神经酰胺通过JNK-c-Jun信号通路诱导胶质瘤细胞自噬性死亡

目的探讨神经酰胺对大鼠脑胶质瘤细胞C6自噬性死亡的影响及其作用机制。方法不同浓度神经酰胺作用于C6细胞后,用MTT法检测细胞的存活率,流式法检测细胞凋亡的改变;Western blotting及电镜的方法观察细胞自噬水平的改变,以及JNK及其下游靶分子c-Jun的磷酸化水平变化;最后进一步借助JNK特异性抑制剂SP600125抑制JNK的活性,观察其对神经酰胺诱导的细胞自噬情况的影响。结果与对照组相比,神经酰胺作用24 h后,C6细胞存活率明显降低,且具有剂量依赖性,差异有统计学意义(P<0.05);与对照组相比,神经酰胺作用24 h后,C6细胞死亡明显升高且具有剂量依赖性,差异有统计学意义(P<0.05),但其中凋亡性死亡比例较低;神经酰胺作用后细胞内自噬小体数目,LC3B/LC3A的比值,Beclin-1的表达水平,以及JNK和c-Jun磷酸化水平都显著升高,差异具有统计学意义(P<0.05);提前给予JNK特异性抑制剂SP600125抑制JNK的活性后,显著阻断神经酰胺诱导的细胞自噬。结论神经酰胺可诱导胶质瘤细胞C6发生自噬性死亡,其诱导胶质瘤细胞发生自噬的机制可能与激活JNK信号通路有关。     

血清GP73和AFP对肝细胞癌诊断的临床价值比较

目的 比较血清GP73和AFP检测对肝细胞癌( HCC)诊断的临床应用价值. 方法 用化学发光免疫分析法测定63例HCC、56例肝硬化、60例慢性肝炎和68健康对照血清AFP水平,ELISA法测定血清GP73水平. 结果 HCC患者血清GP73和AFP水平与肝硬化、慢性肝炎和健康人群间的差异有统计学意义( P＜0. 05 ). 血清GP73对HCC的灵敏度( SEN)、特异性( SPE)和准确度分别为73. 0%、89. 7%和85. 4%. 血清AFP对HCC的SEN、SPE和准确度分别为57. 1%、88. 0%和80. 2%. 血清GP73 +AFP并联试验对HCC的SEN、SPE和准确度分别为81. 0%、81. 0%和81. 0%.GP73和AFP的ROC曲线下面积分别为0. 889和0. 796. 结论 血清GP73对肝细胞癌的诊断效能优于血清AFP,GP73是HCC诊断的较好血清标志物.     

急性肺栓塞不同危险分层与心电变化的关系

目的探究急性肺栓塞不同危险分层与心电变化的关系。方法选取2016年1月至2019年1月急性肺栓塞患者90例,根据危险分层进行分组。其中,低危组35例,中危组30例,高危组25例。均行心电图及动态心电图检查,心电图观察指标为心率、P波、QRS波群、T波、ST段变化,动态心电图观察指标心率变异性及心律失常。结果高危组窦性心动过速、肺型P波、SⅠQⅢTⅢ、ⅢST段抬高、V1ST段抬高、V1~V4T波倒置发生率均高于低危组,高危组ⅢST段抬高、V1ST段抬高、V1~V4T波倒置发生率高于中危组,差异均有统计学意义(均P<0.05)。高危组心率变异性指标正常RR间期标准差(SDNN)、每5min正常RR间期平均值的标准差SDANN均低于中、低危组,差异有统计学意义(均P<0.05)。高危组患者室性心律失常、室上性心律失常、房室传导阻滞及束支传导阻滞阳性率均高于中危组和低危组,差异均有统计学意义(均P<0.05)。结论急性肺栓塞时心电图改变与危险分层相关。     

Adjuvant chemotherapy versus surgery alone for esophageal squamous cell carcinoma: a meta‐analysis of randomized controlled trials and nonrandomized studies

The effect of adjuvant chemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas is still controversial, and the subgroup of patients who will most likely benefit from the adjuvant chemotherapy on long‐term survival has not yet been identified clearly. Studies published from 1995 to May 2012 were searched in Medline, Embase, PubMed, Cancerlit, the Cochrane Library, CNKI and major scientific meetings. Randomized controlled trials and nonrandomized studies comparing surgery plus adjuvant chemotherapy with surgery alone in patients with resectable thoracic esophageal squamous cell carcinomas were included. Eleven studies with a total of 2047 patients were identified, consisting of the adjuvant chemotherapy arm (n = 887) and surgery‐alone arm (n = 1160). There was not statistically significant benefit on 3‐year overall survival for adjuvant chemotherapy (risk ratio [RR] = 0.89, 95% confidence interval [CI], 0.72 to 1.09; P = 0.25). Adjuvant chemotherapy could significantly prolong the 1‐year disease‐free survival (DFS) (RR = 0.68, 95%CI, 0.51 to 0.89; P = 0.006), but not 3‐year DFS (RR = 0.97, 95%CI, 0.73 to 1.29; P = 0.84). Further analysis showed that patients with stage III‐IV diseases could benefit from adjuvant chemotherapy on 3‐year overall survival (RR = 0.43, 95%CI, 0.31 to 0.61; P = 0.00001), but not in the case of patients with stageI‐IIdiseases (RR = 1.12, 95%CI, 0.65 to 1.93; P = 0.68). Additionally, patients with positive lymph node could benefit on 5‐year DFS from adjuvant chemotherapy (RR = 0.79, 95%CI, 0.64 to 0.99; P = 0.04). The modality treatment with adjuvant chemotherapy for patients with squamous cell carcinoma of thoracic esophagus might be determined according to pathological stage or the status of lymph node metastasis.     

