Identification of differentially expressed miRNAs and key genes involved in the progression of alcoholic fatty liver disease using rat models

BackgroundAlcoholic fatty liver disease (AFLD) is a liver disease caused by prolonged heavy drinking and has a poor prognosis in the clinic. This study aimed to explore the differential miRNAs expression profiles in the AFLD rat model.MethodsThe rat model of AFLD was established by ethanol intragastric administration and was used to explore the differential miRNAs expression profiles. We further analyzed the potential target mRNAs using the bioinformatics technique. GO and KEGG pathway enrichment analyses were carried out to better understand the biological function of differential expression genes (DEGs). We used the human Gene Expression Omnibus (GEO) dataset GSE28619 to further screen the key differentially expressed genes. The integration between the differentially expressed genes from the AFLD model and GEO was conducted and the key genes were identified.ResultsThe serum ALT, AST, TG, and TC levels in the AFLD model group were significantly higher than those in the normal control group. There are 45 miRNAs with significant changes including 26 upregulated and 19 down-regulated miRNAs. GO and KEGG enrichment showed various metabolic processes and signaling pathways were enriched in the progression of AFLD. After integrating the results of GSE28619 and DEGs, we observed that there are 12 genes with significant changes in two data sets, including PSAT1, TKFC, PTTG1, LCN2, CXCL1, NR4A1, RGS1, VCAN, FOS, CXCL10, ATF3, and CYP1A1.ConclusionAFLD showed differentially expressed miRNAs, which may be involved in the occurrence and progression of AFLD. Meanwhile, some signal metabolic pathways may be related to the pathogenesis of AFLD.     

直肠脱垂的外科治疗

直肠脱垂的发病机制尚未明确,幼儿直肠脱垂多采用非手术治疗,成人完全性直肠脱垂以手术为主。目前手术方法繁多,疗效不一。本文介绍了直肠脱垂经腹和经肛门两种入路的多种手术方式以及注射疗法、激光手术等常用的外科治疗方法,各有利弊。直肠脱垂的外科治疗提倡个体化治疗,应综合考虑患者的病因、年龄及病情,选择合适的治疗手段。     

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.     

Identification of peptides presented through the MHC-II of dendritic cells stimulated with Mycobacterium avium

Mycobacterium avium (M. avium) represents a species of concern, because of its ability to modulate the host’s innate immune response, and therefore influence trajectory of adaptative immunity. Since eradicative response against mycobacteria, and M. tuberculosis/M. avium, relies on peptides actively presented on a Major Histocompatibility complex-II (MHC-II) context, we assessed paradoxical stimulation of Dendritic Cell resulting on immature immunophenotype characterized by membrane minor increase of MHC-II and CD40 despite of high expression of the pro-inflammatory tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in supernatants. Identification of M. avium leucine rich peptides forming short α-helices shutting down Type 1T helper (Th1), contribute to the understanding of immune evasion of an increasingly prevalent pathogen, and may provide a basis for future immunotherapy to infectious and non-infectious disease.     

遗传性非息肉病性大肠癌(10个家族27例报告)

分析遗传性非息肉病性大肠癌(HNPCC)的临床特点。方法:对10个家族27例HNPCC患者(A组)进行回顾性分析,并设30例一般大肠癌为对照组(B组)进行比较。结果:<50岁患者A组占59.3%(16/27),B组占23.3%(7/30),P<0.05。脾曲以上癌灶A组为40.0%(12/30),B组为16.1%(5/31),P<0.05。大肠多原发癌A组占10.0%(3/30),B组占3.2%(1/31)。大肠外肿瘤A组6例,B组2例。结论:HNPCC具有典型的临床特征,这些特征可以对HNPCC患者进行早期诊断及治疗,以得到较好的预后。     

Factors Associated With Nurses' Job Satisfaction In Residential Long-term Care: The Importance of Organizational Context

