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Objective: Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder caused by abnormal glucose metabolism during pregnancy. Trophoblast dysfunction induced by hyperglycemia during pregnancy is the main factor leading to the development of GDM. In this study, we evaluated the expression of miR-942-5p in the placenta of patients with GDM and its regulation of trophoblast cell biological function. Methods: HTR-8/SVneo trophoblast cells were incubated with glucose to establish in vitro models, and miR-942-5p mimics transfected cells were added. The expression levels of miR-942-5p, CCAAT-enhancer-binding protein alpha (CEBPA) and N-cadherin in tissues and cells were detected by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), protein blotting and immunohistochemistry (IHC). MTT, flow cytometry and Transwell assays were used to determine changes in cell proliferation, apoptosis and invasion. Dual-luciferase reporter assay and Pearson analysis were used to confirm the association between miR-942-5p and CEBPA. Results: miR-942-5p and N-cadherin were decreased in placental tissue and in human placental trophoblast cells (HTR-8/SVneo) exposed to high glucose (HG) conditions, while CEBPA was increased in placental tissue and HTR-8/SVneo exposed to HG conditions. Elevated levels of miR-942-5p suppressed apoptosis induced by HG and facilitated the proliferative and invasive capacities of HTR-8/SVneo. Mechanistically, we confirmed that miR-942-5p overexpression directly targeted CEBPA and suppressed CEBPA expression, while upregulating N-cadherin expression, which is involved in the EMT process of trophoblast cells and alleviated the dysfunction of trophoblast cells induced by HG in GDM. Conclusion: Overexpression of miR-942-5p promotes proliferation, invasion and EMT of trophoblast cells by targeting and negatively regulating CEBPA. These findings offer novel understanding regarding the treatment of GDM.
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BACKGROUND: Preeclampsia (PE) is one of the leading causes of maternal mortality and placental trophoblastic disorders. Recent studies reported that circular RNAs (circRNAs) were involved in PE pathogenesis. However, the role of circ_0001861 in PE progression is largely unknown. METHODS: The RNA expression of circ_0001861, forkhead box protein 1 (FOXP1) and microRNA-296-5p (miR-296-5p) was detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Western blot assay was performed to examine the protein levels of FOXP1 and epithelial-mesenchymal transition (EMT) markers. Cell viability, proliferation, migration and invasion were detected by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and transwell assays. Luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation (RIP) assay were conducted to explore the interaction between miR-296-5p and circ_0001861 or FOXP1. RESULTS: Circ_0001861 and FOXP1 were downregulated but miR-296-5p was upregulated in PE placenta. Upregulation of circ_0001861 facilitated trophoblast cell proliferation, migration, invasion and EMT. Mechanistically, circ_0001861 sponged miR-296-5p to elevate FOXP1 expression, thus promoting trophoblast cell progression. CONCLUSION: The circ_0001861/miR-296-5p/FOXP1 axis plays a critical role in trophoblast cell proliferation, migration, invasion and EMT, which may provide a novel insight into developing potential therapeutic targets for PE.
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MicroARNs , Preeclampsia , Embarazo , Humanos , Femenino , Placenta , Preeclampsia/genética , Trofoblastos , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Factores de Transcripción Forkhead , MicroARNs/genética , Movimiento Celular/genética , Proteínas RepresorasRESUMEN
Convergence of mcr and carbapenemase genes has been sporadically detected in Enterobacter cloacae complex (ECC) with an upward trend. However, the state of the epidemic and underlying mechanism of such convergence has been poorly understood. In this study, the co-occurrence of MCR and carbapenemases was systematically analyzed in 230 clinical ECC isolates collected between 2000 and 2018 together with a global dataset consisting of 3,559 ECC genomes compiled from GenBank. We identified 48 mcr-9/mcr-10-positive isolates (MCR-ECC) (20.9%) in our collection, and a comparable ratio of MCR-ECC (720/3559, 20.2%) was detected in the global dataset. A high prevalence of carbapenemase-producing MCR-ECC (MCR-CREC) was further identified in the MCR-ECC of both datasets (16/48, 33.3%; 388/720, 53.9%), demonstrating a frequent convergence of mcr-9/10 and carbapenemase genes in ECC worldwide. An epidemic IncHI2/2A plasmid with a highly conserved backbone was identified and largely contributed to the dissemination of mcr-9 in ECC worldwide. A highly conserved IncX3-type NDM-1-carrying plasmid and IncN-type IMP-4-carrying plasmid were additionally detected in MCR-CREC isolated in China. Our surveillance data showed that MCR-CREC emerged (in 2013) much later than MCR-ECC (in 2000), indicating that MCR-CREC could be derived from MCR-ECC by additional captures of carbapenemase-encoding plasmids. Tests of plasmid stability and incompatibility showed that the mcr-9/mcr-10-encoding plasmids with the NDM-1-encoding plasmids stably remained in ECC but incompatible in Escherichia coli, suggesting that the convergence was host-dependent. The findings extend our concern on the convergence of resistance to the last resort antibiotics and highlight the necessity of continued surveillance in the future.
