miR-146a-5p regulates autophagy and NLRP3 inflammasome activation in epithelial barrier damage in the in vitro cell model of ulcerative colitis through the RNF8/Notch1/mTORC1 pathway

Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon that can be influenced by microRNAs (miRNAs). This study aims to investigate the impact of miR-146a-5p on lipopolysaccharide (LPS)-induced Caco-2/HT-29 cell autophagy and NLRP3 inflammasome activation and the underlying mechanism, with the aim of identifying potential therapeutic targets. We used LPS to establish Caco-2/HT-29 cell models and measured cell viability by CCK-8. The levels of miR-146a-5p, RNF8, markers of NLRP3 inflammasome activation and autophagy, proteins involved in the Notch1/mTORC1 pathway, and inflammatory factors were assessed by RT-qPCR, Western blot, and ELISA. Intestinal epithelial barrier function was evaluated by measuring transepithelial electrical resistance. Autophagic flux was measured using tandem fluorescent-labeled LC3. miR-146a-5p was highly-expressed in LPS-induced Caco-2/HT-29 cells, and autophagy flux was blocked at the autolysosomal stage after LPS induction. Inhibition of miR-146a-5p suppressed NLRP3 inflammasome activation, reduced intestinal epithelial barrier damage, and facilitated autophagy inhibition in LPS-induced Caco-2/HT-29 cells. The autophagy inhibitor NH4Cl partially nullified the inhibitory effects of miR-146a-5p inhibition on NLRP3 inflammation activation. miR-146a-5p targeted RNF8, and silencing RNF8 partly abrogated the action of miR-146a-5p inhibition on promoting autophagy and inhibiting NLRP3 inflammasome activation. miR-146a-5p inhibition suppressed the Notch1/mTORC1 pathway activation by upregulating RNF8. Inhibition of the Notch1/mTORC1 pathway partially nullified the function of silencing RNF8 on inhibiting autophagy and bolstering NLRP3 inflammasome activation. In conclusion, miR-146a-5p inhibition may be a potential therapeutic approach for UC, as it facilitates autophagy of LPS-stimulated Caco-2/HT-29 cells, inhibits NLRP3 inflammasome activation, and reduces intestinal epithelial barrier damage by upregulating RNF8 and suppressing the Notch1/mTORC1 pathway.     

血红蛋白浓度对非小细胞肺癌放疗疗效的影响

目的:探讨分析血红蛋白浓度与非小细胞肺癌放射治疗后的生存率及局部肿瘤控制率之间的关系。方法:1993年3月—1999年1月,选择收治非小细胞肺癌(Ⅰ期~Ⅲ期,T1~4N0~3M0)218例,于放射治疗前根据血红蛋白(Hb)浓度分3组(贫血组、正常组和高血红蛋白组)。根据放射治疗中血红蛋白浓度的变化分为2组(Hb升高组及Hb降低组)。全部病例均予以根治性放射治疗,常规分割。对其生存率及局部肿瘤控制率予以观察、对比分析。结果:放射治疗前升高血红蛋白量可提高非小细胞肺癌患者的局部肿瘤控制率及生存率;放射治疗中血红蛋白量的升高及降低对非小细胞肺癌患者的生存率有影响。结论:升高血红蛋白量可提高非小细胞肺癌患者的生存率及局部肿瘤控制率。     

NEK7在原发性肝细胞肝癌患者中表达及其临床意义

目的 探究肝癌患者NEK7表达情况与患者临床生物学特征及预后的关系。方法 基于TCGA数据库提供的肝癌mRNA数据,以Cox回归及LASSO筛查选择重要的预后变量,Spearman相关性分析进行肝癌预后密切相关分子与NEK7表达的相关性分析。免疫组化检验肝癌标本癌组织、癌旁组织及非肿瘤肝脏组织中的NEK7表达的差异性,分析其不同表达情况与肝癌患者病理学特征之间的关系,并探究其不同表达水平肝癌患者预后差异性。结果 与肝癌预后密切相关的mRNA分子CCDC21及GTF3C2与NEK7之间的表达具有显著的相关性,单因素分析表明影响肝癌患者预后的因素主要有肿瘤分化程度、是否合并癌栓及NEK7表达情况,相较于癌旁组织及正常肝脏组织,肝癌组织中NEK7表达显著升高,且其表达水平及强度与肝癌分化程度、Child分级及是否合并有癌栓相关,高表达NEK7的肝癌患者,其生存时间较低表达者显著缩短。结论 肝癌患者预后因素主要有肿瘤分化程度、是否合并癌栓及NEK表达情况。NEK7在肝癌组织呈高表达状态,其表达水平及强度与肿瘤组织分化程度、Child分级及是否合并有癌栓相关,阳性表达NEK7肝癌患者生存时间显著缩短。     

