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INTRODUCTION: The traditional Chinese medicine (TCM) Potentilla anserina L. can use both as food and medicine. At present, the market mainly depends on experience to identify the species and determine the production areas of P. anserina. To ensure the quality of P. anserina, it is essential to improve the level of quality control. OBJECTIVE: We aimed to establish a rapid and nondestructive discrimination model to identify P. anserina from different production areas by near-infrared spectroscopy. METHODS: The spectra of complete P. anserina medicinal materials and their powder of the same variety from four production areas were collected, and principal component analysis discriminant analysis and partial least squares discriminant analysis (PLS-DA) were conducted based on different pretreatment methods and band selection methods. Then, the spectra of complete medicinal materials were converted into the spectra of medicinal powder for nondestructive identification. RESULTS: The correct recognition rate (CRR) of the PLS-DA discriminant model was the best after spectral preprocessing using autoscaling and competitive adaptive reweighted sampling for band selection. The CRRs of the calibration set and validation set were 100%, the CRRs of the external test set were 95%, 90%, 82%, and 88%, respectively, and the CRRs of the transfer external test set were 84%, 80%, 82%, and 86%, respectively. CONCLUSION: We realized the nondestructive and effective identification of P. anserina from different origins and laid a foundation for the industrialization and upgrading of TCM.
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Potentilla , Análise de Componente Principal , Espectroscopia de Luz Próxima ao Infravermelho , Potentilla/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Análise dos Mínimos Quadrados , Análise Discriminante , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/químicaRESUMO
INTRODUCTION: Calculus bovis (C. bovis) is a typical traditional Chinese medicine (TCM) derived from animals, which has a remarkable curative effect and high price. OBJECTIVES: Rapid identification of C. bovis from different types was realized based on spectral technology, and a rapid quantitative analysis method for the main quality control indicator bilirubin was established. METHODS: We conducted a supervised and unsupervised pattern recognition study on 44 batches of different types of C. bovis by five spectral pretreatment methods. Three variable selection methods were used to extract the essential information, and the partial least squares regression (PLSR) quantitative model of bilirubin by near-infrared (NIR) spectroscopy was constructed. RESULTS: The partial least squares discriminant analysis (PLS-DA) model could achieve 100% accuracy in identifying different types of C. bovis. The R2 of the NIR quantitative model was 0.979, which is close to 1, and the root mean square error of calibration (RMSEC) was 2.3515, indicating the good prediction ability of the model. CONCLUSION: The study was carried out to further improve the basic data of quality control of C. bovis and help the high-quality development of TCM derived from animals.
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Medicina Tradicional Chinesa , Controle de Qualidade , Espectroscopia de Luz Próxima ao Infravermelho , Animais , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Análise dos Mínimos Quadrados , Medicamentos de Ervas Chinesas/química , Análise Discriminante , Bilirrubina/análiseRESUMO
BACKGROUND: Clostridium difficile (C. difficile) is a Gram-positive, anaerobic, spore-forming bacillus that can cause pseudomembranous colitis and other C. difficile-associated diseases, resulting in significant morbidity and mortality. The incidence and clinical features vary by geography. METHODS: In this cross-sectional study, we examined the incidence and clinical features of C. difficile infection (CDI) within a 2,900-bed academic medical center in a southern area of China from January 1, 2017, to December 31, 2020. All adult inpatients (aged ≥ 18 years) who submitted loose stool samples for C. difficile testing over this period were considered for the study. RESULTS: This cross-sectional study showed that the average incidence of CDI was 2.07 cases/100,000 hospital patient-days. The mean age of these inpatients was 71.21 ± 2.83 years (range 30 - 93 years), and 83.61% (51/61) were treated in medical units. We found that 85.25% (52/61) of inpatients with CDI were aged > 60 years. Multivariate logistic regression analysis revealed that age > 60 years, and admission to the geriatric treatment unit or neurosurgery treatment unit were indeed independent risk factors for CDI in inpatients. CONCLUSIONS: The incidence of CDI in the southern area of China was low. Age > 60 years, and treatment in geriatric or neurosurgery units were independent risk factors for CDI inpatients.
