2009年 · 第122卷第01期

Hepatitis B virus (HBV) infection is a global public health problem. According to the data of World Health Organization (WHO), 2 billion people worldwide have been infected with HBV, and among them 350-400 million are chronic HBV carriers. Hepatitis B causes about 1 million deaths of HBV related liver failure, cirrhosis, and hepatocellular carcinoma annually.

Abstract：Background MicroRNAs (miRNAs) are highly conserved small non-coding RNAs of 18-25 nucleotides (nt) that mediate post-transcriptional gene regulation. Hepatitis B virus (HBV) can cause either acute or chronic hepatitis B, and is a high risk factor for liver cirrhosis and hepatocellular carcinoma. Some mammalian viruses have been shown to modulate the expression of host cellular miRNAs. However, interactions between the HBV and the host cellular miRNAs are largely unknown. Methods miRNA microarray and Northern blotting analysis were used to compare the expression profile of cellular miRNAs of a stable HBV-expressing cell line HepG2.2.15 and its parent cell line HepG2. mRNA microarray assay and the miRanda program were used to predict the miRNA targets. A flow cytometric assay was further used to investigate the expression of human leukocyte antigen (HLA)-A. Results Eighteen miRNAs were differentially expressed between the two cell lines. Among them, eleven were up-regulated and seven were down-regulated in HepG2.2.15 cells. Northern blotting analysis confirmed that the expression of miR-181a, miR-181b, miR-200b and miR-146a were up-regulated and the expression of miR-15a was down-regulated, which was in consistent with the results of the microarray analysis. Furthermore, some putative miRNA targets were predicted and verified to be linked with mRNA expression. The 3'-UTR of HLA-A gene had one partially complementary site for miR-181a and miR-181a might down-regulate the expression of HLA-A. Conclusion HBV replication modulates the expression of host cellular miRNAs, which may play a role in the pathogenesis of HBV-related liver diseases.

Abstract：Background Hepatitis B virus encoded X protein (HBx) is a trans-activating protein that may be involved in hepatocarcinogenesis, although few natural effectors of HBx that participate in this process have been identified. We screened, by comparative proteomics method, effectors of HBx associated with hepatocaroinogenesis. Methods HBx positive and negative HepG2 cells were constructed and expression patterns of cellular proteins were obtained by high resolution, two dimensional electrophoresis. Comprehensive analyses of proteins associated with hepatocellular carcinoma (HCC) were focused on the differently expressed proteins (more than two-fold increase or decrease, P<0.05) from HBx positive and negative HepG2 cells. For peptide mass fingerprinting, protein spots with different intensity between HBx positive and negative HepG2 cells were directly cut out of gels and processed for matrix assisted, laser desorption/ionization, time of flight mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) analysis. Results The mean number of protein spots for HBx negative and HBx positive HepG2 cells were 2095±137 and 2188±105, respectively. The analysis of paired cells showed 75 spots with significant differences in expression between HBx negative and HBx positive cells: 37 spots corresponding to 32 different proteins; 25 proteins were upregulated, 7 downregulated. We found 7 proteins not previously reported differentially expressed in HBx positive HepG2 cells. Variations in protein accumulation were confirmed for four (HSP90AB1, BCL2 associated athanogene 2, nucleophosmin and chloride intracellular channel 1) by Western blotting in HBx positive HepG2 cells. Conclusions Numerous effectors of HBx that may promote the development of HCC are identified, of which 7 are newly noted in HepG2 cells. Several of these effectors of HBx may help in elucidating the roles of HBx in hepatocarcinogenesis and diagnostics or targets for therapeutic intervention。

