s:Objective To investigate the possible role of basic ifbroblast growth factor (bFGF) and transforming growth factorβ1 (TGF-β1) in mice with Coxsackie viral myocarditis and their relationship. Methods Eighty male BALB/c mice, 4 weeks old, were divided randomly into study group (n=40) and control group (n=40). The study group was repeated intraperitoneally injected with Coxasckie viral B3 to establish the model of viral myocarditis, while the control group was injected with virus-free Eagle’s medium in the same period. On the 7th, 14th, 28th and 42th day after the ifrst injection, 8 alive mice selected randomly from each group were sacriifced to examine the myocardial collagen volume fraction (CVF) by Masson dyeing, and to detect the protein and mRNA expression of bFGF and TGF-β1 by RT-PCR and immunohistochemistry. The correlations were analyzed. Results At each time point, the expressions of protein and mRNA of bFGF and TGF-β1 both in study group were signiifcantly higher than those in control group (P<0.01), and gradually increased over time. The expressions of protein and mRNA of bFGF and TGF-β1 were positively correlated with CVF (r=0.86~0.95, all P<0.01). In addition, the expressions of protein and mRNA of bFGF also had positive correlation with the expression of protein and mRNA of TGF-β1 (r=0.94, 0.92, P<0.01). Conclusion bFGF and TGF-β1 may promote the occurrence and development of myocardial ifbrosis in viral myocarditis, which may provide a new target for future treatment of myocardial ifbrosis.

Objective To study the role of transforming growth factor-β1 (TGF-β1),connective tissue growth factor (CTGF)and endothelin-1 (ET-1) in myocardial tissues of the mice with myocardial fibrosis induced by coxsachievirus B3 (CVB3) and the effect of Carvedilol intervention for it in acute stage and chronic phase of viral myocarditis.Methods Forty male BALB/c mice were randomly divided into 4 groups (10 cases in each group):control group,model group,Carvedilol acute phase intervention group,the chronic phase intervention group.Mice in model group and Carvedilol intervention groups were inoculated with CVB3 (100TCID50/0.1 mL) by peritoneal injection fortnightly.Mice in control group were given normal saline(NS) instead equivalently.Mice were poured Carvedilol (10 mg/kg per day for 2 weeks) from the second day in acute phase intervention group and from the fourth week in the chronic phase intervention group,while mice of control group and model group were poured with equivalent NS instead.At the end of 6 weeks,mice were sacrificed.Heart weight index (HWI) was determined.The collagen volume fraction (CVF) of left ventricular myocardial tissue were examined after Masson staining.Expressions of ET-1,TGF-β1 and CTGF were detected by enzyme linked immunosorbent assay and immunohistochemistry staining respectively; the mRNA expression was tested by reverse transcription-polymerase chain reaction.Results Compared with the control group,HWI and CVF of model group increased significantly(all P ＜ 0.01),those of the intervention groups decreased than those of the model group(all P ＜ 0.01),and in the acute phase those of the intervention group were significantly lower than those in chronic phase intervention group(all P ＜ 0.05).The expressions of TGF-β1,CTGF,ET-1 and their mRNA in model group were increased significantly than those in the control group(all P ＜0.01),and were decreased in acute and the chronic phase intervention group than those in model group(all P ＜0.01),while those were significantly lower in acute phase intervention group than those in chronic phase intervention group (all P ＜ 0.01).Conclusions TGF-β1,CTGF and ET-1 may be involved in myocardial fibrosis induced by CVB3.Compared with the chronic phase intervention,the acute phase intervention of Carvedilol can reduce myocardial fibrosis more efficiently by down-regulating the excessive expression of inflammatory factors.

ObjectiveTo investigate the association of common clinical indices and noninvasive liver fibrosis scores with hepatic-type Wilson’s disease (WD) in Chinese patients and their ability to identify advanced liver fibrosis. MethodsA retrospective analysis was performed for the clinical data of 236 Chinese patients with WD who were diagnosed and treated in Beijing YouAn Hospital and China-Japan Friendship Hospital from May 1996 to April 2020. A total of 26 patients with hepatic-type WD who underwent liver pathological examination and had complete clinical data were enrolled; the METAVIR score was used to determine liver fibrosis stage, and the patients were divided into advanced liver fibrosis (F3 and F4 stages) group and non-advanced liver fibrosis (F0, F1, and F2 stages) groups. Three noninvasive liver fibrosis scores ［Sheth index, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) index］ were calculated for both groups, and the above indices and related clinical indices were compared between the two groups. The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the Fisher’s exact test was used for comparison of categorical data between two groups. The Spearman rank correlation test was used for further analysis of indices with statistical significance, and the clinical indices and scoring criteria correlated with liver fibrosis degree were screened out; the receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUC) was calculated. ResultsMost of the patients in this study developed the disease in childhood and adolescence, and among these patients, 10 (38.5%) had positive K-F ring and 17 (65%) were in the stage of advanced liver fibrosis. There were significant differences between the advanced liver fibrosis group and the non-advanced liver fibrosis group in white blood cell count (WBC) (Z=-2.102, P=0.036), hemoglobin (Hb) (t=-2.860, P=0009), platelet count (PLT) (t=-4.053, P＜0.001), direct bilirubin (DBil) (Z=-2.130, P=0.033), albumin (Alb) (t=-2.875, P=0.008), and Sheth index (Z=-3.369, P=0.001). WBC, Hb, PLT, and Alb were negatively correlated with liver fibrosis degree in WD patients (r=-0.587, -0.610, -0.656, and -0.411, all P＜0.05), and DBil and Sheth index were positively correlated with liver fibrosis degree (r=0.486 and 0.711, both P＜0.05). The ROC curve analysis showed that WBC, DBil, Sheth index, Hb, PLT, and Alb had an AUC of ＞0.7, among which Sheth index had the largest AUC of 0.908, with a sensitivity of 70.6%, a specificity of 100.0%, a positive predictive value of 100.0%, and a negative predictive value of 64.3%. ConclusionSheth index has a better diagnostic efficiency than the other clinical indices alone and can well identify advanced liver fibrosis in Chinese patients with hepatic-type WD.

OBJECTIVE: To explore the correlation between endothelial microparticles(EMPs) and subacute 1,2-dichloroethane(1,2-DCE) toxic encephalopathy. METHODS: A total of 24 patients with subacute 1,2-DCE toxic encephalopathy were selected as the case group, and 24 healthy individuals were selected as the control group using a convenient sampling method. Blood plasma was collected from the fasting venous blood of patients in these two groups, and the level of EMPs in the plasma was detected by flow cytometry. RESULTS: The levels of plasma EMPs of patients in the control group and the case group were(692.0±174.4) ×10~3/L and(839.8±155.8) ×10~3/L respectively. The levels of plasma EMPs in patients with mild, moderate and severe case subgroups were(691.6±101.9) ×10~3/L,(900.6±46.6) ×10~3/L and(1 026.8±69.8)×10~3/L respectively. The EMPs level of patients in the case group was higher than that of the control group(P<0.01). The level of EMPs in the moderate and severe case subgroups was higher than that of the control group and mild case subgroup(P<0.01). CONCLUSION: Endothelial injury was found in patients with subacute 1,2-DCE toxic encephalopathy and endothelial injury is related to the severity of poisoning.

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.