Objective To investigate the changes in intrapulmonary shunting during controlled hypotension induced by sodium nitroprusside(SNP)in patients undergoing naso-endoscopic operation.Methods Forty ASAⅠorⅡpatients of both sexes(23 male,17 female)aged 16-50 yrs weighing 50-75 kg undergoing naso-endoscopic operation under general anesthesia with muscle relaxation and mechanical ventilation were studied.Radial artery was cannulated for direct BP monitoring and blood sampling.Right internal jugular vein was cannulated and the catheter was advanced into right ventricle.Blood sample taken from right ventricle was used as mixed venous blood instead of blood from pulmonary artery.ECG,MAP,HR and P_(ET) CO_2 were continuously monitored during operation Cardiac output was monitored with noninvasive cardiac function monitor(NC-COM.)based on impedance principle.SNP infusion was started at the beginning of operation at 1-3?g?kg~(-1)?min~(-1) and was then adjusted.MAP was reduced by 30%-40% and maintained at this level until the end of operation.Blood samples were taken from artery and right ventricle simultaneously before SNP infusion(T_1,baseline)at 30 and 60 min of hypotension(T_2,T_3)and at 20 min after BP returned to the baseline level(T_4)for blood gas analysis.Qs/Qt was calculated.Results Qs/Qt was significantly increased during controlled hypotension at T_2 and T_3 as compared to the baseline value(P＜0.01)and returned to the baseline level at T_4.HR was increased and cardiac output and stroke volume was significantly reduced during hypotension as compared to the baseline value.Conclusion The intrapulmonary shunting is increased and the hemodynamics is depressed during SNP-induced controlled hypotension and they return rapidly to baseline level after SNP is discontinued.No hypoxemia develops during SNP- induced hypotension.

Objective To establish an allele-specific PCR method for the detection of cytochrome P-450 CYP3A5 (A6986G) and multiding resistance gene MDR-1 (C3435T) polymorphisms,and investigate the correlations of their polymorphisms with blood tacrolimus (Tac) concentration/dose (C/D) ratio in renal transplant recipients.Methods The allele-specific PCR primers were designed according to the polymorphism sites of CYP3A5 (A6986G) and MDR-1 (C3435T) genes.Then,their polymorphisms in the genomic DNA of peripheral blood samples from 72 renal transplant recipients were analyzed,and the results were validated by DNA sequencing.The blood Tac concentration was determined by the chemiluminescence microparticle immunoassay and the differences of concentration,dose and C/D ratio of blood Tac in renal transplant recipients with different genotypes were compared at 1 month after transplantation.Results The coincidence rate between the established allele-specific PCR and DNA sequencing was 100％.The frequencies of CYP3A5 * 1/* 1,* 1/* 3 and * 3/* 3 genotypes in 72 renal transplant recipients were 18.1％,31.9％ and 50.0％,respectively,and those of MDR-1 C/C,C/T and T/T genotypes were 27.8％,58.3％ and 13.9％,respectively.There were significant differences in blood Tac concentration (P =0.014) and Tac C/D ratio (P =0.019) between different CYP3A5 genotypes of renal transplant recipients.Further analysis found that the Tac C/D ratio of CYP3A5 * 3/* 3 genotype was significantly higher than that of CYP3A5 * 1/* 1 and * 1/* 3 genotypes (P ＜ 0.05).Conclusion The allele-specific PCR method for the detection of CYP3A5 and MDR-1 polymorphisms is successfully established and the polymorphism of CYP3A5 * 3 gene in renal transplant recipients is obviously correlated with the pharmacokinetics of Tac.