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Enterobacteriaceae Resistentes a los Carbapenémicos , Enterobacter cloacae , Antibacterianos/farmacología , Proteínas Bacterianas , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Farmacorresistencia Bacteriana/genética , Enterobacter cloacae/genética , Escherichia coli/genética , Pruebas de Sensibilidad Microbiana , Plásmidos/genética , beta-Lactamasas/genéticaRESUMEN
BACKGROUND: The use of antibiotic adjuvants is a complementary strategy to the development of new antibiotics. The essential role of the ArnA dehydrogenase domain (ArnA_DH) in the addition of 4-amino-L-arabinose (L-Ara4N) to lipid A makes it a potential target in polymyxin adjuvant design. PURPOSE: This study aimed to identify a dehydrogenase inhibitor that enhances the antibacterial effect of polymyxin B (PB) and to further understand the mechanism of this drug combination. METHODS: A susceptible K. pneumoniae strain, ATCC13883, was used to screen a dehydrogenase inhibitor library based on 3-(4,5)-dimethylthiazol(-z-y1)-2,5-diphenyltetrazolium bromide (MTT) and chequerboard assays. The protein- and cell-based effects of disulfiram (DSF) on ArnA activity were assessed, and the transcription levels of genes in the arn operon were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Lipid A was isolated, and a structural analysis was performed. The cell wall function was evaluated through membrane integrity and bacterial viability assays. The in vivo antibacterial activity was evaluated using a mouse pulmonary infection model. RESULTS: We screened a dehydrogenase inhibitor library and found that the anti-alcoholism drug DSF significantly enhanced the antibacterial activity of PB in vitro and in vivo. The protein-based enzyme activity assay showed that DSF exerted no direct effect on the dehydrogenase activity of ArnA. Treatment with the combination of DSF and PB but not with PB alone decreased both the transcription level of genes in the arn operon and the modification level of lipid A. DSF also strengthened the disruption of the cell membrane integrity of PB. Moreover, the enhanced PB antibacterial activity was effective against clinical PB-resistant strains. CONCLUSION: We identified a new drug combination that can be used to reduce the necessary dosage of PB and overcome PB resistance, and this drug combination has good prospects for clinical application.
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The ability of VITEK mass spectrometry (MS) in detection of bacterial resistance is currently under exploration and evaluation. In this study, we developed and validated a VITEK MS method to rapidly test carbapenemase-producing Klebsiella pneumoniae (CPKP). Solvents, antibiotic concentrations, crystal conditions and times, centrifugation speeds, and other factors were optimized to design a rapid sample pretreatment process for CPKP detection by VITEK MS. The related parameters of the mass spectrum were adjusted on the instrument to establish an CPKP detection mode. 133 clinically isolated strains of CPKP in the microbiology laboratory at the Shenzhen People's Hospital from 2004 to 2017 were selected for accuracy evaluation. The fresh suspected strains from the microbiology laboratory in 2020 were used to complete the clinical verification. Two antibiotics, meropenem (MEM) and imipenem (IPM), were used as substrates. These two substrates were incubated with suspected CPKP, and the results were obtained by VITEK MS detection. Using this method, different types of CPKP showed different detection results and all the CPKP strains producing KPC-2 and IMP-4 carbapenemase were detected by VITEK MS. Thus, VITEK MS can be used for rapid detection of CPKP, especially for some common types of CPKP. This method provides high accuracy and speed of detection. Combined with its cost advantages, it can be intensely valuable in clinical microbiology laboratories after the standard operating procedures are determined.
