OBJECTIVETo evaluate the antiviral activity and safety of entecavir in patients with chronic HBV infection as a preliminarily step in selecting 0.1 mg or 0.5 mg as a better dosage for a further large scale clinical trial.

METHODSThis was a randomized, double-blinded, placebo-controlled and dose-ranging trial of entecavir usage in 212 patients with chronic HBV infection. The patients were randomly assigned to 3 groups: 0.1 mg entecavir (69), 0.5 mg entecavir (72) and, placebo (71) groups and treated for 28 days. The patients were then followed for 56 days without treatment.

RESULTSThe proportion of subjects who achieved the primary endpoint at day 28, with their HBV DNA level decreased >2 log or undetectable, was significantly greater in the entecavir 0.1 mg and 0.5 mg dose groups compared with the placebo group (P < 0.01 for both comparisons). The mean change from baseline in HBV DNA levels at day 28 was greater for entecavir 0.1mg and 0.5 mg groups compared with the placebo group (both P < 0.01). The mean change from baseline in HBV DNA levels at day 28 for entecavir 0.5 mg group was greater than that of the entecavir 0.1 mg group (P < 0.01). During the 56-day post-dosing follow-up phase, the entecavir 0.5 mg group was associated with greater and more sustained suppression of viral replication than the entecavir 0.1 mg group (P < 0.01). There were no clinically meaningful differences in the incidence of any adverse events between the entecavir dosing and the placebo groups.

CONCLUSIONEntecavir at both 0.1 mg and 0.5 mg doses demonstrated superior antiviral activity compared with a placebo. Since the entecavir 0.5 mg dose appears to have greater antiviral activity than the 0.1 mg dose and with a comparable safety and tolerability profile, the 0.5 mg entecavir dose could be used in further trials.

Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; therapeutic use ; DNA, Viral ; blood ; Double-Blind Method ; Female ; Follow-Up Studies ; Guanine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Hepatitis B virus ; drug effects ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Treatment Outcome

Objective To explore the effect of silencing metastasis-associated in colon cancer 1 ( MACC1 ) gene on proliferation and invasion of cervical cancer Hela cells. Methods siRNA MACC1 and siRNA NC were transfected into cervical cancer Hela cells with liposomes. The expression of MACC1 protein and mRNA was detected by western blot and RT-PCR. Cell viability and invasion ability were measured by MTT and transwell assay, respectively. The expression of cyclin D1, cyclin E matrix metalloproteinase 2 (MMP2), MMP9 and the level of extracellular regulated protein kinases ( ERK) phosphorylation was detected by western blot. Results Compared with siRNA NC, the expression of MACC1 protein and mRNA was down-regulated, cell viability and invasion ability were reduced ( P < 0. 01 ) , cell cycle was arrested at G1 phase (P < 0. 01), the expression of cyclin D1, cyclin E, MMP2, MMP9 and p-ERK1/2 was down-regulated (P< 0. 01). Conclusions siRNA MACC1 can inhibit proliferation and invasion of cervical cancer Hela cells, which migiht be related to down-regulation of p-ERK.

Objective To explore the clinical features and video-electroencephalogram (VEEG) monitoring of nonconvulsive status epilepticus (NCSE) in children.Methods 1.Object of study:Seventeen patients of NCSE diagnosed with Kaplan's criteria were analyzed in Children's Hospital of Fudan University between Oct.2009 and Sep.2012.2.Data analysis:Data on demographics,etiology,clinical manifestation and response to clonazepam therapy were analyzed.3.Therapies:Clonazepam 0.05 mg/kg was intravenously injected twice a day.Treatment of poor efficacy patients was combined with other antiepileptic drugs.4.Therapeutic effect:Clinical assessment of cognitive improvement and VEEG monitoring of background activity or paroxysmal abnormalities were analyzed.Results Nine male and 8 female of 17 patients with NCSE were involved,from 11 months to ll.4-year old.The clinical attacks lasted ranging variously time from 4 hours to 3 months.Each patient had a prolonged change of consciousness,accompanied by psychological or behavioral changes.Definite medical causes were identified in 65％ (11/17 cases) of the patients.Secondary epilepsy was the dominating cause.The characteristics of ictal VEEG in NCSE generally included slow activity and focal or generalized δ or θ activity.After clonazepam treatment,the conditions of 13 patients were under complete control,in which 4 had improvement.Six cases of unknown cause were fully controlled within 72 hours after intravenous injection of clonazepam.The prognosis of CNS infection sequelae patients,metabolism disorders and brain structural damage was poor.Conclusions NCSE may present with confusion,behavioral disturbances and psychiatric conditions.The diagnosis can be made by the ictal and interictal VEEG monitoring.It is necessary to make the diagnosis and control the seizures as quickly as possible.Clonazepam is useful in NCSE.