布地奈德对脂多糖诱导大鼠急性肺损伤的影响

目的探讨布地奈德对脂多糖(LPS)诱导大鼠急性肺损伤的影响。方法将30只雄性Sprague Dawley大鼠随机分为3组:对照组、LPS组和布地奈德组,每组10只。采用经气管插管给予LPS(5 mg/kg)制备大鼠急性肺损伤模型;布地奈德组给予LPS 24 h后经气道给予布地奈德(500μg/kg)。3组均于48 h后测定肺水清除率,称量肺湿干重比,采用酶联免疫吸附试验测定支气管肺泡灌洗液中白细胞介素1β的水平,HE染色观察肺组织病理学改变,免疫组织化学法观察细胞间黏附分子1的表达。结果与LPS组相比,布地奈德干预后,肺组织结构破坏明显减轻,炎症细胞浸润减少,肺水清除率提高(P值均<0.01),肺湿干重比降低(P<0.05),支气管肺泡灌洗液中蛋白含量及中性粒细胞、巨噬细胞等的渗出减少(P<0.05或P<0.01),细胞间黏附分子1表达减少。结论布地奈德对LPS诱导的急性肺损伤大鼠具有肺保护作用,其机制考虑与减少细胞炎症反应、减少炎症因子对内皮细胞的活化、加强肺水清除作用有关。     

局部治疗联合EGFR-TKIs在晚期耐药肺腺癌中的临床应用研究

目的探讨表皮细胞生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)使用后耐药进展的肺腺癌患者给予局部治疗(冷冻消融、支气管动脉栓塞)联合EGFR-TKIs的临床疗效。方法回顾性分析2012年3月至2018年10月应急总医院经病理证实并完成随访的原发性EGFR敏感突变型晚期肺腺癌患者,进展后再行EGFR基因检测为T790M阴性,继续应用EGFR-TKIs的同时联合局部治疗,分别统计PFS1(从使用EGFR-TKIs到疾病进展时间)、PFS2(从冷冻消融到疾病进展时间)、OS(总生存期)、OS1(冷冻消融后的生存期),及冷冻消融后的并发症情况。分析OS及PFS的统计学相关影响因素。结果32例符合入组标准的晚期肺腺癌患者,PFS1平均时间为(12.4±8.6)个月。其中14例患者冷冻消融前行支气管动脉栓塞治疗,共消融病灶38个。PFS2为(6.7±2.9)个月。OS为(31.5±13.5)个月,其中OS1为(15.5±7.6)个月。统计分析显示PFS1与PFS2与OS存在显著相关性(P<0.05),靶向治疗进展后至氩氦冷冻消融的时间与患者的OS及OS1存在相关性,支气管动脉栓塞联合氩氦消融治疗后并发症主要为气胸及肺内出血,对症处理后均可缓解。结论EGFR-TKIs耐药进展后晚期肺腺癌中,EGFR-TKIs继续使用并联合冷冻消融等局部治疗可延长患者生存,并发症少,取得临床获益。     

How Can I Manage Thrombocytopenia in Hemodialysis Patient? A Review

Hemodialysis (HD) is the most important treatment for patients with end‐stage renal disease (ESRD). Thrombocytopenia is a potential treatment complication related to dialysis. Under normal circumstances, the platelet count would slightly decrease within the first hour of HD, but get restored towards the end of procedure. In most patients, the platelet count can be maintained within the normal range, and the occurrence of thrombocytopenia is relatively rare in clinical practice. Therefore, the possibility of thrombocytopenia in HD patients is often ignored. Moreover, thrombocytopenia might be misdiagnosed and mistreated. At present, almost all articles on the subject, apart from some case reports, focus on pseudothrombocytopenia and heparin‐induced thrombocytopenia. In this review, we summarized various underlying causes, mechanisms, and diagnostic approaches to thrombocytopenia in HD patients. The review aims to provide a guide for clinicians interested in the causes and adequate treatment of thrombocytopenia.     

Causes of Death after Congenital Heart Surgery in Children

Background: This retrospective cohort study aimed to explore the causes of death in children with congenital heart disease (CHD) after cardiac surgery in one of the biggest cardiac centers for children with CHD in China. Methods: A total of 26,856 children undergoing cardiac surgery from January 1, 2012 to December 31, 2019 were included. Based on the clinical data, the causes of death were divided into ten categories and further compared among different periods, types of CHD and surgical procedures. Results: Of all patients, 513 (1.9%) died (median age 162 d, median weight 5.6 kg). The mortality in 2016–2019 was lower than that in 2012–2015 (1.4 ± 0.3% vs. 2.5 ± 0.3%, p = 0.005). A total of 42.5% of children died of heart failure, and 32.9% died of residual anatomic defects. Patients with transposition of the great arteries tended to die from residual anatomic defects (21.9%), while those with double-outlet right ventricle (20%) and single ventricle (20%) tended to die from pulmonary hypertension (PH) (p = 0.006). After biventricular repair, children tended to die from heart failure (90.4%), while after single-ventricle repair, children tended to die from PH (50%) (p < 0.0001). There is a negative correlation between mortality and the ECMO implantation rate (r = −0.898, p = 0.002). Conclusions: Heart failure and residual anatomic defects were the main causes of death after cardiac surgery. The cause of death patterns differed among CHD types and surgical strategies. ECMO may be a life-saving tool when other conventional therapies do not work.