Staging of liver fibrosis in chronic hepatitis B patients with a composite predictive model:A comparative study

AIM:To evaluate the efficacy of 6 noninvasive liver fibrosis models and to identify the most valuable model for the prediction of liver fibrosis stage in chronic hepatitis B(CHB) patients.METHODS:Seventy-eight CHB patients were consecutively enrolled in this study.Liver biopsy was performed and blood serum was obtained at admission.Histological diagnosis was made according to the METAVIR system.Significant fibrosis was defined as stage score ≥ 2,severe fibrosis as stage score ≥ 3.The diagnostic accuracy of 6 noninvasive liver fibrosis models,including serum aspartate aminotransferase(AST) to platelet ratio index(APRI),FIB-4,Forn's index,Fibrometer,Hepascore,and Shanghai Liver Fibrosis Group's index(SLFG),was investigated.RESULTS:The APRI,FIB-4 and Forn's index under receiver operating characteristic curve(AUROC) for sig-nificant fibrosis were 0.71,0.75 and 0.79,respectively,with a diagnosis accuracy of 67%,77% and 80%,respectively,and 0.80,0.87 and 0.86,respectively,under the AUROC for severe fibrosis.The Hepascore,SLFG,and Fibrometer were 0.80,0.83 and 0.85,respectively under the AUROC for significant fibrosis(P < 0.01).The diagnosis accuracy of Hepascore and SLFG was 86% and 88%,respectively.The Hepascore,SLFG,and Fibrometer were 0.95,0.93,and 0.94,respectively,under the AUROC for severe fibrosis(P < 0.01).CONCLUSION:The models containing direct serum markers have a better diagnostic value than those not containing direct serum markers.

Effect of Helicobacter pylori infection on gastric epithelial cell proliferation

INTRODUCTION Helicobacter pylori(H.pylori)infection is one ofthe main pathogens of chronic gastritis and duodenalulcer(DU),and it may be considered as a riskfactor in the incidence of gastric cancer.H.pylori infection may lead to the anomaly of gastricepithelial cell proliferation which is closely relatedto the development of gastric cancer.Vacuolatingcytotoxin(VacA)is an important virulence andvacA subtype determines the toxic activity.According to its signal sequence,it can be groupedinto type sla,slb,slc and s2.Strains harboringvacAsla are more closely related with digestivediseases and may be the strains with high toxicity.The effect of H.pylori infection on

Effect of sodium salicylate on oxidative stress and insulin resistance induced by free fatty acids

BACKGROUND: It has been reported that high-dose salicylates improve free fatty acids (FFAs)-induced insulin resistance and beta-cell dysfunction in vitro, but the mechanism remains uncertain. In insulin-resistant rats, we found that the supplementation of sodium salicylate is associated with a reduction of plasma malondialdehyde (MDA), a marker of oxidative stress. Few studies have investigated the effects of salicylates on oxidative stress levels in insulin-resistant animal models. This study aimed to assess the effect of sodium salicylate on insulin sensitivity and to explore the potential mechanism by which it improves hepatic and peripheral insulin resistance. METHODS: Intralipid+heparin (IH), saline (SAL), or intralipid+heparin+sodium salicylate (IHS) were separately infused for 7 hours in normal Wistar rats. During the last 2 hours of the infusion, hyperinsulinemic-euglycemic clamping was 3 performed with [6-(3)H] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassay. MDA levels and glutathione peroxidase (GSH-PX) activity in the liver and skeletal muscle were measured with colorimetric kits. RESULTS: Compared with infusion of SAL, IH infusion increased hepatic glucose production (HGP), and decreased glucose utilization (GU) (P<0.05). The elevation of plasma free fatty acids increased the MDA levels and decreased the GSH-PX activity in the liver and muscle (P<0.01). Sodium salicylate treatment decreased HGP, elevated GU (P<0.05), reduced MDA content by 60% (P<0.01), and increased the GSH-PX activity by 35% (P<0.05). CONCLUSIONS: Short-term elevation of fatty acids induces insulin resistance by enhancing oxidative stress levels in the liver and muscle. The administration of the anti-inflammatory drug sodium salicylate reduces the degree of oxidative stress, therefore improving hepatic and peripheral insulin resistance. IKK-beta and NF-kappa B provide potential pathogenic links to oxidative stress.