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Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Adulto , Humanos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos Transversais , Pacientes Internados , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/epidemiologia , Fatores de Risco , Diarreia/diagnóstico , Diarreia/epidemiologia , Diarreia/induzido quimicamente , Antibacterianos/efeitos adversos , Infecção Hospitalar/tratamento farmacológicoRESUMO
A new layered compound LaOTlF2 is designed and investigated using first-principles calculations in this work. The parent compound is an insulator with an indirect band gap of 3.88 eV. Electron-doping of the parent compound makes the material metallic. In the meantime, several lattice vibrational modes couple strongly to the conduction band, leading to a large electron-phonon coupling constant and conventional superconductivity. The highest superconducting transition temperature Tc is predicted to be approximately 8.6 K with λ about 1.25 in the optimally doped LaO0.95F0.05TlF2, where λ is calculated using the Wannier interpolation technique.
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During the COVID-19 pandemic, the mental health state of adolescents had caused widespread concern, especially the various problems caused by the relationship between adolescents and their parents in the long isolation at home. Based on the mindfulness reperceiving model and Rogers's Self-theory, this study aimed to explore the roles of adolescents' self-concept clarity and mindfulness level in the relationship between parental psychological control and adolescent depression. A total of 1,100 junior high school students from China completed the questionnaires regarding parental psychological control, depression, self-concept clarity, and mindfulness. Moderated mediation analyses suggest that parental psychological control affects adolescent depression via self-concept clarity. The association between parental psychological control and depression is moderated by self-concept clarity. The effect was stronger among adolescents with high mindfulness levels than those with low. This study suggests that it is necessary to consider both parental factors and adolescents' factors in the future. The interventions on self-concept or mindfulness may ameliorate adolescent mental problems more effectively.
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Plasma-derived extracellular vesicles (EV) can serve as markers of cell damage/disease but can also have therapeutic utility depending on the nature of their cargo, such as miRNA. Currently, there are challenges and lack of innovations regarding early diagnosis and therapeutic options within different aspects of management of patients suffering from chronic pancreatitis (CP). Use of EV as biomarkers for pancreatic health and/or as adjuvant therapy would make a difference in management of these patients. The aim of this study was to characterize the miRNA cargo of EV purified from the plasma of CP patients and compared to those of healthy participants. EVs were isolated from plasma of 15 CP patients and 10 healthy controls. Nanoparticle tracking analysis was used to determine frequency and size, while NanoString technology was used to characterize the miRNA cargo. Relevant clinical parameters were correlated with EV miRNA cargo. ~ 30 miRNA species were identified to have significantly (p < 0.05) different expression in EV from individuals with CP compared to healthy individuals; ~ 40 miRNA were differentially expressed in EV from pre-diabetic versus non-diabetic CP patients. miR-579-3p, while exhibiting significantly lower (~ 16-fold) expression in CP compared to healthy and lower (~ 24-fold) in CP narcotic users compared to the non-users, is actually enriched (~ 32-fold) within EV in pre-diabetic CP patients compared to non-diabetic CP patients. A unique pattern was identified in female CP patients. These data support the prospect of using a plasma-derived EV cargo to assess pancreatic health and its therapeutic potential in CP patients.
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Vesículas Extracelulares/genética , MicroRNAs/genética , Pancreatite Crônica/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pancreatite Crônica/sangue , Pancreatite Crônica/patologiaRESUMO
Although accumulating evidence has revealed that metallothioneins (MTs) and its family member MT2A are strongly linked to the risk of various solid tumors, researches on the occurrence and development of acute myeloid leukemia (AML) have rarely been investigated. Here, we constructed a lentiviral vector with MT2A over-expression and the interfering plasmids with MT2A expression inhibition to study the influence of MT2A on the bioactivities of HL60 cells. After cells were infected with a lentiviral vector containing the MT2A gene, both transcription and translation levels of MT2A were significantly increased in the over-expressed group in comparison with control groups. In vitro experiments, all results demonstrated that cell reproductive capacity was inhibited, but cell apoptosis rate was significantly increased. Together, the expression of apoptosis-related protein Bcl2 was remarkably reduced, while a high expression level of Bax protein was detected. Further experiments revealed that up-regulation of MT2A induced cell apoptosis and promoted G2/M phase arrest. The mechanism may be associated with down-regulated p-IκB-α and cyclinD1 expression and up-regulated IκB-α expression in the nuclear factor-kappaB (NF-κB) pathway. On the contrary, MT2A expression was down-regulated by interfering plasmids. We found that cell proliferative potential was notably increased in the interfering group compared with the negative and untreated group. What's more, MT2A may be closely related to AML cell proliferation and function via the NF-κB signal pathway.
