Intravesical Bacillus Calmette-Guérin Treatment Is Inversely Associated With the Risk of Developing Alzheimer Disease or Other Dementia Among Patients With Non–muscle-invasive Bladder Cancer

BackgroundThe immune system plays an important role in the pathogenesis of Alzheimer disease (AD), but it remains unclear whether bacillus Calmette-Guérin (BCG) may affect the risk of AD or not.MethodsUsing retrospective chart review, we collected data regarding demographics, comorbidities, cancer diagnosis, BCG treatment, and subsequent diagnosis of AD or other dementia in a racially/ethnically diverse cohort of patients with non–muscle-invasive bladder cancer (NIMBC) receiving treatment between 1984 and 2020 in the Bronx, New York. We used Cox proportional hazard models to examine association between BCG treatment and risk of incident AD or other dementia, adjusting for age, gender, race/ethnicity, and major comorbidities.ResultsIn our cohort of 1290 patients with NMIBC, a total of 99 (7.7%) patients developed AD or other dementia during follow-up. Patients who received BCG treatment (25%) had a 60% lowered incidence of AD or other dementia (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.21-0.80) in comparison to those who did not receive BCG. There was also suggestive evidence that the reduction in risk of AD or other dementia associated with BCG treatment was stronger in men (adjusted HR, 0.34; 95% CI, 0.15-0.81) but not in women (adjusted HR, 0.75; 95% CI 0.25-2.24). When we stratified the patients who received BCG by type of treatments, patients who received both induction and maintenance rounds of BCG had a further lowered incidence of AD or other dementia (HR, 0.23; 95% CI, 0.06-0.96) than patients who did not receive BCG.ConclusionsTo our knowledge, our study is one of the first to suggest that BCG treatment is associated with a reduced risk of developing AD or other dementia in a multiethnic population, independent of significant comorbidities. Larger cohort studies are needed to corroborate our findings.     

Myeloid-derived suppressor cell (MDSC) key genes analysis in rat anti-CD28-induced immune tolerance kidney transplantation

BackgroundIn the field of transplantation, inducing immune tolerance in recipients is of great importance. Blocking co-stimulatory molecule using anti-CD28 antibody could induce tolerance in a rat kidney transplantation model. Myeloid-derived suppressor cells (MDSCs) reveals strong immune suppressive abilities in kidney transplantation. Here we analyzed key genes of MDSCs leading to transplant tolerance in this model.MethodsMicroarray data of rat gene expression profiles under accession number {"type":"entrez-geo","attrs":{"text":"GSE28545","term_id":"28545"}}GSE28545 in the Gene Expression Omnibus (GEO) database were analyzed. Running the LIMMA package in R language, the differentially expressed genes (DEGs) were found. Enrichment analysis of the DEGs was conducted in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database to explore gene ontology (GO) annotation and their Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Their protein-protein interactions (PPIs) were provided by STRING database and was visualized in Cytoscape. Hub genes were carried out by CytoHubba.ResultsThree hundred and thirty-eight DEGs were exported, including 27 upregulated and 311 downregulated genes. The functions and KEGG pathways of the DEGs were assessed and the PPI network was constructed based on the string interactions of the DEGs. The network was visualized in Cytoscape; the entire PPI network consisted of 192 nodes and 469 edges. Zap70, Cdc42, Stat1, Stat4, Ccl5 and Cxcr3 were among the hub genes.ConclusionsThese key genes, corresponding proteins and their functions may provide valuable background for both basic and clinical research and could be the direction of future studies in immune tolerance, especially those examining immunocyte-induced tolerance.     

层面递进法激光腔内剜除高危前列腺增生的治疗体会

目的探讨1 470 nm激光剜除治疗高危前列腺增生的手术技巧及临床效果。 方法回顾分析2018年6月至2018年9月中山大学附属第三医院泌尿外科采用1 470 nm激光治疗共89例高危前列腺增生患者的临床资料，年龄平均（68±3）岁，前列腺体积（57.4±2.6）ml。所有患者均采用"寻找层面，先易后难，剜切结合"的层面递进法思路行激光腔内前列腺剜除术，比较患者术中及术后情况。 结果89例均顺利完成手术，与术前相比，术后3个月患者最大尿流率明显增加，[（6.9±2.1） ml/s vs（19.8±3.6） ml/s]。国际前列腺症状评分显著好转，[（24.6±1.7） vs（8.0±1.2）]。术中无输血、无电切综合征、无直肠和膀胱穿孔病例，无输尿管损伤、大出血、心脑血管意外等严重并发症发生。 结论层面递进法激光剜除技术构想对于高危前列腺增生外科包膜层面的寻找、减少术后并发症有独到优势，且易于掌握，或可为业界同行提供一个新的思路。     

Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma

PurposeTo investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC).Materials and MethodsThis single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A–B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses.ResultsThe median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6–11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1–3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9–23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6–26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2–7.2), and progression-free survival was 5.7 months (95% CI, 4.3–7.1).ConclusionsRadioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.     

Actin binding proteins,actin cytoskeleton and spermatogenesis – Lesson from toxicant models

Actin cytoskeleton is crucial to support spermatogenesis in the mammalian testis. However, the molecular mechanism(s) underlying changes of actin cytoskeletal organization in response to cellular events that take place across the seminiferous epithelium (e.g., self-renewal of spermatogonial stem cells, germ cell differentiation, meosis, spermiogenesis, spermiation) at specific stages of the epithelial cycle of spermatogenesis remain largely unexplored. This, at least in part, is due to the lack of suitable study models to identify the crucial regulatory proteins and to investigate how these proteins work in concert to support actin dynamics. Much of the information on the role of actin binding proteins in the literature, namely the actin bundling proteins, actin nucleation proteins and motor proteins, are either findings based on genetic models or morphological analyses. While this information is helpful to delineate the function of these proteins to support spermatogenesis, they are not helpful to identify the regulatory signaling proteins, the signaling pathways and the cascade of events to modulate actin cytoskeleton dynamics. Recent studies based on the use of toxicant models, both in vitro and in vivo, however, have bridged this gap by identifying putative regulatory and signaling proteins of actin cytoskeleton. Herein, we summarize and critically evaluate these findings. We also provide a hypothetical model by which actin cytoskeletal dynamics in Sertoli cells are regulated, which in turn supports spermatid transport across the seminiferous epithelium, and at the blood-testis barrier (BTB) during the epithelial cycle of spermatogenesis.     

层级质量控制在外科ICU护理管理中的应用

目的探讨在外科ICU护理管理中实施层级质量控制的效果。方法选择2016年1-12月为实施前,2018年1-12月为实施后,实施前后均选取50例外科ICU患者及护理人员为研究对象,对实施前后外科ICU护理管理质量进行观察。结果实施后外科护理人员在工作人员素质、环境管理、护理质量管理及质量总分上均显著高于实施前(P<0.05);实施后ICU患者对护理管理的总满意率为98.00%,明显高于实施前总满意率86.00%,差异有统计学意义(P<0.05)。结论在外科ICU护理管理中,实施层级质量控制的护理管理模式,可显著提高ICU病房护理治疗,提高患者的满意率,值得推广。     

Étude exploratoire de la santé musculo-squelettique du rachis d’étudiants en ostéopathie

BackgroundDuring their training, students in osteopathy regularly undergo spinal manipulation exercises. This exposes the students’ spine to unskilled gestures performed by their colleagues learning spinal manipulation. Discomfort, muscle soreness or moderate pain following spinal manipulations lasting two or three days are commonly reported. In addition, some students may have ongoing spinal musculoskeletal disease (SMSD) during their studies. The purpose of this study was to evaluate the prevalence of SMSDs and their maximum intensity in a population of osteopathy students and to determine whether individual differences exist.MethodAn exploratory cross-sectional study took place over three years. Data were collected by means of a self-administrated standardised questionnaire screening for MSD: the Nordic questionnaire.ResultsThere were 733 exploitable questionnaires, giving an average response rate of 91.5%. Average prevalence of SMSD was 98.4% during the last 12 months. Average maximum intensity perceived was 6/10 and 45% of students experienced an intense SMSD (scored between 7 and 10/10). Variation of the maximum intensity of SMSD between “before osteopathy studies” and “the last 12 months” was 1.2/10. This variation was influenced by the number of days students were manipulated during a week (p < 0.0001). On average, students underwent manipulation three days a week.ConclusionThis study confirms the important prevalence of SMSD among osteopathy students. This result led us to carry out a qualitative study for exploring students’ conceptions in health and spinal manipulative practices.