Cyclosporin A protects Balb/c mice from liver damage induced by superantigen SEB and D-GaIN

AIM To investigate the pathogenic effect ofSEB and D-GalN on liver and the protection ofcyclosporin A, the relationship between hepaticapoptosis and necrosis and the possiblemechanism of acute hepatic necrosis.METHODS After staphylococcal enterotoxin B(SEB ) mixed with D--galactosamine (D-GaiN )were injected intraperitoneally into Balb/c miceand those previously treated with cyclosporin A,blood samples were collected and livers wereisolated at 2, 6, 12 and 24 h. Patterns othepatocellular death were studiedmorphologically and biochemically, circulatingcytokines (TNF-a, IFN--y ) and mice mortalitywithin 24h was assessed.RESU’LTS The SEB could induce the typicalapoptotic changes of hepatocytes, the D-GaiNcould induce hepatocytes apoptosis anddegeneration at the same time, and the micehaving received the SEB + D-GaiN injectionsdeveloped apoptosis at 2 and 6 h, but after 12 hhepatocytes were characterized by severein jury, whereas all the examinations in thecyclosporin A treated mice were normal.CONCLUSION Hepatic cell apoptosis might berelated to necrosis, and massive hepatocyteapoptosis is likely the initiating step of acutehepatic necrosis in mice. The effects induced bySEB and D--GaiN on hepatocytes might bemediated by T cells, and could be prevented bycyclosporin A.

Checkpoint inhibitor-induced hepatotoxicity:Role of liver biopsy and management approach

Immunological checkpoint inhibitors(ICIs)have revolutionized therapy of many different malignanices.Concomitant immune-mediated adverse effects are common and can affect many organs such as the skin,lungs,gastrointestinal and endocrine organs as well as the liver.Liver injury has been reported in 3%-8%of patients with grade III-IV hepatitis in retrospective studies.The liver injury is characterized by hepatocellular injury resembling autoimmune hepatitis biochemically but not immunologically as patients with ICI induced hepatoxicity rarely have auto-antibodies or IgG elevation.The role for liver biopsy(LB)in patients with suspected liver injury due to ICIs is controversial and it is not clear whether results of a LB will change clinical management.LB can be helpful when there is diagnostic uncertainty and pre-existing liver disease is suspected.Although there are no distinctive histological features,the finding of granulomas and endothelitis may suggest a specific type of hepatitis induced by ICIs.The natural history of hepatotoxicity of ICI therapy is not well known.Recent studies have demonstrated that 33%-50%of patients improve spontaneously with discontinuation of ICIs.In patients with jaundice and/or coagulopathy corticosteroids are used.The high doses of corticosteroids with 1-2 mg/kg/d of methylprednisolone recommended by the oncological societies are controversial.Recently it has shown that initial treatment with 1 mg/kg/d provided similar liver tests improvement which was also associated with a reduced risk of steroid-induced adverse effects in comparison with higher-dose regimens.Secondary immunosuppression mostly with mycophenolate mofetil has been reported to be helpful.

Expression of leptin and leptin receptor in gastric carcinoma

To determine the expression of leptin and leptin receptor in gastric carcinoma and investigate their role in carciagenesis and development of gastric carcinoma.Methods The expression of leptin and leptin receptor protein was detected in 54 cases of gastric carcinoma tissues by immunohistochemistry.The correlatin between their expression and clinicallpathological parameters was also analysized.Results The expression rate of leptin and leptin receptor in gastric carcinoma was 72.22%(39/54) and 74.07%(40/54) respectively.The expression rate of leptin in intestinal-type gastric cancer was significantly higher than in diffuse-type gastric cancer.The expression rate of leptin was associated with differentiation,tumor size,metastasis,and TNM stage.Conclusion Leptin and leptin receptor were dually expressed in gastric carcinoma.They participate in the early stage of malignant transformation and have certain role in the advanced stage.3 refs,1 tab.

Effects of glucose and insulin on the H9c2 （2-1） cell proliferation may be mediated through regulating glucose transporter 4 expression

Background The change of glucose transporter 4 （GLUT4） expression could influence glucose uptake in the myocardial cells and then effect myocardial metabolism, which maybe one of the factor for the diabetes cardiovascular disease. This study aimed to explore the influence of glucose and insulin at different concentrations on H9c2 （2-1） cell proliferation and its GLUT4 expression in vitro, and evaluate the correlation between myocardial cells proliferation and GLUT4 expression. This might be helpful for understanding the relationship between glucose metabolism and cardiovascular disease. Methods According to glucose concentrations in culture medium, cultured H9c2 rat myocardial cells were divided into five groups： control group （NC, glucose concentration 5.0 mmol/L）, low glucose group （LG, glucose concentration 0.1 mmol/L）, high glucose group 1 （HG1, glucose concentration 10 mmol/L）, high glucose group 2 （HG2, glucose concentration 15 mmol/L）, high glucose group 3 （HG3, glucose concentration 20 mmol/L）. Then according to different insulin concentrations in culture medium, each group was further divided into two subgroups： normal insulin subgroup （INSc, insulin concentration 3.8 mU/L）, high insulin subgroup （INSh, insulin concentration 7.6 mU/L）. H9c2 （2-1） cells were cultured for 1, 2, 3 days, the proliferation of cells were assayed by cell counting Kit-8 assay, the expressions of GLUT4 mRNA and protein were detected with RT-PCR and Western Blotting technique, and the relation between myocardial cells proliferation and GLUT4 expression was evaluated.

