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.

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

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.

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.

[ ABSTRACT] AIM: To determine the aberrant methylation status in the gene promoter regions of CDH13, RASSF1A, DLEC1, SEPT9 and RUNX3 by detecting the plasma specimens and the value of their combined detection for di-agnosis of lung cancers.METHODS:Nest methylation specific PCR ( nMSP) was used to detect the promoter methylation status of the 5 genes in the plasma from 106 normal controls, lung cancer tissues, lung benign tissues and the plasma from 106 patients with lung cancers.Multiple displacement amplification ( MDA) was used to amplify modified genomic DNA to solve the problem of insufficient of plasma DNA template.RESULTS: The positive rates of promoter methylation of CDH13, RASSF1A, DLEC1, SEPT9 and RUNX3 in the lung cancer tissues were 51.9%, 44.3%, 54.7%, 36.8%, 24.5%, respectively, and those in the plasma were 46.2%, 41.5%, 50.9%, 31.1%, 19.8%, respectively.The re-sults of the Kappa consistency check showed that the lung cancer tissues and the plasma had obviously coherence in the methylation status of the 5 gene promoter regions.Combination of DLEC1, CDH13, RASSF1A, and SEPT9 had a higher di-agnostic efficiency than the others, as their ACC value was 0.8208 and youden index was 0.6415 ( with the sensitivity of 81.13% and the specificity of 83.02%) .CONCLUSION:Combination detection of promoter methylation of lung cancer-related genes in the plasma is expected to apply to the early diagnosis of lung cancer.

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 .

Human enterovirus 71 (EV71) is the main causative pathogen of hand, foot, and mouth disease (HFMD) in children. The epidemic of HFMD has been a public health problem in Asia-Pacific region for decades, and no vaccine and effective antiviral medicine are available. Curcumin has been used as a traditional medicine for centuries to treat a diversity of disorders including viral infections. In this study, we demonstrated that curcumin showed potent antiviral effect again EV71. In Vero cells infected with EV71, the addition of curcumin significantly suppressed the synthesis of viral RNA, the expression of viral protein, and the overall production of viral progeny. Similar with the previous reports, curcumin reduced the production of ROS induced by viral infection. However, the antioxidant property of curcumin did not contribute to its antiviral activity, since N-acetyl-l-cysteine, the potent antioxidant failed to suppress viral replication. This study also showed that extracellular signal-regulated kinase (ERK) was activated by either viral infection or curcumin treatment, but the activated ERK did not interfere with the antiviral effect of curcumin, indicating ERK is not involved in the antiviral mechanism of curcumin. Unlike the previous reports that curcumin inhibited protein degradation through ubiquitin-proteasome system (UPS), we found that curcumin had no impact on UPS in control cells. However, curcumin did reduce the activity of proteasomes which was increased by viral infection. In addition, the accumulation of the short-lived proteins, p53 and p21, was increased by the treatment of curcumin in EV71-infected cells. We further probed the antiviral mechanism of curcumin by examining the expression of GBF1 and PI4KB, both of which are required for the formation of viral replication complex. We found that curcumin significantly reduced the level of both proteins. Moreover, the decreased expression of either GBF1 or PI4KB by the application of siRNAs was sufficient to suppress viral replication. We also demonstrated that curcumin showed anti-apoptotic activity at the early stage of viral infection. The results of this study provide solid evidence that curcumin has potent anti-EV71 activity. Whether or not the down-regulated GBF1 and PI4KB by curcumin contribute to its antiviral effect needs further studies.