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Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/genética , Metalotioneína/metabolismo , Apoptose/genética , Proliferação de Células/genética , Regulação para Baixo , Células HL-60 , Humanos , Leucemia Mieloide Aguda/patologia , Metalotioneína/genética , Inibidor de NF-kappaB alfa/metabolismo , Transdução de Sinais/genética , Regulação para CimaRESUMO
Pseudomonas aeruginosa is a common opportunistic pathogen that causes infections in vulnerable patients including those with metabolic disorders, hematologic diseases, and malignancies, and in those who have undergone surgery. In addition, P. aeruginosa exhibits high intrinsic resistance to numerous antibiotics and tends to form biofilms rendering it even more refractory to treatment. Among the mechanisms used by P. aeruginosa to adapt to environmental stresses are those involving small regulatory RNAs (sRNAs), which are 40-500 nucleotides long and are ubiquitous in bacteria. sRNAs play important regulatory roles in various vital processes in diverse bacteria, with their quantity and diversity of regulatory functions exceeding those of proteins. In this study, we show that deletion of the sRNA, rgsA, decreased the growth rate of P. aeruginosa. Furthermore, ΔrgsA P. aeruginosa exhibited decreased ability to resist the stress induced by exposure to different concentrations and durations of peroxides in both planktonic and biofilm growth modes compared with the wild-type strain. These results highlight the role of rgsA in the defense of P. aeruginosa against oxidative stress.
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Infecções por Pseudomonas , Pseudomonas aeruginosa , Antibacterianos , Proteínas de Bactérias/genética , Biofilmes , Regulação Bacteriana da Expressão Gênica , Humanos , Estresse Oxidativo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismoRESUMO
BACKGROUND: Xanthogranulomatous pyelonephritis (XGP) is an uncommon form of chronic pyelonephritis. Most patients of XGP are diffuse in radiology and the clinical features are typical. CASE PRESENTATION: We present a case of 24-year-old female with the absence of symptoms and normal laboratory examinations. Contrast computed tomography and intravenous pyelography demonstrate infiltrative renal mass and renal cell carcinoma is presumed. Laparoscopic right radical nephrectomy is performed, but the final pathological result shows XGP. CONCLUSIONS: As far as we know, this is the first case report of XGP without any symptoms/signs and with normal laboratory examinations. The diagnosis of atypical XGP is challenging and preoperative renal mass biopsy should be considered in special cases.
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Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Pielonefrite Xantogranulomatosa/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Adulto JovemRESUMO
BACKGROUND: Acute kidney injury (AKI) is a critical clinical syndrome characterised by a rapid decrease in renal filtration, with the accumulation of products of metabolism such as creatinine and urea. In recent years, the incidence of AKI has increased not only in critically ill hospitalised patients but also in community patients. Also, the prognosis of AKI is poor and treatment is limited in these populations. The increasing incidence and poor prognosis may be the reasons why more investigators are involved in epidemiological and risk factor analysis of AKI. AIMS: To investigate the effects of these risk factors on outcomes in both community-acquired and hospitalised AKI populations to provide certain guidance for clinics and to explore the prognostic value of prealbumin on all-cause mortality in patients with community-acquired and post-operative AKI. METHODS: From 2000 to 2010, 477 patients diagnosed with AKI and treated in the Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University, were enrolled in the community-acquired AKI (CA-AKI) group and 138 patients diagnosed with AKI after an operation were enrolled in the post-operative AKI (PO-AKI) group. Data were collected at AKI onset and 1 year after discharge and analysed retrospectively. RESULTS: Compared with PO-AKI patients, more patients in CA-AKI group had chronic kidney disease, obesity and hyperlipidaemia, and fewer patients had cerebrovascular disease (CVD), anaemia, shock or arrhythmia. Risks for CA-AKI were atherosclerosis, CVD, arrhythmia, multiple organ dysfunction syndrome and usage of vasoactive agents, and risks for PO-AKI were elderly, arrhythmia and requirement of renal replacement therapy. A higher level of serum PA was associated with a better outcome in the CA-AKI group (hazard ratio 0.92, 95% confidence interval 0.85-0.996) and PO-AKI group (hazard ratio 0.91, 95% confidence interval 0.84-0.99). In the CA-AKI group, the cumulative survival rate of patients with a normal PA level (PA >20 mg/dL) was higher than that among patients with a lower PA (PA ≤20 mg/dL; 95.4% vs 88.3%, P = 0.031). Similarly, in the PO-AKI group, a normal PA level was associated with a higher survival rate (74.1% vs 47.6%, P = 0.019). CONCLUSION: Serum PA may serve as a prognostic marker for CA-AKI and PO-AKI, and further research is warranted to confirm this finding.
