Efficacy of telbivudine in the treatment of chronic hepatitis b and liver cirrhosis and its effect on immunological responses.

This study was aimed to evaluate the long-term effects of telbivudine (LdT) in the treatment of chronic hepatitis B (CHB) and HBV-related liver cirrhosis (LC) and to observe the changes of immunological responses during LdT treatment. Clinical data of 80 CHB and 28 HBV-related LC patients who were administered with LdT for 108 weeks and followed up were retrospectively analyzed. The liver function indicators including ALT, AST and γ-GT, HBV DNA copy number in serum and the rates of hepatitis B e antigen (HBeAg) seroconversion were analyzed before and 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks after LdT treatment in CHB and LC groups. Four serum fibrosis-related markers, including hyaluronic acid (HA), human laminin (LN), human type IV collagen (IV-C) and human N-terminal procollagen III peptide (PC-III), were detected before and after LdT treatment in LC group. The results showed favorable viral suppression and biochemical responses after treatment with LdT for 12 weeks, and a high rate of virological and biochemical control was maintained during the course of 108-week treatment in both CHB and LC groups. The four fibrosis-related markers, especially HA and LN, were down-regulated to some degrees in LC group. Moreover, LdT treatment led to the fluctuation of the circulating interferon-γ (IFN-γ) and interleukin-10 (IL-10) levels at different time points in CHB group. It was concluded that LdT could favorably lead to the virological suppression and biochemical remission. Besides, IFN-γ and IL-10 may represent a suitable and effective predictor of responsiveness during LdT therapy.

Risk Factors of Enternal Nutrition Intolerance in Septic Patients: A Case-control Study.

OBJECTIVE: This study aimed to investigate the incidence of enteral nutrition intolerance (ENI) in patients with sepsis and explore potential risk factors. METHODS: A case-control study was conducted in patients with sepsis who were receiving enteral nutrition (EN) at a tertiary hospital in China. The included patients were divided into the ENI group and the non-ENI group. Univariate and multivariate analyses were performed to identify the risk factors for ENI. RESULTS: A total of 859 patients were included in the study. Among them, 288 (33.53%) patients experienced symptoms of ENI, including diarrhea, vomiting, bloating, and gastric retention. Logistic regression analysis revealed that the Acute Physiology and Chronic Health Evaluation H (APACHE H) score, thoracocentesis, and usage of cardiotonic drugs (namely, inotropes) were independent predictors of the ENI. CONCLUSION: The incidence of ENI is relatively high in patients with sepsis, especially in those who have higher APACHE H scores, have undergone thoracocentesis, and have received inotropes.

[Effects of anandamide on proliferation of and pErk expression in primary hepatic stellate cells of schistosome-induced liver fibrosis mice].

OBJECTIVE: To investigate the potential therapeutic properties of the endogenous cannabinoid N-arachidonic acid aminoethanols (anandamide, AEA) in liver fibrosis by observing its affects on proliferation of and expression of phosphorylated-Erk (pErk) in primary hepatic stellate cells (HSCs) from a mouse model of schistosome-induced liver fibrosis. METHODS: The schistosome-induced liver fibrosis model was established by attaching cercaria to the skin on the ventral side of the mouse and allowing infection to occur via direct penetration. Six weeks later, the model was confirmed by pathological analysis of liver, with Masson trichrome staining showing collagen fiber deposition around the blood vessels and hematoxylin-eosin staining showing eosinophilic granuloma formation. Primary HSCs were isolated by discontinuous density gradient centrifugation, confirmed by immunofluorescence detection of double-staining for a-smooth muscle actin and desmin (95% purity), and cultured in the presence of absence of various concentrations of AEA. Proliferative ability was evaluated by MTT assay and the expression of pErk was observed by Western blotting. RESULTS: AEA treatment inhibited the proliferation of the primary HSCs in a concentration-dependent manner (AEA: 5 mumol/L, inhibition: 7.68%; 10 mumol/L, 11.65%; 20 mumol/L, 14.70%; 40 mumol/L, 15.07%; 60 mumol/L, 18.18%; 80 mumol/L, 20.26%; 100 mumol/L, 20.17%; 120 mumol/L, 29.24%). AEA treatment increased pERK expression in both a concentration-dependent manner (AEA: 20 mumol/L, average gray value: 39.90+/-4.61; 60 mumol/L, 43.45+/-0.91; 120 mumol/L, 52.91+/-1.97; vs. negative control, all P less than 0.05) and a time-dependent manner (time: 15 min, average gray value: 85.05+/-15.80; 30 min, 103.41+/-11.89; 1 h, 118.02+/-12.24; 3 h, 109.17+/-15.69; 6 h, 100.86+/-10.55; 12 h, 71.70+/-12.87; 24 h, 34.62+/-14.85; 48 h, 22.84+/-11.73; vs. negative control, all except 48 h had P less than 0.05). CONCLUSION: AEA can suppress the proliferative capacity of primary HSCs from schistosome-induced fibrotic livers through activation of the Erk signaling pathway.

[Expression of ASMase in alcoholic liver fibrosis in rats].

