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Objective: To analyze the blood test indicators of patients after infection of COVID-19 in Chongqing and analyze the clinical indicators of 8 patients with diarrhea. Materials and Methods: From January 26, 2019 to February 13, 2020, 70 patients diagnosed with 2019-nCoV according to the World Health Organization interim guidance for NCP and divided into diarrhea and non-diarrhea groups. The laboratory tests liver and kidney function, blood routine, coagulation function, and immune status. Results: The study population included 70 hospitalized patients with confirmed CONV-2019. NCP patients (43males and 27 females) with a mean age of 48.57±17.80 (9~82) years and only 4.3% of patients have lung-related diseases. The positive rate of ESR, CRP, PT, IL6, lymphocyte count, GGT, Prealbumin and CD4 was more than 50%. We further analyzed the differences between 8 diarrhea patients and 62 non-diarrhea patients. Among these indicators, only Lymphocyte, CRP, Prealbumin and Cystatin C positive rate is more than 50%. Although there is no statistical difference in GGT, 100% of the 7 patients tested decreased. Conclusion: Our data recommended that the ESR, CRP, PT, IL6, lymphocyte count, GGT, prealbumin and CD4 have important value in the diagnosis of COVID-19, and the decrease of GGT may be an important indicator for judging the intestinal dysfunction of patients.
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Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Diarreia/diagnóstico , Pneumonia Viral/complicações , gama-Glutamiltransferase/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19 , Criança , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Diarreia/sangue , Diarreia/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , SARS-CoV-2 , Adulto JovemRESUMO
Previous studies indicated that the human X-ray repair complementing group 3 gene (XRCC3) plays an important role in hepatocellular carcinoma (HCC) susceptibility. We aimed to investigate the association of XRCC3 genetic polymorphism with HCC risk. This study was conducted in a Chinese Han population consisting of 300 HCC cases and 300 sex- and age-matched cancer-free controls. Three genetic variants (rs861539, rs12432907, and rs861537) were genotyped by the TaqMan® SNP Genotyping Assay. Our findings suggested that the TT genotype and T allele from rs861539 genetic variants were statistically associated with HCC risk. The TT genotype was statistically associated with the increased risk of HCC compared to CC wild genotype (P < 0.001). And the T allele was more common in the HCC patients than that in the control subjects. (OR = 1.97, 95% confidence interval (CI) 1.457 ~ 2.659, P < 0.001). Haplotype-based case-control study analysis indicated that TTG haplotype was more frequent in HCC groups than in the control group (odds ratio (OR) = 1.967, 95% CI 1.456 ~ 2.658); however, the CTG haplotype is more common in the control group than that in the HCC group (OR = 0.550, 95 % CI 0.430 ~ 0.703; P < 0.001). Our data indicated that genetic variants of the XRCC3 gene were statistically associated with HCC risk in a Chinese population.
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Carcinoma Hepatocelular/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Haplótipos , Neoplasias Hepáticas/genética , Adulto , Idoso , Povo Asiático/genética , Carcinoma Hepatocelular/etiologia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Emtricitabine (FTC) is used for the treatment of HIV infection and pre-exposure chemoprophylaxis. It is often used in combination with tenofovir disoproxil fumarate (TDF). This study was designed to evaluate FTC pharmacokinetics in healthy male Chinese volunteers. Sixty subjects were recruited into this single-centre, randomised, open-label study and randomly received single (groups A, B and C) or multiple oral doses (once daily for 6 days; groups D, E and F) of 200-mg FTC capsules alone (A and D), or combined with 300-mg TDF tablets (B and E), or 200 mg of FTC plus 300 mg of TDF with a high-fat diet (C and F), respectively. FTC was well-tolerated in all groups. After a single dose, there were no differences in the mean AUC0-∞ values; however, there were significant differences in the mean Tmax values (1.05, 1.40 and 2.10 h for groups A, B and C, respectively; p < 0.05). In the multiple-dose study, our results were significantly different from published t1/2 values following single-dose FTC.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/farmacocinética , Desoxicitidina/análogos & derivados , Interações Alimento-Droga , Ácidos Fosforosos/farmacologia , Adenina/administração & dosagem , Adenina/farmacologia , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Área Sob a Curva , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/farmacocinética , Dieta Hiperlipídica , Esquema de Medicação , Emtricitabina , Meia-Vida , Humanos , Masculino , Ácidos Fosforosos/administração & dosagem , Adulto JovemRESUMO
BACKGROUND & AIMS: Even though various experimental therapeutic approaches for chronic hepatitis B infection have been reported, few of them have been verified by clinical trials. We have developed an antigen-antibody (HBsAg-HBIG) immunogenic complex therapeutic vaccine candidate with alum as adjuvant (YIC), aimed at breaking immune tolerance to HBV by modulating viral antigen processing and presentation. A double-blind, placebo-controlled, phase II B clinical trial of YIC has been reported previously, and herein we present the results of the phase III clinical trial of 450 patients. METHODS: Twelve doses of either YIC or alum alone as placebo were administered randomly to 450 CHB patients and they were followed for 24weeks after the completion of immunization. The primary end point was HBeAg seroconversion, and the secondary end points were decrease in viral load, improvement of liver function, and histology. RESULTS: In contrast to the previous phase II B trial using six doses of YIC and alum as placebo, six more injections of YIC or alum resulted in a decrease of the HBeAg seroconversion rate from 21.8% to 14.0% in the YIC group, but an increase from 9% to 21.9% in the alum group. Decrease in serum HBV DNA and normalization of liver function were similar in both groups (p>0.05). CONCLUSIONS: Overstimulation with YIC did not increase but decreased its efficacy due to immune fatigue in hosts. An appropriate immunization protocol should be explored and is crucial for therapeutic vaccination. Multiple injections of alum alone could have stimulated potent inflammatory and innate immune responses contributing to its therapeutic efficacy, and needs further investigation.
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Antígenos de Superfície da Hepatite B/uso terapêutico , Hepatite B Crônica/terapia , Imunoglobulinas/uso terapêutico , Vacinas Virais/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Adulto , Compostos de Alúmen/administração & dosagem , Complexo Antígeno-Anticorpo/administração & dosagem , Complexo Antígeno-Anticorpo/uso terapêutico , Citocinas/sangue , Método Duplo-Cego , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/administração & dosagem , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/patologia , Humanos , Imunoglobulinas/administração & dosagem , Masculino , Vacinas Virais/efeitos adversos , Adulto JovemRESUMO
We compared a novel real-time genotyping and quantitative PCR (GQ-PCR) assay, direct sequence analysis, reverse hybridization, and multiplex PCR for genotyping hepatitis B virus (HBV) in 127 HBV-infected patients. We found that GQ-PCR had the highest concordance with sequence analysis and the highest detection rate for mixed genotype detecting.
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Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Hibridização de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Análise de Sequência de DNA/métodos , Virologia/métodos , Genótipo , Hepatite B/virologia , Vírus da Hepatite B/isolamento & purificação , Humanos , Tipagem Molecular/métodosRESUMO
OBJECTIVE: To evaluate the clinical efficacy and safety of antofloxacin hydrochloride tablet for the treatment of acute bacterial infections. METHODS: A multi-center randomized control, double blind and double dummy clinical trial was conducted; levofloxacin tablet was closed as controlled drug. The duration of treatment was 7-14 days in both groups. RESULTS: A total of 719 patients were enrolled in the study, in which 359 patients treated with antofloxacin and 360 patients treated with levofloxacin were included. Three hundred and thirty and 337 patients completed the study and met with all the criteria for per-protocol analysis, respectively. By the end of chemotherapy, the cured rates in per protocol set (PPS) population were 79.7% and 77.4%, the effective rates were 95.2% and 96.7%, and the bacterial clearance were 96.7% and 97.5% for the treating and control group, respectively. The clinical and bacterial efficacy of antofloxacin and levofloxacin was comparable by the analysis of infectious sites. Three hundred and fifty-seven and 356 patients in antofloxacin and levofloxacin groups were evaluated the safety. The drug adverse events occurred both in 10.1%, and drug adverse reactions occurred in 7.8% and 7.9% patients in the two groups. The most common drug adverse reactions were mild gastroenteric symptoms. No QTc prolongation was detected in all the patients. One patient in each group had mild blood glucose increase at the end of therapy, but the glucose returned to normal level without any intervention. No statistic significant difference between the two groups in clinical efficacy and safety was detected (P > 0.05). CONCLUSIONS: Antofloxacin hydrochloride tablet was effective and safe for the treatment of acute bacterial infections.
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Anti-Infecciosos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Levofloxacino , Ofloxacino/análogos & derivados , Ofloxacino/uso terapêutico , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The asymmetric unit, 2CH(4)N(2)O·C(7)H(12)O(4), of the title cocrystal contains one urea mol-ecule and a half-mol-ecule of pimelic acid; the latter, together with a second urea mol-ecule, are completed by symmetry, with the central atom of the whole pimelic acid moiety placed on a twofold crystallographic axis. The crystal packing is stabilized by O-Hâ¯O and N-Hâ¯O hydrogen-bond, generating a chain along [10[Formula: see text]]. Additionally, the chains are assembled into a three-dimensional framework via weak N-Hâ¯O inter-chain inter-actions.
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The asymmetric unit of the binuclear centrosymmetric title compound, [Er(2)(C(12)H(14)O(4))(2)(C(12)H(15)O(4))(2)(C(12)H(8)N(2))(2)(H(2)O)(2)]·2H(2)O, contains one Er(III) atom, one coordinated water mol-ecule, one 1,10-phenanthroline (phen) ligand, two differently coordinated adamantane-1,3-dicarboxyl-ate (H(2)L) ligands and one lattice water mol-ecule. The Er(III) ion is eight-coordinated by four O atoms from bridging L(2-), one O atom from HL(-), one O atom from the coordinated water and two N atoms from a phen ligand. Extensive O-Hâ¯O hydrogen-bonding inter-actions result in the formation of chains which are further linked into a layer-like network by π-π stacking inter-actions centroid-centroid distance = 3.611â (3)â Å] between adjacent phen ligands belonging to neighbouring chains. The carboxy group of the HL(-) ligand is equally disordered over two positions.
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The asymmetric unit of the title compound, C(10)H(8)N(2)·C(9)H(10)O(8), contains a half-molecule of 2,2'-bipyridine and a half-molecule of 1,2,3,4-cyclopentanetetracarboxylic acid, both components being completed by crystallographic inversion symmetry. In the crystal, the mol-ecules are assembled into chains extending along [010] by O-Hâ¯N hydrogen bonds; adjacent chains are linked by O-Hâ¯O hydrogen bonds into a three-dimensional network.
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BACKGROUND: The management of discharge COVID-19 patients with recurrent positive SARS-CoV-2 RNA is challenging. However, there are fewer scientific dissertations about the risk of recurrent positive. The aim of this study was to explore the relationship between SARS-COV-2 RNA positive duration (SPD) and the risk of recurrent positive. METHODS: This case-control multi-center study enrolled participants from 8 Chinese hospital including 411 participants (recurrent positive 241). Using unadjusted and multivariate-adjusted logistic regression analyses, generalized additive model with a smooth curve fitting, we evaluated the associations between SPD and risk of recurrent positive. Besides, subgroup analyses were performed to explore the potential interactions. RESULTS: Among recurrent positive patients, there were 121 females (50.2%), median age was 50 years old [interquartile range (IQR): 38-63]. In non-adjusted model and adjusted model, SPD was associated with an increased risk of recurrent positive (fully-adjusted model: OR = 1.05, 95% CI: 1.02-1.08, P = 0.001); the curve fitting was not significant (P = 0.286). Comparing with SPD < 14 days, the risk of recurrent positive in SPD > 28 days was risen substantially (OR = 3.09, 95% CI: 1.44-6.63, P = 0.004). Interaction and stratified analyses showed greater effect estimates of SPD and risk of recurrent positive in the hypertension, low monocyte count and percentage patients (P for interaction = 0.008, 0.002, 0.036, respectively). CONCLUSION: SPD was associated with a higher risk of recurrent positive and especially SPD > 28 day had a two-fold increase in the relative risk of re-positive as compared with SPD < 14 day. What's more, the risk may be higher among those with hypertension and lower monocyte count or percentage.
Assuntos
COVID-19/virologia , RNA Viral/isolamento & purificação , SARS-CoV-2/isolamento & purificação , Adulto , COVID-19/epidemiologia , COVID-19/patologia , Estudos de Casos e Controles , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Faringe/virologia , RNA Viral/genética , Recidiva , Fatores de Risco , SARS-CoV-2/genética , Fatores de Tempo , Eliminação de Partículas ViraisRESUMO
Hepatitis B virus (HBV) is an important cause of human chronic liver diseases and is a major public health problem. Viral load and HBV genotype play critical roles in determining clinical outcomes and response to antiviral treatment in hepatitis B patients. Viral genotype detection and quantification assays are currently in use with different levels of effectiveness. In this study, the performance of a real-time genotyping and quantitative PCR (GQ-PCR)-based assay was evaluated. Through the use of genotype-specific primers and probes, this assay provides simultaneous identification and quantification of genotypes B and C in a single reaction. Our GQ-PCR correctly identified all predefined genotypes B and C, and no cross-reaction between genotypes B and C were observed. The GQ-PCR identified more cases of HBV infections with mixed genotypes B and C than direct sequencing did. Samples from 127 HBV-infected Chinese patients were genotyped with GQ-PCR, revealing 56.7% HBV as genotype B, 13.4% as genotype C, and 29.8% as mixed genotypes B and C. This assay provides a reliable, efficient, and cost-effective means for quantification of the B and C genotypes of HBV in single or mixed infections. This assay is suitable for sequential monitoring of viral load levels and for determining the relationship between the genotype viral load and stage of disease in Asians.
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DNA Viral/genética , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/virologia , Reação em Cadeia da Polimerase/métodos , Carga Viral , Primers do DNA/genética , DNA Viral/química , Genótipo , Humanos , Dados de Sequência Molecular , Sondas de Oligonucleotídeos/genética , Sensibilidade e Especificidade , Análise de Sequência de DNARESUMO
In the title complex, [Cu(C(7)H(5)O(2))(C(12)H(8)N(2))(2)]Cl·2C(6)H(5)CO-OH, the Cu(II) ion is coordinated by one carboxyl-ate O atom from a benzoate anion and four N atoms from two phenantroline ligands in a distorted five-coordinate trigonal-bipyramidal CuON(4) chromophore. The Cu(2+) and the Cl(-) ion are imposed by a twofold rotation axiss which also bisects the equally disordered benzoate anion. In the crystal, the mol-ecules are assembled into chains along [010] by C-Hâ¯Cl, O-Hâ¯Cl and C-Hâ¯O hydrogen-bonding inter-actions. The resulting chains are further connected into two-dimensional supra-molecular layers parallel to [100] by inter-chain πâ¯π stacking inter-actions [centroid-centroid distance = 3.823â (5)â Å] between the phenanthroline ligands and the benzoic acid mol-ecules, and by C-Hâ¯O hydrogen-bonding inter-actions. Strong πâ¯π stacking inter-actions between adjacent phenantroline ligands [3.548â (4)â Å] assemble the layers into a three-dimensional supra-molecular architecture.
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AIM: Data are limited on clinical characteristics and outcomes of recovered the 2019 coronavirus disease (COVID-19) patients with the reoccurrence of SARS-CoV-2 RNA. PATIENTS & METHODS: Discharged patients in our hospital were included, who had recovered from COVID-19 with the reoccurrence of SARS-CoV-2 RNA. RESULTS: Six patients were redetectable and positive for SARS-CoV-2 RNA after discharge from 3 to 15 days. The main symptoms, although no fever, included fatigue, dry cough and pharyngeal or chest discomfort, which were generally milder in the repositive period compared with the period of initial infection. Their laboratory indexes were significantly improved compared with the initial infection, and the pulmonary lesions were continuously improving. All close contacts were SARS-CoV-2 RNA-negative. CONCLUSION: No worsening outcomes or active transmission to close contacts were found for the repositive COVID-19 patients.
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BACKGROUND: Since December 2019, a new outbreak of the coronavirus disease 2019 (COVID-19) in Wuhan (Hubei, China) and rapidly spread throughout China, however, confirmed cases are still increasing worldwide. OBJECTIVES: To investigate the epidemiological history and initial clinical characteristics of 10 patients with family aggregation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Western Chongqing, China. STUDY DESIGN: Ten patients positive for SARS-CoV-2 nucleic acid detection by real time Reverse Transcription-Polymerase Chain Reaction (RT-PCR), were collected from The People's Hospital of Dazu District, Chongqing. Epidemiological data and laboratory and imaging results were collected on the first day of admission, and analyzed based on the Diagnosis and Treatment Guideline for COVID-19 (5th edition, China). RESULTS: Of the 10 cases, case A had a history of a temporary stay in Wuhan and transmitted the virus to the others through family gathering, living together, and sharing vehicles. The average age was 56.5 years (± 11.16), six patients were males, and the incubation period was 2-14 days. Dry cough was the main symptom, followed by fever and fatigue. Most patients were clinically classified as ordinary-type, with three cases being severe-type. Chest computed tomography results were nonspecific, mainly with ground-glass attenuation and/or shadow images. Extensive lesion distribution was seen in severe cases. CD4+ lymphocyte counts were 61, 180, and 348 cells/uL in severe-type patients, respectively. Notably, viral nucleic acid values in nasopharyngeal swabs were lower (19, 25, and 26) than those of ordinary-type patients, suggesting a higher viral load. Neutrophil-lymphocyte ratio (NLR) was also higher in severe-type patients CONCLUSIONS: Initial examination results of lower CD4+ lymphocyte counts and RT-PCR-CT values coupled with higher NLR may indicate the severity of COVID-19 infection for these family clusters.
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Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Saúde da Família , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Idoso , Betacoronavirus , Contagem de Linfócito CD4 , COVID-19 , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Tosse/virologia , Feminino , Febre/virologia , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Pandemias , Pneumonia Viral/diagnóstico , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Viagem , Carga ViralRESUMO
BACKGROUND AND AIM: In China, clinical experience with direct-acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C-CORAL is a phase 3, multinational, placebo-controlled, double-blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia-Pacific region and Russia. Here, we report the data from participants enrolled in China. METHODS: Treatment-naive participants with chronic HCV genotype (GT) 1, GT4, or GT6 infection were randomly assigned to receive 50 mg EBR/100 mg GZR for 12 weeks (immediate-treatment group, ITG) or placebo followed by deferred treatment with EBR/GZR (deferred-treatment group, DTG). The primary efficacy end-point was sustained virologic response at 12 weeks after completing treatment (SVR12), and the primary safety end-point was a comparison of safety between participants receiving EBR/GZR and placebo (NCT02251990; Protocol PN-5172-067). RESULTS: A total of 152 participants in China were randomly assigned (ITG, n = 115; DTG, n = 37). SVR12 was achieved in 96.7% (146/151) participants overall and in 97.3% (142/146) of those with GT1b infection. Four participants relapsed (GT1b, n = 3; GT6a, n = 1). Drug-related AEs were reported in 25 (21.7%) and 9 (24.3%) participants receiving EBR/GZR and placebo, respectively; no drug-related serious adverse events (AEs) occurred. Two (1.7%) participants receiving EBR/GZR had late hepatic transaminase elevations. Patient-reported outcomes indicate improved quality of life at follow-up week 4 in participants receiving EBR/GZR compared to placebo. CONCLUSION: EBR/GZR administered for 12 weeks represents a highly effective and safe treatment option for Chinese individuals with HCV GT1 infection.
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OBJECTIVES: There are country and regional variations in the prevalence of hyperuricaemia (HUA). The prevalence of HUA and non-valvular atrial fibrillation (NVAF) in southern China is unknown. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: A total of 11 488 permanent residents aged 35 or older from urban and rural areas of Guangzhou, China were enrolled. A questionnaire was used to compile each participant's demographic information and relevant epidemiological factors for HUA and NVAF. All participants were assessed using a panel of blood tests and single-lead 24-hour ECG. MAIN OUTCOME MEASURES: HUA was defined as serum uric acid level >420 µmol/L in men and >360 µmol/L in women. NVAF was diagnosed as per guidelines. RESULTS: The prevalence of HUA was 39.6% (44.8% in men and 36.7% in women), and 144 residents (1.25%) had NVAF. Prevalence of HUA increased with age in women but remained stably high in men. After adjusting for potential confounders, age, living in urban areas, alcohol consumption, central obesity, elevated fasting plasma glucose level, elevated blood pressure, lower high-density lipoprotein cholesterol level and elevated triglycerides level were associated with increased risk of HUA. Residents with HUA were at higher risk for NVAF. Serum uric acid level had a modest predictive value for NVAF in women but not men. CONCLUSIONS: HUA was highly prevalent among citizens of southern China and was a predictor of NVAF among women.
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Fibrilação Atrial/epidemiologia , Hiperuricemia/epidemiologia , Distribuição por Idade , China/epidemiologia , Análise por Conglomerados , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Saúde da População Rural/estatística & dados numéricos , Distribuição por Sexo , Saúde da População Urbana/estatística & dados numéricosRESUMO
BACKGROUND: QacA, a main exporter mediating the multidrug-resistance of Staphylococcus aureus to a variety of antiseptics and disinfectants, possesses a topology of 14 alpha-helical transmembrane segments (TMS). Our study aimed to determine the importance and topology of amino acid residues in and flanking the cytoplasmic end of TMS5. METHODS: Site-directed mutagenesis was used to mutate 5 residues, including L146, A147, V148, W149 and S150, into cysteine. A minimum inhibitory concentration (MIC) and transport assay with or without N-ethylmaleimide (NEM) were performed to analyse the function of these mutants. RESULTS: All of the mutants showed comparable protein expression levels. MIC analysis suggested that mutant W149C showed low resistance levels to the drugs, but the mutations at L146, A147, V148, and S150C had little or no effect on the resistance level. And the results of the fluorimetric transport assay were in agreement with those of MIC analysis, that is to say, W149C did not allow transport to the substrates to be tested, while the other mutants retained significant transport ability. The reaction of the different mutant proteins with Fluorescein-NEM revealed that the mutant L146C was highly reactive with NEM; the W149C and S150C mutants were moderately reactive; A147C was barely reactive and V148C showed no reactivity. CONCLUSIONS: The study identified that residues W149 and S150 situated at the interface of the aqueous: lipid junction as functionally important residues, probably involved in the substrate binding and translocation of QacA.
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Proteínas de Bactérias/fisiologia , Farmacorresistência Bacteriana , Proteínas de Membrana Transportadoras/fisiologia , Proteínas de Bactérias/química , Etilmaleimida/farmacologia , Indóis/metabolismo , Proteínas de Membrana Transportadoras/química , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To establish a set of suitable and reliable methods for HBV genotyping and to study the distribution of HBV genotypes. METHODS: Type-specific nucleotides were searched through alignment of S genes (more than 1000 sequences) listed in GenBank. Then, type-specific primers were designed and type-specific primer PCR was used to genotype the 238 HBV strains. S genes of the untyped strains were further amplified and sequenced to find out their genotypes with type-specific nucleotide analysis. RESULTS: All the 238 HBV strains were genotyped. 159 (66.8%) cases were genotype B, 69 (28.9%) were genotype C, 6 (2.5%) were mixtures of genotypes B and C and 4 (1.6%) were mixtures of genotypes B and D. No genotypes of A, E, F, G, and H were found. CONCLUSION: Genotypes B and C are the most common types for HBV strains. Mixtures of genotypes B and C or genotypes B and D coinfection rarely existed. There is no relationship between the gender of the patients and HBV genotypes (X2 = 0.794, P more than 0.05).
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Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Nucleotídeos/genética , Primers do DNA , DNA Viral/sangue , DNA Viral/genética , Feminino , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNARESUMO
OBJECTIVE: To investigate the role of HBV genotypes on their response to adefovir dipivoxil (ADV) antiviral therapy. METHODS: HBV genotypes from 177 HBeAg-positive chronic hepatitis B (CHB) patients were identified and the patients were treated with ADV 10 mg per day for 48 weeks. The clinical data in terms of serum HBV DNA seroclearance, mean HBV DNA reduction (log value), HBeAg loss, anti-HBe seroconversion and serum ALT of those patients were analyzed against their HBV genotypes. RESULTS: Genotype B and genotype C were found in 102 and 65 cases, respectively. The mean HBV DNA reduction in patients with genotype B and genotype C at their treatment times of 12, 24 and 48 weeks was 2.2 log10copies/ml, 2.1 log10copies/ml (P more than 0.05), 2.7 log10copies/ml, 2.4 log10copies/ml (P more than 0.05) and 3.6 log10copies/ml, 3.1 log10copies/ml (P less than 0.05), respectively. At the end of the therapy (48 weeks), 43 (42.2%) patients with genotype B HBV infection and 22 (33.8%) patients with genotype C HBV infection had achieved HBV DNA seroclearance (P less than 0.05). CONCLUSIONS: Our results suggest that genotype B HBV has a better virological response to ADV therapy in HBeAg-positive chronic hepatitis B patients than that of genotype C. Longer terms of ADV treatment are needed to confirm this conclusion.
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Adenina/análogos & derivados , Antivirais/farmacologia , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Organofosfonatos/farmacologia , Adenina/farmacologia , Adenina/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , DNA Viral , Feminino , Genótipo , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To construct a hyaluronidase (hyl) gene mutant strain of Enterococcus faecium and to study the function of hyl gene. METHODS: An isogenic hyl-deficient mutant (*hyl) with suicide plasmid pTX4577 was constructed and screened by allelic replacement. The mutant strain and wild type strain TX2466 were cultured to observe the growth curves. Both *hyl and TX2466 strains were cultured in solid with kanamycin (KAN) to detect the tolerance to KAN. The study of virulence in mice peritonitis and rabbit endocarditis models in vivo were made. RESULTS: A mutant strain, *hyl, was selected by KAN and identified by PCR, pulsed field gel electrophoresis, and Southern blotting. The growth ability of the *hyl strain was remarkably reduced in comparison with the wide-type strain. The survival rate of the mice within 100 h after the inoculation of Enterococcus faecium. TX2466 was 0, significantly lower than that of the *hyl group (50%, P<0.01). The numbers of colonies in the aortic valve and ventricular wall vegetations of the TX2466 group rabbits were (3.04+/-0.63)x10(6) and (6.87+/-0.58)x10(6) CFU/g respectively, both significantly higher than those of the *hyl group [(0.21+/-0.06)x10(6) and (0.66+/-0.05)x10(6) CFU/g respective, both P<0.01]. CONCLUSION: Probably a major virulence factor of Enterococcus faecalis, hyl gene is important in the pathogenesis of this bacterium.