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Injúria Renal Aguda , Albumina Sérica , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Idoso , China/epidemiologia , Mortalidade Hospitalar , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background: Both soluble suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are promising biomarkers associated with the adverse clinical outcomes of dialysis patients. Our research aims at exploring and comparing the roles of sST2 and NT-proBNP in predicting the short-term and long-term mortality of maintenance hemodialysis (MHD) patients.Methods: A prospective cohort study was performed. Patients undergoing hemodialysis in July 2014 were enrolled from the Blood Purification Center of Ruijin Hospital. MHD patients were followed up for 3 years. The primary outcome was all-cause mortality at the 1-year and 3-year follow-up, while the secondary outcome was cardiovascular mortality. Serum sST2 level was detected by quantified ELISA kits. Clinical data were analyzed by SPSS 23.0 version.Results: 205 patients were recruited. The median sST2 level was 15.99 (11.60, 20.49) ng/ml. After 3 years of follow-up, both all-cause and cardiovascular mortality in 1 year and all-cause and cardiovascular mortality in 3 years increased significantly with serum sST2. For short-term mortality, no significant difference was observed in patients with increasing NT-proBNP levels. Cox regression analysis indicated that only sST2 was independent in predicting the risk of short-term outcomes. For long-term mortality, both sST2 and NT-proBNP were independent risk factors, while a higher hazard ratio was observed for NT-proBNP.Conclusions: Serum sST2 is a novel biomarker associated with adverse clinical outcomes in MHD patients. It was significant for both all-cause and cardiovascular mortality in MHD patients and may provide better prognostic value in short-term prognosis than the classic biomarker NT-proBNP.
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Doenças Cardiovasculares/mortalidade , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Diálise Renal , Idoso , Biomarcadores/sangue , Causas de Morte , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
G protein-coupled receptors (GPCRs) in the kidney regulate the reabsorption of essential nutrients, ions, and water from the glomerular filtrate. Abnormalities in renal epithelial ion transport play important roles in the pathogenesis of essential hypertension. The orphan G protein-coupled receptor 37L1 (GPR37L1), also known as endothelin receptor type B-like protein (ETBR-LP2), is expressed in several regions in the brain, but its expression profile and function in peripheral tissues are poorly understood. We found that GPR37L1 mRNA expression is highest in the brain, followed by the stomach, heart, testis, and ovary, with moderate expression in the kidney, pancreas, skeletal muscle, liver, lung, and spleen. Immunofluorescence analyses revealed the expression of GPR37L1 in specific regions within some organs. In the kidney, GPR37L1 is expressed in the apical membrane of renal proximal tubule cells. In human renal proximal tubule cells, the transient expression of GPR37LI increased intracellular sodium, whereas the silencing of GPR37LI decreased intracellular sodium. Inhibition of Na+/H+ exchanger isoform 3 (NHE3) activity abrogated the GPR37L1-mediated increase in intracellular sodium. Renal-selective silencing of Gpr37l1 in mice increased urine output and sodium excretion and decreased systolic and diastolic blood pressures. The renal-selective silencing of GPR37L1 decreased the protein expression of NHE3 but not the expression of Na+-K+-ATPase or sodium-glucose cotransporter 2. Our findings show that in the kidney, GPR37L1 participates in renal proximal tubule luminal sodium transport and regulation of blood pressure by increasing the renal expression and function of NHE3 by decreasing cAMP production. The role of GPR37L1, expressed in specific cell types in organs other than the kidney, remains to be determined.
