腹腔镜联合醋酸亮丙瑞林对子宫内膜异位症合并不育症疗效

目的:探讨腹腔镜联合醋酸亮丙瑞林治疗子宫内膜异位症(EMS)合并不育症对患者妊娠结局的影响。方法:选取2017年3月-2019年3月本院收治的80例EMS合并不育症患者,随机分为对照组(n=40)和观察组(n=40),对照组给予腹腔镜治疗,观察组给予腹腔镜联合醋酸亮丙瑞林治疗,比较两组临床疗效、绝经症状(Kupperman)评分、盆腔疼痛程度(VAS)评分、血清学指标以及1年内复发率和妊娠率。结果:治疗后观察组治疗有效率(95.0%)高于对照组(67.5%),Kupperman(5.80±2.11分)、VAS评分(1.59±0.22分),低于对照组(8.52±3.84分、2.04±0.51分),血清卵泡刺激素、黄体生成素、雌二醇、基质金属蛋白酶-9、基质金属蛋白酶抑制剂-1、人附睾蛋白、糖类抗原125、糖类抗原199水平均低于对照组(均P<0.05),1年复发率(5.0%)低于对照组(25.0%),1年受孕率(45.0%)高于对照组(20.0%)(P<0.05)。结论:腹腔镜联合醋酸亮丙瑞林治疗EMS合并不育症疗效显著,可缓解临床症状和疼痛程度,改善性激素水平,降低复发率,提高受孕率。     

穿透性胃溃疡恶变12例影像学分析

目的提高对穿透性胃溃疡恶变的影像学诊断及鉴别诊断的认识。方法经手术病理证实的12例穿透性胃溃疡恶变病例，均行胃钡餐造影，10例加行CT扫描。结果胃钡餐造影出现深大龛影12例，其中腔外龛影10例，部分腔内龛影2例，出现穿孔2例。CT见胃壁增厚8例，胃内软组织块影2例，胃外软组织块影2例，腹腔、肝门、腹膜后淋巴结肿大6例。结论胃钡餐造影对穿透性胃溃疡有良好的显示，还可以发现CT显示不理想的胃黏膜面，对估计病变的范围和溃疡、穿孔方面优于CT。但CT能清楚观察胃壁的厚度、胃外肿块、与周围脏器的关系以及胃外有无淋巴结肿大，能对判断穿透性胃溃疡有无恶变等提供更多准确的信息。     

完全性左束支阻滞的临床意义探讨

目的：探讨完全性左束支阻滞（complete left bundle branch block,CLBBB）的临床意义。方法：对常规心电图检查为CLBBB的162例住院患者的动态心电图、超声心动图及冠状动脉造影检查结果进行回顾性分析。结果：动态心电图显示：97例患者合并各种类型心律失常。超声心动图显示：111例发生不同程度左房、左室肥大及心脏瓣膜病变,左室射血分数（LVEF）≤50%者80例。37例冠脉造影显示：以左前降支为主的单支及多支病变16例。结论：CLBBB多发生于老年患者,常见于器质性心脏病,主要为高血压、冠心病、退行性心脏瓣膜病、扩张性心肌病等,且多伴发各种类型心律失常,易导致心功能不全。临床应对CLBBB尤其是新发的CLBBB患者进行动态心电图及超声心动图评估,必要时行冠脉造影及心脏电生理检查以明确原因,及时采取治疗措施。     

C2-神经酰胺在A549/PC9细胞凋亡中的作用及影响

目的 探讨C₂神经酰胺(鞘磷脂类物质之一)对非小细胞肺癌(A549和PC9)细胞凋亡的影响。方法 培养非小细胞肺癌细胞系(A549和PC9),提取总蛋白进行Western blot,检测两种细胞中凋亡蛋白Caspase-3及cleaved Caspase-3蛋白的表达情况;使用CCK-8比色法筛选药物浓度;Hoechst 33258凋亡染色检查细胞凋亡情况;流式细胞化学术检测细胞凋亡比率,RT-PCR检测凋亡蛋白Caspase-3的表达。结果 神经酰胺在50μmol/L浓度处理后细胞活力均在70%左右;与对照组相比,神经酰胺组凋亡蛋白表达升高(P<0.05);流式细胞化学术及凋亡染色检测显示神经酰胺处理组凋亡率与对照组相比增加(P<0.05);在基因水平检测mRNA显示凋亡蛋白Caspase-3表达增加(P<0.05)。结论 C₂-神经酰胺可以促使非小细胞肺癌细胞凋亡,从而为临床肺癌的化疗提供新的治疗靶点。     

MDSC subtypes and CD39 expression on CD8+ T cells predict the efficacy of anti-PD-1 immunotherapy in patients with advanced NSCLC

The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune cells include hindering T-cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of circulating MDSC subtypes in patients with non-small cell lung cancer (NSCLC) whether those suppressive immune cells hinder T-cell activities leading to poor clinical outcomes. First, we verified PMN-MDSCs, monocytic-MDSCs (M-MDSCs), and Treg cells increased according to the stages of NSCLC, and MDSCs effectively suppressed T-cell activities and induced T-cell exhaustion. The analysis of NSCLC patients treated with anti-PD-1 immunotherapy demonstrated that low PMN-MDSCs, M-MDSCs, and CD39⁺CD8⁺ T cells as an individual and all together were associated with longer progression free survival and overall survival, suggesting PMN-MDSCs, M-MDSCs, and CD39⁺CD8⁺ T cells frequencies in peripheral blood might be useful as potential predictive and prognostic biomarkers.     

