RESUMEN
Several scores have been proposed in untreated or treated patients with chronic hepatitis B (CHB) to predict risks of hepatocellular carcinoma (HCC) occurrence. However, it is still unclear which score suits all chronic hepatitis B virus (HBV)-infected patients well, regardless of whether they are chronic carriers or CHB patients. In this study, we validated and compared the predictability of CU-HCC, REACH-B, PAGE-B and mPAGE-B in patients with chronic HBV infection in China. 1,786 patients with no history of HCC were recruited, with 978 carriers and 808 CHB patients on antiviral therapy. Patients were classified into low- and high-risk groups according to the predefined cut-off values of 5, 8, 10 and 9 for CU-HCC, REACH-B, PAGE-B and mPAGE-B. The median follow-up period was 43.7months, during which 18 (1.0%) patients developed HCC. The areas under the receiver operating characteristic curves (AUROCs) of CU-HCC, REACH-B, PAGE-B and mPAGE-B scores to predict HCC risk at 36 months were 0.815, 0.703, 0.794 and 0.825, respectively (all p < 0.05). No significant difference among AUROCs of these scores was observed except those of mPAGE-B and REACH-B at 36 months. The cumulative incidence of HCC in low- and high- risk groups based on CU-HCC, REACH-B, PAGE-B and mPAGE-B were 0.4% vs. 3.2%, 0.7% vs. 1.5%, 0.2% vs. 1.3%, and 0.2% vs. 1.7% at 36 months, respectively (all p < 0.05, except PAGE-B, log-rant test). Both CU-HCC and mPAGE-B scores accurately predict HCC risk in Chinese chronic HBV-infected patients. Patients with CU-HCC <5 or mPAGE-B <9 could be exempt from HCC surveillance within 36 months.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/epidemiología , China/epidemiología , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/epidemiología , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND Hepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be an ideal endpoint for antiviral therapy and a final therapeutic target for chronic hepatitis (CHB). This study aimed to evaluate the HBsAg kinetics in CHB patients during peginterferon-alpha (Peg-IFN-alpha) treatment. MATERIAL AND METHODS A retrospective cohort study was performed using a case database, which included 151 patients who received Peg-IFN-alpha treatment and with HBsAg load of no less than 4 time points from May 1, 2018 to January 31, 2019. The HBsAg kinetic pattern was analyzed by Q-type clustering, and a clinical prognostic empirical model was constructed based on the HBsAg kinetic pattern of uncured patients. RESULTS Changes of HBsAg in 13 functionally cured patients were attributed to 3 kinetic patterns by cluster analysis, and there was a significant positive correlation between functionally cure time and baseline HBsAg. For uncured 116 patients with treatment duration longer than or equal to 56 days, 5 HBsAg kinetic patterns were obtained by cluster analysis, and the clinical prognosis empirical model was established. Finally, 13 new functionally cured patients preliminarily confirmed the rationality of the proposed empirical model. CONCLUSIONS According to empirical model, we recommend that the therapeutic regime should be timely adjusted to improve sustained response rate and reduce patients' medical burden for patients with second (Z type) and fifth (Z+W type) kinds of patterns. While for the rest of patterns' patients, it is recommended to continue treatment for a longer period of time to achieve the desired therapeutic goal.
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Antivirales/uso terapéutico , Duración de la Terapia , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica/tratamiento farmacológico , Interferón alfa-2/uso terapéutico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Adulto , Análisis por Conglomerados , Femenino , Hepatitis B Crónica/sangre , Humanos , Cinética , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
To explore the effect and persistent effect of thiolated montmorillonite (TM) on safe production in cadmium (Cd) contaminated cropland, a two-year field experiment was conducted with different application amounts of TM. By adding to highly contaminated soils containing 2.46-3.81 mg·kg-1 Cd with no replenishment, the impacts of TM on concentrations of Cd in different parts of rice and available Cd in soils were investigated. The results showed that TM could significantly reduce the contents of Cd in brown rice as well as the contents and proportions of available Cd in soils, and its persistent effects on the passivation of Cd were obvious. After applying 0.5% or 1% TM to soils, the contents of Cd in different parts of the rice decreased significantly in the first season compared with that in the control. The contents of Cd in brown rice in the first season decreased to 0.16 mg·kg-1 and 0.08 mg·kg-1, respectively, by 84.0% and 91.9% compared with that of the control (0.98 mg·kg-1). Contents of Cd in brown rice were significantly lower than the maximum allowable amount (0.2 mg·kg-1) set by China (GB 2762-2017). Under the 0.5% and 1% treatments, the contents of Cd in brown rice of the subsequent three seasons under successive planting decreased by 50.2%-67.8% and 56.0%-81.6%, respectively, which were within the allowable amount. The proportions of available Cd in soils in the first season decreased from 48.4% under the control to 27.9% and 18.4%, respectively, which decreased by 20.5% and 29.9% under the 0.5% and 1% treatments. Compared with that in the control, proportions of available Cd in soils of the following three seasons decreased by 10.0%-17.1% and 12.4%-20.8%. There was a significant positive correlation between available Cd contents in soils and Cd contents in various parts of the rice. TM mainly reduced available Cd contents in soils, then reduced the absorption and accumulation of Cd in rice. The results of the two-year field experiment showed significant and continuous effects of TM on inhibiting Cd uptake by rice, which could be applied to the safe production in heavily Cd contaminated cropland.
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Oryza , Contaminantes del Suelo , Cadmio/análisis , Bentonita , Contaminantes del Suelo/análisis , Suelo , Productos AgrícolasRESUMEN
Two conjugated polymers (CPs) P-tCzC12 and P-tCzC16 comprising alternating dithieno[3,2-b:6,7-b]carbazole and 4,4'-dihexadecyl-2,2'-bithiophene units have been designed and synthesized. Upon thermal annealing, they can form ordered thin films in which the polymer backbones dominantly adopted an edge-on orientation respective to the substrate with a lamellar spacing of ≈24 Å and a π-stacking distance of ≈3.7 Å. Organic thin-film transistors (OTFTs) were fabricated by solution casting. A hole mobility of 0.39 cm(2) V(-1) s(-1) has been demonstrated with P-tCzC16. This value is the highest among the CPs containing heteroacenes larger than 4 rings.
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Carbazoles/química , Polímeros/química , Transistores Electrónicos , Soluciones/química , Tiofenos/químicaRESUMEN
The seroprevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) in Chinese patients with chronic hepatitis B, the relationship between KSHV and hepatitis B virus (HBV) infection, and the influence of glycyrrhizic acid on KSHV replication in vivo are undefined. Plasma was collected from 211 patients with chronic hepatitis B. Antibody to KSHV ORF65 was evaluated by ELISA, and real-time PCR was used to quantify KSHV DNA and HBV DNA. The KSHV ORF65 positivity rate in patients with chronic hepatitis B was found to be 28% (59/211): 27.3% (44/161) in males and 30% (15/50) in females (P > 0.05). The seroprevalence of KSHV increased with age until reaching the highest rate (37.1%) in the 31-40 years age group. HBV DNA loads in patients with chronic hepatitis B infected with KSHV were higher than those without KSHV infection (9.2 log (10) IU/ml vs. 7.8 log (10) IU/ml, P < 0.05). The average KSHV DNA loads in patients with HBV genotype B, C, and mixed (B/C) were 409.1, 484.5, and 352 copies/ml, respectively (P > 0.05). Patients treated with glycyrrhizic acid had lower KSHV DNA levels than those without therapy (204.7 copies/ml vs. 533.9 copies/ml, P < 0.05). The KSHV ORF65 positivity rates tended to increase with age, but were not related to gender or HBV genotypes. The data indicated the interaction between KSHV and HBV, and the inhibiting effect of glycyrrhizic acid on KSHV replication in patients with chronic hepatitis B.
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Hepatitis B Crónica/complicaciones , Infecciones por Herpesviridae/epidemiología , Herpesvirus Humano 8/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Pueblo Asiatico , Niño , Preescolar , China/epidemiología , Comorbilidad , ADN Viral/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/inmunología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Plasma/inmunología , Reacción en Cadena de la Polimerasa , Estudios Seroepidemiológicos , Carga Viral , Proteínas Virales/genética , Adulto JovenRESUMEN
BACKGROUND: Telbivudine showed greater antiviral suppression than lamivudine in phase II and III clinical trials. AIMS: The present phase IIIb, randomized, double-blind, multicentre global trial assessed the antiviral efficacy and safety of telbivudine switch in chronic hepatitis B (CHB) patients who exhibited persistent viraemia under lamivudine therapy. METHODS: HBeAg-positive and HBeAg-negative adult patients (N=246) with persistent viraemia [hepatitis B virus (HBV) DNA>3 log(10) copies/ml] under lamivudine treatment for 12-52 weeks were randomized (1:1) to continue lamivudine 100 mg/day or switch to telbivudine 600 mg/day for 1 year. Primary endpoint was the reduction in serum HBV DNA levels from baseline at Week 24. RESULTS: The mean reduction in serum HBV DNA levels from baseline with telbivudine was significantly higher than lamivudine at Week 24 (-1.9 ± 0.18 vs. -0.9 ± 0.27 log(10) copies/ml; P<0.001) and maintained through 1 year. The rate of treatment failure was significantly lower (P<0.001) for patients who switched to telbivudine (5%) compared with those who continued lamivudine (20%) after 52 weeks of treatment. In the telbivudine group, treatment failure occurred in only five patients with >24 weeks of prior lamivudine treatment, all associated with pre-existent lamivudine-resistant mutations. Genotypic resistance rates were higher in patients continuing lamivudine compared with those who switched to telbivudine with <24 weeks of lamivudine exposure. Both treatments were well tolerated with similar safety profiles. CONCLUSIONS: Early (≤ 24 weeks) switch to telbivudine improves virological outcomes in CHB patients with persistent viral replication under lamivudine treatment.
Asunto(s)
Antivirales/administración & dosificación , Sustitución de Medicamentos , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/administración & dosificación , Nucleósidos/administración & dosificación , Pirimidinonas/administración & dosificación , Adulto , Antivirales/efectos adversos , Biomarcadores/sangre , Distribución de Chi-Cuadrado , ADN Viral/sangre , Método Doble Ciego , Esquema de Medicación , Farmacorresistencia Viral/genética , Femenino , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/diagnóstico , Humanos , Lamivudine/efectos adversos , Masculino , Nucleósidos/efectos adversos , Pirimidinonas/efectos adversos , Telbivudina , Timidina/análogos & derivados , Factores de Tiempo , Resultado del Tratamiento , Carga Viral , Replicación ViralRESUMEN
White teeth can make people full of confidence and satisfy the concept of modern life from the love of beauty. Due to the fusion of computer-aided design and teeth, invisible orthodontics has become the focus of research. Invisible orthodontic treatment technology can predict the results of orthodontics. How to automatically calculate the position and posture of the teeth in the middle stage of orthodontics is the key point of the treatment technology. In order to solve this problem, this article is divided into two parts to start research. Aiming at the problem of tooth orthodontic path planning, quaternion is used to define the tooth posture, combined with the initial posture and target posture of the tooth. A two-stage method is given to plan a collision-free path for the orthodontic tooth. In the first stage, the quaternion spherical linear interpolation and position linear interpolation are used to obtain the intermediate posture of the tooth during orthodontics, and the initial value of the orthodontic stage is obtained, and the obtained intermediate posture is used as a sampling node to apply to the next stage. In the second phase, considering the problem of orthodontic collision and interference, a scheme for calculating the priority of orthodontics is proposed, and the random node expansion part in the RRT (Rapid-exploration Random Tree) algorithm is improved. The initial value of the orthodontic phase is used to calculate the initial value of the iteration. Finally, a path with no collision and the least number of orthodontic stages is searched from the random tree of each tooth node. The experimental results and analysis show that this method can quickly and effectively solve the orthodontic path of teeth, and it is used clinically. The clasp-free invisible correction technology pushes the molars far away to leave gaps for treating patients with mild to moderate overcrowding. The treatment time should be reduced by at least 30%; the stability of the gaps and the long-term healing effect of the treatment provide a reference.
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Ortodoncia , Dispositivos Electrónicos Vestibles , Humanos , Diente Molar , Lengua , Técnicas de Movimiento DentalRESUMEN
BACKGROUND: Reducing hepatitis B virus (HBV) replication to minimal levels is emerging as a key therapeutic goal for chronic hepatitis B. METHODS: In this double-blind, phase 3 trial, 1370 patients with chronic hepatitis B were randomly assigned to receive 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy end point was noninferiority of telbivudine to lamivudine for therapeutic response (i.e., a reduction in serum HBV DNA levels to fewer than 5 log10 copies per milliliter, along with loss of hepatitis B e antigen [HBeAg] or normalization of alanine aminotransferase levels). Secondary efficacy measures included histologic response, changes in serum HBV DNA levels, and HBeAg responses. RESULTS: At week 52, a significantly higher proportion of HBeAg-positive patients receiving telbivudine than of those receiving lamivudine had a therapeutic response (75.3% vs. 67.0%, P=0.005) or a histologic response (64.7% vs. 56.3%, P=0.01); telbivudine also was not inferior to lamivudine for these end points in HBeAg-negative patients. In HBeAg-positive and HBeAg-negative patients, telbivudine was superior to lamivudine with respect to the mean reduction in the number of copies of HBV DNA from baseline, the proportion of patients with a reduction in HBV DNA to levels undetectable by polymerase-chain-reaction assay, and development of resistance to the drug. Elevated creatine kinase levels were more common in patients who received telbivudine, whereas elevated alanine aminotransferase and aspartate aminotransferase levels were more common in those who received lamivudine. CONCLUSIONS: Among patients with HBeAg-positive chronic hepatitis B, the rates of therapeutic and histologic response at 1 year were significantly higher in patients treated with telbivudine than in patients treated with lamivudine. In both the HBeAg-negative and the HBeAg-positive groups, telbivudine demonstrated greater HBV DNA suppression with less resistance than did lamivudine. (ClinicalTrials.gov number, NCT00057265 [ClinicalTrials.gov].).
Asunto(s)
Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Nucleósidos/uso terapéutico , Pirimidinonas/uso terapéutico , Adolescente , Adulto , Anciano , Antivirales/efectos adversos , ADN Viral/sangre , ADN Viral/clasificación , Método Doble Ciego , Farmacorresistencia Viral/genética , Femenino , Genotipo , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Humanos , Lamivudine/efectos adversos , Masculino , Persona de Mediana Edad , Mutación , Nucleósidos/efectos adversos , Pirimidinonas/efectos adversos , Telbivudina , Timidina/análogos & derivadosRESUMEN
BACKGROUND & AIMS: The GLOBE trial has compared the efficacy and safety of telbivudine versus lamivudine treatment over 2 years in patients with chronic hepatitis B. METHODS: Hepatitis B e antigen (HBeAg)-positive (n = 921) and HBeAg-negative (n = 446) patients received telbivudine or lamivudine once daily for 104 weeks. The primary outcome, assessed in the intent-to-treat population, was therapeutic response (hepatitis B virus DNA <5 log(10) copies/mL and either HBeAg loss or normalization of alanine aminotransferase [ALT] level). RESULTS: The therapeutic response to telbivudine was superior to that of lamivudine in HBeAg-positive (63% vs 48%; P < .001) and HBeAg-negative (78% vs 66%; P = .007) patients. HBeAg-positive patients given telbivudine also had better outcomes compared with lamivudine in terms of nondetectable viremia (< 300 copies/mL) at 55.6% versus 38.5% (P < .001), HBeAg loss at 35.2% versus 29.2% (P = .056), and viral resistance at 25.1% versus 39.5% (P < .001). Hepatitis B e antigen seroconversion was 29.6% versus 24.7% (P = .095) in all patients and 36% versus 27% (P = .022) in patients with baseline ALT level > or = 2 times normal. Telbivudine-treated HBeAg-negative patients showed higher rates of nondetectable viremia compared with lamivudine at 82.0% versus 56.7% (P < .001) and less resistance at 10.8% versus 25.9% (P < .001). Adverse events occurred with similar frequency, whereas grade 3/4 increases in creatine kinase levels were more common in patients given telbivudine (12.9% vs 4.1%, P < .001). Multivariate logistic regression analyses identified telbivudine treatment, among other variables, as an independent predictor of better week 104 outcomes. CONCLUSIONS: Telbivudine is superior to lamivudine in treating patients with chronic hepatitis B over a 2-year period.
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Antivirales/uso terapéutico , Salud Global , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Nucleósidos/uso terapéutico , Pirimidinonas/uso terapéutico , Adolescente , Adulto , Anciano , Alanina Transaminasa/sangre , Antivirales/efectos adversos , Antivirales/farmacología , ADN Viral/efectos de los fármacos , Método Doble Ciego , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Humanos , Lamivudine/efectos adversos , Lamivudine/farmacología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Nucleósidos/efectos adversos , Nucleósidos/farmacología , Estudios Prospectivos , Pirimidinonas/efectos adversos , Pirimidinonas/farmacología , Análisis de Regresión , Telbivudina , Timidina/análogos & derivados , Resultado del Tratamiento , Replicación Viral/efectos de los fármacos , Adulto JovenRESUMEN
A total of 264 nonduplicate strains of imipenem (IPM)-nonsusceptible Pseudomonas aeruginosa were isolated from hospitals in 16 different regions throughout China. These 264 IPM-nonsusceptible clinical isolates of P. aeruginosa were examined by PCR, a metallo-beta-lactamase (MBL) Etest, a double-disk synergy test (DDST), and a test using combined IPM disks supplemented with various amounts of EDTA. A total of 24 strains positive for MBLs were confirmed by PCR and DNA sequence analysis: 10 strains positive for the bla(VIM-2) gene, 13 strains positive for the bla(IMP-9) gene, and 1 strain positive for the bla(IMP-1) gene. Real-time reverse transcriptase PCR (RT-PCR) was used to verify whether the isolates harboring MBL genes produced the enzyme and was considered the standard for evaluation of the methodology in this study. Of these 24 MBL-positive stains, 21 were confirmed as MBL-producing strains by real time RT-PCR for MBL expression and the other 3 had no expression of MBLs. The sensitivities, specificities, and positive and negative predictive values for the MBL Etest, the DDST, and the combined disk (CD) assay were evaluated. The best method for screening for MBL production in P. aeruginosa strains from China was the CD assay (IMP-EDTA) using 750 microg of EDTA/disk with a breakpoint of >or=6 mm. In the CD assay (IPM-EDTA) with 290 microg and 750 microg EDTA, the zone diameter increases for VIM-2-producing P. aeruginosa isolates were greater than those for IMP-9-producing P. aeruginosa isolates (P = 0.00).
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Antibacterianos/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/enzimología , beta-Lactamasas/biosíntesis , beta-Lactamas/farmacología , China , ADN Bacteriano/genética , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Reacción en Cadena de la Polimerasa/métodos , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/aislamiento & purificación , ARN Bacteriano/biosíntesis , ARN Bacteriano/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , beta-Lactamasas/genéticaRESUMEN
UNLABELLED: Chronic hepatitis B and its life-threatening sequelae are highly prevalent in China. There is a need for effective new therapies to suppress hepatitis B virus (HBV) replication and ameliorate liver disease. In this study, we compared the efficacy of telbivudine, a nucleoside analogue, with lamivudine in Chinese patients. In this phase III, double-blind, multicenter trial conducted in China, 332 patients with compensated hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B were randomly assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine daily for 104 weeks. The primary efficacy endpoint was reduction in serum HBV DNA levels at week 52 of treatment. Secondary endpoints included clearance of HBV DNA to undetectable levels, HBeAg loss and seroconversion, therapeutic response, and alanine aminotransferase (ALT) normalization. Viral resistance and safety were assessed. At week 52, among 290 HBeAg-positive patients, mean reductions of serum HBV DNA were significantly greater in telbivudine recipients than lamivudine recipients (6.3 log(10) versus 5.5 log(10), P < 0.001), and HBV DNA was polymerase chain reaction-negative in significantly more telbivudine recipients than lamivudine recipients (67% versus 38%, P < 0.001). ALT normalization (87% versus 75%, P = 0.007), therapeutic response (85% versus 62%, P = 0.001), and HBeAg loss (31% versus 20%, P = 0.047) were also significantly more common in the telbivudine group. Treatment effects showed similar patterns in the smaller HBeAg-negative group (n = 42). Viral resistance in telbivudine recipients was approximately half that observed with lamivudine; however, this difference was not statistically significant. Clinical adverse events were similar in the two treatment groups. CONCLUSION: In Chinese patients with chronic hepatitis B, telbivudine treatment for 52 weeks provided greater antiviral and clinical efficacy than lamivudine, with less resistance.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Nucleósidos/uso terapéutico , Pirimidinonas/uso terapéutico , Adolescente , Adulto , China , ADN Viral/análisis , Método Doble Ciego , Femenino , Genotipo , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Humanos , Masculino , Persona de Mediana Edad , Telbivudina , Timidina/análogos & derivadosRESUMEN
BACKGROUND: Consensus interferon (CIFN) is a newly developed type I interferon. AIMS: This multicentre, controlled trial was conducted to determine the efficacy of CIFN and to compare it with alpha-1b-interferon (IFN-alpha1b) in the treatment of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. METHODS: 144 Patients were randomly assigned to receive 9 microg CIFN (CIFN group) or 50 microg INF-alpha1b (IFN-alpha group) subcutaneously 3 times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) levels and the non-detectability of serum hepatitis B virus DNA or HBeAg at the end of treatment and 24 weeks after stopping treatment. RESULTS: There was no statistically significant difference in the serological, virological and biochemical parameters between CIFN and IFN-alpha1b groups at the end of the therapy and follow-up period (p > 0.05). Overall, at the end of treatment, 7.0% (5/71) and 35.2% (25/71) of patients in the CIFN group showed a complete or partial response compared with 7.4% (5/68) and 33.8% (23/68) of the IFN-alpha group (p = 0.10). At 24 weeks after stopping treatment, 6.9% (5/72) and 37.5% (27/72) of patients in the CIFN group showed complete response or partial response compared with 7.1% (5/70) and 34.3% (24/70) of the IFN-alpha group (p = 0.10). CONCLUSION: These findings suggest that 9 microg CIFN is effective in the treatment of patients with HBeAg-positive chronic hepatitis B. It can gradually induce ALT normalization and HBV DNA clearance and HBeAg loss or HBeAg/HBeAb seroconversion.
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Antivirales/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/tratamiento farmacológico , Interferón Tipo I/uso terapéutico , Adolescente , Adulto , Alanina Transaminasa/sangre , Antivirales/administración & dosificación , ADN Viral/sangre , Femenino , Virus de la Hepatitis B/efectos de los fármacos , Humanos , Inyecciones Subcutáneas , Interferón Tipo I/administración & dosificación , Interferón-alfa/administración & dosificación , Interferón-alfa/uso terapéutico , Masculino , Proteínas Recombinantes , Resultado del Tratamiento , Adulto JovenRESUMEN
The aim of this study was to investigate the prevalence and characteristics of ACME (arginine catabolic mobile element)-arcA-positive isolates among meticillin-resistant Staphylococcus haemolyticus (MRSH). ACME-arcA, native arcA and SCCmec elements were detected by PCR. Susceptibilities to 10 antimicrobial agents were compared between ACME-arcA-positive and -negative isolates by chi-square test. PFGE was used to investigate the clonal relatedness of ACME-arcA-positive isolates. The phylogenetic relationships of ACME-arcA and native arcA were analysed using the neighbour-joining methods of mega software. A total of 42 (47.7 %) of 88 isolates distributed in 13 PFGE types were positive for the ACME-arcA gene. There were no significant differences in antimicrobial susceptibility between ACME-arcA-positive and -negative isolates. A novel ccr allotype (ccrAB(SHP)) was identified in ACME-arcA-positive isolates. Among 42 ACME-arcA-positive isolates: 8 isolates harboured SCCmec V, 8 isolates harboured class C1 mec complex and ccrAB(SHP); 22 isolates harbouring class C1 mec complex and 4 isolates harbouring class C2 mec complex were negative for all known ccr allotypes. The ACME-arcA-positive isolates were first found in MRSH with high prevalence and clonal diversity, which suggests a mobility of ACME within MRSH. The results from this study revealed that MRSH is likely to be one of the potential reservoirs of ACME for Staphylococcus aureus.
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Arginina , Hidrolasas/genética , Secuencias Repetitivas Esparcidas , Resistencia a la Meticilina , Recombinasas/genética , Staphylococcus haemolyticus , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Electroforesis en Gel de Campo Pulsado , Humanos , Hidrolasas/metabolismo , Resistencia a la Meticilina/genética , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Filogenia , Recombinasas/metabolismo , Análisis de Secuencia de ADN , Infecciones Estafilocócicas/microbiología , Staphylococcus haemolyticus/efectos de los fármacos , Staphylococcus haemolyticus/enzimología , Staphylococcus haemolyticus/genéticaRESUMEN
The susceptibility to triclosan of 732 clinical Acinetobacter baumannii isolates obtained from 25 hospitals in 16 cities in China from December 2004 to December 2005 was screened by using an agar dilution method. Triclosan MICs ranged between 0.015 and 16 mg l(-1), and the MIC(90) was 0.5 mg l(-1), lower than the actual in-use concentration of triclosan. Twenty triclosan-resistant isolates (MICs >or=1 mg l(-1)) were characterized by antibiotic susceptibility, clonal relatedness, fabI mutation, fabI expression, and efflux pump phenotype and expression to elucidate the resistance mechanism of A. baumannii to triclosan. The resistance rates of triclosan-resistant isolates to imipenem, levofloxacin, amikacin and tetracycline were higher than those of triclosan-sensitive isolates. Triclosan resistance was artificially classified as low level (MICs 1-2 mg l(-1)) or high level (MICs >or=4 mg l(-1)). High-level triclosan resistance could be explained by a Gly95Ser mutation of FabI, whilst wild-type fabI was observed to be overexpressed in low-level resistant isolates. Active efflux did not appear to be a major reason for acquired triclosan resistance, but acquisition of resistance appeared to be dependent on a background of intrinsic triclosan efflux.
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Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Triclosán/farmacología , Acinetobacter baumannii/genética , Proteínas Bacterianas/genética , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Regulación Bacteriana de la Expresión Génica/fisiología , Pruebas de Sensibilidad Microbiana , MutaciónRESUMEN
BACKGROUND: Sepsis due to Enterobacter aerogenes (E. aerogenes) is rare after liver transplantation but is also a serious infection that may cause liver abscess. The purpose of this case report is to relate an unusual presentation of liver transplantation to show how successive treatment can be an appropriate option in septic patients after liver transplantation. METHOD: We report on a patient with liver transplantation who developed sepsis due to extended spectrum beta-lactamases and AmpC-producing E. aerogenes. RESULTS: A 39-year-old man had a biliary fistula and then was found to have multiple liver abscesses through abdominal ultrasound and an abdominal computed tomography scan, and carbapenem-sensitive E. aerogenes infection was confirmed. The patient was not successfully treated with conservative treatment consisting of intravenous carbapenems, percutaneous transhepatic cholangial drainage, and biliary stent placement by endoscopic retrograde cholangiopancreatography, so a second liver transplantation followed. Carbapenem-resistant E. aerogenes was detected in bile and blood after a five-week course of carbapenem therapy. The patient developed septic shock and multiple organ dysfunction syndrome. CONCLUSIONS: We first report an unusual case of sepsis caused by E. aerogenes after liver transplantation in China. Carbapenem-resistant E. aerogenes finally leads to uncontrolled sepsis with current antibiotics. We hypothesize that the infection developed as a result of biliary fistula and predisposing immunosuppressive agent therapy. Further research is progressing on the aspect of immunomodulation therapy.
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Carbapenémicos/uso terapéutico , Farmacorresistencia Bacteriana , Enterobacter aerogenes/fisiología , Infecciones por Enterobacteriaceae/etiología , Trasplante de Hígado/efectos adversos , Cuidados Posoperatorios , Adulto , Infecciones por Enterobacteriaceae/complicaciones , Humanos , Absceso Hepático/microbiología , Masculino , Insuficiencia Multiorgánica/microbiología , Choque Séptico/microbiologíaRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of Magnesium isoglycyrrhizinate in treatment of chronic liver diseases. METHODS: It is a randomized, double-blind, multi-doses, active drug controlled, multi-center study. 480 proper patients were randomly divided into group A (180 patients), group B (180 patients) or group C (120 patients). Patients in group A received magnesium isoglycyrrhizinate 100 mg once daily. Patients in group B received magnesium isoglycyrrhizinate 150 mg once daily. Patients in group C received compound glycyrrhizin 120 mg once daily. The treatment course was 4 weeks. Patients were followed up 2 weeks after the treatment. Patients visited once every 2 weeks. Clinical symptoms, ALT, AST were evaluated in all the patients before treatment, at week 2, at week 4 and at 2 weeks later after treatment. The other liver function test was done before treatment and at week 4. RESULTS: 412 patients completed the study according to the protocol,152 in group A, 160 in group B and 100 in group C. ALT and AST level were significantly decreased in all groups at week 2 and week 4 (P < 0.05). The degree of ALT decrease is greater in group B than in group C at week 2 (P < 0.01). The degree of ALT decrease was not significant different among three groups at week 4 (P > 0.05). The rates of ALT improvement at week 4 in group A, B, C were 92.59%, 91.76%, 88.29%, respectively (P > 0.05). The rates of symptoms improvement at week 4 in group A, B, C were 90.41%, 89.86%, 86.46% and 72.22%, 73.53%, 68.47%, respectively (P > 0.05). No relapse were found in all three groups after treatment. The rate of adverse event in three groups was similar (P > 0.05). CONCLUSION: Magnesium isoglycyrrhizinate is an effective and safe treatment for chronic liver diseases.
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Alanina Transaminasa/sangre , Antiinflamatorios/uso terapéutico , Ácido Glicirrínico/uso terapéutico , Hepatopatías/tratamiento farmacológico , Saponinas/uso terapéutico , Triterpenos/uso terapéutico , Antiinflamatorios/efectos adversos , Antiinflamatorios/farmacología , Aspartato Aminotransferasas/sangre , Enfermedad Crónica , Método Doble Ciego , Hígado Graso/sangre , Hígado Graso/tratamiento farmacológico , Femenino , Ácido Glicirrínico/efectos adversos , Ácido Glicirrínico/farmacología , Humanos , Inyecciones Intravenosas , Hígado/efectos de los fármacos , Hígado/patología , Hepatopatías/sangre , Hepatopatías Alcohólicas/sangre , Hepatopatías Alcohólicas/tratamiento farmacológico , Masculino , Saponinas/efectos adversos , Saponinas/farmacología , Triterpenos/efectos adversos , Triterpenos/farmacologíaRESUMEN
BACKGROUND: The epidemiology and strain features of Kaposi's sarcoma-associated herpesvirus (KSHV) in transplant recipients and HIV-infected patients in China is not well described. OBJECTIVES: To determine KSHV seroprevalence and characterize strains of KSHV in transplant recipients and HIV-infected patients in China. METHODS: Patients were screened for KSHV infection using a KSHV open reading frame (ORF) 65 recombinant protein-dependent ELISA. The 172bp fragment of KSHV ORF26 was amplified by nested PCR and bilaterally sequenced from KSHV-seropositive peripheral blood mononuclear cells. ORF26 gene diversity and cladograms were analyzed and compared to predominant international strains. RESULTS: KSHV seroprevalence in renal transplant recipients [41% (44/107)] and HIV-infected patients [39% (29/74)] were significantly higher than in healthy people [13% (16/122)] (P<0.01), but KSHV seroprevalence in liver transplant recipients [15% (5/33)] was similar to that of healthy people (P>0.05). ORF26 DNA was detected in 47% (23/49) of KSHV-seropositive organ transplant recipients; 28% (8/29) of KSHV-seropositive HIV-infected patients; and 19% (3/16) of KSHV-seropositive healthy people. Organ transplant recipients had a significantly higher rate of KSHV DNAemia than healthy people (P<0.05). The 13 KSHV strains that were analyzed were genetically close to the Hungary AY707887 strain and belonged to the A3 subtype. CONCLUSIONS: The seroprevalence of KSHV was elevated in renal transplant recipients and HIV-infected patients in China, and KSHV DNAemia was more common in these patients and liver transplant recipients. KSHV strains from Zhejiang Province belonged to the A3 subtype.