Abstract：Background Epidermic studies have suggested a pathophysiological link between obstructive sleep apnea hypopnea syndrome (OSAHS) and atherosclerosis (AS); for which carotid intima-media thickness (IMT) has been considered as an early marker. The pathogenesis by which OSAHS can induce AS has not been elucidated. This study was conducted to investigate the association among plasma interleukin-18 (IL-18) levels, carotid IMT and the severity of OSAHS.Methods Based on the apnea hypopnea index (AHI) during sleep monitored by polysomnography, 52 male patients with OSAHS were recruited as the OSAHS group which was further divided into mild OSAHS (n=16), moderate OSAHS (n=18), and severe OSAHS (n=18) subgroups. Eighteen healthy subjects were selected as the control group. Of all OSAHS patients, 20 with moderate-to-severe OSAHS underwent continuous positive airway pressure (CPAP) treatment for 90 days. HDL5000 color Doppler ultrasonography was used to measure carotid IMT. Plasma IL-18 levels were measured by ELISA. Results Compared with the plasma lL-18 levels in the control group ((250.27±76.48) pg/ml), there was a significant increase in the mild OSAHS subgroup ((352.08±76.32) pg/ml), the moderate subgroup((600.17±83.91) pg/ml), and the severe OSAHS subgroup ((9797.64±109.83) pg/ml) (all P<0.01). Moreover, there was a significant difference in plasma IL-18 levels among the three OSAHS subgroups (P<0.01). Carotid IMT was significantly greater in the severe OSAHS subgroup than in the mild OSAHS subgroup (P<0.01). Before CPAP treatment, plasma IL-18 levels were positively correlated with carotid IMT (r=0.486, P <0.001) and with AHI (r=0.865, P<0.001). On day 90 of CPAP treatment, plasma IL-18 levels were significantly declined but carotid IMT was not changed significantly. Conclusions In untreated OSAHS patients carotid IMT and plasma IL-18 were positively correlated and were significantly higher than in normal controls; the elevation of plasma IL-18 levels was correlated with the severity of OSAHS. Inflammatory response associated with OSAHS may be related to the development of AS. By improving AHI, miniSaO2, and reducing plasma IL-18 levels, CPAP treatment may slow down or prevent the development of AS in OSAHS patients。

Abstract：Background Congenital heart disease is a diverse group of diseases determined by genetic and environmental factors. Considerable research has been done on genes associated with development of the heart. A recent focus is the role of transcription factor TBX5 in the development of atria, left ventricle and conduction system. As part of a larger study, high density, single nucleotide polymorphism (SNP) scanning was used to explore the relationship between TBX5 gene polymorphism and susceptibility to ventricular septal defect not associated with forelimb malformation in the Chinese Han population. Methods One hundred and ninety two paediatric patients with congenital ventricular septal defect and 192 matched healthy control subjects were studied. The haplotype reconstructions were calculated by PHASE2.0 software. Haploview software was used to 15erform linkage disequilibrium assessment and defining of haplotype blocks. The algorithm used for defining of blocks was the confidence interval method. Results The TBX5 gene region can be divided into 3 haplotype blocks of 27, 15 and 2 SNPs. Strong linkage disequilibrium exists within each block. SNP rs11067075 within the TBX5 gene had significant correlation with ventricular septal defect (P=0.0037) by single marker association analysis. In addition, a 20 kb haplotype composed of 27 SNPs correlated with ventricular septal defect (P=0.05, multiple loci regression analyses based on reconstructed haplotype blocks). Conclusions TBX5 is associated with the occurrence of ventricular septal defect and may be a predisposing gene to congenital heart disease in Hart Chinese. This finding has set a direction for further genetic and functional studies.

Abstract：Background Malignant tumor is the most common complication occurred in transplant recipients. It is widely recognized that immunosuppressive treatments increase the risk of cancer in transplant recipients. The efficacy and safety of rapamycin (RPM) in combination with low-dose calcineurin inhibitor (CNI) in treating 15 renal allograft recipients which developed urothelial carcinoma were observed. Methods Immunosuppressive regimen in all recipients was altered with rapamycin to replace mycophenolate mofetil (MMF) or azathioprine (Aza). The initial loading dosage was 2 mg/d, and the next dosage was 1 mg/d. The dosage of rapamycin was carefully adjusted according to the blood drug level and concentration of the drug was maintained at 4-6 ug/L. In all the 15 patients, the calcineurin inhibitor was reduced down to one third of the original dosage after the rapamycin blood concentration became stable. Surgical treatment and intravesical instillation chemotherapy were carried out in all patients. Recurrence of the tumor was monitored throughout the study. Post-transplant renal function and side effects were also closely monitored. Results Among the 15 patients, 9 had no tumor recurrence in 2 years, 2 had tumor recurrences twice, and 4 had once. There was no acute rejection observed during RPM treatment. Post-transplant renal function in 11 patients was improved, with a decreased creatinine level. Hyperlipoidemia and thrombocytopenia were the most frequent adverse events which responded well to corresponding treatments. Conclusion Among the renal allograft recipients with urothelial carcinoma, combination of rapamycin and low dose calcineurin inhibitor treatment is effective and safe.

