Bioinformatics analysis of prognosis and immune microenvironment of immunological cell death-related gemcitabine-resistance genes in bladder cancer

BackgroundBladder cancer (BC) is the most common malignant tumor of the urinary system. Gemcitabine resistance partly accounts for treatment failure and recurrence in BC. Immunological cell death (ICD) is correlated with chemoresistance. The prognosis of patients with similar tumor stage still varies in response to chemotherapy, recurrence, and disease progression. Therefore, our study aimed to provide a prognostic model based on ICD-related and gemcitabine-resistance genes for BC.MethodsThe data of BC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs), and differentially expressed gemcitabine resistance-related genes (DEGRRGs) were identified using the edgeR package. The survival-associated DEGRRGs were identified by univariate Cox analysis. A prognostic model was established by univariate Cox regression analysis and validated by GEO dataset. The outcome of low-risk group and high-risk group was analyzed by the Kaplan-Meier curve. The relationship between risk score and immune cell infiltration was investigated using the TIMER online database.ResultsThe prognosis of patients in the ICD-high group was significantly better than ICD-low group. A prognostic model containing 5 gemcitabine resistance-related ICD-associated genes, including PTPRR, HOXB3, SIGLEC15, UNC5CL, and CASQ1, was established. In both TCGA prognostic model and GEO validation model, patients in the low-risk group had better outcomes than high-risk group. According to the receiver operating characteristic (ROC) curves, the risk score area under ROC curve (AUC) of the TCGA prognostic model were calculated to be 0.705, while the risk score of the GEO validation model were calculated to be 0.716. Patients in the high-risk group had a significantly higher immune score, stromal score, and infiltration of M0 macrophages, M1 macrophages, M2 macrophages, and activated CD4⁺ T cells. Patients in the high-risk group had significantly lower infiltration of the regulatory T cells, resting dendritic cell (DCs), and activated DCs.ConclusionsThe present study highlighted the functional role of gemcitabine resistance-related ICD-associated genes, constructed a prognostic score for the outcome evaluation and searched for potential targets to overcome gemcitabine chemoresistance in BC.     

Elevated Remnant Cholesterol is Associated with Adverse Cardiovascular Outcomes in Patients with Acute Coronary Syndrome

Aims: This study aimed to investigate the association of elevated RC levels with adverse cardiovascular outcomes in acute coronary syndrome (ACS) patients with and without diabetes. Methods: We analyzed data from 1716 patients with ACS undergoing percutaneous coronary intervention. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. RC ＞75th percentile of the cohort (＞0.79 mmol/L) was defined as abnormally elevated RC. Cox-regression models and Kaplan-Meier analyses were used to assess the relationship between RC ＞0.79 mmol/L and major adverse cardiovascular events (MACE). Results: During a median follow-up of 927 days, a total of 354 patients had at least one event. In the overall population, compared with those with RC ≤ 0.79 mmol/L, patients with RC ＞0.79 mmol/L had a significantly higher risk of MACE after adjustment for potential confounders (hazard ratio: 1.572, 95% confidence interval: 1.251-1.975,P＜0.001). In addition, RC ＞0.79 mmol/L was associated with an increased risk of MACE of 66.7% (P=0.001) and 50.1% (P=0.022) in the diabetic and non-diabetic subgroups (P for interaction=0.073), respectively. The addition of RC significantly improved the predictive ability of baseline models for MACE in diabetic patients (allP＜0.05), but not in non-diabetic patients (allP＞0.05). Conclusion: Abnormally elevated RC was significantly associated with worse prognosis in both diabetic and non-diabetic patients with ACS; however, the prognostic value of RC might be superior among diabetic patients.     

In lung adenocarcinoma,low expression of the cell surface extracellular nucleotidase CD39 is related to immune infiltration and a poor prognosis

BackgroundExtracellular nucleotidase on the cell surface CD39 plays a crucial role in the tumor microenvironment in the immunosuppressive adenosine pathway. However, the association between CD39 and lung adenocarcinoma has rarely been recorded. This study aimed to explore the involvement of CD39 in the biological processes of lung cancer.MethodsFirst, a prediction model was established by analyzing the expression of CD39 in lung adenocarcinoma and its relationships with clinical evidence of lung adenocarcinoma using The Cancer Genome Atlas (TCGA) and Tumor IMmune Estimation Resource (TIMER) databases. In the TCGA and TIMER databases, the relationship between CD39 and immune cells and the relationship with immune-related expressed genes were studied. Subsequently, using gene set enrichment analysis (GSEA), the potential mechanism of action was investigated.ResultsLung adenocarcinoma patients with elevated CD39 expression had improved overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). CD39 expression was reduced in lung adenocarcinoma tumor tissue in the TCGA and TIMER databases. The nomogram’s C-index was 0.688 (0.665–0.712), indicating some consistency in the prediction model. According to the TIMER and TCGA databases, CD39 expression was strongly connected with several immune cells invading and with immune checkpoint-related markers such as PDCD1, CD274, CTLA-4, and several functional T cells. GSEA revealed that CD39 influences the extracellular matrix, immunological microenvironment, programmed death 1 (PD-1) expression, glucose metabolism, PTEN stability, inflammatory response, and angiogenesis in lung cancer.ConclusionsThe current study’s findings demonstrated that CD39 can be employed as a possible predictive biomarker for lung adenocarcinoma and may enhance the patients’ poor prognosis by preventing the immunological escape of tumor cells from the lung adenocarcinoma tumor microenvironment.     

