Left Ventricular Systolic Dysfunction and Cardiovascular Outcomes in Tetralogy of Fallot: Systematic Review and Meta-analysis

BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem.     

Coronary Artery Disease Manifestations in HIV: What,How, and Why

Understanding why persons with human immunodeficiency virus (HIV) have accelerated atherosclerosis and its sequelae, including coronary artery disease (CAD) and myocardial infarction, is necessary to provide appropriate care to a large and aging population with HIV. In this review, we delineate the diverse pathophysiologies underlying HIV-associated CAD and discuss how these are implicated in the clinical manifestations of CAD among persons with HIV. Several factors contribute to HIV-associated CAD, with chronic inflammation and immune activation likely representing the primary drivers. Increased monocyte activation, inflammation, and hyperlipidemia present in chronic HIV infection also mirror the pathophysiology of plaque rupture. Furthermore, mechanisms central to plaque erosion, such as activation of toll-like receptor 2 and formation of neutrophil extracellular traps, are also abundant in HIV. In addition to inflammation and immune activation in general, persons with HIV have a higher prevalence than uninfected persons of traditional cardiovascular risk factors, including dyslipidemia, hypertension, insulin resistance, and tobacco use. Antiretroviral therapies, although clearly necessary for HIV treatment and survival, have had varied effects on CAD, but newer generation regimens have reduced cardiovascular toxicities. From a clinical standpoint, this mix of risk factors is implicated in earlier CAD among persons with HIV than uninfected persons; whether the distribution and underlying plaque content of CAD for persons with HIV differs considerably from uninfected persons has not been definitively studied. Furthermore, the role of cardiovascular risk estimators in HIV remains unclear, as does the role of traditional and emerging therapies; no trials of CAD therapies powered to detect clinical events have been completed among persons with HIV.     

A Minimum Of 100 Tumor Cells in a Single Biopsy Sample Is Required to Assess Programmed Cell Death Ligand 1 Expression in Predicting Patient Response to Nivolumab Treatment in Nonsquamous Non–Small Cell Lung Carcinoma

IntroductionProgrammed death ligand 1 (PD-L1) expression is a predictive biomarker for patient response to nivolumab in nonsquamous NSCLC. However, the number of biopsy samples and tumor cells (TCs) required to assess PD-L1 expression remains unclear.MethodsA total of 222 biopsy samples from 80 patients with nonsquamous NSCLC treated with nivolumab were collected. Number of TCs and PD-L1 score were compared among the sample containing the largest number of TCs (Max-TC), the sample containing the smallest number of TCs (Min-TC), and the total samples from each patient. The impact of the number of samples and TCs on the prediction of patient response to nivolumab with use of PD-L1 scores was evaluated.ResultsThere was a mismatch in PD-L1 scores less than 1% and those of at least 1% between Max-TC and the total samples in one patient (1%) and between Max-TC and Min-TC in six patients (8%). The optimal number of TCs to match PD-L1 expression less than 1% versus at least 1% between Max-TC and Min-TC was 100 (sensitivity = 0.676 and 1 – specificity = 0.333). PD-L1 expression of at least 1% in Min-TCs containing at least 100 TCs was associated with longer progression-free survival (median 7.6 versus 1.8 months [p < 0.01]) and overall survival (median not reached versus 9.9 months [p = 0.04]) compared with PD-L1 expression less than 1%. However, there were no differences in progression-free survival (median 3.9 versus 2.3 months [p = 0.37]) or overall survival (median 9.7 versus 7.6 months [p = 0.60]) between PD-L1 expression of at least 1% and PD-L1expression less than 1% in Min-TCs containing fewer than 100 TCs.ConclusionSingle biopsy samples containing at least 100 TCs are required to evaluate PD-L1 expression for predicting patient response to nivolumab.     