ObjectivesWe examined demographic, individual, and organizational context factors associated with nurses' job satisfaction in residential long-term care (LTC) settings. Job satisfaction has implications for staff turnover, staff health, and quality of care.DesignA cross-sectional analysis of survey data collected in the Translating Research in Elder Care program.Setting and participantsN = 756 nurses (registered nurses: n = 308; licensed practical nurses: n = 448) from 89 residential LTC settings in 3 Western Canadian provinces.MethodsWe used a generalized estimating equation model to assess demographic, individual, and organizational context factors associated with job satisfaction. Job satisfaction was measured using the Michigan Organizational Assessment Questionnaire Job Satisfaction Scale.ResultsDemographic, individual, and organizational context factors were associated with job satisfaction among nurses in residential LTC settings. At the demographic level, hours worked in 2 weeks (B = 0.002, P = .043) was associated with job satisfaction. At the individual level, emotional exhaustion-burnout (B = −0.063, P = .02) was associated with lower job satisfaction, while higher scores on empowerment (meaning) (B = 0.140, P = .015), work engagement (vigor) (B = 0.096, P = .01), and work engagement (dedication) (B = 0.129, P = .001) were associated with higher job satisfaction. With respect to organizational context, culture (B = 0.175, P < .001), organizational slack-space (eg, perceived availability and use of adequate space; B = 0.043, P = .040), and adequate orientation (B = 0.092, P < .001) were associated with higher job satisfaction.Conclusions and implicationsWe identified previously unexamined modifiable organizational features (organizational slack-space and adequate orientation) as factors associated with LTC nurses' job satisfaction in the Canadian context. Our findings support future efforts to improve job satisfaction through improvements in organizational space and provision of adequate workplace orientation.     

臀沟中线小凹切除术治疗骶尾部藏毛窦伴大范围感染

目的探讨臀沟中线小凹切除术在治疗骶尾部藏毛窦伴大范围感染中的应用。方法我院2011-09~2013-09收治骶尾部藏毛窦伴大范围感染的患者共14例,采用臀沟中线小凹切除术治疗,术中偏离中线切开引流骶尾部感染灶,逐个切除患者臀沟中线小凹后缝合伤口,术后换药至伤口愈合。评价指标包括治愈率、手术时间、住院时间、伤口愈合时间、术后伤口并发症、术后复发情况。结果 14例患者全部治愈。手术时间30-60 min,中位手术时间40 min。住院时间12-20 d,中位住院时间17 d。伤口愈合时间3-4周,中位伤口愈合时间3.5周。术后2例患者臀沟中线小凹处伤口裂开,经换药愈合。术后随访1年以上,无复发。结论臀沟中线小凹切除术是治疗骶尾部藏毛窦伴大范围感染的安全有效、微创的手术方式。     

改良侧位纵切横缝术治疗对慢性肛裂的疗效分析

目的探讨改良侧位纵切横缝术在慢性肛裂治疗中的临床实际疗效。方法选取2011年1月至2013年11月期间我院收治的120例慢性肛裂治疗患者为研究对象,将其随机分为常规组和实验组,每组各60例。常规组患者给予常规手术治疗,实验组患者则给予改良侧位纵切横缝术。术后对患者进行随访,对比两组患者的临床治疗效果、伤口愈合时间和并发症发生情况。结果治疗后,实验组患者的总有效率为98.3%,显著高于常规组的76.7%,差异具有统计学意义(P<0.01)。实验组患者的伤口愈合时间明显短于常规组患者,差异具有统计学意义(P<0.01);实验组患者的并发症发生情况明显少于常规组患者,差异具有统计学意义(P<0.01)。结论改良侧位纵切横缝术在慢性肛裂的治疗中疗效显著,且患者术后恢复好,值得临床推广应用。     

MCCC2基因变异致3-甲基巴豆酰辅酶A羧化酶缺乏症患儿的家系分析

目的对1例临床疑诊3-甲基巴豆酰辅酶A羧化酶缺乏症(3-methylcrotonyl-coenzyme A carboxylase deficiency,MCCD)患儿及其父母进行基因变异分析,寻找该家系的致病变异,为临床诊断提供分子遗传学依据。方法抽提先证者及其父母的外周血基因组DNA,应用全外显子组基因测序技术对疑似为MCCD疾病的先证者进行致病基因筛查。根据高通量测序结果,对先证者及其父母进行变异位点的Sanger测序验证分析。应用计算机软件预测变异位点氨基酸进化保守性和变异可能导致的蛋白质结构和功能变化,分析变异位点的性质。结果Sanger测序结果显示先证者为MCCC2基因c.1342G>A(p.Gly448Ala)纯合错义变异,为未报道过的新变异。先证者母亲为c.1342G>A(p.Gly448Ala)杂合变异携带者,父亲未检测到该变异。用PolyPhen-2和Mutation Taster软件预测该变异为致病性,变异区域序列在不同物种间高度保守。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,MCCC2基因c.1342G>A(p.Gly448Ala)变异判定为可能致病性变异(PM2+PP2~PP5)。结论先证者MCCC2基因c.1342G>A(p.Gly448Ala)纯合错义变异是其分子发病机制,基因变异分析有助于明确临床诊断。