OBJECTIVETo investigate the findings of contrast-enhanced multislice computed tomography (MSCT) that characterize intraductal papillary neoplasms of bile ducts (IPNB).

METHODSThe MSCT findings and clinical data of 16 cases of IPNB proven by surgical pathology were reviewed retrospectively.

RESULTSAmong the 16 cases, nine were adenoma (multi-lesions, n = 5; single lesions, n = 4) and seven were adenocarcinoma (multi-lesions, n = 4; single lesions, n = 3). Among the nine adenoma cases, seven showed nodules or masses in the expanding intrahepatic bile ducts with asymmetrical low density on plain scan, and two showed obvious expansion of biliary ducts and the inner wall of bile ducts was rough. All seven of the adenocarcinoma cases showed nodules or masses in the expanding intrahepatic bile ducts with asymmetrical low density-like adenoma. When contrast enhancement was applied, the nine adenoma cases manifested slight-to-moderate degrees of asymmetrical enhancement. For the seven adenocarcinoma cases, two showed asymmetrical enhancement similar to that of the adenoma cases and five showed continued enhancement; one case showed malignant infiltration of the bile duct and evident damage in the adjacent hepatic tissue. The CT plain scan findings for the two groups (adenoma and adenocarcinoma) were not significantly different (t = -1.17, P = 0.2632). Significantly different findings were obtained with the MSCT imaging analysis for the arterial phase (t = 6.53, P less than 0.01) and the portal vein phase (t = 5.63, P less than 0.01). All cases showed asymmetrical expansion of intrahepatic biliary ducts, diffuse or local, and four cases showed moderate expansion of the common bile duct. One adenocarcinoma case showed intumescence in the celiac lymph node by moderate asymmetrical enhancement.

CONCLUSIONMSCT is helpful for the differential diagnosis of IPNB from other hepatic lesions.

Adult ; Aged ; Bile Duct Neoplasms ; diagnostic imaging ; Bile Ducts, Intrahepatic ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Papilloma, Intraductal ; diagnostic imaging ; Retrospective Studies ; Tomography, X-Ray Computed ; methods

OBJECTIVETo evaluate the virological, serological and biochemical outcomes of 3 years of entecavir (ETV) treatment in nucleoside-naive chronic hepatitis B patients.

METHODSThis study was divided into two stages: Patients receiving either ETV 0.5 mg/d (n = 258) or lamivudine (LAM) 100 mg/d (n = 261) entered the initial 96-week randomized, double blind, controlled efficacy study. Patients not achieving a consolidated response (HBV DNA less than 0.7 MEq/ml, ALT less than 1.25 times*ULN, and if HBeAg-positive at baseline, loss of HBeAg for >or= 24 weeks), or those experienced viral breakthrough or relapse, entered a 48-week entecavir rollover study.