Abstract：Background The authors found no study to compare the efficacy of bolus dose fentanyl and remifentanil blunting the cardiovascular intubation response in children, so they designed this randomized, double-blind clinical study to assess the effects of remifentanil 2 ug/kg and fentanyl 2 ug/kg by bolus injection on the cardiovascular intubation response in healthy children.Methods One hundred and two children, the American Society of Anesthesiologists (ASA) physical status 1-2 and scheduled for elective plastic surgery under general anesthesia, were randomly divided into one of two groups to receive the following treatments in a double blind manner: remifentanil 2 ug/kg (Group R) and fentanyl 2 ug/kg (Group F) when anesthesia was induced with propofol and vecuronium. The orotracheal intubation was performed using a direct laryngoscope. Blood pressure (BP) and heart rate (HR) were recorded before anesthesia induction (baseline values), immediately before intubation, at intubation and every minute for 5 minutes after intubation. The percent changes of systolic blood pressure (SBP) and HR relative to baseline values and the rate pressure product (RPP) at every observing point were calculated. The incidences of SBP and HR percent changes >30% of baseline values and RPP >22 000 during the observation were recorded. Results There were no significant differences between groups in the demographic data, baseline values of BP and HR and the intubation time. As compared to baseline values, BP, HR and RPP at intubation and their maximum values during observation increased significantly in Group F, but they all decreased significantly in Group R. BP, HR and RPP at all observed points, and their maximum values during the observation, were significantly different between groups. There were also significant differences between groups in the percent change of SBP and HR relative to baseline values at all observed points and their maximum percent changes during the observation. The incidences of SBP and HR percent increased >30% of the baseline values and RPP >22 000 during the observation, were significantly higher in Group F than in Group R, but the incidences of SBP and HR percent decreased >30% of baseline values were significantly lower in Group F compared with Group R. Conclusions When used as part of routine anesthesia induction with propofol and vecuronium in children, fentanyl 2 IJg/kg by bolus injection fails to effectively depress the cardiovascular intubation response. Remifentanil 2 ug/kg by bolus injection can completely abolish the cardiovascular intubation response, but also cause more adverse complications of temporary significant cardiovascular depression.

Abstract：Background Hepatitis C virus (HCV) infection may induce autoimmune response and autoantibodies can be detected in chronic hepatitis C (CHC) patients. However, the reported positive rate of autoantibodies in CHC patients in China varies considerably. In this study, we investigated the prevalence of antinuclear antibodies (ANA) and anti-liver-kidney-microsome type 1 autoantibodies (anti-LKM-1) in a large cohort of CHC patients, and analyzed the factors related to the presence of the autoantibodies. Methods A total of 360 CHC patients were enrolled in this study. Serum ANA and anti-LKM-1 were detected by indirect immunofluorescence and enzyme-linked immunosorbent assay, respectively. Clinical analysis was performed to disclose the related factors to autoantibody production. Results The prevalence of ANA and anti-LKM-1 in CHC patients was 12.5% (45/360) and 2.5% (9/360), respectively. Women had a higher prevalence than men (18.9% vs 11.4%, P=0.046). Patients with positive autoantibodies had lower HCV RNA levels (1.2x107 copies/L vs 7.2x107 copies/L, P <0.05). Positive ANA was associated with higher serum globulin (P<0.05). Stratified analysis showed that there were no significant differences in age, HCV genotype, disease course, clinical stage, prevalence of cirrhosis and interferon therapy between autoantibody-positive and-negative subgroups. Conclusion Autoantibodies can be induced in the course of CHC, and some CHC patients can even develop autoimmune hepatitis。

