Hepatic sinusoidal obstruction syndrome (HSOS) is a type of secondary vascular disease of the liver that is mainly associated with the ingestion of pyrrole alkaloids (PAs) and hematopoietic stem cell transplantation (HSCT) treatment, resulting in severe liver dysfunction, multiple organ failure, and even death. Hepatic sinusoidal dilatation and obstruction, hepatocyte coagulative necrosis, and hepatic lobular inflammation are the main pathological manifestations of HSOS. The key initiating process for the pathogenesis of HSOS is damage to liver sinusoidal endothelial cells (LSECs). Currently, it is believed that LSECs are damaged by the involvement of multiple etiologies and mechanisms, and secondary coagulation and fibrinolysis disorders, oxidative stress, and inflammatory responses are the occurrence contributors to HSOS; however, the mechanism has not been fully elucidated. Therefore, the role of immune-inflammatory mechanisms has received increasing attention in LSEC damage. This article provides an overview of the epidemiology, etiology, and pathological changes of HSOS and reviews the physiological functions, common etiological damage mechanisms, and the key role of LSEC damage in the pathogenesis of HSOS, with a special focus on the role and research progress of immune-inflammatory mechanisms for LSEC damage in recent years. Furthermore, we believe that in-depth study and elucidation of the role of immune-inflammatory mechanisms in LSEC damage and the pathogenesis of HSOS and diagnosis will provide feasible research and development ideas for the screening and identification of new markers and drug treatment targets for HSOS.

The incidence and mortality rates of cholangiocarcinoma (CCA) are increasing constantly, and it is of great importance to explore new therapeutic targets. Ferroptosis, a unique pattern of cell death caused by iron-dependent cellular oxidative injury, is closely associated with iron metabolism and oxidative stress imbalance in cancer and has become a research hotspot in the field of tumor. This article introduces the mechanism of ferroptosis and the research advances in ferroptosis involved in the development and progression of CCA, and it is pointed out that the regulatory mechanism of ferroptosis has an important clinical value in the malignant progression of CCA.

In recent years, with the changes in living standards and dietary structure, the incidence of non-alcoholic fatty liver disease has been increasing year by year in China, and the incidence rate in the general population is as high as 29.81%. An increasingly epidemiological evidence suggests that non-alcoholic fatty liver disease has become one of the causes of increasing liver cirrhosis and liver cancer. However, its etiology and pathogenesis are complex and have not yet been fully elucidated. Therefore, establishing an appropriate non-alcoholic fatty liver disease animal models for pre-clinical research is essential to elucidate its pathogenesis. This article summarizes the latest research progress of non-alcoholic fatty liver disease animal models, which are common at home and abroad in recent years.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease in children and adults, and is closely related to obesity and metabolic factors. In recent years, with the changes in living standards and dietary structure, the incidence of NAFLD has been increasing year by year. Pediatric NAFLD has many similarities with adult NAFLD in terms of epidemiology, etiology, pathogenesis, and diagnosis and treatment strategies; however it has its own unique characteristics. This paper reviews the latest research progress of pediatric NAFLD in recent years at home and abroad.

ObjectiveTo investigate clinical features and outcomes in acute ischemic stroke patients with remote symptomatic intracranial hemorrhage (sICHr) after intravenous thrombolysis.MethodsThe acute ischemic stroke patients with sICHr after intravenous thrombolysis therapy were enrolled retrospectively.The clinical data were collected and the related literature was analyzed and summarized.ResultsA total of 6 acute ischemic stroke patients with sICHr were enrolled, including 4 males.Three patients had a history of using antiplatelet agents, 2 with atrial fibrillation, 4 with hypertension, 3 with previous stroke history, 4 with smoking history, and 4 had sICHr at 2 h after intravenous thrombolysis.Of the 14 hemorrhagic foci (except in the infarct areas), 10 were in the cerebral cortex.Three patients died within 1 week, and 1 was in a persistent vegetative state.Conclusions SICHr after intravenous thrombolysis in patients with acute ischemic stroke is mainly located in the cerebral cortex.The outcomes in acute ischemic stroke patients with SICHr after intravenous thrombolysis are poor, and the mortality is high.

OBJECTIVETo investigate expression of the cysteinyl leukotriene receptor (CysLT1R) in hepatocellular carcinoma (HCC) tissues and determine its clinical significance.

METHODSCancerous and paraneoplastic liver tissues were collected from 30 patients with HCC and from 12 patients with liver hemangioma patients (controls). Real-time PCR and immunohistochemistry were used to evaluate the expression of CysLT1R in these tissues and assess the relationship with clinical pathological features. T-test,?Fisher's exact test and Kaplan-Meier survival analysis were used for statistical analysis.

