血清窖蛋白-1在慢性阻塞性肺疾病相关肺动脉高压患者中的表达及意义

目的 研究血清窖蛋白-1 （Cav-1） 在慢性阻塞性肺疾病 （COPD） 相关肺动脉高压 （PAH） 患者中的表达及其意义。方法 选取稳定期COPD患者65例， 根据是否合并PAH分成COPD组 ［肺动脉收缩压 （PASP） ＜40 mmHg， 35例］ 及COPD-PAH组 （PASP ≥40 mmHg， 30例）。另选取在本院健康体检的志愿者30例作为对照组。对比各组基线资料、 动脉血气分析、 肺功能指标， 以及血清Cav-1、 白细胞介素 （IL） -6和肿瘤坏死因子-α （TNF-α） 的表达水平。绘制受试者工作特征 （ROC） 曲线， 评价Cav-1对COPD合并PAH的诊断价值。结果 COPD-PAH组与COPD组第一秒用力呼吸容积 （FEV1） /用力肺活量 （FVC）、 FEV1占预计值百分比 （FEV1%） 及氧分压 ［p （O2 ）］ 低于对照组， 而二氧化碳分压 ［p （CO2 ）］、 PASP均高于对照组 （P＜0.01）。COPD-PAH组p （O2 ） 低于COPD组， p （CO2 ）、 PASP均高于COPD 组 （P＜0.01）。对照组、 COPD组及COPD-PAH组Cav-1表达水平呈逐渐降低趋势， 而IL-6、 TNF-α表达水平呈逐渐升高趋势 （P＜0.01）。血清Cav-1诊断COPD合并PAH的ROC曲线下面积为0.902 （0.821～0.955）， 最佳截断值为 6.66 μg/L， 此时诊断敏感度为76.7%， 特异度为85.7%， 与多普勒超声诊断仪测量PASP结果比较一致性较好 （Kappa 值=0.627）。结论 血清Cav-1在COPD相关PAH患者表达明显下调， 可以作为预测COPD相关PAH的新型血清标志物。     

Severe periodontitis is associated with the serum levels of hypersensitive C reactive protein and lipoprotein-associated phospholipase A2 in the patients of acute ischemic stroke

BackgroundPeriodontitis is associated with the pathogenesis of atherosclerotic plaque, and hypersensitive C reactive protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) are the serum biomarkers of the stability of atherosclerotic plaque. Whether periodontitis is associated with the serum level of hs-CRP and Lp-PLA2 of acute ischemic stroke remains unclear.Material and MethodsWe recruited 103 cases with acute ischemic stroke within 7 days after stroke onset. Pocket depth and clinical attachment loss were assessed by oral examination to define the severe periodontitis. Demographic information including gender, age and body weight index, income level, education level, past medical history include smoking history, drinking history, ischemic stroke history, coronary heart disease, hypertension, diabetes and hyperlipidemia were collected, and serum biomarkers including white blood cell (WBC), fibrinogen, total cholesterol (TC), triglyceride (TG), lower density lipoprotein (LDL-C), high density lipoprotein (HDL-C), hs-CRP, HemoglobinA1c (HbAlc), Homocysteine (HCY) and Lp-PLA2 were tested.Results65 (63.1%) cases were diagnosed as severe periodontitis. Severe periodontitis group showed more male, age, drinking history, higher levels of hs-CRP and Lp-PLA2. Multivariate logistic regression showed that severe periodontitis was were significantly associated with hs-CRP (OR = 2.367, 95%CI: 1.182–4.738; P = .015) and Lp-PLA2 (OR = 2.577, 95% CI: 1.010–6.574; P = .048).ConclusionsSevere periodontitis is independently associated with the serum Level of hs-CRP and Lp-PLA2 in patients with acute ischemic stroke. Whether the improvement of periodontitis could decrease the occurrence and re-occurrence of ischemic stroke by stablizating atherosclerotic plaque need be further studied in future.     

Review of clinical characteristics,immune responses and regulatory mechanisms of hepatitis E-associated liver failure

Hepatitis E virus (HEV) is the most common cause of acute liver failure (LF) and one of the most common factors causing acute injury in acute-on-chronic LF (ACLF). When HEV-related LF occurs, a series of changes take place in both the intrahepatic environment and extrahepatic microenvironment. The changed types and distribution of immune cells (infiltrating macrophages and increased lymphocytes) in liver tissue, as well the increased proinflammatory cytokines and chemokines in the blood, indicate that the occurrence and progression of HEV-related LF are closely related to immune imbalance. The clinical features and immune reaction in the body during HEV-related acute LF (ALF) and ACLF are complicated. This review highlights recent progress in elucidating the clinical manifestations of HEV-associated ALF and ACLF and discusses the corresponding systemic immune changes and possible regulatory mechanisms.     

B细胞介导的体液免疫应答在肝移植急性排斥反应中的作用

目前，国内外肝移植学界对肝移植术后急性排斥反应(AR)的机制阐释为T细胞介导的细胞免疫应答，但为获得长期生存仍需长期乃至终身服用免疫抑制剂。即使如此，临床上AR仍时有发生，并导致相当一部分受者移植肝功能丧失，更重要的是受者术后还受到感染、肿瘤和其他一系列不良反应及沉重经济负担的影响。因此，为肝移植AR机制提出新的理论解释，更全面深入阐明肝移植免疫排斥反应的内在机制，进而依据新的机制研制出新型免疫抑制剂已势在必行。本文就B细胞介导的体液免疫应答在肝移植AR中的作用作一综述。     

NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine

6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP. One hundred and sixty-nine pediatric patients were enrolled and their genotypes were determined. Patients who carried NUDT15¹3 and NUDT15¹2 genotypes were at a 10–15 fold higher risk of severe neutropenia than those of the wild-type during the early months of the maintenance phase. Risk of neutropenia was not significantly increased in patients with other NUDT15 variants as well as in patients with TPMT, ITPA or ABCC4 variants. These results suggest that NUDT15 polymorphisms particularly, NUDT15¹3 and NUDT15¹2, play major roles in 6-MP-induced severe hematotoxicity even when using a standard low dosage of 6-MP and genotyping of these variants is necessary in order to obtain precise tolerance doses and avoid severe hematotoxicity in pediatric patients.     

The prognostic value of elevated neutrophil–lymphocyte ratio for cardiac surgery-associated acute kidney injury: A systematic review and meta-analysis

Background

Patients undergoing cardiac surgery are at significant risk of developing postoperative acute kidney injury (AKI). Neutrophil–lymphocyte ratio (NLR) is a widely available inflammatory biomarker which may be of prognostic value in this setting.

Methods

We conducted a systematic review and meta-analysis of studies reporting associations between perioperative NLR with postoperative AKI. We searched Medline, Embase and the Cochrane Library, without language restriction, from inception to May 2022 for relevant studies. We meta-analysed the reported odds ratios (ORs) with 95% confidence intervals (CIs) for both elevated preoperative and postoperative NLR with risk of postoperative AKI and need for renal replacement therapy (RRT). We conducted a meta-regression to explore inter-study statistical heterogeneity.

Results

Twelve studies involving 10,724 participants undergoing cardiac surgery were included, with eight studies being deemed at high risk of bias using PROBAST modelling. We found statistically significant associations between elevated preoperative NLR and postoperative AKI (OR 1.45, 95% CI 1.18–1.77), as well as postoperative need for RRT (OR 2.37, 95% CI 1.50–3.72). Postoperative NLR measurements were not of prognostic significance.

Conclusions

Elevated preoperative NLR is a reliable inflammatory biomarker for predicting AKI following cardiac surgery.