖可加重PCOS糖脂代谢紊乱;肥胖型PCOS还表现脂肪代谢的异常。综述肥胖型PCOS患者的临床特征、性激素水平、糖脂代谢特征,旨在为肥胖型和非肥胖型PCOS患者新的分型诊治提供参考。     

Deciphering the molecular landscape of microcephaly in 87 Indian families by exome sequencing

Microcephaly is a frequent feature of neurodevelopmental disorders (NDDs). Our study presents the heterogeneous spectrum of genetic disorders in patients with microcephaly either in isolated form or in association with other neurological and extra-neural abnormalities. We present data of 91 patients from 87 unrelated families referred to our clinic during 2016–2020 and provide a comprehensive clinical and genetic landscape in the studied cohort. Molecular diagnosis using exome sequencing was made in 45 families giving a yield of 51.7%. In 9 additional families probable causative variants were detected. We identified disease causing variations in 49 genes that are involved in different functional pathways Among these, 36 had an autosomal recessive pattern, 8 had an autosomal dominant pattern (all inherited de novo), and 5 had an X-linked pattern. In 41 probands where sequence variations in autosomal recessive genes were identified 31 were homozygotes (including 16 from non-consanguineous families). The study added 28 novel pathogenic/likely pathogenic variations. The study also calls attention to phenotypic variability and expansion in spectrum as well as uncovers genes where microcephaly is not reported previously or is a rare finding. We here report phenotypes associated with the genes for ultra-rare NDDs with microcephaly namely ATRIP, MINPP1, PNPLA8, AIMP2, ANKLE2, NCAPD2 and TRIT1.