Purpose To detect the expression of autophagic genes Beclin 1 and MAP1LC3 in cutaneous malignant melanoma and to ex-plore the relationship between autophagia and malignant melanoma. Methods 85 cases of speicmens including normal skin tissue, in-tradermal nevi, radial growth phase melanomas, vertical growth phase melanomas, and metastatic melanoma were collected, and the protein expression of Beclin 1 and MAP1LC3 were evaluated by immunohistochemistry of SP methods. Results The Beclin 1 and MAP1LC3 expression were pretended to be 100% in normal skin tissue, and they were declined to 85% and 95% in intradermal nevi, 58% and 50% in radial growth phase melanomas, 49. 5% and 44. 4% in vertical growth phase melanomas, both of 17% in melanoma metastases (P<0. 05). Conclusion Beclin 1 and MAP1LC3 autophagic gene expression were significantly decreased with tumor pro-gression, as well as was correlated with conventional histopathologic prognostic factors.

{L-End}Objective To investigate the effect and mechanism of low dose metformin in delaying pulmonary fibrosis in silicosis mice. {L-End}Methods The specific pathogen free C57BL/6 male mice were randomly divided into four groups,with six mice in each group. Mice in the silicosis model group and the metformin intervention group were given 20 μL of a mass concentration of 250 g/L silica suspension, and mice in the blank control group and the drug control group were given 20 μL of 0.9% sodium chloride solution, using tracheal exposure method. After 72.0 hours of dust exposure, the mice of drug control group and metformin intervention group were intraperitoneally injected with metformin at a dose of 65 mg/kg body mass, while the mice in the blank control group and the silicosis model group were given 0.9% sodium chloride solution at the same volume, once every other day for 28 days. After the treatment, histopathological change of the lungs was observed, lung organ coefficient was calculated, degree of pulmonary fibrosis was evaluated with Ashcroft score, and mRNA expression of fibronectin (Fn)1 and collagen typeⅠ(COLⅠ) alpha 1 (Col1a1) in lung tissues were detected by real-time fluorescence quantitative polymerase chain reaction. The relative expression of FN and COLⅠ in lung tissues was determined by Western blot. {L-End}Results The results of histopathological examination of the lungs showed that there were no inflammation and fibrosis in the lungs of mice in the blank control group and the drug control group; mice in silicosis model group had inflammation and fibrosis in lung; the degree of lung inflammation and fibrosis was reduced in the mice of metformin intervention group compared with the silicosis model group. The lung organ coefficient, Ashcroft score, the relative expression of Fn1 and Col1a1 mRNA, the relative expression of FN and COLⅠprotein in lung tissues increased in silicosis model group (all P<0.05), compared with those in both blank control group and drug control group. The indexes above decreased of mice in the metformin intervention group than those in the silicosis model group (all P<0.05). {L-End}Conclusion Low-dose metformin can delay the progression of pulmonary fibrosis in silicosis mice. The mechanism may be related to metformin's improving excessive deposition of extracellular matrix induced by silica.

Objective To explore the mechanism of action of curcumin in the treatment of silicosis by network pharmacology combined with molecular docking technology. Methods The targets prediction network of curcumin in treating silicosis was established based on the collection of targets of curcumin and silicosis in multiple databases, cross-targets were submitted to the STRING database, and their connectivity was analyzed by Cytoscape software. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the top 20 genes. The molecular docking was performed on the key targets to study the mechanism of action of curcumin in treating silicosis. Results A total of 311 targets related to curcumin, 270 targets related to silicosis, and 74 cross-targets were obtained from the databases. GO function analysis revealed 2 665 related pathways, and KEGG pathway enrichment analysis revealed 188 related pathways. Molecular docking results showed that curcumin had good binding ability with the targets of mitogen-activated protein kinase 3 (MAPK3), interleukin (IL) 6, serine/threonine kinase 1 (AKT1), vascular endothelial growth factor A (VEGFA), signal transducer and activator of transcription 3, albumin, Jun proto-oncogene, tumor necrosis factor (TNF), IL1B, tumor protein p53, C-C motif chemokine ligand 2 and fibronectin 1. Conclusion The therapeutical effects of curcumin on silicosis were implemented through multi-targets and multi-pathways. Curcumin may play a role in the treatment of silicosis by binding to the core targets MAPK3, IL6, AKT1, VEGFA and TNF and regulating the MAPK, IL6, TNF, phosphatidylinositol 3-kinase/protein kinase B and VEGF signaling pathways.

