Volume 120  ·   Issue 24  ·  2007

Hepatitis B virus (HBV) infection is a worldwide health problem.According to WHO estimation,about 2 billion people globally have been infected With HBV and 350 million of them have chronic HBV infection.1

Chronic hepatitis B is one of the most common epidemic diseases in China and has become a major health issue.To help standardize the prevention,diagnosis,and treatment of chronic hepatitis B,the Guideline on prevention and treatment of chronic hepatitis B (abbr.Guideline) was created by a group of appropriate experts belonging to the Society of Hepatology and the Society of Infectious Disease,the Chinese Medical Association according to the principles of evidence-based medicine using the latest clinical research data。

Abstract：Background In recent years the interest of sustained drug delivery into inner ear is promising,at the same time a great deal of novel oral drugs using biodegradable vehicles have been produced to achieve sustained drug release.The aim of this study was to use biodegradable vehicles to release dexamethasone in the round window membrane application.Methods Dexamethasone gels composed of alginate and chitin were prepared and the release-permeating profiles were studied using a reproducible in vitro apparatus.A longer-period time course was simulated using the parameters acquired in this study.The data obtained in this study was compared with those of other studies in intratympanic drug delivery,and an appropriate initial dosage was extrapolated.Results The combination of alginate and chitin could efficiently restrict dexamethasone diffusion and the time course suggested a sustained drug concentration within 24 hours.A higher initial dosage was estimated to achieve a stable therapeutic concentration in vivo.Conclusion The combination of alginate and chitin could be used as vehicle for sustained release of dexamethasone in intratympanic application。

Abstract：Background The discovery of water channel aquaporins(AQPs)has greatly expanded the understanding of the regulation of the water permeability of biological membranes.Aquaporin-1(AQP1)may be involved in fluid transport in numerous pathological conditions.The objective of the present study was to examine whether AQP1 is present in cultured rat pleural mesothelial cells(PMCs)and to investigate the specific inhibitory effect of RNA interference(RNAi) on AQP1 expression in PMCs,which may provide a new method for the further studies on the relation between expression of AQP1 in PMCs and pleural fluid removal in vivo.Methods PMCs were isolated and cultured from rat pleura.The expression of AQP1 in PMCs was confirmed by immunocytochemical staining and reverse transcriptase-polymerase chain reaction(RT-PCR).Two eukaryotic expression plasmid vectors of short hairpin RNA(shRNA)specific for the AQP1 gene of rat sapien were designed and constructed.The recombinant plasmid vectors were transfected into cultured rat PMCs by cation liposomes.Flow cytometry was used to screen the most effective shRNA at 48 hours after transfection.The expressions of AQP1 mRNA and protein were detected by RT-PCR and Western blotting method at 48 hours after transfection.Results RT-PCR and immunostaining revealed that AQP1 mRNA and protein were present in cultured rat PMCs.Two effective eukaryotic expression plasmid vectors of shRNA specific for the AQP1 gene were constructed successfully.The levels of the expression of AQP1 were inhibited by 83.45%,90.93%,respectively,at mRNA level and 41.24%,67.60%,respectively at protein level by two recombinant plasmids at 48 hours after transfection.The expression of AQP1 in PMCs transfected with plasmid was significantly lower than that of the cells transfected with the control plasmid HK and that of the untransfected cells(P<0.01).There was no significant difference in AQP1 expression between the control group and the group transfected with AQP1 nonspecific shRNAs (P<0.05).Conclusions The expression of AQP1 was present in rat PMCs.The application of shRNA-AQP1 could markedly inhibit the expression of AQP1 in cultured rat PMCs.The use of RNAi is a promising tool for future research into the mechanisms of pleural fluid in vivo。