Tumor necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine, acting as a regulator of inflammation and immunity. TNFalpha plays a critical role in the pathogenesis of rheumatoid arthritis. Blocking of TNFa activity suppressed inflammatory tissue damage. In present study, the chimeric gene of soluble TNF receptor and IgG Fc fragment (sTNFR-IgG FC) was cloned into the mammalian cell expression vector pStar. When the plamid pStar/sTNFR-IgGFc-GFP was transfected into endothelial cells, a considerable expression of the sTNFR-IgG Fc fusion protein was detected. Moreover, the product in 100microL expression supernatant could completely antagonize the cytolytic effect of 1ng TNFa on L929 cells, even at 1/64 dilution. Then the plasmid was delivered into CIA-induced rheumatoid arthritis mice by tail vein injection. The expression of sTNFR-IgG Fc was detected in liver by RT-PCR. Animals in treatment group showed reduced symptoms of arthritis and more active. This treatment induced decrease of synovial incrassation and prevented the cartilage destruction of the mice RA model. These results show that tail vein injection is an effective way for gene therapy and sTNFR-IgGFc expression plasmid is potential for the treatment of rheumatoid arthritis.
Animals ; Arthritis, Rheumatoid ; chemically induced ; therapy ; Collagen Type II ; Endothelial Cells ; metabolism ; Escherichia coli ; genetics ; metabolism ; Etanercept ; Genetic Therapy ; Humans ; Immunoglobulin G ; biosynthesis ; genetics ; therapeutic use ; Male ; Mice ; Mice, Inbred DBA ; Receptors, Tumor Necrosis Factor ; biosynthesis ; genetics ; therapeutic use ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; therapeutic use ; Transfection ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo analyze the association of variants of hepatocyte nuclear factor-1alpha (HNF-1alpha) gene with type 2 diabetes in Chinese population.

METHODSIn 152 unrelated type 2 diabetes patients and 93 unrelated controls, eleven single nucleotide polymorphisms (SNPs) were identified and genotyped. Statistical analyses were performed to investigate whether these SNPs were associated with diabetes status in our samples.

RESULTSIn the individual SNP study, no SNP differed significantly in frequency between type 2 diabetes patients and controls. In the haplotype analysis, two haplotype blocks were identified. In haplotype block 1, no evidence was found between common HNF-1alpha haplotypes and type 2 diabetes. However, in haplotype block 2, a common haplotype GCGC formed by four tagging SNPs (tSNPs) was found to be associated with decreased risk of type 2 diabetes (odds ratio [OR] 0.6011, 95% confidence interval [CI] 0.4138-0.8732, P = 0.0073, empirical P = 0.0511, permutation test). A similar trend was also observed in the diplotype analysis, indicating that the increasing copy number of the haplotype GCGC was associated with the decreased frequency of diabetes (P = 0.0193).

CONCLUSIONThe results of this study provide evidence that the haplotype of HNF-1alpha decreases the risk of type 2 diabetes in Chinese individuals.

Adult ; Aged ; Case-Control Studies ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; epidemiology ; genetics ; Genetic Predisposition to Disease ; Haplotypes ; Hepatocyte Nuclear Factor 1-alpha ; genetics ; Humans ; Middle Aged ; Polymorphism, Single Nucleotide

Aim To investigate the potential molecular basis of Epimedium and to clarify the molecular mechanism of Epimedium in the treatment of osteoporosis.Methods The method of network pharmacology was used to determine and screen the known compounds corresponding to Epimedium,and predict the drug-related gene/protein targets,and combined with bioinformatics,the specific target of osteoporosis prevention and treatment of Epimedium was determined,and then the signal pathway enrichment was analysed,the molecular mechanism of Epimedium in treatment of osteoporosis was further explored.Results A total of 130 corresponding compounds were retrieved in the TCMID database from Epimedium.According to the values of OB and DL,23 blood transfusion components were screened,in which 101 targets were obtained using the related target prediction technique.Through the secondary mining of the gene chip of GEO chip database,we obtained a total of 124 significantly different genes.And a total of 355 known target genes closely related to the development of osteoporosis were retrieved in the disease-related database.Using the cytoscape to construct and synthesize the protein-protein interaction network of active ingredients and diseases,221 key genes were screened out by network topological analysis.Using ClueGO analysis,it was shown that Epimedium was directly engaged in the signal pathways involved in the key nodes of osteoporosis,which were mainly related to the direct regulation of bone metabolism,such as Wnt signaling pathway,TGF-β signaling pathway and Notch signaling pathway,and that Epimedium regulated other signal pathways,such as PI3K-Akt signaling pathway,VEGF signaling pathway and thyroid hormone signaling pathway.Conclusions Epimedium has the characteristics of multiple targets and multicomponent in the treatment of osteoporosis,which could not only be directly involved in bone cell differentiation and regulation of the balance of osteogenesis and osteoclasts,but also affect and interfere with the bone microenvironment through other systemic systems,such as circulatory system,nervous system,which is consistent with the current mechanism of treatment of osteoporosis.

