Objective:Bioinformatics and experimental validation reveal the core genes of neutrophil extracellular traps(NETs)in chronic obstructive pulmonary disease(COPD).Methods:Chip data GSE8545,GSE10006,GSE11906,GSE19407 and GSE20257 were downloaded from GEO database,and the common differential expression genes(DEGs)of the first 4 datas were ob-tained through intersection and enrichment analysis were performed.Neutrophil extracellular traps differential expression genes(NETs-DEGs)were obtained by overlapping the NETs-related genes and the common DEGs,and GSE20257 was used to verify the NETs-DEGs and evaluate the diagnostic efficacy,and enrichment analysis was performed and mRNA expression level was verified in lung tissue of mice emphysema model.Results:A total of 149 common DEGs were acquired.DO analysis mainly concentrated in lung disease and COPD.GO functional annotation mainly involved in olefin metabolism,cytohormone metabolism,endoplasmic reticulum lumen,signaling receptors and oxidative stress activities.KEGG enrichment analysis mainly involved in cytochrome P450 metabo-lism,chemical carcinogenic reactive oxygen species,steroid hormone biosynthesis and phagosome,etc.GSE20257 dataset verifica-tion showed that NETs-DEGs TLR7 and CYP4F3 were up-regulated,and AUC values were 0.750 and 0.947.GO and KEGG mainly focused on fat-soluble vitamin catabolic signaling pathways,phagosomes,arachidonic acid monooxygenase activity,pattern recogni-tion receptors,arachidonic acid metabolism,Toll-like receptor signaling pathways and formation of NETs.Compared with air exposure group,mRNA expression levels of TLR7 and CYP4F3 in lung tissue of emphysema mice induced by cigarette smoke exposure were sig-nificantly increased(P<0.05).Conclusion:TLR7 and CYP4F3 may be the core genes in formation and release of NETs during the pathogenesis of COPD,which are expected to become the targets of immunotherapy for COPD.

Objective:Bioinformatics and experimental validation reveal the core genes of neutrophil extracellular traps(NETs)in chronic obstructive pulmonary disease(COPD).Methods:Chip data GSE8545,GSE10006,GSE11906,GSE19407 and GSE20257 were downloaded from GEO database,and the common differential expression genes(DEGs)of the first 4 datas were ob-tained through intersection and enrichment analysis were performed.Neutrophil extracellular traps differential expression genes(NETs-DEGs)were obtained by overlapping the NETs-related genes and the common DEGs,and GSE20257 was used to verify the NETs-DEGs and evaluate the diagnostic efficacy,and enrichment analysis was performed and mRNA expression level was verified in lung tissue of mice emphysema model.Results:A total of 149 common DEGs were acquired.DO analysis mainly concentrated in lung disease and COPD.GO functional annotation mainly involved in olefin metabolism,cytohormone metabolism,endoplasmic reticulum lumen,signaling receptors and oxidative stress activities.KEGG enrichment analysis mainly involved in cytochrome P450 metabo-lism,chemical carcinogenic reactive oxygen species,steroid hormone biosynthesis and phagosome,etc.GSE20257 dataset verifica-tion showed that NETs-DEGs TLR7 and CYP4F3 were up-regulated,and AUC values were 0.750 and 0.947.GO and KEGG mainly focused on fat-soluble vitamin catabolic signaling pathways,phagosomes,arachidonic acid monooxygenase activity,pattern recogni-tion receptors,arachidonic acid metabolism,Toll-like receptor signaling pathways and formation of NETs.Compared with air exposure group,mRNA expression levels of TLR7 and CYP4F3 in lung tissue of emphysema mice induced by cigarette smoke exposure were sig-nificantly increased(P<0.05).Conclusion:TLR7 and CYP4F3 may be the core genes in formation and release of NETs during the pathogenesis of COPD,which are expected to become the targets of immunotherapy for COPD.

Objective:To analyze and assess the reliability of autoclaves of medical institution based on the failure data of the autoclaves of hospital.Methods:The failure data of autoclaves were analyzed by using four statistical models:Weibull distribution,Exponential distribution,Log-Normal distribution,and q-Weibull distribution.Chart tools were used to show the performance of different statistical distribution models in fitting data.Results:Comparisons of 4 kinds of statistical models revealed that the corrected Akaike Information Criterion(AICc)of statistical model of Log-Normal distribution was 564.4512,and the Bayesian Information Criterion(BIC)value(568.7691)of that was the lowest,and KS statistic(0.0739)of that was the smallest(P>0.05).Therefore,fitting effect of statistical model of Log-Normal distribution was the best fit,which was the most suitable model for analyzing the failure data set of autoclaves.Conclusion:Utilizing different statistical models to conduct the reliability analysis for failure data of autoclave can provide references for clinical engineers in optimizing maintenance strategies for autoclave.