Abstract：Background Increased reactive oxygen species(ROS)formation,which in turn promotes cardiomyocytes apoptosis,is associated with the pathogenesis and progression of various cardiac diseases such as ischemia and heart failure.Recent studies have shown that over expression of heat shock protein 27(Hsp27)confers resistance to cardiac ischemia/reperfusion injury.However,not much is known about the regulation of myocyte survival by Hsp27.Methods The rat cardiac cell line H9c2,with a stable overexpression of Hsp27,was established,with empty vector transfected H9c2 cells as controls.Following the cells challenged by Hydrogen Peroxide(H2O2),lactate dehydrogenase (LDH)release,apoptosis,intracellular ROS,cell morphology,mitochondrial transmembrane potential and the activation of serine/threonine kinase Akt were determined.Results Along with marked suppression of H2O2-induced injury by Hsp27 overexpression in H9c2 cells,ROS generation and the loss of mitochondrial membrane potential were also significantly depressed.Furthermore,augmented Akt activation was observed in Hsp27 overexpressed H9c2 cells following H2O2 exposure.Conclusions Hsp27 inhibits oxidative stress-induced H9c2 damage and inhibition of ROS generation and the augmentation of Akt activation may be involved in the protective signaling。

Abstract：Background Esophageal adenocarcinoma is becoming an increasingly important problem.It has been the most rapidly increasing malignancy in western countries in the last decades,and its prognosis is poor.The aim of this study was to evaluate the relationship between tumor invasion depth and lymph node metastasis for adenocarcinoma of the esophagus and esophagogastric junction,and to analyze the impact of lymph node metastases on survival of the patients.Methods The study group comprised 121 patients with adenocarcinoma of the esophagus or esophagogastric junction,who underwent esophagectomy between January 1985 and December 2003 at either the Royal Adelaide Hospital or the Flinders Medical Center,Australia.Overall,there were 101 males and 20 females,with a mean age at surgery of 62 years(range 36-80).All of them were followed up for 6 months to 13 years(mean,6.5 years).The relationship between tumor invasion depth and lymph node metastasis,as well as between survival and lymph node metastasis in these patients were analyzed by Chi-square or Fisher's exact test.A P<0.05 was considered statistically significant.Results The tumors were located entirely within the esophagus in 83 patients,and involved the gastro-esophageal junction in 38.The overall resection rate was 96.7%(117/121).When tumor invasion was within mucosa or submucosa of the esophagus(T1),the lymph node metastasis rate was 22.2%(10/45),the mean number of metastatic lymph nodes was 0.3,and the proportion of more than 4 lymph nodess metastases was 0% (0/45).When tumor invaded the adjacent structures of the esophagus(T4),the lymph node metastasis rate was 85.7%(6/7);the mean number of metastatic lymph nodes was 5.1,and the proportion of more than 4 lymph nodes metastases was 71.4%(5/7).There was a significant difference between T1 and T4(P<0.01).The 5-year survival rate for patients without lymph node metastasis was 52.9%,for those with 1-4 nodes involved was 11.5%,and for patients with more than 4 positive nodes was 0.O%(P<0.01).Conclusions There is a close association between tumor invasion depth and lymph node metastasis for adenocarcinoma of the esophagus and esophagogastric junction.Both the number and rate of lymph node metastasis are significantly correlated to the depth of tumor invasion.Moreover,when the tumor invades deeper into the esophageal wall,the percentage of patients with more than 4 involved nodes increases.Both the lymph node status and the number of metastatic nodes are important prognostic factors for the disease。

Abstract：Background External stents have been used to reduce intimal hyperplasia of vein grafts.The aim of the present study was to define the size of an external stent appropriate for a particular graft by comparing vein grafts with different sizes of external stents.Methods A series of paired trials was performed to compare femoral vein grafts with different sizes of external stents,where 30 modeled canines were equally divided into three groups:6-mm external stent vs non-stent control,4-mm vs 6-mm external stent,and 4-mm vs 8-mm external stent.At day 3 after operation,color Doppler flow imaging(CDFI)was done to observe blood flow in the lumen.Four weeks later,CDFI was re-checked and the veins were harvested,stained and measured.Results All grafts were patent without formation of thrombosis.External stents significantly reduced intimal thickness of the vein grafts with a 6-mm external stent compared with the vein grafts without external stents(P<0.05).The vein grafts with the 4-mm external stent had similar intimal, medial and adventitial thicknesses compared with those with the 6-mm external stent and the 8-mm external stent.Conclusions External stents can reduce intimal hyperplasia of vein grafts.Stents of different diameters exert the similar effect on prevention of intimal hyperplasia。

