Prevention of alloimmune rejection using XBP1-deleted bone marrow-derived dendritic cells in heart transplantation

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Dectin-2受体介导宿主抵抗烟曲霉菌感染的研究

目的探讨C型凝集素受体Dectin-2在烟曲霉菌感染中的作用及机制。方法用紫外线灭活的烟曲霉菌膨胀态分生孢子刺激野生型(wild type, WT)和Dectin-2缺失(Clec4n-/-)小鼠骨髓来源的巨噬细胞(bone marrow derived macrophages, BMDMs)。刺激20min及40min后，利用Western印迹法检测BMDMs中脾酪氨酸激酶(spleen tyrosine kinase, Syk)和核转录因子κB抑制因子(inhibitor-κB, IκBα)的磷酸化水平。刺激16h后，利用酶联免疫吸附法(enzyme-linked immunosorbent assay, ELISA)检测BMDMs细胞上清液中IL-6、TNF-α和IL-12p40的水平。另一方面，利用压舌感染的方法在WT和Clec4n-/-小鼠中构建烟曲霉菌肺部感染模型。感染2d后，统计小鼠整个肺脏荷菌量，并检测肺脏匀浆液中IL-6和IL-12p40水平。结果体外试验提示，烟曲霉菌刺激后，Dectin-2缺失的BMDMs中Syk和IκBα的磷酸化水平及IL-6、TNF-α和IL-12p40水平显著下降(P＜0.05)。体内试验发现，烟曲霉菌感染后，Dectin-2缺失小鼠中肺脏荷菌量显著升高(P＜0.05)，肺脏匀浆液内IL-6、IL-12p40水平显著降低(P＜0.05)。结论C型凝集素受体Dectin-2激活烟曲霉菌诱导的NF-κB信号通路并介导促炎细胞因子的产生，可在小鼠肺烟曲霉菌病动物模型中发挥保护性作用。     

Prognostic validity of the American joint committee on cancer eighth edition staging system for well-differentiated pancreatic neuroendocrine tumors

BackgroundThe American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included.MethodsWe collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs.ResultsCompared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762).ConclusionThese findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage.     

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.     

El papel de la resonancia magnética multiparamétrica en el diagnóstico de la recidiva local tras la prostatectomía radical y antes de la radioterapia de rescate

PurposeAssess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of prostate cancer (PCa) after radical prostatectomy (PR) and before radiation therapy (RT).Materials and methodsA total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into 2 groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between 2 groups using Student-t test; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables.ResultsPCa recurrence (reduction of PSA levels after RT) was 89.8% in group A and 80.3% in group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. Diffusion weighted imaging is the most specific MRI-sequence and dynamic contrast enhanced the most sensitive. For PSA = 0.5 ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA = 0.9 ng/ml, dynamic contrast enhanced-AUC increases significantly.Conclusionmp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of diffusion weighted imaging for PSA ≤ 0.5 ng/ml.     

Work-related injuries in the Australian education sector: A retrospective cohort study

IntroductionEducators are exposed to several work-related hazards. Evidence suggests musculoskeletal pain, psychological distress, and student-inflicted violence-related injuries are common. However, there is little evidence on the burden of workplace injury among Australian educators.AimTo compare incidence of injury claims and duration of compensated time off work between educators and non-educators, and associated factors.MethodsRetrospective cohort study of 1,559,676 Australian workers’ compensation claims, including 84,915 educator claims, lodged between July 2009 to June 2015, from the National Dataset for Compensation-based Statistics. Cases were included if aged 18+ years and working in the education sector less than 100 h per week. Negative binomial regression models estimated the relative risk of making a compensation claim and survival analyses calculated disability duration within educators by sex, age, injury type and mechanism, socioeconomic area, remoteness, and jurisdiction.ResultsCompared to non-educators, educators had lower rates of injury claims and shorter disability durations. However, educators had a higher rate of claims for mental health conditions and assault, with the highest risk being among those in special education and education aides. Among educators, injury claim rates were highest among special educators, education aides, and secondary educators.Discussion and ConclusionThough surveys indicate Australians in the education sector have higher incidences of work-related injuries, this study found lower incidence of injury claims and shorter disability durations than others. Educators’ injury-reporting and absenteeism behaviors may be constrained by ethical, social, and administrative attitudes. Educators had higher rates of claims for mental health and assault-related injury, particularly special educators, and education aides, which suggests a need for targeted prevention efforts.     

高强度聚焦超声消融治疗子宫肌瘤时妊娠一例报告并文献复习

高强度聚焦超声(high-intensity focused ultrasound,HIFU)消融治疗子宫肌瘤作为一种新的非侵入性的治疗方式,已越来越广泛地用于子宫肌瘤的治疗。但是对于HIFU治疗时妊娠的处理及妊娠结局鲜有文献报道。本文报道1例HIFU消融治疗子宫肌瘤时妊娠的病例,结合文献复习,探讨子宫平滑肌瘤对妊娠的影响、子宫平滑肌瘤不同处理方式对妊娠的影响、HIFU消融治疗子宫肌瘤时机选择的问题、HIFU消融治疗子宫肌瘤若同时合并妊娠时胎儿去留的问题以及近期HIFU消融治疗子宫肌瘤后对流产手术操作的影响等,以期对HIFU治疗子宫肌瘤的适应证、选择合适的治疗时间及术后选择合适的妊娠时机展开讨论。