Objective: To understand the etiology of hepatopathy of unknown etiology in patients undergoing liver biopsy. Methods: Demographic data and pathological examination reports of patients with hepatopathy of unknown etiology who underwent liver biopsy examination at outpatient and inpatient of the Second Hospital of Nanjing between January 2017 and June 2018 were retrospectively collected. All liver histopathological sections combined with clinical and pathological features based on liver biopsy examinations were diagnosed by a reputed clinician and a pathologist. Results: A total of 470 cases with hepatopathy of unknown etiology who underwent liver biopsy were enrolled. Of these, 425 cases (90.4%) had a definite diagnosed disease after comprehensive analysis of pathological and clinical data. The diagnosis of hepatopathy of unknown etiology included 11 diseases: 90 cases with autoimmune hepatitis had autoimmune liver disease (19.1%), 38 cases had primary biliary cholangitis (8.1%), 43 cases with overlap syndrome of autoimmune hepatitis had primary biliary cholangitis (9.1%), 118 cases had drug-induced liver injury (25.1%), 75 cases had nonalcoholic fatty liver disease (NAFLD) (16.0%), 12 cases had alcoholic liver disease (2.6 cases) %), 15 cases (3.2%) had vascular liver disease, 7 cases (1.5%) had hereditary metabolic liver disease, 5 cases (1.1%) had other systemic diseases, 16 cases (3.4%) had more than two kinds of liver diseases, and 6 cases (1.3%) had others rare liver diseases. Conclusion Over 90% cause of the hepatopathy of unknown etiology in the long run can be determined, and the main causes are autoimmune liver disease, drug-induced liver injury, and nonalcoholic fatty liver disease, which needs multidisciplinary cooperation to diagnose, and clinicians need to master the basic and clinical knowledge of liver diseases as well as liver pathology, hepatobiliary imaging, and genetics.

Objective: To compare and analyze patient’s general condition, changes in laboratory parameters, and the spectrum of UGT1A1 mutations in patients with inherited non-hemolytic unconjugated hyperbilirubinemia. Methods: A retrospective study was conducted at Nanjing Second Hospital from January 2015 to July 2018 and patients’ demographic characteristics, liver function test, and UGT1A1 gene were analyzed. The categorical variable data were compared by χ ² test. The normal distribution continuous variable data were compared by t-test and the non-normal distribution continuous variable data were compared using Mann-Whitney U test. Results: Of the 51 patients with inherited non-hemolytic unconjugated hyperbilirubinemia, 44 (86.3%) were Gilbert’s syndrome (GS) and seven (13.7%) were Crigler-Najjar syndrome type II (CNS- II). The male to female ratio was 2.9:1 and the average age was 36.11 ± 13.17 years. Six variant types were detected: C. -40_-39insTA, C. -3279T > G, c.211G > A (p.G71R), c.686C > A (p.P229Q), c.1091C > T (p.P364L), c.1456T > G (P.Y486D). Among them, c.211G > A accounted for 58.82% (30/51), c.-40_-39insTA accounted for 27.5% (14/51), and c.1456T > G accounted for 25.5% (13/51). The total bilirubin(TB) and unconjugated bilirubin (UCB) in CNS-II patients were significantly higher than GS patients[155.91 (130 ~ 207) vs. 38.25(29 ~ 52.15) μmol/L, U = 0, P < 0.01; 144.13 (120.8 ~ 197) vs. 30.00 (21.7 ~ 46.75) μmol/L, U = 0.00, P < 0.01, respectively]. Exon mutations of c.1091C > T and c.1456T > G were statistically significant(P < 0.01).There were no differences in age, TB, UCB, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the c.211G > A homozygous variants and heterozygous variants (P > 0.05). Conclusion The common pathogenic mutations of UGT1A1 gene were c.211G > A, c.-40_-39insTA, c.1456T > G. c.211G > A. The mutation has little effect on the level of total bilirubin, but c.1091C > T, c.1456T > G mutations has great influence on the level of total bilirubin.

Silicon carbide (SiC) film and silicon dioxide (SiO ) film were deposited on the surface of carbon/carbon composite (C/C) by low pressure chemical vapor deposition (LPCVD). The biocompatibility of the three carbon-based composites, e. g. C/C, C/C-SiC, C/C-SiO were investigated by cytotoxicity test, cell direct contact and cell adhesion experiments. Cytotoxicity, cell direct contact and cell adhesion showed that the three materials had no toxic effect on mouse fibroblasts (L929 cells). However, the particles dropped off from the three materials had a great impact on evaluation accuracy of the thiazolyl blue (MTT) test. More the particles were lost, more growth inhibition to L929 cells. The evaluation accuracy of MTT method can be kept with the filtered extract of materials. Furthermore, the results of surface particles shedding experiment showed that the amount of surface particles shed from C/C-SiO was the most, followed by C/C and C/C-SiC in 72 hours. Particles shedding curves showed there was a peak reached at eighth hour and then declined to the thirty-sixth hour. The filtrate analysis showed that there was no ion exchange between the three materials and simulated body fluid (SBF) solution. The results of this study on biocompatibility of carbon-based composites have certain guiding significance for their future application in clinical filed.