Objective:To explore the prevalence of hepatitis C virus (HCV) infection, influence factors and interaction on HCV infection in patients receiving methadone maintenance treatment (MMT) in Taiyuan.Methods:Between April-June 2019, three MMT clinics in Taiyuan were selected to conduct a face-to-face questionnaire survey among MMT patients to collect the information about their socio-demographic characteristics, drug use, MMT, sexual behavior and health status. Software EpiData 3.1 was used for real-time double entry to establish the database. Software SAS 9.4 was used to analyze the data, and χ 2 test was used for univariate analysis and logistic regression model was used for multivariate and interaction analyses. Results:A total of 903 subjects were surveyed among MMT patients, the male to female ratio of was 7.21∶1(743∶103), and the rate of HCV infection was 12.53% (106/846). After adjusting for the confounding factors, being women ( OR=1.936, 95% CI: 1.023-3.662), having sex with drug users ( OR=2.073, 95% CI: 1.110-3.871) and injection drug use ( OR=7.737, 95% CI: 4.614-12.973) might be the risk factors for HCV infection in patients receiving MMT. The results showed that there were multiplicative interactions among women, having sex with drug user and injection drug use on HCV infection. Conclusions:Being women, having sex with drug user and injection drug use were associated with higher risk for HCV infection in patients receiving MMT in Taiyuan. There were multiplication interactions between being women and having sex with drug user, being female and injection drug use, and having sex with drug use and injection drug use on HCV infection.

Objective To evaluate the feasibility and accuracy of mitral valve prolapse( M VP) model made by three‐dimensional( 3D) printing based on three‐dimensional transesophageal echocardiography ( 3D‐T EE) data and the application value for mitral valvuloplasty . Methods 3D‐T EE volumetric data of 28 patients with M VP were acquired and postprocessed ,13 patients underwent mitral valve replacement and 15 patients underwent mitral valvuloplasty . A flexible material was used to made the valve 3D model by molding . T he areas of M VP identified by models were compared with surgical findings ,the circumference and the length and thickness of anterior and posterior mitral leaflets obtained from the valve specimens and the models were compared in the mitral valve replacement group . T he diameter between anterior and posterior ,the diameter between anterolaterior and posteromedial ,annulus area ,height of prolapsed leaflet and area of prolapsed leaflet were measured from 3D models and 3D‐T EE images in mitral valvuloplasty group . Surgical simulations were performed on the 3D models of the mitral valvuloplasty group ,and the water injection test was used to evaluate the surgical results and compared with the surgical results . Results 3D‐T EE volumetric data were successfully postprocessed and made as 3D M VP models in all patients . T he consistency of M VP location based on 3D models and surgical findings was 0 .92 . T he differences between the mitral valve replacement group and mitral valvuloplasty group were not significant ( P＞ 0 .05 ) . A simulation valvuloplasty was successfully performed on the 3D model in mitral valvuloplasty group ,2 patients underwent mitral valve replacement after water injection test . T he remaining 3D models successfully simulated the operation . Conclusions The M VP model made by 3D‐T EE and 3D printing technique has high feasibility and accuracy ,w hich may be promising for the mitral valvuloplasty of M VP .

To follow up and analyze patients with ventricular septal rupture( VSR) after acute myocardial infarction ( AM I) w ho underwent VSR occlusion ,screen the main risk factors of survival in perioperative patients with VSR after AM I ,and observe the postoperative cardiac function and hemodynamic changes by echocardiography . Methods Seventeen VSR patients were divided into the survival group ( 11 cases) and the death group ( 6 cases) within 30 days according to the survival time . T he changes of cardiac ultrasound parameters before and after the operation of VSR survivors were compared , and the hemodynamic recovery characteristics of VSR survivors were analyzed . Results Age ,the time to VSR occlusion ,preoperative left ventricular ejection fraction ,cardiogenic shock ,and the size of VSR were all the factors that were closely related to the 30‐day mortality of VSR with odds ratio of 0 .90 ( 95% CI 0 .73 to 1 .14 , P ＝0 .045) ,1 .89( 95% CI 1 .35 to 2 .23 , P ＝0 .003) ,0 .89( 95% CI 0 .57 to 1 .24 , P ＝0 .039) ,1 .45 ( 95% CI 1 .12 to 1 .78 , P ＝0 .027) and 11 .45( 95% CI 7 .89 to 15 .56 , P ＝0 .012) ,respectively ( all P＜0 .05 ) . Compared with the preoperative measurements , the left ventricular end‐diastolic volume and pulmonary artery systolic pressure were significantly reduced in the VSR survival group ( P ＜ 0 .05 ) . Conclusions The decrease of left ventricular end diastolic volume and pulmonary artery systolic pressure after operation indicates a better prognosis in the short period . Echocardiography is a vital tool in preoperative screening ,intraoperative monitoring and postoperative follow‐up in VSR occlusion .