OBJECTIVETo investigate the relationship between the vascular endothelial growth factor A gene (VEGFA) rs9369425 single nucleotide polymorphism (SNP) and type 2 diabetes in Chinese Han population.

METHODSOne thousand eight hundred and ninety two type 2 diabetes patients and 1808 controls with normal glucose were recruited in this study. Phenotypes including body mass index, waist, waist hip ratio, plasma glucose and serum insulin levels of blood obtained both at 0 and 120 minute during standard 75-gram glucose oral glucose tolerance tests, were analyzed. Insulin resistance and beta cell function were assessed by homeostasis model assessment (HOMA-IR and HOMA-B). Genotyping was performed by time-of-light mass spectrum using a Sequenom platform.

RESULTSThe frequencies of minor allele G in the diabetic patients and controls were 10.8% and 11.3% respectively. No significant difference of allele distribution was detected between the cases and controls (P=0.5086). No significant difference (P>0.05) was detected on the association between rs9369425 SNP and clinical phenotypes.

CONCLUSIONVEGFA rs9369425 was not associated with type 2 diabetes in Chinese Han population. Whether there is association in any other loci in this gene remained to be investigated.

Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glucose Tolerance Test ; Humans ; Insulin Resistance ; genetics ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; genetics ; Population Groups ; genetics ; Vascular Endothelial Growth Factor A ; genetics

OBJECTIVETo observe the effect of postoperative anti-viral therapy using lamivudine and thymosin alpha1 on recurrence of hepatocellular carcinoma (HCC) coexisting with active hepatitis B.

METHODSFrom Jan. 2000 to Dec. 2002, 33 HCC patients with coexisting with active hepatitis B were randomized into two groups: Group I (n = 17) received hepatectomy only, and Group II (n = 16) received hepatectomy and postoperative therapy using lamivudine plus thymosin alpha1. The suppression of HBV-DNA, HBeAg seroconversion rate, tumor recurrence rate and median survival in the two groups were observed and compared.

RESULTSIn Group II and Group I, the 1-year HBV-DNA suppression rate was 100.0% vs 6.0% (P < 0.01), HBeAg seroconversion rate was 62.5% vs 5.9% (P < 0.05), tumor recurrence rate was 81.3% vs 95.5% (P > 0.05), the recurrence time was 7.0 vs 5.0 months (P < 0.01) and median survival 10.0 vs 7.0 months (P < 0.01).

CONCLUSIONAnti-viral therapy using lamivudine and thymosin alpha1 postoperatively may suppress the HBV reaction, delay the recurrence and prolong the survival for patients with HCC with coexisting active hepatitis B.

Adult ; Aged ; Carcinoma, Hepatocellular ; surgery ; therapy ; virology ; DNA, Viral ; drug effects ; Female ; Hepatectomy ; methods ; Hepatitis B ; genetics ; therapy ; Humans ; Lamivudine ; therapeutic use ; Liver Neoplasms ; surgery ; therapy ; virology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Postoperative Period ; Reverse Transcriptase Inhibitors ; therapeutic use ; Survival Rate ; Thymosin ; analogs & derivatives ; therapeutic use

OBJECTIVETo explore the role of BM2 protein in the life cycle of influenza B virus.