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Enterobacteriaceae Resistentes a los Carbapenémicos , Klebsiella pneumoniae , beta-Lactamasas , Antibacterianos/farmacología , Proteínas Bacterianas , Enterobacteriaceae Resistentes a los Carbapenémicos/enzimología , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Klebsiella pneumoniae/enzimología , Klebsiella pneumoniae/aislamiento & purificación , Espectrometría de Masas , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Endometrial carcinoma is a prevalent form of cancer. In fact, its incidence ranks fourth among European and North American females. Moreover, it is the most common gynecological malignant disease. Laparotomy, bilateral salpingo-oophorectomy, total abdominal hysterectomy, etc were common methods adopted in conventional open surgery. Recent developments in laparoscopic surgery (LPS) has made it more effective. The present study aims to compare the outcomes between LPS and a conventional open surgical procedure to treat stage II endometrial carcinoma patients. METHODS: A comprehensive search will be conducted on Cochrane library, PubMed, Web of Science, EMBASE, and China National of Knowledge Infrastructure to collect LPS and conventional open surgery in treating stage II endometrial carcinoma. The search will consider all articles published since the inception of the databases till July 2021. A pair of scholars will perform independent screening of the literature and extracted data to evaluate the bias risk in the selected studies. Afterwards, RevMan5.3 software will be used to conduct a meta-analysis. CONCLUSION: This study will conduct a meta-analysis to compare the clinical efficacy of LPS and conventional open surgery in the treatment of stage II endometrial carcinoma.
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Neoplasias Endometriales , Femenino , Humanos , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Histerectomía , Laparoscopía , Metaanálisis como Asunto , Estadificación de Neoplasias , Complicaciones Posoperatorias , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: ST11 is the most prevalent sequence type of clinical Klebsiella pneumoniae in China. METHODS: We investigated the characteristics of the ST11 subclones using core genome multi-locus sequence typing (cgMLST). Ninety-three carbapenemase-producing K. pneumoniae isolates were collected at Shenzhen People's Hospital. Then, whole-genome sequencing and cgMLST were used to discriminate apparent subclones within the ST11 group. RESULTS: We analyzed the prevalence and genetic relationships of these subclones. ST11 and K. pneumoniae carbapenemase (KPC-2) were the predominant genotype and carbapenemase, respectively, in the clinical carbapenemase-producing K. pneumoniae strains. cgMLST scheme genotyping divided the ST11 group into two clades across seven complex types (CTs). CT1313 was the most prevalent subclone. The deletion of galF and a high frequency of SNPs in genes associated with the stress- and SOS-responses were found in CT1291 and CT2405 over time, respectively. CONCLUSION: Our results indicated that the subclones of the ST11 group had different patterns of prevalence. Highly discriminatory genotyping techniques, such as cgMLST scheme, should be used in further molecular epidemiology investigations.
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The threat of antimicrobial resistance calls for more efforts in basic science, drug discovery, and clinical development, particularly gram-negative carbapenem-resistant pathogens. We sought to identify novel antibacterial agents against Acinetobacter baumannii ATCC19606 using whole cell-based screening. A small molecule named 6D1 with the chemical structure of 6-fluorobenzo[d]isothiazol-3(2H)-one was identified and exhibited activity against A. baumannii ATCC19606 strain (minimal inhibitory concentration, MIC = 1 mg l-1). The mutation in the plasmid-derived ohrB gene that encodes a peroxidase was identified in spontaneously resistant mutants. Treatment of the bacteria with 6D1 resulted in increased sensitivity to peroxide, such as tert-butyl hydroperoxide. The binding of 6D1 and OhrB was confirmed by surface plasmon resonance. Interestingly, the MIC of kanamycin and gentamicin against spontaneously resistant mutants decreased. Finally, we identified the effect of 6D1 on enhancing the antibacterial activity of kanamycin and gentamicin, including against New Delhi metallo-ß-lactamase (NDM-1)-producing carbapenem-resistant Klebsiella pneumoniae, but not in strains carrying aminoglycosides resistance genes. In this study, we identified a small molecule that suppresses the growth of A. baumannii, interacts with hydroperoxide reductase from A. baumannii ATCC19606 plasmid pMAC, and enhances the antibacterial activity of kanamycin and gentamicin. We propose that peroxidase may be potentially used as a target for aminoglycosides adjuvant development.
