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。     

奥地利维也纳医科大学医学考试形式介绍及启示

医学生需要具备不同层次的能力,所以需要不同的考试形式来衡量能力的高低。不同考试方法的选择对于反映所选课程的学习效果至关重要。本文主要介绍了维也纳医科大学的考试设计及其作用,以及对我国医学教育评估的启示。通过学习奥地利先进的教学评估理念和方法,可为我国医学教育评估方式改革、培养高素质医学人才提供借鉴。     

置管引流结合九一丹灌注治疗高位复杂性肛瘘临床观察

目的:观察置管引流结合九一丹灌注术治疗高位复杂性肛瘘的临床疗效。方法:选择高位复杂性肛瘘患者100例,随机分为两组:治疗组(n=50)例和对照组(n=50)例。治疗组采用置管引流结合九一丹灌注,对照组采用低位切开高位挂线术,对两组患者的一般资料、治愈时间、治愈率、复发率、以及肛门功能保护情况进行统计分析。结果:治疗组未愈2例,对照组未愈1例,术后随访均无复发病例,两组患者在治愈率、复发率方面无统计学差异(P>0.05);治疗组伤口愈合时间(33.4±4.8)d,较对照组(36.5±5.0)d明显缩短,有显著性差异(P<0.01);在伤口痊愈时、随访6月时两组的静息压、肛管最大收缩压均有显著性差异(P<0.01,P<0.01),治疗组肛门自制功能损伤小。结论:置管引流结合九一丹灌注治疗高位复杂性肛瘘,可缩短治疗时间,肛门括约肌功能得到较好的保护。     

“镜面人”保留左结肠动脉腹腔镜低位直肠癌根治术1例

<正>“镜面人”是指胸、腹腔内所有内脏器官的完全性反位,其解剖位置与正常人完全相反,像镜子中的影像一样。这是一种极为罕见的先天性疾病。国外文献报道,“镜面人”发病率为1/(4 000～8 000)^[1]。有肠癌和内脏转位的患者更是罕见,反位结直肠癌(situs inversus colorectal cancer,SCRC)中最常见的突变基因为APC、TP53、CHEK2、MDC1、GNAQ、KRAS和SMAD4,并且DNA损伤修复基因突变的发生率很高^[2]。2017年韩国Hong SK等^[3]报道了1例镜面人行腹腔镜右半肝切除术,但国内相关报道极少。     

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.