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Pressão Sanguínea/fisiologia , Transporte de Íons/fisiologia , Rim/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sódio/metabolismo , Animais , Encéfalo/metabolismo , Linhagem Celular , AMP Cíclico/metabolismo , Humanos , Túbulos Renais Proximais/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Camundongos , Músculo Esquelético/metabolismo , Receptores Acoplados a Proteínas G/genética , Trocadores de Sódio-Hidrogênio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
PURPOSE: To evaluate the audiological effectiveness of Bonebridge implantation in patients with bilateral congenital malformation of the external and middle ear. METHODS: Twenty-eight cases [17 boys and 11 girls; median age, 12 years (range 8-36 years)] had unilateral Bonebridge implantation. Audiological tests were performed preoperatively and postoperatively, and included the pure-tone audiometry test, speech discrimination score (SDS), and evaluation of the unaided and aided hearing thresholds in sound fields. For the group of patients aged > 12 years, Mandarin Speech Test Materials were used to determine the SDS. For the other cases, the Mandarin Lexical Neighborhood Test was used. The daily life efficacy was assessed using the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire postoperatively. The t and t' tests were used in the statistical analyses. RESULTS: The hearing threshold with the Bonebridge improved by 25-35 dB HL, compared to that of the unaided condition. The SDS of patients aged > 12 years improved by about 50%; the SDS also improved by 10-20% in the three patients aged < 12 years. According to the APHAB, the mean Bonebridge scores of ease of communication, background noise, and reverberation decreased by 60.3 ± 15.7, 50.2 ± 11.1, and 59.4 ± 7.8, respectively, compared to the preoperative scores, and the Bonebridge score of aversiveness was higher (69.8 ± 10.8) than the unaided score. CONCLUSIONS: The audiological effectiveness of the Bonebridge was significant and noticeable in bilateral congenital malformation of the external and middle ear. The Bonebridge can be an alternative and effective solution for those patients to improve hearing.
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Condução Óssea , Orelha Externa/anormalidades , Orelha Média/anormalidades , Auxiliares de Audição , Perda Auditiva Condutiva/cirurgia , Adolescente , Adulto , Limiar Auditivo , Criança , Feminino , Perda Auditiva Bilateral/cirurgia , Humanos , Masculino , Testes de Discriminação da Fala , Adulto JovemRESUMO
AIMS/HYPOTHESIS: We hypothesised that renal sorting nexin 5 (SNX5) regulates the insulin-degrading enzyme (IDE) and, thus, circulating insulin levels. We therefore studied the dynamic interaction between SNX5 and IDE in human renal proximal tubule cells (hRPTCs), as well as in rat and mouse kidneys. METHODS: The regulation of IDE by SNX5 expressed in the kidney was studied in vitro and in vivo. Snx5 or mock siRNA was added to immortalised hRPTCs (passage <20) in culture or selectively infused, via osmotic mini-pump, into the remnant kidney of uninephrectomised mice and rats. RESULTS: SNX5 co-localised with IDE at the plasma membrane and perinuclear area of hRPTCs and in the brush border membrane of proximal tubules of human, rat, and mouse kidneys. Insulin increased the co-localisation and co-immunoprecipitation of SNX5 and IDE in hRPTCs. Silencing SNX5 in hRPTCs decreased IDE expression and activity. Renal-selective silencing of Snx5 (SNX5 protein: 100 ± 25 vs 29 ± 10, p < 0.05 [% of control]) in C57Bl/6J mice decreased IDE protein (100 ± 13 vs 57 ± 6, p < 0.05 [% of control]) and urinary insulin excretion, impaired the responses to insulin and glucose, and increased blood insulin and glucose levels. Spontaneously hypertensive rats (SHRs) had increased blood insulin and glucose levels and decreased renal SNX5 (100 ± 27 vs 29 ± 6, p < 0.05 [% of control]) and IDE (100 ± 5 vs 75 ± 4, p < 0.05 [% of control]) proteins, compared with normotensive Wistar-Kyoto (WKY) rats. Kidney Snx5-depleted WKY rats also had increased blood insulin and glucose levels. The expression of SNX5 and IDE was decreased in RPTCs from SHRs and hypertensive humans compared with cells from normotensive volunteers, indicating a common cause for hyperinsulinaemia and hypertension. CONCLUSIONS/INTERPRETATION: Renal SNX5 positively regulates IDE expression and function. This study is the first to demonstrate the novel and crucial role of renal SNX5 in insulin and glucose metabolism.
