Association between de novo lipogenesis susceptibility genes and coronary artery disease

Background and aimsCoronary artery disease (CAD) is the principal cause of death in individuals with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to use genetic epidemiology to study the association between de novo lipogenesis (DNL), one of the major pathways leading to NAFLD, and CAD risk.Methods and resultsDNL susceptibility genes were used as instruments and selected using three approaches: 1) genes that are associated with both high serum triglycerides and low sex hormone-binding globulin, both downstream consequences of DNL (unbiased approach), 2) genes that have a known role in DNL (biased approach), and 3) genes that have been associated with serum fatty acids, used as a proxy of DNL. Gene-CAD effect estimates were retrieved from the meta-analysis of CARDIoGRAM and the UK Biobank (～76014 cases and ～264785 controls). Effect estimates were clustered using a fixed-effects meta-analysis. Twenty-two DNL susceptibility genes were identified by the unbiased approach, nine genes by the biased approach and seven genes were associated with plasma fatty acids. Clustering of genes selected in the unbiased and biased approach showed a statistically significant association with CAD (OR:1.016, 95%CI:1.012; 1.020 and OR:1.013, 95%CI:1.007; 1.020, respectively), while clustering of fatty acid genes did not (OR:1.004, 95%CI:0.996–1.011). Subsequent exclusion of potential influential outliers did reveal a statistically significant association (OR:1.009, 95%CI:1.000; 1.018).ConclusionsDNL susceptibility genes are associated with an increased risk of CAD. These findings suggest that DNL may be involved in the pathogenesis of CAD and favor further development of strategies that target NAFLD through DNL.     

Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.     

Can hepatokines be regarded as novel non-invasive serum biomarkers of intrahepatic lipid content in obese children?

PurposeHepatokines are proteins produced by the liver and involved in regulating glucose and lipid metabolism. However, their role as the biomarkers of intrahepatic lipid content is not clear. The aim of the study was to evaluate the serum concentration of selected hepatokines: fibroblast growth factor-21 (FGF-21), selenoprotein P (SELENOP) and sex hormone-binding globulin (SHBG) in obese children.Patients and methodsThe cross-sectional study included 86 obese children with suspected liver disease. Nonalcoholic fatty liver disease (NAFLD) was diagnosed in children with liver steatosis in ultrasound with elevated alanine aminotransferase (ALT) serum activity and excluded other liver diseases. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (¹H-MRS).ResultsThe concentration of FGF-21 and SELENOP was significantly higher and SHBG significantly lower in children with NAFLD compared to controls. Only FGF-21 level was significantly higher in NAFLD children than in obese patients without NAFLD. The significant positive correlation of FGF-21 with ALT, gamma glutamyltransferase (GGT), triglycerides, homeostatic model assessment–insulin resistance (HOMA-IR), the degree of liver steatosis in ultrasound and TILC in ¹H-MRS were found. The ability of serum FGF-21 to diagnose severe liver steatosis was significant.ConclusionsFGF-21 can be considered as a suitable biomarker in predicting TILC and fatty liver in obese children.     

防芷鼻炎片联合氯雷他定治疗变应性鼻炎的临床研究

目的探讨防芷鼻炎片联合氯雷他定治疗变应性鼻炎的临床疗效。方法选取2016年8月—2017年6月于鄂州市中心医院耳鼻喉科就诊的变应性鼻炎患者78例,随机分为对照组(38例)和治疗组(40例)。对照组患者口服枸地氯雷他定片,1片/次,1片/d。治疗组患者在对照组的基础上,口服防芷鼻炎片,5片/次,3次/d,饭后服用,两组患者均治疗28 d。观察两组患者临床疗效,比较治疗前后两组患者鼻功能评分、肺功能和血清学指标。结果治疗后,对照组和治疗组的总有效率分别为73.68%和92.50%,两组比较差异具有统计学意义(P0.05)。治疗后,两组鼻痒、鼻塞、喷嚏、流涕评分均明显降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗后治疗组上述鼻功能评分均显著低于对照组,两组比较差异有统计学意义(P0.05)。两组患者最大呼气流速(PEF)、1秒用力呼气容积(FEV1)/用力肺活量(FVC)均明显升高,PEF变异率明显降低,同组治疗前后差异有统计学意义(P0.05);且治疗后治疗组的肺功能指标显著优于对照组,两组比较差异有统计学意义(P0.05)。两组患者免疫球蛋白Ig E、Ig G4、白细胞介素(IL)-4、IL-5明显降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗后治疗组的血清学指标显著低于对照组,两组比较差异有统计学意义(P0.05)。结论防芷鼻炎片联合氯雷他定治疗变应性鼻炎有较好的临床疗效,可改善患者临床症状和肺功能,并减轻机体变态反应和炎症反应,具有一定的临床应用价值。     

