Objective To explore possible role of cellular repressor of E1A-stimulated genes(CREG) in the process of phenotypic switching of adventitial fibroblasts(AFs). Methods Immunofluorescent staining was performed with tissue sections from mouse carotid arteries to evaluate the relationship between the expression of CREG and smooth muscle actin-α(α-SMA) in injured arteries, especially in the adventitia. Tissue block pasted culture method was used to isolate and culture AFs. RT-PCR and Western-blot were used to detect the change of CREG andα-SMA mRNA and protein expression in AFs in the presence of different concentrations of AngⅡfor 12 h/24 h or in the presence of 100 nmol/L Ang Ⅱ for different times. Results Normal mouse carotid arteries had little α-SMA expression throughout the tunica adventitia. Arteries at day 1 and day 3 post-injury exhibited significantly higher immunofluorescence of α-SMA compared with non-injured arteries. Alpha-SMA expression began to decrease on day 7 and progressively declined on day 14. In contrast, immunofluorescent staining revealed that CREG was expressed in the adventitia of normal arteries. Expression of CREG in the adventitia of injured arteries was decreased on the 1st day, reached its lowest value on the 3rd day, and increased gradually from the 7th day, and was higher compared with that in non-injured arteries on the 14th day after injury. Similarly, the expression of CREG in AFs was very high, and AngⅡremarkably decreased mRNA and protein expression levels of CREG in a dose-dependent and time-dependent manner. Conclusions The changes in CREG expression correlate with AF phenotypic modulation, and CREG down-regulation may facilitate AF phenotypic switching into myofibroblasts (MFs).

[Summary] The relationship between serum bilirubin and serum C-peptide levels in patients with type 2 diabetes mellitus was investigated. The clinical and laboratory data of 206 healthy subjects and 271 type 2 diabetic patients were collected. The partial correlation analysis and multiple linear regression analysis showed that serum bilirubin was positively correlated with fasting C-peptide, postprandial C-peptide, and the difference between postprandial C-peptide and fasting C-peptide levels(β=0. 171, 0. 111,0. 052,P<0. 05 or P<0. 01).

Objective To investigate the effects of capparis spinosa total alkaloid on type collagen (ColⅣ - ),Ⅳmatrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) in bleomycin-induced systemic sclerosis (SSc) mice; To explore the effective mechanism of capparis spinosa total alkaloid on fibrosis of SSc. Methods Totally 90 BALB/c mice were randomly divided into control group, model group, penicillamine group and capparis spinosa total alkaloid low-, medium- and high-dose group. Mice models with SSc were established by repeated local injections of bleomycin in mice back, except for the control group. Mice in medication groups received external application with capparis spinosa total alkaloid cream;mice in penicillamine group were given penicillamine for gavage; mice in the control and model group received external application without substance, one time a day, for 60 days. The contents of MMP-9, TIMP-1 and PAI-1 in serum and Col- in skin tissue were dⅣ etected respectively by ELISA after the last medication. Results Compared with the model group, the levels of MMP-9 and ratio of MMP-9/TIMP-1 markedly increased and the levels of Col-Ⅳand TIMP-1 markedly decreased in medium and high- dose of capparis spinosa total alkaloid group (P<0.05, P<0.01). But the level of PAI-1 was not influenced (P>0.05). Conclusion Capparis spinosa total alkaloid is effective in treating fibrosis of SSc by adjusting imbalance of MMP-9/TIMP-1 and decreasing expression of Col-Ⅳ.