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Acinetobacter baumannii/efectos de los fármacos , Aminoglicósidos/farmacología , Antibacterianos/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Peroxirredoxinas/metabolismo , Pseudomonas aeruginosa/efectos de los fármacos , Aminoglicósidos/administración & dosificación , Farmacorresistencia Bacteriana Múltiple , Sinergismo Farmacológico , Regulación Bacteriana de la Expresión Génica , Genoma Bacteriano , Pruebas de Sensibilidad Microbiana , Secuenciación Completa del GenomaRESUMEN
OBJECTIVE: We aimed to establish a tool for rapid identification of KL49 Acinetobacter baumannii. METHODS: Based on the capsular polysaccharide (CPS) synthesis genes database, we investigated the distribution of K locus type 49 (KL49) genes in other KL types and established a rapid identification method for KL49. We collected 61 clinical carbapenem-resistant A. baumannii (CRAB) strains, identified KL49 by gtr100 detection, and used whole genome sequencing (WGS) for verification. A mouse pneumonia model was used to confirm the hypervirulence phenotype. We tested the presence of gtr100 gene in 165 CRAB strains from three provinces in China and evaluated the correlation of gtr100 carrying CRAB infection with mortality. RESULTS: The gtr100 gene is the CPS synthesis gene found only in KL49. We screened out nine WGS-validated KL49 strains from 61 CRAB clinical strains using polymerase chain reaction (PCR) to detect the gtr100 gene. The survival rates of KL49 strains were significantly lower than nonKL49 strains in a mouse pneumonia model. The survival rates of LAC-4 gtr100 knockout strain decreased significantly. Analysis of phylogenetics showed the worldwide spread of KL49 A. baumannii. Infection of gtr100 carrying CRAB is an independent risk for mortality (OR, 10.76; 95%CI: 3.08-37.55; p<0.001). CONCLUSION: The hypervirulence phenotype of KL49 CRAB and the association with mortality highlight the urgent need for implementing control measures. The rapid identification assay has the potential to facilitate early medical intervention and worldwide surveillance.
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BACKGROUND: Particulate matter (PM) exposure is closely associated with male infertility. Even though an association between poor semen quality and PM exposure has been widely accepted, which and when the semen parameter could be affected are still controversial. The purpose of this study is to estimate the effects of PM exposure on semen quality in Huai'an, China. OBJECTIVES AND METHODS: The study included 1955 men with 2073 semen samples between 2015 and 2017 with moderate to high exposure to air pollution in Huai'an, China. Three multivariable linear regression models were used to conduct exposure-response analyses for PM exposure and semen quality and to estimate the influence during different exposure periods by every 15 days period before ejaculation in all participants group and normal semen quality participants group. RESULTS: The average age of the observations was 28.9 ± 5.4 old years and the average abstinence period was 4.2 ± 1.5 days. The results showed high correlations between both PM2.5 and PM10 exposures throughout entire spermatogenesis and the declines of sperm count (ß: -0.93, p < 2 × 10-16 and ß: -1.00, p < 2 × 10-16), and sperm concentration (ß: -1.00, p < 2 × 10-16 and ß: -1.06, p < 2 × 10-16), and PM10 exposure decreased sperm total motility (ß: -0.60, p = 2.56 × 10-7), but not sperm progressive motility. Furthermore, PM2.5 exposure decreased sperm count and concentration during 15-75 lag days, and PM10 exposure showed significant association with sperm count and concentration during 0-75 lag days. PM2.5 and PM10 exposures during 45-59 lag days were both inversely associated with sperm total motility (all p value < 0.05). CONCLUSION: The present study revealed that ambient PM exposure throughout spermatogenesis during a long period, especially at early and middle stage were adversely associated with semen quality, sperm count and sperm concentration in particular.