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Insulisina/metabolismo , Nexinas de Classificação/metabolismo , Animais , Western Blotting , Linhagem Celular , Humanos , Imunoprecipitação , Técnicas In Vitro , Resistência à Insulina/genética , Insulisina/genética , Rim/metabolismo , Masculino , Camundongos , Camundongos Mutantes , Microscopia Confocal , Microscopia de Fluorescência , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/fisiologia , Ratos , Ratos Endogâmicos WKY , Reação em Cadeia da Polimerase em Tempo Real , Nexinas de Classificação/genéticaRESUMO
Background: Carbapenem-resistant Enterobacteriaceae (CRE) strains are a major threat to global health. The development of effective control measures requires more detailed phenotypic and genotypic characterization of CRE. Methods: CRE isolates were collected from 65 hospitals in 25 provinces across China between January 1, 2012, and December 31, 2016. The isolates were characterized by antimicrobial susceptibility testing and multilocus sequence typing. Genes encoding carbapenemases, mobilized colistin resistance (mcr-1), and ß-lactamases were detected by polymerase chain reaction and DNA sequencing. Results: A total of 1801 independent CRE isolates (1201 Klebsiella pneumoniae, 282 Escherichia coli, and 179 Enterobacter cloacae) were collected during the study period. Overall, 96.9%, 89.7%, 54.5%, 49.9%, and 40% of CRE strains were susceptible to colistin, tigecycline, amikacin, minocycline, and fosfomycin, respectively. Notably, 1091/1201 (91%) K. pneumoniae, 225/282 (80%) E. coli, and 129/179 (72%) E. cloacae harbored carbapenemase gene. K. pneumoniae carbapenemase (KPC) was predominant in K. pneumoniae (77%), whereas New Delhi metallo-ß-lactamase (NDM) was predominant in E. coli (75%) and E. cloacae (53%). The mcr-1 gene was detected in 13 NDM-carrying E. coli isolates (4.6%). Sequence type (ST)11 and ST167 were predominant among the 100 K. pneumoniae and 47 E. coli STs, respectively. KPC-ST11, which accounted for 64% of K. pneumoniae isolates, had higher levels of resistance than non-ST11 strains to aztreonam, fosfomycin, and amikacin (P < .001). The proportions of KPC and NDM enzymes in CRE increased from 2012 to 2016 (54%-59% and 12%-28%, respectively). Conclusions: The number of CRE strains harboring carbapenemase is increasing. KPC-ST11 K. pneumoniae, the predominant strain, shows a reduced susceptibility to most available antibiotics.
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Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/classificação , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Carbapenêmicos/farmacologia , Infecções por Enterobacteriaceae/epidemiologia , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , China/epidemiologia , DNA Bacteriano/genética , Enterobacter cloacae/classificação , Enterobacter cloacae/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Monitoramento Epidemiológico , Escherichia coli/classificação , Escherichia coli/efeitos dos fármacos , Proteínas de Escherichia coli/genética , Genótipo , Humanos , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/efeitos dos fármacos , Estudos Longitudinais , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Fenótipo , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , beta-Lactamases/genéticaRESUMO
Carbapenem-resistant Enterobacteriaceae (CRE) infection is highly endemic in China, but estimates of the infection burden are lacking. We established the incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem-nonsusceptible Citrobacter freundii, Escherichia coli, Enterobacter cloacae, or Klebsiella pneumoniae infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase gene identification were performed. Among 664 CRE cases, most were caused by K. pneumoniae (73.9%), followed by E. coli (16.6%) and E. cloacae (7.1%). The overall CRE infection incidence per 10,000 discharges was 4.0 and differed significantly by region, with the highest in Jiangsu (14.97) and the lowest in Qinghai (0.34). Underlying comorbidities were found in 83.8% of patients; the median patient age was 62 years (range, 45 to 74 years), and 450 (67.8%) patients were male. Lower respiratory tract infections (65.4%) were the most common, followed by urinary tract infection (16.6%), intra-abdominal infection (7.7%), and bacteremia (7.7%). The overall hospital mortality rate was 33.5%. All isolates showed nonsusceptibility to carbapenems and cephalosporins. The susceptibility rate of polymyxin B was >90%. Tigecycline demonstrated a higher susceptibility rate against E. coli than against K. pneumoniae (90.9% versus 40.2%). Of 155 clinical isolates analyzed, 89% produced carbapenemases, with a majority of isolates producing KPC (50%) or NDM (33.5%)-type beta-lactamases among K. pneumoniae and E. coli The incidence of CRE infection in China was 4.0 per 10,000 discharges. The patient-based disease burden in tertiary hospitals in China is severe, suggesting an urgent need to enhance infection control.