BACKGROUND:It has been found that cel ular repressor of E1A-stimulated genes (CREG) is a lysosomal protein binding directly to the mannose-6-phosphate (M6P)/insulin-like growth factor II receptor (IGFIIR) and depends on the interaction with M6P receptors for efficient delivery to lysosomes OBJECTIVE:To study the interactions between the exogenous CREG protein and cathepsins and M6P/IGFIIR and to confirm the effect of CREG protein on expression and distribution of M6P/IGFIIR. METHODS:Double-stained immunofluorescence and coimmunoprecipitation were applied to observe the interactions between the exogenous CREG protein and cathepsin B, cathepsin L and M6P/IGFIIR. Using gain-of-function and loss-of-function approaches, the effect of CREG on expression and distribution of M6P/IGFIIR were studied by western blot assay and immunofluorescence staining. RESULTS AND CONCLUSION:Double-stained immunofluorescence and coimmunoprecipitation analyses confirmed the direct interactions between the exogenous CREG protein and cathepsin B, cathepsin L and M6P/IGFIIR. It was verified that CREG plays a critical role not in the expression but in the distribution of M6P/IGFIIR using gain-of-function and loss-of-function approaches. These findings provide evidence that exogenous CREG protein is located in lysosomes and has interactions with cathepsins and M6P/IGFIIR, also CREG plays a critical role in the distribution of M6P/IGFIIR.

Objective To study the curative effect of transcatheter arterial chemoembolization( TACE) combined with conventional percutaneous ethanol injection therapy ( PEIT) in the treatment for primary liver cancer?Methods Forty cases patients with primary liver cancer(the diameter was equal or more than 8 cm) who were treat in the Third Hospital of Qinhuangdao from January 2007 to May 2013 were selected,and randomly divided into treatment group(20 cases) and control group(20 cases)?The control group underwent TACE,the treatment group were given TACE combined with PEIT, the clinical effect of the two groups were observed?Results The effective rate of the treatment group was 80%,significantly higher than that of the control group( 50%) ,the difference was statistically significant( P=0?04)?During the follow?up of 3 years,there were 3 cases of portal vein tumor thrombus,5 cases of hepatic metastasis,1 case of upper gastrointestinal bleeding and 2 cases of liver failure in the control group;there were 1 case of liver metastasis,1 case of liver failure and death in the treatment group?Conclusion The test of the curative effect of patients with huge hepatocellular carcinoma after combination therapy with TACE and PEIT proved combination therapy can increase the curative effect, decrease impairment of liver funvtion?It was a palliation road to treat huge hepatocellular carcinoma.

Objective To investigate the effects of capparis spinosa total alkaloid on the pathological changes and the type Ⅲ collagen(COL?Ⅲ)expression in systemic sclerosis(SSc)mice. Methods Mice models with SSc were established by repeated local injection of bleomycin in BALB/c mice back. After administration of capparis spinosa total alkaloid ,the pathological changes of skin and lung tissue were observed ,and the COL?Ⅲ expression was detected by ELISA. Results Compared with the model group,the inflammation and fibrosis of skin and lung tissue were improved,and the level of COL?Ⅲ was markedly reduced by treatment of high dose capparis spinosa total alkaloid(P<0.05). Conclusion Cap?paris spinosa total alkaloid is effective in treating fibrosis of SSc.

Objective:To explore the clinical characteristics and influencing factors of myocarditis induced by immune checkpoint inhibitors (ICIs).Methods:Using programmed death receptor-1 (PD-1), nivolumab, pembrolizumab, programmed cell death receptor ligand-1 (PD-L1), atezolizumab, durvalumab, avelumab, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), ipilimumab, tremelimumab as keywords respectively, we combined these words with myocarditis or the corresponding Chinese to search.Results:A total of 49 articles were reported, including 64 patients. Nivolumab was the most reported, followed by pembrolizumab and ipilimumab. The average age was (65.47±13.24)years, mainly elderly patients; 37 cases (57.81%) were male; the overall mortality rate was 31.25%(20/64). The clinical symptoms were diverse and nonspecific, with dyspnea being the most common (39/64, 60.94%). Heart biomarkers were elevated in 94.64%(53/56) of the patients. 35 patients (54.69%, 35/64) developed myocarditis after 1-2 doses and 17 patients died. 60 patients received steroids as initial treatment, and immunosuppressive therapies such as infliximab, intravenous immunoglobulin, antithymic globulin, and/or plasmapheresis were used in 25 patients, symptoms improved in 17 cases (68.00%).Conclusions:ICIs can cause myocarditis, with high mortality, and should be closely monitored and timely treatment. Steroids can be used as initial first-line therapy and immunosuppressants and/or plasmapheresis may improve clinical symptoms and survival rate.