Abstract：Background Alleviation of microcirculation disorders in severe acute pancreatitis(SAP)can improve survival rates,and low molecular weight heparin(LMWH)is well known to have potent ameliorative effect On microcirculation disorders caused by anti-coagulant activity.The aim of this study was to investigate the effects of LMWH on pancreatic microcirculation in SAP in rats.Methods SD rats were randomly divided into 3 groups:sham operation(S)group,SAP group,and LMWH treatment (LT)group.The concentrations of serum amylase,tumor necrosis factor-alpha(TNF-α),endothelin-1(ET-1),pancreatic ultrastructure were examined at 24 hours after the models were set up in each group.Results Compared with S group,the concentration of serum amylase,ET-1,and TNF-α in SAP group were significantly increased(P<0.001);After LMWH treatment,the concentration of serum amylase,ET-1,TNF-α were decreased significantly compared with SAP group(P<0.001,0.01,0.001,respectively).On electron microscopy,the microthrombosis in LT group was significantly less than that in SAP group.The 3-day survival rate in SAP group(25.0%) was significantly lower than that in S group(100.0%,P<0.05)and in LT group(87.55,P<0.05).Conclusions The disorder of pancreatic microcirculation may be involved in the inflammatory response of rats with SAP.LMWH can effectively improve the survival rate of SAP,and alleviate the severity of microcirculation disorders through its antithrombin effects and down-regulate the levels of serum ET-1 and TNF-α。

Abstract：Background Intermediate filament(IF)proteins have been thought to play a role in nuclear centration,organelle movement and maintenance of cell shape.dl-praeruptorin A(Pd-la),a novel Ca2+-influx blocker and K+-channel opener isolated from Chinese traditional herbal medicine Qian-Hu,has been demonstrated to inhibit expression of apoptosis related proteins and reduce the level of proinflammatory factors in ischemia/reperfusion myocardiocytes.Morphologically,whether Pd-la effects myocardiocyte IFs remains unclear.The purpose of this study was,for the first time,to evaluate the in vivo effects of Pd-la on IF desmin and vimentin content in order to further explore its cardioprotection against ischemia and elucidate its mechanism of action.Methods Rats underwent a 30 minutes coronary occlusion followed by 120 minutes reperfusion.Assessment of desmin and vimentin content of myocardiocytes was performed by immunohistochemistry,Western blot,Hematoxylin-Eosin staining and densitometry.Results Pretreatment with i.v. infusion of Pd-la prior to ischemia significantly increased desmin and vimentin content and alleviated defects caused by the ischemia/reperfusion insult,e.g.with Pd-la at a dose of 0.5 or 1.0 mg/kg,integrated density values of desmin were increased from 61 478±10 074 to 177 408±10 395 and 195 784±20 057,and vimentin from 59 189±19 853 to 164 781±19 543 and 185 696±20 957(P<0.01,vs placebo),respectively.The recovery of desmin seemed to be stronger and appeared earlier than that of vimentin.Conclusion Pd-la protectively increased IF desmin and vimentin content in ischemia/reperfusion myocardiocytes,which might be partially responsible for its cardioprotection against ischemia。