Abstract：Background It is important to analyze and compare soft tissue sarcomas periodically so as to update the incidence, the clinical diagnosis, the treatment, and the ongoing research. The present study was conducted to determine the relative frequency of each type of soft tissue sarcoma. Methods A total of 1118 cases of primary soft tissue sarcomas treated between January 1993 and December 2006 were evaluated in a retrospective analysis. Results According to the pathologic grouping, the diseases with the highest proportion were malignant fibrous histiocytomas (35.24%), synovial sarcomas (17.08%), liposarcomas (16.28%), and rhabdomyosarcomas (12.61%). Soft tissue sarcomas were detected in every age group and occurred in all parts of the body. The number of cases increased gradually over the years. Conclusions Malignant fibrous histiocytomas had the highest frequency among the soft tissue sarcomas. The number of cases increased gradually over the years.

Abstract：Background Connexin 43 (Cx43) is one of the major components of human keratinocyte gap junctions. To study whether gap junctional intercellular communication participates in the transfer of acupoint signals and acupuncture analgesia, the expression of Cx43 was studied in Zusanli (ST36) acupoints compared with control non-acupoint regions in rats after acupuncture. In addition, Cx43 heterozygous gene knockout mice were used to further explore the relationship between Cx43 and acupuncture analgesia. Methods The expression of Cx43 was detected by immunohistochemistry, immunoblotting, and RT-PCR for the Cx43 protein and mRNA. The influence of the Cx43 gene knockout on acupuncture analgesia was measured by a hot plate and observing the writhing response on Cx43 heterozygous gene knockout mice. Results Immunohistochemistry showed abundant Cx43 expression in some cells in the skin and subcutaneous tissue of rat ST36 acupoints. The mRNA and protein levels of Cx43 in acupoints were significantly higher than those in the control points in the non-acupuncture group, and even more so after acupuncture. The hot plate and writhing response experiments showed that partial knockout of the Cx43 gene decreased acupuncture analgesia. Conclusion Cx43 expression and acupuncture analgesia showed a positive correlation.

Abstract：Background Myocyte apoptosis is considered to be the major causative factor of left ventricular (LV) remodeling following myocardial infarction (MI). We previously reported that 3', 4'-dihydroxyflavonol (DiOHF), was able to suppress oxidative stress and preserve the expression of endothelial nitric oxide synthase during myocardial reperfusion injury, which may benefit the reduction of myocyte apoptosis. We therefore aimed to evaluate the potential actions of DiOHF against myocyte apoptosis and post-infarction LV remodeling in this study. Methods Following experimental MI, surgical instrumented goats were randomly assigned into vehicle and DiOHF (2 mg/kg; i.v., daily) groups to receive 4 weeks of reperfusion with corresponding treatments. LV pressure recordings and echocardiogram were performed at baseline, 2 and 4 weeks of reperfusion. Myocardial tissues were collected in the end to determine infarct size and apoptosis related assays. Results LV end-diastolic volume and diameter were significantly increased 4 weeks after MI in the vehicle group, accompanied by reduced posterior wall thickness, septal thickness and LV mass, whereas those changes were markedly prevented by DiOHF treatment. Similarly, significantly reduced infarct size was found in DiOHF group as compared to vehicle group, and DiOHF dramatically inhibited the increase in LV end-diastolic pressure and the reductions in ejection fraction, fraction shortening and dP/dtmax. Moreover, DiOHF treatment significantly reduced the extent of myocyte apoptosis detected by TUNEL assay, enhanced the protein expression of caspase-3, Fas, Bax and cytochrome c in the non-infarcted myocardium in comparison to vehicle. Conclusions Daily DiOHF treatment during the reperfusion period after MI in the ovine hearts markedly reduced the magnitude of post-infarction LV remodeling through the inhibition of myocyte apoptosis in the remote non-infarcted myocardium.