RESULTS96 weeks after the treatment, 79% of ETV treated and 46% of LAM treated patients had HBV DNA less than 300 copies/ml (P < 0.0001), 96% of ETV treated and 92% of LAM treated patients had normalized ALT (P = 0.06). 21% of ETV treated and 23% of LAM treated patients achieved HBeAg seroconversion. Among the 160 patients received continuous ETV for 144 weeks, 89% had undetectable serum HBV DNA, 86% showed ALT normalization, and 27% achieved HBeAg seroconversion. ETV resistance was rare: only 3 patients showed ETV resistance 96 weeks after the treatment, and additional 2 patients developed ETV resistance during the following 48 weeks, genotyping indicated the ETV resistance was caused by gene mutation. Adverse event rates in ETV-treated patients were similar to those in LAM-treated patients, but fewer ALT flares were observed in ETV-treated patients.

CONCLUSIONSThis study demonstrates that ETV treatment results in long-term HBV suppression and ALT normalization in Chinese CHB patients, and is associated with low rate of drug resistance.

Adolescent ; Adult ; Aged ; Alanine Transaminase ; blood ; Antiviral Agents ; administration & dosage ; therapeutic use ; DNA, Viral ; blood ; Double-Blind Method ; Drug Resistance, Viral ; Female ; Guanine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Lamivudine ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Time Factors ; Treatment Outcome ; Viral Load ; Young Adult

The biological characterization, differentiation and regeneration of hepatic stem/progenitor cells are the one of very active and interested fields. In this report, intravenous injection of human umbilical cord blood (HUCB) cells into the BALB/c-nu and SCID mice, an animal model for transplantation and liver injury, was reported. Using of flow cytometry and tissue typing (HLA), it was found that the HUCB cells were survived in mouse liver for 9 weeks. After separation from perfused liver, HUCB cells were detected by hematopoietic colonies (CFU-GEM M) in hepatocyte culture. It was concluded that the transplanted HUCB hematopoietic stem/progenitor cells can be survived in the liver over a long period of time.
Animals ; Cell Division ; Fetal Blood ; cytology ; Flow Cytometry ; HLA-DR Antigens ; analysis ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; physiology ; Humans ; Infant, Newborn ; Liver ; cytology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, SCID

Objective To observe the impact of growth-factor hormone control on the outcome of acromegalic cardiomyopathy by reviewing cases from our own center and from literatures.Methods Two cases of acromegalic cardiomyopathy from Tongji hospital and 29 acromegalic cardiomyopathy cases with fully accessible data retrieved from PnbMed and CNKI websites were included in present study for analysis.They were divided into "Controlled (＜5 μg/L)" or "Uncontrolled" group according to the serum level of growth factor hormone after treatments.Outcome of patients was evaluated by symptom,NYHA class,LV size and function status.Results Incidence of patients with improved symptoms and cardiac performance was significantly higher in "Controlled" group (18/19) compared to those in "Uncontrolled" group (0/12;P ＜0.01,χ~2 = 27.1).Post-treatment growth-factor hormone level＜5 μg/L is significantly associated with a satisfactory outcome of acromegaiic cardiomyopathy (r = 0.935,P＜0.01).Conclusions Control of serum growth-factor concentration to a value＜5 μg/L is critical and associated with a favorable outcome for patients with acromegalic cardiomyopathy.

BACKGROUNDVon Hippel-Lindau disease (VHL), a heritable autosomal dominant disease characterized by neoplasia in multiple organ systems, has rarely been reported in Asia. We genetically investigated a unique Chinese family with VHL disease and performed an analysis of the VHL protein stability.

METHODSGenomic deoxyribonucleic acid (DNA) extracted from peripheral blood was amplified by polymerase chain reaction (PCR) to three exons of the VHL gene in 9 members of the Chinese family with VHL disease. PCR products were directly sequenced. We estimated the effects of VHL gene mutation on the stability of pVHL, which is indicated by the free energy difference between the wild-type and the mutant protein (ΔΔG).

RESULTSThe Chinese family was classified as VHL type 1. Three family members, including two patients and a carrier, had a T to G heterozygotic missense mutation at nucleotide 515 of the VHL gene exon 1. This missense mutation resulted in the transition from leucine to arginine in amino acid 101 of the VHL protein. There was low stability of the VHL protein (the ΔΔG was 12.71 kcal/mol) caused by this missense mutation.

CONCLUSIONSWe first reported a family with this VHL gene mutation in Asia. This missense mutation is predicted to significantly reduce the stability of the VHL protein and contribute to the development of the renal cell carcinoma (RCC) phenotype displayed by this family. The genetic characterization and protein stability analysis of families with VHL disease are important for early diagnosis and prevention of the disease being passed on to their offspring.

Adult ; China ; Female ; Humans ; Male ; Middle Aged ; Mutation, Missense ; Protein Stability ; Von Hippel-Lindau Tumor Suppressor Protein ; chemistry ; genetics ; von Hippel-Lindau Disease ; genetics

This study aimed to characterize and identify the non-volatile components in Pogostemonis Herba by using ultra-perfor-mance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with UNIFI and an in-house library. The chemical components in 50% methanol extract of Pogostemonis Herba were detected by UPLC-Q-TOF-MS in both positive and negative MS~E continuum modes. Then, the MS data were processed in UNIFI combined with an in-house library to automatically characterize the metabolites. Based on the multiple adduct ions, exact mass, diagnostic fragment ions, and peak intensity of compounds and the fragmentation pathways and retention behaviors of reference substances, the structures identified by UNIFI were further verified and those of the unidentified compounds were tentatively elucidated. A total of 120 compound structures were identified or tentatively identified, including flavonoids, phenylpropanoids, phenolic acids, terpenes, fatty acids, alkaloids, and phenylethanoid glycosides. Sixteen of them were accurately identified by comparison with reference substances, and 53 compounds were reported the first time for Pogostemonis Herba. This study systematically characterized and identified the non-volatile compounds in Pogostemonis Herba for the first time. The findings provide a scientific basis for revealing the pharmacodynamic material basis, establishing a quality control system, and developing products of Pogostemonis Herba.

OBJECTIVESTo evaluate the efficacy and safety of famciclovir on the decreasing levels of serum HBV-DNA and ALT and HBeAg/antiHBe seroconversion in chronic hepatitis B patients irresponsive to 3 months treatment with alpha interferon.

METHODSTwo hundred and nineteen patients with chronic HBV infection, defined as positive HBsAg, HBeAg and HBV DNA, were enrolled and randomly half-and- half put into famciclovir and placebo groups. The two groups received either famciclovir 500 mg tid or a placebo treatment for 24 weeks, and then were followed-up for another 24 weeks with no treatment.

RESULTSAt the end of 24 weeks, the log value of HBV DNA dropped from 6.54+/-1.26 to 5.70+/-2.03 in the famciclovirt group and were elevated from 6.30+/-1.32 to 6.51+/-1.65 in the placebo group (P < 0.01). The rate of cases with persistence HBV DNA dropped 2 log of quantity in the famciclovir group and was 28.28% (28/99); it was 9.47% (9/95) in the placebo group (P < 0.01). Those with persistence negative HBV DNA was 28.28% (28/99) in the flamciclovir treated group and 14.74% (14/95) in the placebo group (P < 0.05). Those persistently being HBeAg negative were 7.69% (7/91) in the famciclovir treated group and 3.33% (3/90) in the placebo group (P > 0.05). The HBeAg/antiHBe seroconversion was 4.40% (4/91) in the famciclovir group and 2.22% (2/90) in the placebo group (P > 0.05). The percentage of cases with normal of ALT level was 15.15% in the famciclovir group and 6.35% in the placebo group (P < 0.05).

CONCLUSIONFamciclovir is effective in inhibiting HBV DNA replication and in decreasing serum ALT levels. The rate of HBeAg/antiHBe seroconversion in the famciclovir treated group was similar to that of the placebo group. Famciclovir was well tolerated without severe adverse effects during our treatment.

2-Aminopurine ; adverse effects ; analogs & derivatives ; therapeutic use ; Adolescent ; Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Follow-Up Studies ; Hepatitis B virus ; physiology ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Treatment Outcome ; Virus Replication ; drug effects