Leptin-p38MAPK pathway mediates high glucose-induced injury in H9c2 cardiac cells

Objective To investigate the role of leptin-p38 mitogen-activated protein kinase(MAPK)pathway in high glucose(HG)-induced injury in H9c2 cardiac cells.Methods H9c2 cardiac cells were treated with HG to establish a model of cellular injury induced by HG.Cell viability was tested by cell counter kit 8(CCK-8).The intracellular level of reactive oxygen species(ROS)

Suppressor of cytokine signaling 1 protects rat pancreatic islets from cytokine-induced apoptosis through Janus kinase/signal transducers and activators of transcription pathway

Background Suppressor of cytokine signaling （SOCS） proteins are inhibitors of cytokine signaling pathway involved in negative feedback loops. Although SOCS1 is an important intracellular suppressor of apoptosis in a variety of cell types, its role in cytokine-induced pancreatic β-cell apoptosis remains unclear. The present study investigated potential effects of SOCS1 on the cytokine-induced pancreatic β-cell apoptosis.

Efficacy and significance of various scores for pneumonia severity in the management of patients with community-acquired pneumonia in China

Background Community-acquired pneumonia （CAP） remains one of the leading causes ot death from infectious diseases around the world.Most severe CAP patients are admitted to the intensive care unit （ICU）,and receive intense treatment.The present study aimed to evaluate the role of the pneumonia severity index （PSI）,CURB-65,and sepsis score in the management of hospitalized CAP patients and explore the effect of ICU treatment on prognosis of severe cases.Methods A total of 675 CAP patients hospitalized in the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively investigated.The ability of different pneumonia severity scores to predict mortality was compared for effectiveness,while the risk factors associated with 30-day mortality rates and hospital length of stay （LOS） were evaluated.The effect of ICU treatment on the outcomes of severe CAP patients was also investigated.Results All three scoring systems revealed that the mortality associated with the low-risk or intermediate-risk group was significantly lower than with the high-risk group.As the risk level increased,the frequency of ICU admission rose in tandem and LOS in the hospital was prolonged.The areas under the receiver operating characteristic curve in the prediction of mortality were 0.94,0.91 and 0.89 for the PSI,CURB-65 and sepsis score,respectively.Compared with the corresponding control groups,the mortality was markedly increased in patients with a history of smoking,prior admission to ICU,respiratory failure,or co-morbidity of heart disease.The differences were also identified in LOS between control groups and patients with ICU treatment,heart,or cerebrovascular disease.Logistic regression analysis showed that age over 65 years,a history of smoking,and respiratory failure were closely related to mortality in the overall CAP cohort,whereas age,ICU admission,respiratory failure,and LOS at home between disease attack and hospital admission were identified as independent risk factors for mortality in the high-risk CAP sub-group.The 30-day mortality of patients who underwent ICU treatment on admission was also higher than for non-ICU treatment,but much lower than for those patients who took ICU treatment subsequent to the failure of non-ICU treatment.Conclusions Each severity score system,CURB-65,sepsis severity score and especially PSI,was capable of effectively predicting CAP mortality.Delayed ICU admission was related to higher mortality rates in severe CAP patients.