Abstract：Background Endothelial progenitor cells(EPCs) have been used in both experimental studies and clinical treatments of limb ischemia,as well as in the construction of engineered vascular tissue.The objective of this study was to investigate the effects of transplanted bone marrow-derived EPCs on the vein microenvironment in a rat model of chronic vein thrombosis.Methods Mononuclear cells were isolated from the bone marrow of immature rats by density gradient centrifugation,cultured,and then transplanted into experimentally induced thrombi into inferior vena cava through the femoral vein.Vascular endothelial growth factor(VEGF),angiopoietin-1(ANG-1) and monocyte chemotactic protein-1(MCP-1) mRNA and protein expression levels were measured by real-time quantitative polymerase chain reaction and Western blotting of thrombi and adjacent caval walls 28 days post-transplantation.Results Levels of VEGF,ANG-1,and MCP-1 mRNA in EPC-transplanted thrombi were 100%,230.7%,and 212.5% of levels detected in the sham-operated group(P<0.01),and 99.9%,215.4%,and 177.8% of levels detected in the experimental control group(P<0.01).VEGF,ANG-1 and MCP-1 protein levels exhibited a similar trend.Conclusions Transplanted bone marrow-derived EPCs appear to alter the vein microenvironment in experimentally induced chronic vein thrombosis by upregulating cytokines associated with thrombic organization and recanalization。

Abstract：Background The form deprivation(FD)reduces spatial contrasts and induces myopia. Nitric oxide and cyclic guanosine monophosphate(cGMP)are involved in visual signal transmission.This study investigated changes in nitric oxide synthase(NOS)activity and cGMP concentration in ocular tissues in acute and chronic form deprivation myopia.Methods Guinea pigs had one eye covered by translucent glass for 7,14 or 21 days.Untreated litter mates were used as controls.NOS activity and cGMP concentrations in the retinal,choroidal and scleral tissues of FD eyes and controleyes were analyzed by radioimmunoassay after various durations of FD.The expression of NOS subtypes was identified by immunohistochemistry.Results Myopia was successfully induced in FD eyes after 14 days.Compared with control groups,the retinal NOS activity and cGMP concentrations in the FD eyes significantly increased after 14 and 21 days while the retinal NOS activity in the FD eyes was transiently suppressed by 7 days of FD.The NOS activity and cGMP concentrations of choroid and sclera in the FD eyes were higher than in the control groups at 21 days.The three isoenzymes of nitric oxide synthase were detected in the ocular tissues of guinea pigs.Conclusions The NOS activity and cGMP concentrations were upregulated after chronic FD and the retinal NOS activity was transiently suppressed at acute FD.The function of elevated NOS activity may be mediated by cGMP。

Abstract：Background There are studies suggesting smoking may increase the risk of type 2 diabetes.Effects of smoking on insulin secretion and insulin resistance(IR)are,however,controversial.Methods This is a cross-sectional study.Since there were very few smokers among Hong Kong Chinese women,only men(n=1068) were analyzed in this report.Fasting and 2-hour plasma glucose and insulin were measured.Insulinogenic index as well as beta-cell function and IR based on homeostatic model assessment(HOMA)by computer model(HOMA Calculator v2.2)were calculated.Results Of the 1068 men,147 had newly diagnosed diabetes,131 newly diagnosed impaired glucose tolerance(IGT) and 790 were non-diabetic normal controls.Smokers had similar fasting and 2-hour insulin levels,insulinogenic index and HOMA derived beta-cell function as compared to non-smokers in the groups with diabetes,IGT or normal oral glucose tolerance test(OGTT).IR was also similar between smokers,ex-smokers and non-smokers in those with normal OGTT.In men with IGT or diabetes,after adjustment for age and body mass index,smokers were more insulin resistant as compared to non-smokers(IR,IGT: 1.59±1.07 vs 1.03±0.54,P<0.05;diabetes:1.96±1.36 vs 1.06±0.45,P<0.01).With Logistic regression analysis,comparing smokers and non-smokers,IR was independently associated with smoking(odds ratio(95% CI),IGT: 2.23(1.05,4.71);diabetes:3.92(1.22,12.58)).None of the other insulin parameters enter into the model among those with normal OGTT or comparing ex-smokers and non-smoker or smokers and ex-smokers.Conclusions In Chinese men,smoking did not show any direct association with insulin levels and pancreatic insulin secretion.Smoking men with IGT or diabetes appeared more insulin resistant than their non-smoking counterparts。

Abstract：Background Stimulation of the heart β3-adrenoceptor(AR)may result in a negative inotropic effect.Being up-regulated,β3-AR plays a more important role in the regulation of cardiac function during heart failure.However,the effect of chronic blocking of β3-AR on heart failure has not been fully elucidated.In this study,we used a selective β3-AR antagonist SR59230A to treat a well defined heart failure rat model chronically,then evaluated its effect on cardiac function and investigated the mechanism.Methods Male Wistar rats were chosen randomly as controls (n=8).Isoproterenol induced heart failure rats were randomly divided into ISO group(n=10) and SR group(n=10).The ISO group received intraperitoneal injection of 1 ml saline twice a day;the SR group received intraperitoneal injection of SR59230A 85 nmol in 1 ml saline twice a day;and the controI group received no treatment.The treatment was started 24 hours after the last isoproterenol injection and continued for 7 weeks.Then we measured the following indexes:the ratio of heart weight to body weight(HW/BW) and the ratio of left ventricular weight to body weight(LVW/BW),collagen volume fraction(CVF),left ventricular end diastolic dimension(LVEDd),left ventricular end systolic dimension(LVESd),ejection fraction(EF),fractional shortening(FS)and the ratio of E wave to A wave(E/A),the mRNA and protein expression of β3-AR and eNOS,and cGMP level in the heart.Results The ratios HW/BW and LVW/BW were significantly increased in the ISO group compared with the control group(P<0.01),but they were limited in the SR group(P<0.05 compared with the ISO group).CVF increased in the ISO group and the SR group(P<0.01),but it was significantly attenuated in the SR group(P<0.01).LVESd,LVESd and E/A ratio were significantly increased in the ISO group compared with the control group(P<0.01),while EF and FS were significantly decreased(P<0.01).Compared with the ISO group,the SR group showed that LVEDd,LVESd and E/A ratio were significantly decreased(P<0.01),whereas EF and FS were significantly increased(P<0.01).β3-AR and eNOS mRNA and protein in the ISO group were significantly increased when compared with the control group(P<0.01).These increases were all attenuated in the SR group compared with the ISO group(P<0.01).The level of cGMP in myocardial tissue was significantly increased in the ISO group compared with the control group(P<0.01),whereas SR59230A treatment normalized this increment(P<0.01).Conclusions Chronic blocking of β3-AR could ameliorate cardiac function in heart failure rats and its mechanism involves inhibition of the negative inotropic effect and attenuation of cardiac remodeling。

The liver plays a major role in the regulation of glucose,lipid and energy metabolism.Increased hepatic fat deposit is a very common feature in obese,insulin-resistant patients, in metabolic syndrome,alcoholic steatohepatitis (ASH) and nonalchoholic fatty liver disaseas(NAFLD)。

Abstract：Obiective To review the biological behaviour of endothelial progenitor cells and their role in vascular diseases.Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1985 to March 2007.The search term was "endothelial progenitor cells".Study selection Articles about the biological behaviour of endothelial progenitor cells and their roles in the pathogenesis of vascular diseases such as atherogenesis were used.Results Progenitor cells in bone marrow,peripheral blood and adventitia can differentiate into mature endothelial cells (ECs).The progenitor cells,which express certain surface markers including AC133,CD34 and KDR,enable restoration of the microcirculation and ECs when injury or ischaemia occurs.Endothelial progenitor cells used in experimental models and clinical trials for ischaemic syndromes could restore endothelial integrity and inhibit neointima development.Moreover,their number and functional properties are influenced by certain cytokines and atherosclerotic risk factors.Impairment of the progenitor cells might limit the regenerative capacity,even lead to the development of atherosclerosis or other vascular diseases.Conclusions Endothelial progenitor cells have a particular role in prevention and treatment of certain cardiovascular diseases.However,many challenges remain in understanding differentiation of endothelial progenitor cells,their mobilization and revascularization。

Obstructive sleep apnea syndrome (OSAS) was a disease of breath obstacle happened in the process of sleep.The central mechanism of OSAS has not yet been fully elucidated.1