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Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/aislamiento & purificación , Polimorfismo Genético , Adulto , Anticuerpos Antivirales/sangre , China/epidemiología , Análisis por Conglomerados , ADN Viral/genética , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Genes Virales , Infecciones por VIH/complicaciones , Herpesvirus Humano 8/genética , Humanos , Trasplante de Riñón/efectos adversos , Leucocitos Mononucleares/virología , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Filogenia , Reacción en Cadena de la Polimerasa/métodos , Análisis de Secuencia de ADN , Estudios Seroepidemiológicos , Trasplante/efectos adversosRESUMEN
Four clinical strains of extended-spectrum beta-lactamase- and AmpC-producing Enterobacter aerogenes were isolated successively from a liver transplantation patient. Isolates C(1) and C(2) were isolated prior to carbapenem therapy, whilst isolates C(3) and C(4) were recovered after 40 days of carbapenem therapy. The homology of these strains was analysed by pulsed-field gel electrophoresis (PFGE). beta-Lactamases were analysed by isoelectric focusing, polymerase chain reaction (PCR) and sequencing. Outer membrane proteins were analysed by PCR, sequencing, sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blot. Disruption of OmpE36 in C(1) in vitro was also performed by homologous gene recombination. The isolates demonstrated an indistinguishable PFGE pattern. Molecular characterisation revealed that, in addition to the pre-existing multiple beta-lactamases (DHA-1, TEM-1, SHV-5, CTX-M-3 and CTX-M-14) found in C(1) and C(2), isolates C(3) and C(4) failed to express OmpE36 owing to insertional inactivation by an IS903-like insertion sequence. Other resistance mechanisms, such as production of carbapenem-hydrolysing enzymes or expression of chromosomal efflux, were apparently not involved. Completely replacing OmpE36 by the kanamycin resistance gene (kan) resulted in a significant increase in carbapenem minimum inhibitory concentrations of an ompE36 mutant. Thus, C(3) and C(4) were apparently derived from the previously imipenem-susceptible isolates C(1) and C(2). Following carbapenem exposure, depletion of OmpE36 expression resulted in the collateral effect of carbapenem resistance.
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Carbapenémicos/farmacología , Farmacorresistencia Bacteriana Múltiple , Enterobacter aerogenes/efectos de los fármacos , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Resistencia betalactámica/genética , beta-Lactamasas/biosíntesis , Adulto , Secuencia de Aminoácidos , Proteínas de la Membrana Bacteriana Externa/química , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Bacterianas/biosíntesis , Enterobacter aerogenes/enzimología , Enterobacter aerogenes/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , Resultado Fatal , Humanos , Imipenem/farmacología , Trasplante de Hígado/efectos adversos , Masculino , Meropenem , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Tienamicinas/farmacologíaRESUMEN
An outbreak of 95 clinical infections with imipenem-resistant Acinetobacter baumannii in a Chinese hospital was investigated and the carbapenemase-encoding genes and their relationship with ISAba1 of these and a further 16 isolates recovered from the intensive care unit (ICU) environment were analysed. Almost all isolates were resistant to a wide range of antimicrobials; the lowest resistance rates were found for polymyxin E (17.1 %), cefoperazone/sulbactam (30.6 %) and ampicillin/sulbactam (67.6 %). Six pattern types defined by DNA macrorestriction patterns were distinguished among the clinical isolates with dissemination of pattern A (50 isolates) to patients in seven hospital units and pattern B (35 isolates) to eight units; the environmental isolates from ICUs were also of pattern A. All isolates were positive for the bla(OXA-66) and bla(OXA-23) genes. The OXA-23-encoding gene was located 34 bp downstream of ISAba1. No plasmids were detected and conjugal transfer of resistance was not demonstrated. The bla(OXA-23) probe hybridized with 200 and 220 kb ApaI chromosomal fragments for type patterns A and B, respectively.
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Infecciones por Acinetobacter/epidemiología , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/genética , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Brotes de Enfermedades , Imipenem/farmacología , beta-Lactamasas/genética , China/epidemiología , Farmacorresistencia Bacteriana , Humanos , Unidades de Cuidados Intensivos , Epidemiología Molecular , Datos de Secuencia MolecularRESUMEN
OBJECTIVES: To investigate the possibilities of an association between the degrees of HBV suppression with nucleoside treatments at week 24 and week 52 in hepatitis B patients and to find a useful predictor for treatment efficacy. METHODS: In this phase III, double-blind, multicenter trial, we compared the efficacy of telbivudine treatment with lamivudine treatment in 332 Chinese compensated chronic hepatitis B patients. The patients were randomly assigned to a daily 600 mg telbivudine treatment group or daily 100 mg lamivudine group for 24 weeks. They were then categorized into 4 groups according to their serum HBV DNA levels (copies/ml) at week 24: a PCR-undetectable group (< 300 copies/ml); a QL- < 10(3) copies/ml group; a 10(3)-<10(4) copies/ml group; and a > or = 10(4) copies/ml group. The treatments were continued as they previously had been for another 28 weeks and the patients serum HBV DNA levels were examined again. RESULTS: At week 52, mean reductions of serum HBV DNA were significantly greater in the telbivudine-treated patients than in the lamivudine-treated group (6.2 log10 vs 5.4 log10, t = 3.6, P < 0.01). Viral resistance was twice as common in lamivudine-treated patients compared to those receiving telbivudine. Telbivudine was well-tolerated with an adverse event profile similar to that of lamivudine. The lower the HBV DNA level achieved at week 24, the higher HBV DNA non-detectable by PCR. ALT normalization and HBeAg seroconversion achieved at week 52, and viral resistance at week 48 decreased parallel to the degree of HBV DNA inhibition. CONCLUSION: HBV DNA PCR-undetectable at week 24 in nucleoside-treated hepatitis B patients suggests a better efficacy at week 52 and lower viral resistance at week 48. The degree of suppression of HBV at week 24 may be used as a predictor of 1-year outcome.