Analysis of relationships between polymorphisms in the genes encoding the pentameric complex and neutralization of clinical cytomegalovirus isolates

IntroductionAs congenital cytomegalovirus (CMV) infection is one of the major causes of birth defects and developmental abnormalities, it is essential to develop vaccines and therapeutic antibodies against CMV. Clinical trials demonstrated that the subunit vaccine based on glycoprotein B, which had been believed to be the major target for neutralization, did not induce sufficient protective immunity. On the other hand, it has been reported that the immunization of animals with the Pentamer, the pentameric complex of gH/gL/UL128/UL130/UL131A, induced strong neutralizing antibodies. Here, we sought to clarify whether any polymorphic alterations present in the Pentamer of clinical isolates affect neutralization by anti-Pentamer antibodies.MethodsSequences of the genes encoding the Pentamer components of 25 Japanese clinical isolates were determined. Neutralization of infection by two seropositive sera and by anti-Pentamer serum was measured using a CMV reporter cell line based on ARPE-19.ResultsPolymorphisms of the amino acid sequence of UL128, UL130, and UL131A ORFs were limited and clustered into two major groups. The identified alterations, except UL128 I140T, were mapped outside of the reported regions recognized by neutralizing antibodies. Anti-Pentamer serum neutralized infection with all isolates to a similar degree and had no correlation with the polymorphic groups.ConclusionsOur findings indicate that Pentamer antigens prepared from Merlin Fix strain induce antibodies that neutralize infection with all isolates to a similar level and that anti-Pentamer antibodies neutralize CMV infection better than do human sera, suggesting that vaccines and therapeutic antibodies based on Pentamer as an antigen have some promise.     

温针灸对类风湿性关节炎大鼠血清免疫球蛋白及滑膜组织中VCAM-1的影响

目的:观察温针灸对类风湿性关节炎(Rheumatoid arthritis,RA)大鼠血清免疫球蛋白及滑膜组织中血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)的影响,探讨温针灸改善类风湿性关节炎的作用机制。方法:选取清洁级3月龄SD健康大鼠60只,雌雄各半,体质量(208±4.5)g,先适应性喂养1周,然后按照数字表法随机抽取15只为正常组进行常规喂养,其余大鼠进行模型复制,并随机分为模型组、针刺组和温针灸组,每组15只。采用皮内注射牛Ⅱ型胶原接种诱发制备大鼠类风湿性关节炎模型。温针灸组于造模后第1天取"足三里""肾俞"和"悬钟"温针灸治疗,采用手针,刺激量以大鼠耐受为度,日1次,共治疗21 d。针刺组针刺方法同温针灸组,不用艾灸。模型组不给予任何处理。疗程结束后滑膜取材,采用MD-100自动生化分析仪检测血清中IgG、IgM和IgA的含量,以免疫组化法检测VCAM-1在滑膜组织中的表达。结果:与正常组比较,模型组大鼠血清IgG、IgM、IgA含量和滑膜组织中VCAM-1表达水平显著升高(P0.05);与模型组比较,温针灸组和针刺组大鼠血清IgG、IgM、IgA含量和滑膜组织中VCAM-1表达水平显著降低(P0.05);与针刺组比较,温针灸组大鼠血清IgG、IgM、IgA含量和滑膜组织中VCAM-1表达水平降低幅度更明显(P0.05)。结论:温针灸可升高RA大鼠血清IgG、IgM和IgA的含量,抑制VCAM-1在滑膜组织中的表达,可能是温针灸通过调节RA大鼠慢性炎症以改善关节损伤的调节机制之一。     