Wnt signaling has emerged as a major regulator of tissue development by governing the self-renewal and maintenance of stem cells in most tissue types. As a key upstream regulator of the Wnt pathway, the transmembrane E3 ligase ZNRF3 has recently been established to play a role in negative regulation of Wnt signaling by targeting Frizzled (FZD) receptor for ubiquitination and degradation. However, the upstream regulation of ZNRF3, in particular the turnover of ZNRF3, is still unclear. Here we report that ZNRF3 is accumulated in the presence of proteasome inhibitor treatment independent of its E3-ubiquitin ligase activity. Furthermore, the Cullin 1-specific SCF complex containing β-TRCP has been identified to directly interact with and ubiquitinate ZNRF3 thereby regulating its protein stability. Similar with the degradation of β-catenin by β-TRCP, ZNRF3 is ubiquitinated by β-TRCP in both CKI-phosphorylation- and degron-dependent manners. Thus, our findings not only identify a novel substrate for β-TRCP oncogenic regulation, but also highlight the dual regulation of Wnt signaling by β-TRCP in a context-dependent manner where β-TRCP negatively regulates Wnt signaling by targeting β-catenin, and positively regulates Wnt signaling by targeting ZNRF3.
Cells, Cultured ; Humans ; Proteolysis ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitination ; beta-Transducin Repeat-Containing Proteins ; metabolism

Objective CD8 +T cells increased in the airway of patients with chronic obstructive pulmonary disease and exis -ted constantly .The aim was to investigate the role of CD 8 +T-cells in rats with chronic bronchitis ( CB) which was induced by cigarette smoking and intratracheal injection with lipopolysaccharide ( LPS) . Methods 18 health Wistar rats were radomly divided into sham smoking group(group A), CB group(group B) and N-acetylcysteine prevention group (group C).The rats in group B and group C re-ceived intratracheal injection with LPS twice and exposed to cigarette smoking for 4 weeks to induce CB model .The rats in Group C re-ceiving intragastric administration with N-acetylcysteine (NAC)(200mg/kg) before received LPS and smoking.Group A was the sham smoking group.The lung tissue of all rats were stained by HE then evaluated about pathological scores .The expression of nuclear fac-tor-κB (NF-κB), major histocompatibility complex class I (MHCI), CD8 +T cell and Vascular endothelial growth factor (VEGF) in airway were detected by immunohistochemisty which was stained by labeled streptavidin biotin method . Results The pathological scores of airway ( 10 .83 ±3 .31 ) in group B were higher than (1.17 ±2.40) in group A(P <0.05).The pathological scores of airway(4.66 ±2.25) in group C were less than (10.83 ±3.31) in group B(P <0.05).The expression of NF-κB(4.84), MHC I (2.48),CD8 +T cell(5.35)and VEGF(5.02) in airway increased in group B when compared with (1.18, 1.25, 1.33) and (1.18) in group A respectively(P <0.05).The expression of NF-κB (2.18), MHC I(1.46),CD8 +(2.35)and VEGF(2.02) in airway decreased in group C when compared with (4.84), MHC I(2.48),CD8 +T cell(5.35)and VEGF(5.02) in group B respectively (P<0.05 ). There were positive correlations between the expression of NF-κB, MHC I and CD8 +T cells in airways(r=0.670, r=0.701, respec-tively, all P<0.01).There were positive correlations between the expression of CD 8 +T cells and VEGF the pathological scores of air-ways(r=0.689, r=0.782, respectively, all P<0.01). Conclusion NAC can inhibit airway inflammation which is regulated by CD8 +T-cells and VEGF through suppressing the expression of NF -κB and MHC I.

Objective To investigate the impact of transvaginal natural orifice transluminal endo-scopic surgery(NOTES)-assisted laparoscopic nephrectomy on female sexual function and quality of life . Methods This was a prospective study on the change of female sexual function and quality of life of female patients who underwent transvaginal NOTES-assisted laparoscopic nephrectomy from May .2011 to Nov. 2012.A total of 42 cases were included in this study (28 of them with severe hydronephrosis , non-functio-ning kidney , 11 with pyelonephrosis , 1 with renal tuberculosis , 1 with duplex kidney complicated with hy-dronephrosis, and 1 with renal angiomyolipoma ).The mean age was 36.9±5.3 (26-45) years, and the mean body mass index was 21.7±2.6 (14.7 to 27.1) kg/m2.Twenty-four cases were operated on the left side, 18 cases on the right .The female sexual function and quality of life were assessed before and 4 months, 7 months and 1 year after surgery using the Female Sexual Function Index (FSFI) questionnaire and the MOS 36-item Short-Form Health Survey (SF-36), respectively. Results The mean FSFI of 42 cases preoperatively and 4 months, 7 months and 1 yr postoperatively were 27.74 ±4.34, 27.19 ±4.49, 28.54±4.23, and 28.68 ±4.19, respectively.There was no statistically significant difference among them (F=1.111, P=0.346).Compared with that of preoperation , the physical function, vitality, metal health, body pain, and general health of the patients were improved , but the role-physical, role-emotion and social function were not improved at postoperative month 4 and month 7 (P<0.05).Each item of SF-36 was im-proved after postoperative 1 year ( P<0.05) . Conclusions Transvaginal NOTES-assisted laparoscopic ne-phrectomy does not cause negative effect on the female sexual function .The quality of life can be improved after operation .The physical function is improved at early stage , and the psychological function as well .