Profilin 1, negatively regulated by microRNA-19a-3p,serves as a tumor suppressor in human hepatocellular carcinoma

Profilin 1 (PFN1) is a critical actin-regulatory protein; however, its functional role in hepatocellular carcinoma (HCC) progression remains to be further elucidated. In the present study, we observed that the expression levels of PFN1 were significantly decreased in HCC tissues and cell lines. Low PFN1 expression was significantly correlated with aggressive clinicopathological characteristics and poor prognosis of HCC patients. Further in vitro experiments demonstrated that overexpression of PFN1 remarkably inhibited the proliferation, migration, invasion and EMT of HCC cells. Moreover, we also found that PFN1 was a direct target gene of miR-19a-3p, and in HCC tissues, and there was a significantly inverse correlation between PFN1 mRNA and miR-19a-3p expression. Collectively, our results showed that PFN1 functions as a tumor suppressor in HCC, and might serve as a diagnostic and therapeutic target for HCC patients.     

喉癌患者PAC-1、CD62P表达与临床病理特征和复发的关系

目的探讨喉癌患者血小板表面血小板膜糖蛋白Ⅱb/Ⅲa纤维蛋白原受体(PAC-1)、血小板P-选择素(CD62P)阳性表达率以及与患者临床病理特征和复发的关系。方法选取2014年1月~2015年12月间在我院耳鼻喉科手术治疗的116例喉癌患者,随访≥2年,并选取同期在我院体检的健康人群60例为对照组,采用流式细胞仪检测法检测外周血PAC-1和CD62P阳性率,并分析与临床病理特征、复发的关系。结果喉癌患者PAC-1和CD62P阳性表达率分别为(17.82±1.76)%和(22.87±3.13)%,明显高于健康人群(P<0.05);而且在喉癌患者PAC-1表达和CD62P表达呈正相关性(r=0.238,P<0.05)。T3-T4分期或N2-N3分期患者PAC-1和CD62P阳性表达率高于T1-T2分期或N0-N1分期患者(P<0.05)。另外远处转移组PAC-1和CD62P阳性表达率高于未发生转移组(P<0.05);随访期间有24例患者复发,复发率为20.69%。复发喉癌患者PAC-1、CD62P阳性表达率分别为(17.02±0.85)%和(21.84±1.17)%,明显高于未复发的喉癌患者(P<0.05)。经Logistics回归分析,PAC-1和CD62P是喉癌患者复发的独立危险因素(P<0.05)。结论PAC-1和CD62P阳性表达率与喉癌患者T分期、淋巴结转移和远处转移密切相关,同时可作为喉癌局部复发、区域淋巴结转移、远处转移的预测指标。     

紫癜1号中药熏洗治疗小儿过敏性紫癜临床观察

目的观察紫癜1号中药熏洗治疗小儿过敏性紫癜的临床效果。方法选取收治的过敏性紫癜患者80例,按照研究方法的不同分为观察组和对照组,对照组患者40例,给予喜炎平注射液、维生素C注射液、葡萄糖酸钙注射液等进行治疗;观察组患者在对照组基础上采用紫癜1号中药熏洗进行治疗,比较2组患者的临床治疗效果、皮肤紫癜消退时间及关节肿痛缓解状况等相关指标。结果对照组患者的治疗有效率为75.0%,观察组患者的治疗有效率为97.5%,观察组治疗有效率显著高于对照组;观察组患儿皮肤紫癜消退时间为(4.10±1.02)d,少于对照组(7.69±1.79)d;观察组患者经治疗后关节肿痛情况完全缓解达到50.0%,缓解达到35.0%,明显优于对照组。结论紫癜1号中药熏洗治疗小儿过敏性紫癜,治疗效果明显,有效缩短患者紫癜消退时间及缓解关节痛的程度。     

Magnesium lithospermate B acts against dextran sodiumsulfate-induced ulcerative colitis by inhibiting activation of the NRLP3/ASC/Caspase-1 pathway