Abstract：Background Magnetic resonance spectroscopy (MRS) is one method that can examine noninvasively the alive specimen of the organ, metabolism of the organ and cell, and the biochemistry change. MRS provides the biochemistry information that may be used to diagnose tumors or differentiate the malignant tumor from benign. The objective of this study is to investigate the benign and malignant bone and soft tissue tumors by 1H-MR spectroscopy (1H-MRS) on a 3 Tesla MR scanner, then to assess the usefulness of 'H-MRS in diagnosing bone and soft tissue tumors and distinguishing benign from malignant tumors. Methods Fifty-six patients with bone and soft tissue tumors proved clinically and pathologically were examined with 1H-MRS. 1H-MRS was performed to study malignant musculoskeletal tumors, benign tumors and normal muscle adjacent to lesions to analyze the characteristics, and single-voxel point-resolved spectroscopy sequence was used. Proton brain exam-single voxel of 1H-MRS which directly appeared in the spectrum, was observed to find the peak height of choline compounds (Cho) opposite to the creatine (Cr), and whether there was a Cho peak. Metabolite values were calculated automatically from the area under each metabolite peak by the Functool 3.1 software. Metabolite ratios of Cho/Cr were manually calculated. Then according to the results, it was judged whether there existed benign or malignant tumors. The Kappa statistical test was used to analyze the MRS results, the histopathology data and the surgical situation. Statistics processing was performed using the software package SPSS11.5 for Windows. Results1H-MRS spectra style of bone and soft tissue tumors was different from that of normal muscle, and differences also existed between benign and malignant tumors. Choline level in malignant tumor was markedly higher than that in benign tumors. Cho/Cr in malignant tumor was higher than in benign tumor significantly (P<0.05). The true positive rate of bone and soft tissue between benign and malignant tumors was 34/36, the true negative rate was 15/18, the false positive rate was 3/18 and the false negative rate was 2/36. Therefore in the group, sensitivity of the 1H-MRS was 94% (34/36), specificity was 83% (15/18), positive predictive value was 92% (34/37), negative predictive value was 88% (15/17) and the accuracy rate was 91% (49/54). The MRS results and the histopathology inspection conclusions had very good uniformity. The K value was 0.76±0.10 (P<O.01). Conclusions The increase of Cho level measured by 1H-MRS is related to the bone and soft tissue malignant tumor. Cho/Cr in malignant tumor was higher than in benign tumor, so they will play a vital role in the diagnosis and differential diagnosis of bone and soft tissue tumors.

Abstract：Background The benefits and safety of sirolimus-eluting stent (SES) have not been systematically quantified in different trials in ST-segment elevation myocardial infarction (STEMI) patients with primary or rescue percutaneous coronary intervention (PCI). A meta-analysis of randomised trials comparing SES and bare-metal stent (BMS) was performed. Methods A systematic literature search was conducted to identify all randomized clinical trials. The primary outcome was the rate of major adverse cardiac events (MACEs). The secondary outcomes included death, recurrent myocardial infarction, recurrent revascularization, and stent thrombosis. Results Totally, 1973 STEMI patients were enrolled in seven eligible randomized trials comparing SES with BMS. The pooled rate of major adverse cardiac events was significantly lower in the SES group than in the BMS group (9.7% vs 20.3%, OR 2.45, 95% Cl 1.88-3.19, P < 0.00001). No significant difference in all causes of death was found between the SES and BMS groups, as well as in the pooled recurrent myocardial infarction rates. The pooled recurrent revascularization rate was significantly lower in the SES group than in the BMS group (5.1% vs 14.8%, OR 3.30, 95%Cl 2.37-4.60, P < 0.00001). No significant difference was found between the pooled rates of stent thrombosis (1.2% in the SES group and 2.0% in the BMS group, OR 1.61, 95%Cl 0.79-3.26, P=0.19). Conclusions SES is associated with a decreased risk of major adverse cardiac events compared with BMS by thegreater reduction in repeat revascularization in STEMI patients. Larger trials with longer follow up are warranted to betterdefine the role of SES in STEMI。

Worldwide, the hepatitis C virus (HCV) and humanimmunodeficiency virus (HIV) pandemics poseserious threats to global health, currently infecting 130 million and 40 million people respectively. Of those infected with HIV, an estimated 4-12 million are co-infected with HCV. Due to shared risk factors for transmission, co-infection with HIV and HCV is common in China. Liver disease was the second leading cause of death behind acquired immunodeficiency syndrome (AIDS) in co-infected patients. Several studies have confirmed that HIV co-infection accelerates the clinical course of chronic HCV infection and leads to an increased risk of cirrhosis, hepatocellular carcinoma, and decompensated liver disease. While some studies have shown an increased risk of progression to AIDS andAIDS-related death among HIV-HCV positive persons, others found that HCV may not affect the clinical course of HIV infection. The current optimal therapeutic approach to HCV infection in HIV co-infected patients is peg-IFN plus ribavirin but further investigation is ongoing to improve outcomes.