Azithromycin inhibits neutrophil accumulation in airways by affecting interleukin- 17 downstream signals

Background Azithromycin can reduce neutrophil accumulation in neutrophilic pulmonary diseases.However,the precise mechanism behind this action remains unknown.Our experiment assessed whether azithromycin inhibits neutrophil accumulation in the airways by affecting interleukin-17 （IL-17） downstream signals.Methods Mice were pretreated with azithromycin before murine IL-17A （mlL-17） stimulation.After the mlL-17 stimulation,the levels of six neutrophil-mobilizing cytokines were determined by enzyme-linked immunosorbent assay （ELISA） tests in bronchoalveolar lavage （BAL） fluid; IL-6,CXC chemokine ligand-1 （CXCL-1）,CXCL-5,macrophage inflammatory protein-2 （MIP-2）,granulocyte colony-stimulating factor （G-CSF）,and granulocyte macrophage colony-stimulating factor （GM-CSF）.The number of neutrophils in BAL fluid were evaluated by cytospin preparations.Results （1） Azithromycin pretreatment significantly inhibited both the release of three neutrophil-mobilizing cytokines （MIP-2,CXCL-5 and GM-CSF） and the accumulation of neutrophils in airways caused by mlL-17 stimulation.（2） The levels of three neutrophil-mobilizing cytokines （IL-6,MIP-2 and GM-CSF） were positively correlated with the numbers of neutrophil in BAL fluid.Conclusions Azithromycin can inhibit neutrophil accumulation in the airways by affecting IL-17 downstream signals.This finding suggests that macrolide antibiotic application might be useful in prevention of neutrophilic pulmonary diseases characterized by high levels of IL-17.

Nature:通过控制血管生长来开发治疗癌症等多种疾病的新型疗法

最近，一项刊登在国际杂志Nature上的研究报告中，来自耶鲁大学的研究人员通过研究揭示了如何通过控制血管发育来帮助开发治疗心血管疾病以及癌症的新型疗法。

Basal insulin therapy strategy is superior to premixed insulin therapy in the perioperative period blood glucose management

Background The probability and risk of operations increase in patients with type 2 diabetes mellitus. For diabetic patients, blood glucose control is a key factor to improving the prognosis of surgery. During perioperative period, insulin therapy is usually advised to be used for surgical patients with type 2 diabetes. However, the insulin regimen which one is better remains controversial. In this study, we estimated the efficacy, safety and advantage of different insulin therapy strategy during perioperative period.

Serum cytokine levels in patients with advanced non-small cell lung cancer： correlation with clinical outcome of erlotinib treatment

Background Serum expression of cytokines may provide information about the clinical outcome of advanced non-small cell lung cancer （NSCLC） patients. This study aimed to investigate the relationship between serum cytokine levels and the clinical outcome of erlotinib treatment in a second or third line setting in patients with advanced NSCLC.

Different treatment modes for cerebral microlesions:a comparison of clinical efficacy

Objective To tentatively establish a diagnosis and treatment mode for effectively controlling the progress of cerebral microlesions(CM) and preventing the incidence of cerebral infarction(CI) by comparing different intervention modes for treating CM.Methods Using a

Effect of Peimine on ERCC1 mRNA and LRP expressions of A549 / DDP multidrug resistance cell line

Objective To explore the effect of peimine on excision repair cross-complementation 1(ERCC1)m RNA and lung resistant protein(LRP)expressions in A549/cisplatin(DDP)multidrug resistance(MDR)cell line.Methods Lung cancer A549/DDP cells were cultured in vitro.Cells at logarithmic growth phase were divided

A study on correlation of obstructive sleep apnea-hypopnea syndrome and perihematoma edema of hypertensive cerebral hemorrhage

Objective To analyse the correlation of obstructive sleep apnea-hypopnea syndrome (OSAHS) and perihematoma edema of hypertensive cerebral hemorrhage.Methods One hundred and forty-four patients with hypertensive cerebral hemorrhage were collected and 78

Comparison of clinical characteristics of new onset ulcerative colitis in the elderly versus the youth and middle-aged patients

Objective To analyze the differences in the clinical characteristics,endoscopy,pathology and therapy between the patients with new onset ulcerative colitis(UC)in the elderly versus youth and middle-aged patients.Methods A review analysis was carried out in the 178hospitalized patients with UC in Third Hospital of Peking University from 1994 to 2010.The patients were divided into two groups according to the age of onset:UC onset at age of 60 years and older were enrolled in

Different combination of drugs regarding the damage on organs targeting salt sensitivity or non-salt-sensitive hypertension

Objective To study the damage on organs from salt sensitivity hypertension or non-salt-sensitive hypertension and the selection of drug combination.Methods 120 hypertensive patients including 60 cases salt-sensitive(SS)

Effects of myostatin propeptide gene tranfection on glucose metabolism in cultured C2C12 cells

Objective To investigate the effects of recombinant adeno-associated virus-mediated myostatin propeptide(MPRO)on uptake and oxidation of glucose,and glycogen synthesis in C2C12 myotubes,as well as the associated molecular mechanism.Methods Mature C2C12myotubes were assigned to the following 6 groups:control,insulin,green fluorescent protein(GFP)。