OBJECTIVE: To investigate the expression of the lysosomal enzyme acid sphingomyelinase (ASMase) in alcohol-induced hepatic fibrosis using a rat model. METHODS: The model of liver fibrosis was induced by administration of alcohol and high fat diet using 20 rats. Six rats given no alcohol and normal diet served as the control group. Real-time PCR, western blotting, and immunohistochemistry were used to evaluate fibrosis-related changes in the mRNA and protein expressions of ASMase. RESULTS: The fibrotic liver tissues of the model rats showed significantly higher expression levels of ASMase than the non-fibrotic liver tissues of the control rats (P less than 0.05). CONCLUSION: Expression of ASMase is increased in the fibrotic liver tissue of an alcohol-induced hepatic fibrosis rat model, suggesting that this lysosomal enzyme may contribute to development of this disease condition.

Risk Factors for Generalization in Patients with Ocular Myasthenia Gravis: A Multicenter Retrospective Cohort Study.

INTRODUCTION: Many patients with ocular myasthenia gravis (OMG) progress to generalized disease within the first 2 years of the onset of ocular symptoms. Several retrospective studies have identified risk factors associated with generalization, however these studies included patients on immunosuppression therapy or those undergoing thymectomy, which may reduce the generalization risk. In this study we explored the risk factors for generalization in non-immunosuppressed and non-thymectomized patients with OMG. METHODS: Data from patients with OMG treated at seven tertiary hospitals in China were retrospectively reviewed. Clinical characteristics, including sex, age at onset, symptoms at onset, comorbid autoimmune diseases, neostigmine test response, repetitive nerve stimulation (RNS) findings, presence of serum anti-acetylcholine receptor antibody (AChR-Ab), and thymic status based on radiological and pathological studies, were collected. The main outcome measure was disease generalization. The follow-up period was defined as the date of ocular symptom onset to the date of confirmation of generalization or immunotherapy initiation, or last follow-up (defined as 60 months). The Cox proportional hazards model was used to assess the risk factors for generalization. RESULTS: Overall, 572 patients (269 women) were eligible for inclusion in the analysis, of whom 144 developed generalization. The mean (standard deviation) onset age was 45.5 (19.8) years, and the median (interquartile range) follow-up period was 14.5 (7.0-47.3) months. Multivariable Cox regression analysis demonstrated that both early-onset (adjusted hazard ratio [aHR] 5.34; 95% confidence interval [CI] 1.64-17.36; p = 0.005) and late-onset (aHR 7.18; 95% CI 2.22-23.27; p = 0.001) in adulthood, abnormal RNS findings (aHR 3.01; 95% CI 1.97-4.61; p < 0.001), seropositivity for AChR-Ab (aHR 2.58; 95% CI 1.26-5.26; p = 0.01), and thymoma (aHR 1.62; 95% CI 1.05-2.49; p = 0.03) were independently associated with increased risk of generalization. CONCLUSION: The risk of generalization increased significantly in patients with adult-onset OMG, abnormal RNS findings, seropositivity for AChR-Ab, and thymoma, suggesting that these risk factors may predict OMG generalization.

Schistosoma japonicum egg antigen up-regulates fibrogenesis and inhibits proliferation in primary hepatic stellate cells in a concentration-dependent manner.

AIM: To investigate the effects of different concentrations of Schistosoma japonicum (S. japonicum) egg antigen on fibrogenesis and apoptosis in primary hepatic stellate cells (HSCs). METHODS: A mouse model of schistosomiasis-associated liver fibrosis (SSLF) was established by infecting mice with schistosomal cercaria via the abdomen. HSCs were isolated from SSLF mice by discontinuous density gradient centrifugation, and their identity was confirmed by immunofluorescence double staining of α-smooth muscle actin (α-SMA) and desmin. The growth inhibitory effect and 50% inhibitory concentration (IC50) of S. japonicum egg antigen for primary HSCs (24 h) were determined using a cell counting kit-8 (CCK-8) assay. The expression levels of α-SMA, matrix metalloproteinase-9 (MMOL/LP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in HSCs in response to different concentrations of S. japonicum egg antigen were detected by Western blotting and real-time reverse transcription-polymerase chain reaction. The levels of phospho-P38 (P-P38), phospho-Jun N-terminal kinase (P-JNK) and phospho-Akt (P-AKT) in HSCs were detected by Western blotting. RESULTS: An SSLF mouse model was established, and primary HSCs were successfully isolated and cultured. S. japonicum egg antigen inhibited HSC proliferation in a concentration-dependent manner. The IC50 of the S. japonicum egg antigen was 244.53 ± 35.26 µg/mL. S. japonicum egg antigen enhanced α-SMA expression at both the mRNA and protein levels and enhanced TIMP-1 expression at the mRNA level in HSCs (P < 0.05), whereas the expression of MMOL/LP-9 was attenuated at both the mRNA and protein levels in a concentration-dependent manner (P < 0.05). A high concentration of S. japonicum egg antigen enhanced P-P38, P-JNK and P-AKT activation (P < 0.05). The changes in α-SMA and MMOL/LP-9 expression induced by S. japonicum egg antigen were closely correlated with P-P38 and P-JNK activation (P < 0.05). The attenuation of MMOL/LP-9 was also correlated with P-AKT activation (P < 0.05), but the increase in α-SMA expression was not. TIMP-1 expression was not correlated with P-P38, P-JNK or P-AKT activation. CONCLUSION: S. japonicum egg antigen promotes fibrogenesis, activates the P38/JNK mitogen-activated protein kinase and AKT/PI3K signaling pathways and inhibits proliferation in primary HSCs isolated from SSLF mice in a concentration-dependent manner.