Relationship between plasma cell-free DNA (cfDNA) and prognosis of TACE for primary hepatocellular carcinoma

BackgroundOur study aims to investigate changes in cell-free DNA (cfDNA) concentration and integrity in primary hepatocellular carcinoma (PHC) patients before and after transcatheter arterial chemoembolization (TACE) treatment and their influence on the evaluation of prognosis of the disease.MethodsA total of 84 PHC patients admitted to the Affiliated Hospital of Nanjing University of Chinese Medicine from December 2016 to December 2017 were included as the study group, while 55 healthy people served as the control group. Plasma cfDNA concentration and integrity were determined using qRT-PCR. The correlation between cfDNA concentration/integrity and clinical characteristics of PHC patients were analyzed. A ROC curve was used to investigate the sensitivity and specificity of cfDNA as detection indices. Univariate and multivariate analyses were used to analyze factors affecting recurrence in PHC patients and compare recurrence-free survival (RFS) of PHC patients with high cfDNA expression and low cfDNA expression.ResultsPlasma cfDNA concentration and integrity were significantly higher in PHC patients before TACE treatment than in healthy people and significantly lower after treatment than before (P<0.05). The cfDNA concentration was significantly correlated with tumor size, lymph node metastasis, TNM stage, and BCLC stage, while cfDNA integrity was significantly correlated with tumor size, TNM stage, and BCLC stage (P<0.05). ROC results showed that the area under the curve (AUC) value of cfDNA concentration was the largest, with an optimal cut-off of 10.51 ng/mL. Multivariate regression analysis for COX showed that the TNM stage, cfDNA concentration, and AFP were independent risk factors that affected PHC patients’ survival.ConclusionsPlasma cfDNA concentration in PHC patients is more sensitive and specific than any other tumor marker. It is an independent risk factor for PHC patients treated with TACE. Therefore, it is hypothesized cfDNA is a potential biomarker for prognostic evaluation of PHC patients treated with TACE.     

Cross-species genetic screens identify transglutaminase 5 as a regulator of polyglutamine-expanded ataxin-1

Many neurodegenerative disorders are caused by abnormal accumulation of misfolded proteins. In spinocerebellar ataxia type 1 (SCA1), accumulation of polyglutamine-expanded (polyQ-expanded) ataxin-1 (ATXN1) causes neuronal toxicity. Lowering total ATXN1, especially the polyQ-expanded form, alleviates disease phenotypes in mice, but the molecular mechanism by which the mutant ATXN1 is specifically modulated is not understood. Here, we identified 22 mutant ATXN1 regulators by performing a cross-species screen of 7787 and 2144 genes in human cells and Drosophila eyes, respectively. Among them, transglutaminase 5 (TG5) preferentially regulated mutant ATXN1 over the WT protein. TG enzymes catalyzed cross-linking of ATXN1 in a polyQ-length–dependent manner, thereby preferentially modulating mutant ATXN1 stability and oligomerization. Perturbing Tg in Drosophila SCA1 models modulated mutant ATXN1 toxicity. Moreover, TG5 was enriched in the nuclei of SCA1-affected neurons and colocalized with nuclear ATXN1 inclusions in brain tissue from patients with SCA1. Our work provides a molecular insight into SCA1 pathogenesis and an opportunity for allele-specific targeting for neurodegenerative disorders.     

Complementary role of CD4+ T cells and secondary lymphoid tissues for cross-presentation of tumor antigen to CD8+ T cells

MHC class I-restricted tumor antigens can be presented to CD8+ T cells by two distinct pathways: via direct and indirect presentation. The relative contribution of these two pathways toward the initial activation of tumor antigen-specific CD8+ T cells and their subsequent tumor rejection is still vigorously debated. Using a tumor model able to dissect the relative contributions of direct and indirect presentation, we show unequivocally the inefficiency of direct presentation and the essential requirement of indirect presentation for the priming of naive tumor antigen-specific T cells leading to tumor rejection. Moreover, we characterize the essential environment under which indirect presentation occurs, and find efficient cross-priming of tumor-specific CD8+ T cells in the complete absence of secondary lymphoid tissues. The independence of this process from local lymph nodes is compromised, however, in the absence of CD4+ T cell help. Therefore, our paper demonstrates that effective immune protection against tumors requires the cross-priming of CD8+ T cells under conditions that require either CD4+ T cell help, or draining lymph nodes.     

Long-term survival following heart transplantation is possible

Objective： To determine whether long-term survival （〉10 years） after heart transplantation is possible and identify complications influencing long-term survival. Methods： We analyzed clinical outcomes in the group of 21 patients who had undergone heart transplantation at the Second Affiliated Hospital of Harbin Medical University since 1992 and 4 of them survived more than 10 years. Results： Nine patients are still alive with normal left ventricular function, and 4 of them have survived more than 10 years. The longest survival patient has lived more than 18 years after transplantation, whose survival is the longest in China and in Asia. We have also found that there has been a high incidence of complications, such as rejection episodes during the first 6 months, and transplant vasculopathy in the long-term survival patients. Conclusion： Long-term survivors maintain normal hemodynamic function of their allografts, and long-term survival following cardiac transplantation is possible. Aggressive preventive and therapeutic measures are essential to limit the risk factors for development of complications such as rejection episodes and transplant vasculopathy, and enable long-term survival after cardiac transplantation.