Abstract：Objective To review the implementation of mass vaccination of hepatitis B vaccine and its critical role in prevention of hepatitis B virus infection in China. Data sources The data were mainly from PubMed, China Hospital Knowledge Database, and other popular Chinese journals published from 1980 to 2008. The search term was "hepatitis B vaccine". Study selection Original studies conducted in China and critical reviews authored by principal investigators in the field of hepatology in China were selected. Results Chinese investigators started to develop hepatitis B vaccine in late 1970s. The first home-made plasma-derived vaccine became available in 1986, which has been completely replaced by the domestically produced recombinant (yeast or Chinese hamster ovary cell) vaccine since 2001. China health authority recommended vaccinating all infants in 1992. From then on, China has put tremendous efforts in implementation of mass vaccination. The overall coverage of hepatitis B vaccine in infants has increased steadily and reached more than 95.0% in urban and 83.0%--97.0% in rural areas. The chronic HBV carrier rate in children <10 years of age decreased from 10.0% before the mass vaccination to 1.0%-2.0% in 2006, and that in general population decreased from 10.0% to 7.2%; overall, the nationwide mass hepatitis B vaccination has reduced more than 30 million of chronic HBV infections and HBV related severe sequlae. Conclusion The Chinese successful experience in control of hepatitis B by mass vaccination offers an example for any unindustrialized country whoever is committed to control this disease。

Adjuvant radiotherapy plays a vital role in the treatment of breast cancer, but irradiated area was not standardized. The ipsilateral chest wall and supraclavicular regions with or without internal mammary lymph nodes were reported in patients receiving postmastectomy radiotherapy.1,2 In our study, 133 consecutive patients with breast cancer of stage II/III who had received postmastectomy radiotherapy of supraclavicular and internal mammary regions at Cancer Hospital of Fudan University were analyzed for their survival and locoregional control as well as their relative prognostic predicator.

Chronic heart failure (CHF), as the end-stage presentation of all kinds of heart diseases, is a major public health problem as well as a pressing public policy issue. There are more than 5 million patients diagnosed with CHF in USA alone and approximately 550 000 new cases appear per year. About 0.4%-2% of the European population is affected by symptomatic heart failure. Hence heart failure is the leading cause of hospitalization especially in older people around the world.

An aneurysmal bone cyst is a non-neoplastic, Adestructive and expansile lesion consisting of a "blood-filled sponge" that is defined to represent a benign reactive vascularity.1-3 Szendroi et al4 suggested that the aneurysmal bone cyst corresponds to a haemodynamic disturbance that is primary or secondary venous malformation of the bones. The association with trauma including fracture has also been noted and 25%-71% of such patients have a history of trauma.57 Conventionally, malignant transformation of aneurysmal bone cysts is perceived as a rare occurrence except those induced by irradiation.8-10~ Both malignant fibrous histiocytoma and osteosarcoma have been reported in the malignant transformation cases。

At 14:28 (2:28 pm) on May 12, 2008, a magnitude 8 earthquake, which was a rare event, occurred in Sichuan Province of China and led to deaths of thousands of people. In the Longmen Mountain fault zone, which is located 40 miles from the earthquake center at Wenchuan, the Chinese military used a variety of treatment methods to rescue the injured and successfully treated a victim with severe traumatic brain injury (TBI) who survived without food or water intake for 192 hours. Two hundred and twenty-four hours after the earthquake, the patient underwent craniotomy and removal of an intracerebral hematoma. The injury to the patient was severe and the rescue time was the longest for this earthquake. Detailed information is provided in this report. …… Biography：Dr. GU Jian-wen, Department of Neurosurgery, General Hospital of the People's Liberation Army Chengdu Military Region, Chengdu, Sichuan 610083, China (Fax: 86-28-86570361. Email: gujianwen2000 @yahoo.com.cn)