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Contaminantes Atmosféricos/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Material Particulado/toxicidad , Semen/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Adulto , Contaminantes Atmosféricos/análisis , China , Estudios de Cohortes , Exposición a Riesgos Ambientales/análisis , Humanos , Infertilidad Masculina/inducido químicamente , Infertilidad Masculina/patología , Modelos Lineales , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Material Particulado/análisis , Estudios Retrospectivos , Análisis de Semen , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: Group B Streptococcus (GBS) is a leading cause of early-onset disease (EOD) and late-onset disease (LOD) in infants. We sought to investigate the antibiotic susceptibility profiles, resistance genes, virulence-related genes, serotype distribution and genotypic characteristics of GBS recovered from infected or colonized neonates and pregnant women in a tertiary teaching hospital in Shenzhen, China, from 2008 to 2015. RESULTS: High resistance rates of erythromycin (66.7-100%) were detected among early-onset GBS (EOGBS), late-onset GBS (LOGBS), neonatal colonizing GBS (NCGBS) and maternal colonizing GBS (MCGBS). 89.5-100% of four groups of GBS isolates showed resistance to tetracycline. More than 90 % of erythromycin resistant isolates of EOGBS (8/8, 100%), LOGBS (16/17, 94.1%) and NCGBS (10/11, 90.9%) harbored ermB, while only 9.1-17.6% harbored mefA/E. By contrast, 55.8% (24/43) and 62.8% (27/43) of erythromycin resistant MCGBS isolates carried ermB and mefA/E genes, respectively. The tetO gene was more common in tetracycline resistant EOGBS (10/11, 90.9%), LOGBS (17/17, 100%) and NCGBS (10/11, 90.9%), compared to tetracycline resistant MCGBS (12/51, 23.5%). Additionally, the tetM gene accounted for 90.9% (10/11), 76.5% (13/17), 45.5% (5/11) and 80.4% (41/51) of four groups of isolates, respectively. Serotype III was the most predominant in EOGBS (8/12, 66.7%) and LOGBS (15/17, 88.2%), while serotype Ib accounted for 50.0% (6/12) of NCGBS, and serotype Ia and III accounted for 45.6% (26/57) and 33.3% (19/57) of MCGBS, respectively. Sequence type 17 (ST17) was the most common in EOGBS (6/12, 50%) and LOGBS (12/17, 70.6%), while ST12 was predominant in NCGBS (5/12, 41.7%), and five STs (ST19, ST23, ST12, ST103 and ST485) accounted for 66.7% (38/57) of the MCGBS. All serotype III-ST17 isolates recovered from neonates were associated with invasive infections. CONCLUSIONS: This study shows the meaningful differences in molecular mechanisms of resistance to erythromycin and tetracycline, and the prevalence of serotypes and STs among GBS recovered from neonates and pregnant women. ST17 is predominant in neonatal invasive GBS, but rare in NCGBS and MCGBS.
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Complicaciones Infecciosas del Embarazo/microbiología , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/genética , Adulto , Antibacterianos/farmacología , Proteínas Bacterianas/genética , China , Farmacorresistencia Bacteriana Múltiple , Eritromicina/farmacología , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Fenotipo , Filogenia , Embarazo , Streptococcus agalactiae/clasificación , Streptococcus agalactiae/efectos de los fármacos , Streptococcus agalactiae/aislamiento & purificación , Tetraciclina/farmacología , Adulto JovenRESUMEN
Background. Spinal cord injury (SCI) leads to bowel dysfunction. Electroacupuncture (EA) may improve bowel function. Objective. To assess EA on daily rhythmicity of intestinal movement and circadian rhythmicity of colonic Per2 expression in rats with SCI. Methods. Rats were randomized to the sham, SCI, and SCI+EA groups. EA was performed at bilateral Zusanli point (ST36) during daytime (11:00-11:30) for 14 days following SCI. Intestinal transit and daily rhythmicity of intestinal movement were assessed. Circadian rhythmicity of colonic Per2 expression was assessed by real-time RT-PCR. Results. EA shortened the stool efflux time and increased the dry fecal weight within 24 h in SCI rats. Daily rhythmicity of intestinal movements was unaffected by SCI. The expression of colonic Per2 peaked at 20:00 and the nadir was observed at 8:00 in the SCI and sham groups. In the SCI+EA group, colonic Per2 expression peaked at 12:00 and 20:00, and the nadir was observed at 8:00. Conclusion. SCI did not change the circadian rhythmicity of colonic Per2 expression in rats, and daily intestinal movement rhythmicity was retained. EA changed the daily rhythmicity of intestinal movement and the circadian rhythmicity of colonic Per2 expression in rats with SCI, increasing Per2 expression shortly after EA treatment.