多层螺旋CT诊断肾外肾盂(附47例报告)

目的 研究肾外肾盂的CT表现和鉴别诊断,加强对肾外肾盂的认识,避免误诊发生.方法 回顾分析47例肾外型肾盂的CT轴位平扫、增强扫描及三维重建表现.结果 在CT轴位平扫、增强扫描及三维重建中表现为在肾窦外囊样水密度影,CT增强时对比剂均匀充盈,三维重建显示更直观.其中双侧29例,单侧18例.结论 多层螺旋CT诊断肾外肾盂更为准确可靠.     

Preoperative neutrophil-to-lymphocyte ratio is a more valuable prognostic factor than platelet-to-lymphocyte ratio for nonmetastatic rectal cancer

Several combinations of inflammatory factors, including neutrophil-to- lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been reported to be prognostic factors in various malignant tumors, including colorectal cancer (CRC). The aim of this study was to evaluate the prognostic value of NLR and PLR for patients with rectal cancer (RC) who underwent curative surgery. Data from patients who underwent curative resection for RC were retrospectively reviewed. The cutoff for NLR and PLR was defined as 2.3 and 144 by receiver operating characteristic (ROC) curve. Overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier method. Multivariable Cox regression model was used to evaluate the independent prognostic significance of variables. A total of 140 patients were eligible in the study. High NLR (> 2.3) and high PLR (> 144) both predicted lower OS and DFS according to Kaplan-Meier method. But in the multivariable Cox regression model, only the high NLR retained significance for reduced OS and DFS. According to Chi-square test, patients with higher NLR had larger tumor size and higher pN-stage. While PLR was only associated with the pN-stage. High preoperative NLR was shown to be a negative independent prognostic factor in patients undergoing resection for nonmetastatic RC. It may be helpful as a factor to guide the postoperative therapies.     

Rasch analysis of a Spanish language-screening parent survey

The purpose of this study was to evaluate and refine items from a parent survey designed to screen the language skills of Spanish-speaking preschoolers. This investigation applied Rasch modeling to systematically evaluate and identify items that demonstrated favorable qualities.A set of 124 parent survey items was administered to 107 Spanish-speaking parents of preschool age children. Parents completed survey items intended to provide a global measure of preschool language abilities. Rasch analyses of the survey items were conducted using WINSTEPS.Results indicated that 59 items, all vocabulary items, fit the Rasch model. Sufficient unidimensionality was obtained, with the model accounting for 58% of the variance. Item difficulty estimates ranged from −7.43 to 4.12, with a shortage of items at both the lower ability level and at the higher ability level. Analyses of pruned and remaining items identified the type of items that may be most useful for a refined item bank. These results will inform the development of new items for a Spanish language-screening parent survey for preschool age children.     

TGR5 Attenuated Liver Ischemia-Reperfusion Injury by Activating the Keap1-Nrf2 Signaling Pathway in Mice

Inflammation - Hepatic ischemia/reperfusion injury (IRI) still remains an unavoidable problem in hepatectomy. The inflammatory response plays an important role in its pathogenesis. The plasma...     

脑梗死患者颈动脉粥样硬化与血清超敏C反应蛋白水平的相关性分析

目的探讨脑梗死患者的炎症标记物超敏C反应蛋白(hs-CRP)水平与颈动脉粥样硬化的相关性。方法将107例脑梗死患者按颈总动脉内-中膜厚度(IMT)分为IMT正常组、IMT增厚组和斑块组,或者IMT正常组和动脉粥样硬化组,比较各组间血清hs-CRP水平。结果 IMT增厚组、斑块组血清hs-CRP显著高于IMT正常组,差异均有统计学意义(P<0.05);斑块组血清hs-CRP显著高于IMT增厚组,差异有统计学意义(P<0.05)。动脉粥样硬化组血清hs-CRP显著高于IMT正常组,差异有统计学意义(P<0.05)。结论结合血清hs-CRP水平与颈动脉IMT可以预测脑梗死的发生及预后。     

Clinical characteristics,rates of blindness,and geographic features of PACD in China

ObjectiveTo analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China.MethodsA retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed.ResultsA total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes.ConclusionPACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes.