Objective To investigate the prevalence of HBV infection and the risk of hepatitis B virus (HBV) reactivation in patients with inflammatory arthritis receiving tumour hecrosis factor alpha (TNFα) inhibitors.Methods The liver function,serology of HBV and viral loads (HBV DNA) were tested before using TNFα inhibitors,at 3 months and 6 months.Patients with chronic hepatitis B (CHB) infection (HBV DNA ＞ 1 × 103copies/ml) were eliminated.Results A total of 162 patients were investigated including 156 patients who finished the study.Eleven (7.05％) patients were HBsAg-positive.Two patients with HBV DNA ＞ 1 × 103copies/ml were eliminated before starting anti-TNFα therapy.Among HBsAgpositive patients,HBV reactivation was documented in only one of the 11 patients.This patient with rheumatoid arthritis developed elevation of glutamic-pyruvic transaminase (ALT) and HBV DNA copies three months after infliximab therapy.Therefore lamivudine was given for three months,which translated into the fall of ALT and HBV DNA copies back to normal level.After follow-up for six months,the virology and serology remained stable.In contrast,none of the other 155 patients had demonstrated evidence of HBV infection or HBV reactivation.Conclusion The kinetics of HBV viral loads should be carefully monitored in patients with inflammatory arthritis and HBsAg-positive during anti-TNFα therapy.HBV reactivation should be treated with antiviral medicine through out the period of anti-TNFα therapy.

Coal ; Dust ; analysis ; Gases ; adverse effects ; Humans ; Male ; Middle Aged ; Occupational Exposure ; analysis ; Pulmonary Alveolar Proteinosis ; etiology

OBJECTIVETo investigate the role of Xuebijing injection(XBJI, traditional Chinese medicine), in inhibiting TLR4--NF-kappaB--IL-1beta pathway of myocardial hypoxia/reoxygenation in rats.

METHODSThirty six male SD rats (280 +/- 30) g were randomly divided into six groups (n = 6): normal group (N group), balanced perfusion group (BP group), model group (M group), low dose XBJI group (XBJI(L) group), middle dose XBJI group (XBJI(M) group), high dose XBJI group (XBJI(H) group). By Langendorff isolated heart perfusion device to establish the model of myocardial hypoxia/reoxygenation in rats. ELISA was used to detect the concentration of interleukin-1beta (IL-1beta); Western blot was used to detect the expression of nuclear factor kappa B p65 (NF-kappaB p65) protein and toll like receptor 4 (TLR4) protein; and RT-PCR to determine the expression of NF-kappaB p65 mRNA and TLR4 mRNA;To observe microstructure changes of hypoxia/reoxygenation myocardial by light microscopy.

RESULTSCompared with M group, the IL-1beta concentration, NF-kappaB p65 and TLR4 protein,NF-kappaB p65 and TLR4 mRNA of XBJIL group, XBJI(M) group, XBJI(H) group expression decreased in varying degrees,and decreased most obviously all in XBJI(M) group (P < 0.05, P < 0.01); Myocardical structural damage was serious in M group, and improved after treatment XBJI, the most obvious was the XBJI(M).

CONCLUSIONDifferent dose of XBJI can inhibit TLR4--NF-kappaB--IL-1beta signal transduction pathway and reduce several inflammatory reaction after myocardial hypoxia/reoxygenation injury, the 4 ml/100 ml of XBJI is the best.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Heart ; drug effects ; Inflammation ; Interleukin-1beta ; metabolism ; Male ; Myocardium ; pathology ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; Signal Transduction ; Toll-Like Receptor 4 ; metabolism ; Transcription Factor RelA ; metabolism

OBJECTIVETo investigate the effect of siRNA silencing the role of C-Jun N-terminal Kinase (JNK) gene in excessive endoplasmic reticulum stress on lung ischemia/reperfusion injury.

METHODSMouse model of pulmonary ischemia reperfusion injury (PIRI) in situ was established with unilateral lung in vivo. Seventy experimental mice were randomly allocated into seven groups (n = 10): Sham group (Sham group), ischemia reperfusion group (I/R), PBS+ Lipofectamine2000TM transfection reagent group (I/R + PBS+ Lipo group), negative control group (I/R+ SCR group), JNK-siRNA group (I/R + siRNA(JNK1), siRNA(JNK2), siRNA(JNK3)). Mice were euthanized after experimental time out, and left lung tissue was extracted. Wet/dry lung weight ratio (W/D) and total lung water content (TLW) were tested. Light microscope, alveolar damage quantitative evaluation index (IQA) and electron microscope were observed. The expression levels of JNK and glucose regulatex protein(GRP78) were detected by RT-PCR and Western blot. Apoptosis of lung tissue was determined by TUNEL.

RESULTSCompared with Sham group, all indicators above of I/R + PBS + Lipo group and I/R + SCR group were significantly increased (P < 0.01), and compared with I/R group, those indicators of the three groups all had no notable difference; those indicators were not statistically different between I/R + PBS + Lipo group and I/R + SCR group, and compared to the three groups, the above indicators in JNK-siRNA group were lower (P < 0.05, P < 0.01) except that the expression levels of GRP78 was not statistically different.

CONCLUSIONI/R induces excessive ERS in lung tissue, in which JNK pathway participates in apoptosis, leading to lung tissue injury.

Animals ; Apoptosis ; Endoplasmic Reticulum Stress ; Heat-Shock Proteins ; metabolism ; JNK Mitogen-Activated Protein Kinases ; genetics ; Lung ; physiopathology ; Lung Injury ; genetics ; MAP Kinase Signaling System ; Mice ; RNA, Small Interfering ; Reperfusion Injury ; genetics

Objective To compare the coherence of serum creatinine,creatinine clearance(Ccr), Cystatin C,and estimated glomerular filtration rate(eGFR)in each stage of chronic kidney disease(CKD) patients.Methods Creatinine in serum and urine were determined by Jaffe method;serum Cystatin C was measured by particle enhanced turbidimetric method,while eGFR was calculated using the abbreviated Modification of Diet in Renal Disease(MDRD)equation which was mainly based on the serum creatinine concentration.According to the American national kidney foundation-Kidney Disease Outcome Quality Initiative(NKF-K/DOQI)guideline,all cases were grouped by eGFR into 5 stages.Results In these 228 cases,as eGFR decreased gradually,the average levels of creatinine and Cystatin C increased,while Ccr decreased.The level of each items showed a statistic difference among each stage(P0.05);in eGFR 60-89 ml/min group,the average level of creatinine was 83.3 ?mol/L,the abnormal rate was only 6.8%,it was not a sensitive marker to detect the slightly damaged GFR,the levels of Ccr and Cystatin C showed a marginal decrease and increase,with an abnormal rates of 70% and 86%,there was a statistic difference among the three abnormal rates(P

Animals ; Animals, Newborn ; Cell Hypoxia ; Cell Survival ; drug effects ; Female ; Hippocampus ; cytology ; drug effects ; L-Lactate Dehydrogenase ; secretion ; Male ; Malondialdehyde ; analysis ; Neuroprotective Agents ; pharmacology ; Propofol ; pharmacology ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the distribution of DC-SIGN/DC-SIGNR alleles among drug user (DUs) populations with or without HIV/HCV infection in Shenzhen, and to evaluate the role of these alleles in the construction of genetic resistance to HIV or HCV and screen out the anti-HIV/HCV gene in Shenzhen.

METHODSAll 500 DU blood samples were collected from Shenzhen Detoxification Center, including 313 from injected drug users (IDUs). All samples were screened for HIV and HCV antibody by means of ELISA. The genomic DNA were extracted and amplified by PCR. The neck domain repeat regions of DC-SIGN/DC-SIGNR were sequenced directly from the PCR products to confirm the amplification for some samples and all positive PCR products were analyzed by agarose gel electrophoresis.

RESULTSOf 500 samples, 97 were found HIV positive, all of which were IDUs and HCV positive. The total positive rate of HCV among all HIV negative DU was 57.57% (232/403), and it was 63.89% (138/216) among IDUs; in comparing to the 50.26% (94/187) of DUs with other manners there showed significant difference (chi(2) = 7.61, P = 0.0058). Among HIV + DUs, there was a higher proportion of patient with the DC-SIGNR 5/6 and 5/8 (Fisher's exact, P = 0.043 and P = 0.034) with statistical significance; there was no statistically significant difference between HCV + and HCV-DUs and no significant difference between IDUs and other DUs for the DC-SIGNR polymorphism.

CONCLUSIONThe results might indicate that DC-SIGN/DC-SIGNR polymorphism might not influence the susceptibility to HCV. Genotype 5/6 might probably have a relation with HIV infection, but still need further investigation for the low frequency.

Adolescent ; Adult ; Alleles ; Cell Adhesion Molecules ; genetics ; Drug Users ; Female ; Gene Frequency ; Genotype ; HIV Infections ; genetics ; HIV-1 ; Hepacivirus ; Hepatitis C ; genetics ; Humans ; Lectins, C-Type ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Cell Surface ; genetics ; Young Adult

Objective To study the prevalent status of human immunodeficiency virus-1 (HIV-1) subtypes in IDU (injecting drug users) population in Shenzhen and to study their source of infection in order to predict the epidemic trend and evolution. Methods 166 HIV-1 positive plasma from the IDUs was collected from 1996 to 2008. HIV-1 env genes were amplified by nested-PCR from RNA. The C2-V3 regions (450 bp) of HIV-1 env were sequenced for analyses. Phylogenetic analyses were performed on the nucleotide sequence data. Results Among 166 samples, there were 6 HIV-1 strains including CRF01_AE, CRF08_BC, CRF07_BC 3 circulating recombinant forms (CRFs) and B',C, A1 3 subtypes. Data from the genotype analyses showed that 65.06% (108/166) were CRF01_AE, 19.88% (33/166) were CRF07 BC_6.02% (10/166) were CRF08_BC, 7.23%(9/166) were subtype B', 0.60% (1/166) were subtype C and 1.20% (2/166) were subtype A1. Phylogenetic tree analysis showed that some of HIV-1 clusters defined in CRF01_AE, CRF07_BC and subtype B' in different time groups. Significant increase of gene distance in CRF01_AE and CRF07_BC strains in the three different periods. Conclusion CRF01_AE and CRF07_BC were the major epidemic CRF strains among the IDU population in Shenzhen while the subtype B', C, A1 and CRF08_BC were also circulating in IDU population in this region. The variation of all different subtypes was increasing through these years.

OBJECTIVETo observe the effects of neural stem cells (NSCs) transplantation on the brain derived neurotrophic factor (BDNF) after the spinal cord injury (SCI) of rats, and to investigate the mechanism of repairing the SCI by NSCs transplantation.

METHODSNeural stem cells were cultured from the hippocampus of rats' embryo and identified by immunocytochemistry. Seven days after the operation of SCI, the NSCs were transplanted into the injured site. Sixty adult Wistar rats were randomly divided into three groups: SCI cured with NSCs transplantation (group A), SCI received DMEM solution (group B), control group (group C). Then the expression of BDNF of the lesion and neighbor areas were examined by reverse transcsription polymerase chain reaction (RT-PCR) and immunohistochemistry, so as to investigated the mechanism of repairing the SCI after NSCS transplantation.

RESULTSAccording the RT-PCR results analysis, the expression of BDNF mRNA of group A enhanced higher than that of group B on the 1st, 3rd, 5th day after transplantation of NSCs. According the immunohistochemistry results analysis, the expression of BDNF mRNA of group A enhanced higher than that of group B on the 7th, 14th, 28th day similarly.

CONCLUSIONThe transplantation of NSCs can change the tiny-entironment by upregulating the expression of BDNF. It maybe one of the mechanism of repairing the SCI by NSCs transplantation.

Animals ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; Cells, Cultured ; Disease Models, Animal ; Gene Expression ; Humans ; Male ; Mesenchymal Stem Cell Transplantation ; Neurons ; metabolism ; transplantation ; Random Allocation ; Rats ; Rats, Wistar ; Spinal Cord Injuries ; genetics ; metabolism ; surgery ; therapy ; Up-Regulation

OBJECTIVETo investigate the correlation of hypermethylation of BRCA1 and APC gene promoters with the response to anthracycline-based neoadjuvant chemotherapy in primary breast cancer.

METHODSOne hundred and forty patients with primary breast cancer received anthracycline-based neoadjuvant chemotherapy, and pretreatment hypermethylation status of BRCA1 and APC genes promoters was detected by methylation-specific PCR.

RESULTSOf the 140 patients, 30 (21.4%) achieved pathological complete response (pCR), and methylation rates of BRCA1 and APC gene promoters were 21.4% (30/140) and 18.3% (24/131), respectively. Among the 110 patients with unmethylated BRCA1 gene, 28 (25.5%) achieved pCR, while in the 30 patients with methylated BRCA1 gene, only 2 (6.7%) had a pCR, with a significant difference between the two groups (chi(2) = 4.94, P = 0.026). However, no statistically significant correlation was found between the methylation of APC gene and pCR to neoadjuvant chemotherapy in this cohort of patients (P > 0.05).

CONCLUSIONPrimary breast cancer with an unmethylated BRCA1 gene is prone to achieve a pathological complete response to anthracycline-based neoadjuvant chemotherapy than those with a methylated BRCA1 gene. BRCA1 methylation status may be a useful predictor for anthracycline-based neoadjuvant chemotherapy in primary breast cancer patients.

Adenomatous Polyposis Coli Protein ; genetics ; metabolism ; Adult ; Aged ; Anthracyclines ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; BRCA1 Protein ; genetics ; metabolism ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; CpG Islands ; genetics ; Cyclophosphamide ; therapeutic use ; DNA Methylation ; Epirubicin ; therapeutic use ; Female ; Fluorouracil ; therapeutic use ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Remission Induction ; Young Adult