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Ritmo Circadiano , Colon , Electroacupuntura , Motilidad Gastrointestinal , Regulación de la Expresión Génica , Proteínas Circadianas Period/biosíntesis , Traumatismos de la Médula Espinal , Animales , Colon/metabolismo , Colon/fisiopatología , Femenino , Masculino , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/terapiaRESUMEN
OBJECTIVE: To examine the effect of Tai Chi on cardiopulmonary function and quality of life in chronic obstructive pulmonary disease. DATA SOURCES: Cochrane Library, PUBMED, EMBASE, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang database. METHODS: Articles on randomized controlled trials comparing Tai Chi with other treatments or no treatment were identified. A random-effects model was used to calculate the pooled mean difference (MD) with 95% confidence interval (CI). RESULTS: Fifteen articles involving 1354 participants were included. Compared with the control group, Tai Chi was more effective in improving exercise capacity on 6-minute walking distance (short term: MD = 16.02, 95% CI 2.86 to 29.17; mid term: MD = 30.90, 95% CI 6.88 to 54.93; long term: MD = 24.63, 95% CI 2.30 to 46.95), as well as pulmonary functions on forced expiratory volume in the first second (mid term: MD = 0.10; 95% CI 0.01 to 0.19), and forced vital capacity (mid term: MD = 0.20; 95% CI 0.04 to 0.36). Concerning quality of life, we found Tai Chi was better than the control group for the Chronic Respiratory Disease Questionnaire dyspnoea score (short term: MD = 0.90; 95% CI 0.51 to 1.29), fatigue score (short term: MD = 0.75; 95% CI 0.42 to 1.09), and total score (short term: MD = 1.92; 95% CI 0.54 to 3.31). CONCLUSIONS: Tai Chi may improve exercise capacity in the short, mid, and long terms. However, no significant long term differences in pulmonary function and quality of life were observed for patients with chronic obstructive pulmonary disease.
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Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Calidad de Vida , Taichi Chuan , Humanos , Enfermedad Pulmonar Obstructiva Crónica/complicacionesRESUMEN
BACKGROUND: The prevalence of carbapenem-resistant Acinetobacter baumannii in hospitals has been increasing worldwide. This study aims to investigate the carbapenemase genes and the clonal relatedness among A. baumannii clinical isolates in a Chinese hospital. METHODS: Carbapenemase genes and the upstream locations of insertion sequences were detected by polymerase chain reaction (PCR), and the clonal relatedness of isolates was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. RESULTS: A total of 231 nonduplicate carbapenemase gene-harboring A. baumannii clinical isolates recovered from Shenzhen People's Hospital, were investigated between 2002 and 2009. blaOXA-23-like, blaOXA-58-like, blaOXA-40-like, and ISAba1-blaOXA-51-like were identified in 119, 107, 1, and 4 isolates, respectively. IS1008-ΔISAba3, ISAba3, and ISAba1 were detected upstream of the blaOXA-58-like gene in 69, 35, and 3 isolates, respectively. All blaOXA-23-like genes but one had an upstream insertion of ISAba1. blaOXA-58-like was the most common carbapenemase gene in A.baumannii before 2008, thereafter blaOXA-23-like became rapidly prevalent and replaced blaOXA-58-like in 2009. The majority of blaOXA-58-like-carrying isolates showed lower level of resistance to imipenem and meropenem (minimum inhibitory concentrations (MICs), 1 µg/ml to 16 µg/ml), compared with the majority of blaOXA-23-like-carrying isolates (MICs, 16 µg/ml to 64 µg/ml for both imipenem and meropenem). All 231 blaOXA carbapenemase gene-harboring isolates belonged to 14 PFGE types (A-N), and three dominant clones A, J, and H accounted for 43.3%, 42.0%, and 8.2% of the tested isolates, respectively. Clone A (sequence type ST92/ST208) with blaOXA-58-like was the most prevalent before 2008. Clone H (ST229) with blaOXA-23-like became striking between 2007 and 2008. Clone J (ST381) with blaOXA-23-like rapidly spread and replaced clones A and H in 2009. CONCLUSION: This study is the first to reveal that the distinct blaOXA-23-like-carrying A. baumannii ST381 displaced the previously prevalent blaOXA-58-like-carrying A. baumannii ST92/ST208, resulting in the rapidly increasing resistance to carbapenems in A. baumannii in Shenzhen People's Hospital in 2009.
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Acinetobacter baumannii/genética , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Conjugación Genética , Resistencia betalactámica/genética , beta-Lactamasas/genética , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/epidemiología , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/enzimología , Acinetobacter baumannii/aislamiento & purificación , Proteínas Bacterianas/metabolismo , China/epidemiología , Células Clonales , Expresión Génica , Hospitales , Humanos , Imipenem/farmacología , Unidades de Cuidados Intensivos , Isoenzimas/genética , Isoenzimas/metabolismo , Meropenem , Plásmidos/química , Plásmidos/metabolismo , Estudios Retrospectivos , Tienamicinas/farmacología , beta-Lactamasas/metabolismoRESUMEN
OBJECTIVE: To investigate the clinical features, mechanism of resistance and molecular epidemiology of carbapenem-resistant Acinetobacter baumannii (CRAB) infections at Shenzhen People's Hospital during an 8-year period. METHODS: A. baumannii isolates were recovered from nosocomial infections patients at this hospital from 2002 to 2009. The minimum inhibitory concentrations (MICs) of antimicrobial agents against A. baumannii isolates were detected by agar dilution method. Polymerase chain reaction (PCR) and DNA sequencing were used to examine the carbapenemase genotype among CRAB. All isolates were typed by pulse field gel electrophoresis (PFGE). Clinical cases of CRAB infections were retrospectively analyzed according to Chinese experts' consensus on diagnosis, treatments, preventions and controls of Acinetobacter baumannii infections in China. RESULTS: A total of 87 cases of CRAB nosocomial infections were diagnosed in this study. The most prominent infections caused by CRAB was lung infections, followed by bloodstream infections, wound infections and abdominal infections, accounting for 69.0%, 8.0%, 8.0% and 6.9% of 87 cases, respectively. Approximately 80.5% (70/87) of CRAB isolated from intensive care unit (ICU). A sharp increase of CRAB infections (42/87) occurred in 2009, with the majority of pulmonary infections (34/42). Genotyping by PFGE found eight distinct PFGE patterns among 87 isolates of CRAB. The prominent CRAB clone A, carrying a blaOXA-58-like carbapenemase gene, had been prevalent from 2002 to 2006 at this hospital. The CRAB clone C, harboring a blaOXA-23-like carbapenemase gene, as well as clone A became the prominent clones during 2007 to 2008. The CRAB clone D, carrying a blaOXA-23-like carbapenemase gene, replaced clone A and C, and became the dominant clone in 2009. CONCLUSION: The spread of the CRAB clone D harboring a blaOXA-23-like gene causes a rapid increase of CRAB infections at this hospital during 2009.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Farmacorresistencia Bacteriana , Proteínas Bacterianas , Carbapenémicos , China , Infección Hospitalaria , Genotipo , Hospitales , Humanos , Unidades de Cuidados Intensivos , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular/métodos , Reacción en Cadena de la Polimerasa , beta-LactamasasRESUMEN
The high level of low density lipoprotein (LDL) in plasma is the main cause of atherosclerosis. Hemoperfusion is an ideal therapy to lower the level of LDL in human blood system while therapeutic effect is determined by the adsorbent. The adsorbent must have suitable pore structure and specific functional groups. Carbon nanotubes (CNTs) could be a new adsorbent material because CNTs have high specific surface area and they can be modified by a variety of functional groups. Porous carbon composite beads with the CNTs and phenolic resin mixture were synthesized by suspension polymerization, following with carbonization and steam-activation. Then the porous composite beads were sulfonated with a sulfanilic acid anhydrous by diazotization and coupling reaction. The potential application of the sulfonated porous composite beads in adsorbing low density lipoprotein (LDL) from human serum was investigated. The results showed that the sulfonic acid groups on the composite beads could lower LDL levels greatly by electrostatic interaction with electropositive LDL. The higher 20-100 nm pore volume the composite beads had, the more LDL they could adsorb. The 20-100 nm pore volume was enhanced by adding more CNTs and improving CNTs dispersion (ultrasonic crushing). The sulfonated composite beads containing 45 wt% CNTs presented the highest adsorption capacity to LDL 10.46 mg/g, showing a good prospect as LDL adsorbent in hemoperfusion.