Objective: To investigate the changes of sTNFR in rats with MODS and its clinical implication. Methods: Rat delayed two phase models of MODS were replicated, then serum sTNFR were measured respectively pre and post MODS by ELISA method. Results: Serum sTNFRⅠ pre and post MODS was (112.15?24.95) pg/ml and (438.06? 67.06) pg/ml ( P

Background and purpose: Breast cancer is a group of heterogeneous diseases which has racial disparities. Our study was to elucidate the clinicopathologic features of breast carcinoma in Shanghai Han and Xinjiang Uygur women and to analyze the racial differences. Methods: In this study, 125 cases of breast invasive ductal carcinoma of Shanghai Han women and 85 cases of Xinjiang Uygur women were collected. The clinical stage was analyzed. Histological grading was observed. Immunohistochemical staining of ER, PR, HER-2, CK5/6, CK14, EGFR, Ki-67 was performed. Molecular subtypes were studied. Results:The average age of onset of breast cancer in Xinjiang Uygur women was younger than in Shanghai Han women (P<0.05), and Xinjiang Uygur women were more likely to be diagnosed at less than 35 years old (P<0.01). The proportion of stageⅠwas higher in Shanghai Han women (20.0%vs 8.2%), while the proportion of stageⅢwas higher in Xinjiang Uygur women (50.6%vs 27.2%) (P<0.01). The proportion of grade 2 was higher in Shanghai Han women (67.2% vs 43.5%), while the proportion of grade 3 was higher in Xinjiang Uygur women (47.1%vs 31.2%) (P<0.01). The proportion of luminal A subtype was higher in Shanghai Han women (36.8%vs 18.3%), while the proportion of basal-like subtype was higher in Xinjiang Uygur women (29.6%vs 12.0%) (P<0.01). The molecular subtype was associated with race and histological grade (P<0.05).Conclusion:There are racial differences in clinicopathologic features of breast carcinoma between Shanghai Han and Xinjiang Uygur women.

ObjectiveTo investigate the effect of finasteride on hemorrhage in peri-operation of transurethral plasmakinetic enucleation of prostate (TUPKEP).Methods150 patients with benign prostatic hyperplasia (BPH) were randomly divided into 3 groups:control group without finasteride (n= 50),treatment groupl 1 with finasteride 5 mg daily for 7 days(n= 50) and treatment group 2 with finasteride 10 mg daily for 7 days(n= 50) before and after operation.All patients received TUPKEP and the data were recorded,including total blood loss,operation time,amount of washing fluid during operation,blood loss of per gram tissue,blood loss per minute,washing time after operation,amount of washing fluid after operation,and rebleeding rate within 3 months after operation.ResultsThe 150 patients successfully received TUPKEP.The total blood loss,amount of washing fluid during operation,operation time,blood loss per gram tissue,amount of washing fluid after operation,washing time after operation and rebleeding rate within 3 months after operation in treatment group 1 and 2 significantly reduced as compared with control group (P＜0.05).The blood loss per minute were (1.77±0.89) ml/min,(1.71±0.82) ml/min and (1.70±0.81) ml/min in 3 groups,respectively,and there were no significant differences among groups (P＞ 0.05).There were no significant differences between treatment group 1 and 2 in the total blood loss,operation time,amount of washing fluid during operation,blood loss of per gram tissue,blood loss per minute,washing time and amount of washing fluid after operation (P＞0.05).The rebleeding rate within 3 months after operation in treatment group 1 (8/35) and treatment group 2 (3/26) decreased as compared with control group (17/39) (x2= 3.544 and 7.523,P=0.016 and 0.025)and it was lower in treatment group 2 than in treatment group 1 (x2 = 1.293,P = 0.044).Conclusions The application of finasteride in peri-operation of TUPKEP can reduce hemorrhage.