RESULTSThe expression of CysLT1R in adjacent liver tissues (100%) was higher than that in the HCC (43.33%, P = 0.000) and normal liver tissues (41.67%, P = 0.000). The level of CysLT1R mRNA was also higher in paraneoplastic liver tissues (0.0339+/-0.0221) than in the paired HCC tissues (0.0127+/-0.0116, t = 2.911, P = 0.008) and normal liver tissues (0.0154+/-0.0123, t = -2.310, P = 0.033). There was no difference between the levels in HCC and normal liver tissues (P more than 0.05). Higher level of CysLT1R mRNA, higher level of serum alpha-fetoprotein, and higher tumor stage (III-IV) were associated with poor prognosis (respectively 4.372, P = 0.037; 24.187, P = 0.000; 8.75, P = 0.003). However, no evident relationship between the expression of CysLT1R and other clinical features was observed. Conclusions Overexpression of CysLT1R may contribute to the occurrence and progression of HCC.

Carcinoma, Hepatocellular ; diagnosis ; metabolism ; Case-Control Studies ; Disease Progression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms ; diagnosis ; metabolism ; Neoplasm Staging ; Prognosis ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, Leukotriene ; metabolism ; alpha-Fetoproteins ; metabolism

Objective To investigate the efficacy of sequential add-on of pegylated interferon α-2a (PEGIFN-α-2a) for 48 weeks in chronic hepatitis B (CHB) patients with low serum hepatitis B e antigen (HBeAg) titer after long term adefovir dipivoxil (ADV) monotherapy.Methods This was a randomized,open and prospective clinical trial.Patients who had been treated with ADV for 72 to 144 weeks,with undetectable serum hepatitis B virus (HBV) DNA level,low HBeAg titer (5 S/CO＜ HBeAg＜50 S/CO) and serum hepatitis B surface antigen (HBsAg) ＜5000 IU/mL were included.The patients were categorized into ADV monotherapy group and ADV plus PEGIFN-a-2a combination therapy group by random number table.Patients in ADV group continued ADV monotherapy and patients in combination therapy group added PEGIFN-α-2a to ADV for 48 weeks.After the treatment,efficacy of the two therapies were assessed by comparing the reduction of serum HBeAg reduction,HBeAg loss rate,HBeAg seroconversion rate,and reduction of intrahepatic HBV DNA and HBV covalently closed circular DNA (cccDNA).Pre-and post-treatment results were compared by paired samples t test.Comparison between groups was performed using indepedent samples t test.Comparison of rates between groups was performed using x2 test.Results The trial enrolled 55 CHB patients,and there were 27 patients in ADV monotherapy group,28 patients in combination therapy group.Baseline characteristics including age distribution,sex ratio,alanine aminotransferase (ALT),aspartate aminotransferase (AST),total bilirubin (TBil),serum HBeAg and HBsAg,hepatic HBV DNA and HBV cccDNA were all comparable (all P＞0.05).Twenty-five patients in ADV monotherapy group and 26 patients in combination therapy group completed 48 weeks treatment.HBeAg loss rates and seroconversion rates of combination therapy group were higher than those of ADV monotherapy group (x2 =5.38 and 4.69,respectively,both P＜0.05).HBeAg titers of both groups were significantly lower than those of baseline (t=8.43 and 8.50,respectively,both P＜0.05).The HBeAg titer of combination therapy group was lower than that of monotherapy group (t=5.60,P＜ 0.01).HBV DNA and HBV cccDNA in liver tissue of combination therapy group was (6.934±0.52) lg IU/mg and (5.63±0.54) lg IU/mg post-treatment,respectively,which were both lower than baseline (t＝7.12.6.67,respectively,both P＜0.01).HBV DNA in liver tissue of monotherapy group was (7.09＝0.43) lg IU/mg post-treatment,which was lower than baseline (t=2.67,P=0.02).After treatment,HBV cccDNA in liver tissue of combination therapy group was lower than that of monotherapy group (t =2.87,P=0.00).Conclusions Compared with ADV monotherapy,sequential add-on of PEGIFN-a-2a in combination with ADV can achieve higher serum HBeAg loss rate and seroconversion rate and facilitate the clearance of hepatic HBV DNA and HBV cccDNA in CHB patients with low HBeAg titer after long-term ADV monotherapy.

Objective To investigate the peripheral blood Th17 and CD4 + CD25 + regulatory T cell levels and their correlations in patients with primary hepatocellular carcinoma (PHC).Methods Peripheral blood samples were collected from 30 PHC patients and 25 healthy controls in the First Affiliated Hospital of Zhejiang University from June 2008 to May 2009.Mononuclear cells were isolated and the Th17 and CD4 + CD25 + regulatory T cells were detected by flow cytometry and compared between patients and controls by t test.Spearman test was performed to analyze the correlation of Th17 with CD4 + CD25 +regulatory T cell concentrations.Results The levels of Th17 and CD4 + CD25 + regulatory T cells in peripheral blood in healthy controls were (2.10 ± 0.87) ％ and (7.10 ± 2.32) ％ ; while those in PHC patients were (3.38±1.68)％ and (11.78±5.62)％ (t=3.640 and 4.162,P＜0.01).The level of Th17 cells was positively associated with that of CD4 + CD25 + regulatory T cells in PHC patients (r =0.821,P ＜0.01).Conclusion The levels of Th17 and CD4 + CD25 + regulatory T cells in peripheral blood are high in PHC patients and positively correlated with each other,which indicates that CD4 + CD25 + regulatory T cells may contribute to the disease progression and pathogenesis of carcinoma through inducing Th17 cells differentiation.