This study aimed to observe the therapeutic effects of magnesium lithospermate B on acute and chronic colitis induced by dextran sodiumsulfate (DSS) and the role of inflammasome complex (NOD-like receptor protein, NLRP; apoptosis-associated speck-like protein containing, ASC; caspase-1). Establishment of acute and chronic colitis models were by using 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (240 mg/kg body weight) was given by subcutaneous injection. Samples were collected for biomarker assay, histological examination, immunohistochemical evaluation and western blot. There was obvious increase in TNF-α level and NLPR3, ASC, and caspase-1 expressions in acute and chronic colitis groups compared with the normal control. Significant decrease of the tumor necrosis factor-α level and the expressions of NLPR3, ASC, and caspase-1 were observed after treatment with magnesium lithospermate B. This study showed that magnesium lithospermate B could be used to treat acute and chronic colitis by inhibiting the activation of the NLRP3/ASC/Caspase-1 pathway.     

IFI 30、PD-L1在人脑胶质瘤中的表达及与病人预后的关系

目的 探讨γ干扰素诱导蛋白30（IFI 30）、程序性死亡因子配体1（PD-L1）在人脑胶质瘤中的表达及与病人预后的关系。方法 选择2015年5月~2019年5月手术切除的103例人脑胶质瘤组织和瘤旁组织，采用免疫组织化学染色检测IFI 30、PD-L1表达情况。随访24个月，记录无进展生存期和总生存期。结果 胶质瘤组织IFI 30、PD-L1高表达率[分别为70.87%（73/103）、68.93%（71/103）]明显高于瘤旁组织[分别为19.42%（20/103）、21.36%（22/103）；P<0.001]。胶质瘤组织IFI 30表达水平与PD-L1表达水平呈明显正相关（r=0.583，P<0.05）。随访24个月，生存75例，死亡28例；多因素logistic回归分析显示，IFI 30高表达、PD-L1高表达是增加病人死亡风险的独立危险因素（P<0.05）。生存曲线分析显示，IFI 30高表达组2年累积生存率（64.52%）和2年累积无进展生存率（65.56%）均明显低于低表达组（分别为82.25%、89.45%；P<0.05）。PD-L1高表达组2年累积生存率（61.78%）和2年累积无进展生存率（60.14%）均明显低于低表达组（分别为88.52%、79.86%；P<0.05）。结论 人脑胶质瘤组织IFI 30、PD-L1呈高表达，与病人不良预后密切相关。     

"肾脑相济"电针对阿尔茨海默病模型小鼠行为学及IL-1β、TNF-α表达的影响

目的观察"肾脑相济"电针对阿尔茨海默病(AD)模型小鼠行为学和大脑皮质炎性因子白细胞介素-1β(IL-1b)和肿瘤坏死因子-α(TNF-α)表达的影响,探究"肾脑相济"电针疗法治疗阿尔茨海默病的作用机理。方法将7月龄雄性SAMP8小鼠随机分成模型组、西药组和电针组,每组6只;将SAMR1小鼠作为对照组。西药组给予盐酸多?哌齐灌胃,电针组电针百会、肾俞和三阴交。采用Morris水迷宫观察小鼠行为学,应用免疫组化法、Western Blot法测定大脑皮质区IL-1b、TNF-α的阳性细胞数和蛋白表达。结果与对照组比较,模型组小鼠学习记忆能力明显下降,IL-1b、TNF-α的表达升高,差异有统计学意义(P<0.05);与模型组比较,西药组和电针组小鼠学习记忆能力增强,IL-1b、TNF-α的表达降低,差异有统计学意义(P<0.05);与西药组比较,电针组小鼠学习记忆能力及IL-1b、TNF-α的表达变化不明显,差异无统计学意义(P>0.05)。结论"肾脑相济"电针疗法可以改善SAMP8模型小鼠的学习和记忆能力,降低大脑皮质区IL-1b、TNF-α的含量,从而对阿尔茨海默病达到治疗效果。