糖皮质激素联合丙种球蛋白治疗丙种球蛋白无反应型川崎病的临床疗效

目的 分析糖皮质激素联合静脉注射丙种球蛋白(IVIG)治疗IVIG无反应型川崎病的临床效果。方法 选取2016年6月至2020年6月于我院住院治疗确诊为IVIG无反应型KD患儿68例作为研究对象,依据再次治疗是否联合使用糖皮质激素分为A组(IVIG)和B组(糖皮质激素联合IVIG),其中A组42例、B组26例。分析两组患儿总热程、热退时间、冠状动脉损害情况及再次治疗前、治疗后1周实验室指标白细胞(WBC)、血小板(PLT)、超敏C反应蛋白(hsCRP)、血沉、IL-6的变化。结果 B组患儿的总热程、热退时间均短于A组,差异有统计学意义(P0.05)。B组患儿出现冠状动脉扩张、冠状动脉瘤发生率略高于A组,但差异无统计学意义(P0.05)。B组治疗后WBC高于A组, B组WBC治疗前后差值低于A组;B组治疗前hsCRP及治疗前后hsCRP差值均高于A组;B组治疗后IL-6低于A组,B组IL-6治疗前后差值高于A组,差异均有统计学意义(P0.05)。结论两种方案治疗IVIG无反应型川崎病均有效;两组冠状动脉损害发生率,差异无统计学意义,糖皮质激素联合IVIG没有增加冠状动脉病变的发生风险;不同治疗方案对两组患儿治疗前后WBC、hsCRP、IL-6水平存在影响,与单用IVIG治疗相比,糖皮质激素联合IVIG在KD急性期能更好的控制IVIG无反应型KD患儿的炎症指标并能缩短发热时间。     

大剂量丙种球蛋白辅助治疗成人重症病毒性肺炎临床效果的Meta分析

背景　近年来,病毒性肺炎患病率较高,尤其是流感所致的重症肺炎具有高死亡率,已有研究表明静脉滴注免疫球蛋白可辅助治疗重症肺炎,但是仅有散在研究及案例报道,缺乏系统的临床疗效评价。目的　评价静脉滴注大剂量丙种球蛋白（IVIG）辅助治疗成人重症病毒性肺炎的临床疗效。方法　检索PubMed、EMBase、Web of Science、The Cochrane Library、中国知网、万方数据知识服务平台、中国生物医学文献数据库、维普网中关于两种治疗方案临床疗效对比的随机对照研究,检索时间为建库至2020-03-05。对纳入研究的文献进行质量评价和数据提取,收集患者的临床有效率、C反应蛋白（CRP）、CD4+、CD4+/CD8+、白介素2（IL-2）、不良反应发生率等指标,并进行Meta分析。结果　共纳入9篇文献,1 021例患者,文献质量等级均为B。Meta分析结果显示,试验组临床有效率〔RR=1.24,95%CI（1.18,1.31）,P<0.000 01〕、CD4+水平〔MD=10.05,95%CI（9.19,10.90）,P<0.000 01〕,CD4+/CD8+〔MD=0.75,95%CI（0.68,0.82）,P<0.000 01〕〕高于对照组,治疗后CRP水平〔MD=-3.64,95%CI（-4.23,-3.05）,P<0.000 01〕、IL-2水平〔MD=0.61,95%CI（0.45,0.77）,P<0.000 01〕、不良反应发生率〔RR=0.30,95%CI（0.16,0.55）,P<0.000 01〕低于对照组。结论　静脉滴注大剂量IVIG能改善成人重症病毒性肺炎的临床结局。