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Lipoproteínas LDL/química , Nanotubos de Carbono , Ácidos Sulfónicos/química , Adsorción , Humanos , Tamaño de la Partícula , Espectroscopía Infrarroja por Transformada de Fourier , Análisis Espectral/métodos , Espectrometría Raman , Rayos XRESUMEN
BACKGROUND: Typhoid and paratyphoid fever are endemic in China. The objective of this investigation was to determine the molecular features of nalidixic acid-resistant Salmonella enteric serovar Typhi (S. typhi) and Paratyphi (S. paratyphi) from blood isolates in Shenzhen, China. RESULTS: Twenty-five S. typhi and 66 S. paratyphi were isolated from 91 bacteremic patients between 2002 and 2007 at a hospital in Shenzhen, Southern China. Fifty-two percent (13/25) of S. typhi and 95.3% (61/64) of S. paratyphi A were resistant to nalidixic acid. Sixty-seven isolates of nalidixic acid-resistant Salmonella (NARS) showed decreased susceptibility to ciprofloxacin (MICs of 0.125-1 microg/mL). All 75 NARS isolates had a single substitution in the quinolone resistance-determining region (QRDR) of GyrA (Ser83-->Phe/Pro/Tyr, or Asp87-->Gly/Asn), and 90.7% of these isolates carried the substitution Ser83Phe in GyrA. No mutation was found in the QRDR of gyrB, parC, or parE. Plasmid mediated quinolone resistance genes including qnr and aac(6')-Ib-cr were not detected in any isolate. Twenty-two distinct pulsed field gel electrophoresis (PFGE) patterns were observed among S. typhi. Sixty-four isolates of S. paratyphi A belonged to one clone. Eighty-seven investigated inpatients were infected in the community. Six patients infected by S. paratyphi A had a travel history before infection. CONCLUSIONS: Nalidixic acid-resistant S. typhi and S. paratyphi A blood isolates were highly prevalent in Shenzhen, China. PFGE showed the variable genetic diversity of nalidixic acid-resistant S. typhi and limited genetic diversity of nalidixic acid -resistant S. paratyphi A.
Asunto(s)
Variación Genética , Salmonella paratyphi A/genética , Salmonella typhi/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , China/epidemiología , ADN Bacteriano/genética , Farmacorresistencia Bacteriana , Electroforesis en Gel de Campo Pulsado , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Ácido Nalidíxico/farmacología , Fiebre Paratifoidea/epidemiología , Prevalencia , Salmonella paratyphi A/efectos de los fármacos , Salmonella paratyphi A/aislamiento & purificación , Salmonella typhi/efectos de los fármacos , Salmonella typhi/aislamiento & purificación , Análisis de Secuencia de ADN , Fiebre Tifoidea/epidemiología , Adulto JovenRESUMEN
A simple, sensitive and specific fluorimetric method has been developed for the determination of thioridazine hydrochloride in human plasma involving solid phase extraction (SPE). In a flow-injection system, thioridazine hydrochloride is on-line oxidized into a strongly fluorescent compound with a lead dioxide solid-phase reactor and the fluorescence intensity is measured with a fluorescence detector (lambda(ex)=349nm, lambda(em)=429nm). A comparison of plasma sample pretreatment between SPE procedure and precipitation method was made and the results showed that SPE procedure was better than precipitation method. Under the optimum conditions, the fluorescence intensity is proportional to the concentration of thioridazine hydrochloride in the range from 0.015 to 2.000microg mL(-1). The detection limit is 5.5ng mL(-1) of thioridazine hydrochloride and the relative standard deviation is 1.06%. This method has been applied to determination of thioridazine hydrochloride in real patients plasma samples with the results compared with those obtained by HPLC method.