METHODSThe authors screened human kidney MATCHMAKER cDNA library for new binding partners of BM2 of influenza B virus by using the yeast two hybrid system with truncated BM2 (26-109 aa) as the bait.

RESULTSSix positive plasmids encoding N-acetylneuraminate pyruvate lyase, angiopoietin 3, zinc finger protein 251, ribosomal protein S20, protein arginine N-methyltransferase 1 variant 1 (PRMT) and transcription factor-like 1 (TCFL1) were obtained.

CONCLUSIONThe results suggest that BM2 may play an important role in the life cycle of influenza B virus.

Angiopoietin-like Proteins ; Angiopoietins ; genetics ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Gene Library ; Humans ; Influenza B virus ; genetics ; metabolism ; Kidney ; metabolism ; Oxo-Acid-Lyases ; genetics ; metabolism ; Plasmids ; genetics ; Protein Binding ; Protein-Arginine N-Methyltransferases ; genetics ; metabolism ; Repressor Proteins ; genetics ; metabolism ; Ribosomal Proteins ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism ; Two-Hybrid System Techniques ; Viral Proteins ; genetics ; metabolism ; Zinc Fingers ; genetics

Tricho-rhino-phalangeal syndrome (TRPS) was first reported in 1966. Although mutation of TRPS1 gene is considered to be responsible for the syndromes in 2000, investigation of bone metabolism and changes of serum insulin-like growth factor (IGF)-1 level in this kind of patients is rare. Here, we report a patient with TRPS I (MIM 190350) presenting a novel mutation (1096insA) and abnormal changes of severe osteoporosis as well as low serum IGF-I level.
Adolescent ; DNA-Binding Proteins ; genetics ; Humans ; Langer-Giedion Syndrome ; genetics ; Male ; Mutation ; Osteoporosis ; genetics ; Transcription Factors ; genetics

OBJECTIVETo observe the effect of postoperative transcatheter hepatic arterial chemoembolization (TACE) and thymosin alpha(1) (T(alpha1)) treatment on recurrence of hepatocellular carcinoma (HCC).

METHODSFrom Jan 2000 to Dec 2002, 57 patients with HCC were randomly divided into three groups: group A (n = 18) received hepatectomy plus postoperative TACE and T(alpha1), group B (n = 23) received hepatectomy plus postoperative TACE and group C (n = 16) received hepatectomy only. The recurrence rate, the time to tumor recurrence and the median survival for the three groups were investigated.

RESULTSFor group A, B and C, the 1 year recurrence rate was 83.3%, 87.0% and 87.5% (P = 0.926), respectively. The time to tumor recurrence was 7.0, 5.0 and 4.0 months (P = 0.039), respectively. The median survival was 10.0, 7.0 and 8.0 months (P = 0.002), respectively.

CONCLUSIONPostoperative TACE plus Talpha(1) treatment for HCC patients does not decrease the recurrence rate but may delay its occurrence and prolong surviving time.

Adjuvants, Immunologic ; administration & dosage ; Adult ; Aged ; Antibiotics, Antineoplastic ; administration & dosage ; Antineoplastic Agents ; administration & dosage ; Carboplatin ; administration & dosage ; Carcinoma, Hepatocellular ; surgery ; therapy ; Chemoembolization, Therapeutic ; Doxorubicin ; administration & dosage ; Female ; Hepatectomy ; Humans ; Iodized Oil ; administration & dosage ; Liver Neoplasms ; surgery ; therapy ; Male ; Middle Aged ; Mitomycin ; administration & dosage ; Neoplasm Recurrence, Local ; prevention & control ; Postoperative Period ; Survival Rate ; Thymosin ; administration & dosage ; analogs & derivatives