原发性胃非何杰金淋巴瘤

本文总结了我院1985年～1989年收治的28例原发性胃非何杰金淋巴癌（pgNHL）的临床治疗经验。主要治疗方法包括26例手术切除，2例剖腹探查，3例术后放疗，15例术后化疗，4例术后放疗和化疗。手术切除率92．9％，无1例手术死亡。总5年生存率60．7％，中位生存期79．5个月，Ⅰ＋Ⅱ期患者5年生存率71．4％，Ⅲ＋Ⅳ期28－6％（P＜0．05）。单纯手术患者5年生存率20％，手术＋化疗80％，手术＋放疗和化疗75％（P＜0．01）。作者分析了手术治疗pgNHL的必要性，并强调了联合治疗的意义。     

免疫抑制剂细胞内浓度测定的研究进展

细胞外浓度测定作为目前器官移植临床免疫抑制剂治疗药物监测（TDM）的主要手段,与免疫抑制剂药效之间的相关性不理想。随着液相质谱技术的广泛应用,免疫抑制剂细胞内浓度检测技术逐渐成熟。由于细胞内浓度测定可直接检测靶细胞内的药物暴露水平,理论上能更好地反映免疫抑制剂的药效。本文总结了免疫抑制剂细胞内浓度测定的历史与现状,着重介绍免疫抑制剂细胞内浓度的测定方法及其与药效的相关性。免疫抑制剂细胞内浓度测定具有较好的临床应用价值,值得推广。     

2020年肾移植临床国际前沿热点及新进展荟萃

在浩瀚的肾移植相关文献中, 本文汲取和盘点2020年肾移植临床国际前沿热点和难点, 移植新技术、新方法、新视野及新进展荟萃, 主要内容包括排斥反应, 免疫抑制优化应用与调控, 移植感染, 移植后恶性肿瘤, 无创检测与生物标志物, 供者器官保存、修复及利用, 肾移植术后肾病复发, 多因素影响移植肾长期存活, 计算机与人工智能等。加强对肾移植领域文献的阅读与思考, 站在更高的起点开拓视野, 结合中国肾移植临床实践, 以推动肾移植获得更好的长期效果。     

石杉碱甲对乙酰胆碱酯酶活性选择性抑制作用及促智作用

目的研究石杉碱甲对乙酰胆碱酯酶活性选择性抑制作用及其对东莨菪碱所致的小鼠记忆障碍模型的改善作用.方法用Ellman法分别测石杉碱甲及对照药物他克林抑制小鼠10%脑皮质匀浆上清和血清(119)中胆碱酯酶活性的IC50.用东莨菪碱(2 mg/kg,ip)造成小鼠记忆障碍模型,观察石杉碱甲对模型小鼠上台潜伏期和上台前游泳距离的影响.结果石杉碱甲抑制乙酰胆碱酯酶活性和丁酰胆碱酯酶活性的IC50分别为0.039±0.004 μmol/L和大于10 μmol/L,而他克林抑制这两种酶的IC50分别为1.84±0.09 μmol/L和0.52±0.03μmol/L.石杉碱甲(0.2 mg/kg,ip)组小鼠的潜伏期明显短于东莨菪碱组,两组潜伏期分别为40.9±18.5 s和75.3±19.4 s,上台前路程分别为8.9±2.8m和12.5±5.0m.结论石杉碱甲对乙酰胆碱酯酶活性的抑制作用具有明显的选择性,且其选择性强于他克林.石杉碱甲对东莨菪碱所致的小鼠记忆障碍有明显的改善作用.     

不同季节婴幼儿腹泻的病毒病原学研究

急性传染性腹泻是危害儿童健康的重要公共卫生问题之一。世界卫生组织已将本病列入第3个卫生工作重点,并提出了控制腹泻病的全球方案。     

化浊解毒疏肝方对抑郁症模型小鼠学习记忆的改善作用

目的探讨化浊解毒疏肝方对抑郁症模型小鼠的学习记忆的改善作用。方法 48只ICR小鼠随机分为正常组、模型组、氟西汀组(10 mg/kg)及化浊解毒疏肝方低、中、高剂量组(0.85、1.7、3.4 g/kg),构建小鼠慢性不可预见性温和应激(CUMS)抑郁模型。检测小鼠体质量(1次/周),糖水偏好、水迷宫实验观察小鼠抑郁样行为和学习记忆能力,Western blot、免疫组化检测海马内神经细胞黏附分子(NCAM)、生长相关蛋白(GAP-43)表达。结果与模型组比较,化浊解毒疏肝方高剂量组小鼠糖水偏好分数升高,体质量增加,穿越平台次数多,反向站台潜伏期缩短,NCAM、GAP-43蛋白表达升高(P<0.01)。结论化浊解毒疏肝方可能通过提高海马内NCAM和GAP-43蛋白表达来提高模型小鼠学习记忆能力。