Objective:To compare the anti-HBs level in maintained hemodialysis patients one year after receiving 20 μg and 60 μg hepatitis B vaccination at 0, 1 and 6 months, and explore the influence factors for the immunity persistence and their interactions.Methods:Based on a randomized controlled trial of 20 μg and 60 μg hepatitis B vaccine immunization in maintained hemodialysis patients at 0, 1, and 6 months, follow up was conducted for the patients for one year after the completion of the vaccination for the quantitative detection of anti-HBs, and χ 2 test, t test, unconditional logistic regression and interaction analyses were used for statistical analysis. Results:One year after the vaccination, 125 and 124 patients in the 20 μg and 60 μg groups were tested for anti-HBs, respectively. The positive rate of anti-HBs in the 60 μg group (77.42%, 96/124) was significantly higher than that in the 20 μg group (65.60%, 82/125) ( P<0.05). After adjusting for the confounding factors, the positive probability of anti-HBs in the 60 μg group was 1.925 times higher than that in the 20 μg group (95% CI: 1.068-3.468). Patients with hemodialysis duration ≥5 years ( OR=0.523, 95% CI: 0.293-0.935) and diabetes mellitus ( OR=0.376, 95% CI: 0.173-0.818) had lower positive probability of anti-HBs. Moreover, there were additive and multiplicative interactions between hemodialysis duration ≥5 years and diabetes mellitus. Conclusions:The immunity persistence after one year in 60 μg hepatitis B vaccination group was longer than that in 20 μg hepatitis B vaccination group in maintained hemodialysis patients, vaccine dose, hemodialysis duration and diabetes mellitus were the influencing factors for the immunity persistence, there were additive and multiplicative interactions between hemodialysis duration ≥5 years and diabetes mellitus.

Cancer is a major global health issue. Effective therapeutic strategies can prolong patients’ survival and reduce the costs of treatment. Drug repurposing, which identifies new therapeutic uses for approved drugs, is a promising approach with the advantages of reducing research costs, shortening development time, and increasing efficiency and safety. Disulfiram (DSF), a Food and Drug Administration (FDA)-approved drug used to treat chronic alcoholism, has a great potential as an anticancer drug by targeting diverse human malignancies. Several studies show the antitumor effects of DSF, particularly the combination of DSF and copper (DSF/Cu), on a wide range of cancers such as glioblastoma (GBM), breast cancer, liver cancer, pancreatic cancer, and melanoma. In this review, we summarize the antitumor mechanisms of DSF/Cu, including induction of intracellular reactive oxygen species (ROS) and various cell death signaling pathways, and inhibition of proteasome activity, as well as inhibition of nuclear factor-kappa B (NF-κB) signaling. Furthermore, we highlight the ability of DSF/Cu to target cancer stem cells (CSCs), which provides a new approach to prevent tumor recurrence and metastasis. Strikingly, DSF/Cu inhibits several molecular targets associated with drug resistance, and therefore it is becoming a novel option to increase the sensitivity of chemo-resistant and radio-resistant patients. Studies of DSF/Cu may shed light on its improved application to clinical tumor treatment.

Objective To investigate the effect and mechanism of galactose on the expression of sialic-acid-binding immunoglobulin-like lectin 9(Siglec-9)glycan ligand on human primarily cultured pulmonary artery endothelial cells.Methods The expression of Siglec-9 glycan ligand on the endothelial cell surface and the type of glycosidic bonds at the end of this ligand were identified by flow cytometry.Endothelial cells were treated with L-glucose,glucose,N-acetylglucose,mannose,N-acetylmannose,galactose,sialic acid and sucrose for 48 h,and the expression of Siglec-9 glycan ligand in endothelial cells was detected by flow cytometry.The endothelial cells were divided into the control group and the galactose group(n=3).Western blotting,flow cytometry,and immunofluorescence assay were employed to investigate the impact of galactose on the Siglec-9 glycan ligand in endothelial cells.After α2-3,6,8 sialidase treatment for endothelial cells,Western blotting was used to detected the effect of galactose on the recovery time of Siglec-9 glycan ligand in endothelial cells.Endothelial cells were treated with galactose,Western blotting was used to detect and analyze the expression levels of intracellular sialic acid synthetases(GNE,NANS,NANP,CMAS,NPL and ST3Gals),and the mRNA expression levels of the relevant proteins were verified by RT-qPCR.Western blotting was used to detect the changes of Siglec-9 glycan ligand level in endothelial cells after siRNA knockdown in NANP,CMAS and ST3Gal-Ⅲ.The effect of the increase of Siglec-9 ligand on apoptosis and phagocytosis of macrophages was analyzed by macrophage co-culture experiments.Results Endothelial cells showed the expression of Siglec-9 ligand and the ligand was a sialic acid glycoprotein linked to α 2-3 sialic acid at the end.Compared with the control group,the expression level of this ligand on endothelial cells in the galactose group was increased significantly(P＜0.01),but the addition of galactose had no effect on the self-recovery time of the ligand.Compared with the control group,the expression levels of NANP,CMAS and ST3Gal-Ⅲ in endothelial cells treated with galactose were increased(P＜0.05,P＜0.01),respectively.The results of RT-qPCR verification were consistent with those results.After the expression of NANP,CMAS or ST3Gal-Ⅲ was inhibited,the level of Siglec-9 glycan ligand in endothelial cells was decreased(P＜0.01).In the co-culture experiment,compared with the untreated group,galactose-treated endothelial cells promoted the apoptosis of macrophages(P＜0.01)and reduced their phagocytosis(P＜0.05).Conclusion Galactose up-regulates the level of Siglec-9 glycan ligand on endothelial cells through the NANP-CMAS-ST3Gal-Ⅲ pathway,thereby inhibiting the activity of macrophages.