Hepatocellular carcinoma(HCC)is among the most common tumors worldwide.Despite extensive exploration of novel therapies,the prognosis of HCC patients with intrahepatic metastasis is still poor,and no treatment is effective against metastases.Therefore,more effective therapeutic strategies for treatment of metastasis are urgently needed。

Since its introduction in 1995,laparoscopic living donor nephrectomy (LDN) has been shown to alleviate postoperative pain,shorten hospital stay,reduce loss and improve cosmesis while hastening the recovery of normal activities of donors.1-3 However,there has been much controversy over minimally invasive surgery with transperitoneal or retroperitoneal approach for nephrectomy.In this non-randomized retrospective study,we analyzed some parameters of the donors who had undergone transperitoneal LDN compared with those who had had retroperitoneoscopic nephrectomy。

Pregnancy complicating fulminant hepatitis is characterized by rapid progress,complicated clinical symptoms,and association with blood coagulation dysfunction,hepatic encephalopathy,hepatorenal syndrome,toxic enteroparalysis and infection。

Life expectancy in China doubled from 35 to 71 years between 1949 and 2001.China's human development index has been rising steadily,and it ranked 85th among countries with an index of 0.755 in 2003。

The arachnoid cyst complicated with an inner aneurysm and intracystic hematoma is rarely encountered.In 2005,we treated such a patient by craniotomy through the left pterion approach.The possible causes of the intracystic hematoma and the reasons of the delay of the diagnosis are discussed。

Pituitary apoplexy is a rare clinical syndrome caused by acute enlargement of pituitary adenomas,which may be secreting or nonfunctioning,and symptomatic or asymptomatic,resulted from hemorrhage or infarction.1

Intracranial arachnoid cysts,which often occur in children(75%),account for 1% of intracranial masses.1 The cyst is most commonly located at the middle cranial fossa and more frequently on the left side。

Virus infection and subsequent myocardial damage and repairing were regarded as important aspects in the pathogenesis of dilated cardiomyopathy.…… Biography：Correspondence to:Dr. WANG Hong-yue,Department of Pathology,Fuwai Hospital and Cardiovascular Institute of Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,China(Tel:86-10-88398007.Email:hongyue_w@yahoo.com)

Facial nerve schwannoma involving the middle cranial fossa is quite rare,and its accurate diagnosis is very difficult before SUrgery.Here we present a case of schwannoma of the facial nerve at the middle cranial fossa that was misdiagnosed previously at a local hospital and then cured in our hospital。

Pulmonary actinomycosis is a rare, uncommon pulmonary infection.The word "actinomycosis" is derived from Greek terms aktino,which refers to the radiating appearance of a sulphur granule and myKos,which labels the condition a mycotic disease。

Spontaneous pneumomediastinum (SPM),reported firstly by Hamman in 1939,is an uncommon,and usually benign,and self-limiting clinical disorder found in young people often without apparent precipitating factors or diseases。

Desmoplastic small round cell tumor(DSRCT)is a clinically and morphologically well-defined neoplasm.1 This highly aggressive malignant small cell neoplasm tends to affect adolescents and young adults and occurs predominantly in the abdomen,pelvis,and omentum.1,2 DSRCT in the lung is extremely rare。

Lung autotransplantation is a new procedure with pulmonary preservation for patients in the treatment of lung cancer.It was used to treat the stage Ⅲ central lung cancer of the upper lobe in the patient presented herein when his pulmonary function could not withstand a pneumonectomy and the length of the resected bronchus or pulmonary artery was too long to perform a bronchovascular double sleeve lobectomy.1,2 In order to preserve pulmonary tissue and improve the quality of life,we performed lung autotransplantation for a case。

The most common tumors associated with cardiac metastases are lung carcinoma and melanoma.1 Although the cardiac involvement of lung cancer is common(lung cancer usually directly invades into the pericardium and/or left/right atrium),the primary lung cancer accompanied with metastasis to the left ventricle is extremely rare。