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Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Carbapenêmicos/farmacologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Idoso , Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Proteínas de Bactérias/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/metabolismo , China , Citrobacter freundii/efeitos dos fármacos , Citrobacter freundii/metabolismo , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Feminino , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/metabolismo , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Polimixina B/farmacologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , beta-Lactamases/metabolismoRESUMO
AAV9 vector provides efficient gene transfer in all segments of the renal nephron, with minimum expression in non-renal cells, when administered retrogradely via the ureter. It is important to restrict the transgene expression to the desired cell type within the kidney, so that the physiological endpoints represent the function of the transgene expressed in that specific cell type within kidney. We hypothesized that segment-specific gene expression within the kidney can be accomplished using the highly efficient AAV9 vectors carrying the promoters of genes that are expressed exclusively in the desired segment of the nephron in combination with administration by retrograde infusion into the kidney via the ureter. We constructed AAV vectors carrying eGFP under the control of: kidney-specific cadherin (KSPC) gene promoter for expression in the entire nephron; Na+/glucose co-transporter (SGLT2) gene promoter for expression in the S1 and S2 segments of the proximal tubule; sodium, potassium, 2 chloride co-transporter (NKCC2) gene promoter for expression in the thick ascending limb of Henle's loop (TALH); E-cadherin (ECAD) gene promoter for expression in the collecting duct (CD); and cytomegalovirus (CMV) early promoter that provides expression in most of the mammalian cells, as control. We tested the specificity of the promoter constructs in vitro for cell type-specific expression in mouse kidney cells in primary culture, followed by retrograde infusion of the AAV vectors via the ureter in the mouse. Our data show that AAV9 vector, in combination with the segment-specific promoters administered by retrograde infusion via the ureter, provides renal nephron segment-specific gene expression.
Assuntos
Dependovirus/crescimento & desenvolvimento , Regulação da Expressão Gênica/genética , Técnicas de Transferência de Genes , Genes Virais/genética , Néfrons/metabolismo , Néfrons/virologia , Animais , Células Cultivadas , Terapia Genética/métodos , Vetores Genéticos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Tripartite motif-containing 22 (TRIM22) is reported to participate in numerous cellular activities. Recent studies confirm that TRIM22 is a target gene for P53, and inhibits clonogenic growth of leukemic U-937 cells. The current study aims to discover the effect of TRIM22 in progression of human chronic myeloid leukemia (CML) and explore the related mechanism. TRIM22 was knocked down by siRNA transfection in CML cell K562. We observed that TRIM22 knockdown decreased proliferation and invasion in K562 cells. TRIM22 knockdown significantly induced cell cycle arrest by regulating the level of CDK4, Cyclin D1, P70S6K, and P53 in K562 cell. Moreover, loss of TRIM22 also promoted apoptosis through modulation of Bcl-2, Bax and active Caspase 3 in K562 cell. Furthermore, we demonstrated that TRIM22 knockdown inhibited the activation of PI3K/Akt/mTOR pathway by decreasing the level of the phosphorylated form p-Akt and p-mTOR in K562 cell. In conclusion, loss of TRIM22 suppresses the progression and invasion of CML through regulation of PI3K/Akt/mTOR pathway, suggesting that TRIM22 might be as a potential target for the treatment strategy of CML.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Antígenos de Histocompatibilidade Menor/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Repressoras/deficiência , Proteínas Repressoras/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Proteínas com Motivo Tripartido/deficiência , Proteínas com Motivo Tripartido/metabolismo , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Antígenos de Histocompatibilidade Menor/genética , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Repressoras/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proteínas com Motivo Tripartido/genéticaRESUMO
PURPOSE: Bronchiolitis obliterans (BO) is a highly debilitative and fatal syndrome associated with a series of severe lower airway disorders. The pathogenesis of BO is complicated and not entirely understood. An appropriate animal model of BO may aid research into its pathogenesis. Here, we establish a mouse model of BO to provide insight into this disease. MATERIALS AND METHODS: 6-8 week old BABL/c mice were exposed to 5% nitric acid (NA) aerosol through a nebulizer for 3 hours, and controls were exposed to distilled water instead. Symptoms, airway resistance and pathological process were observed dynamically. The levels of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), 8-isoprostane and myeloperoxidase (MPO) in lung tissue and bronchoalveolar lavage fluids (BLAF) were determined by ELISA on day 3, 7, 14, 28 and 56 after the aerosol nebulization. RESULTS: Typical BO lesions were observed in NA nebulized mice characterized histologically by initial necrotizing bronchiolitis and final airway fibrosis at day 28 after the aerosol nebulization. NA nebulized mice also exhibited labored breathing and significantly increased airway resistance. Expression of MMP-2, MMP-9, TIMP-1, 8-isoprostane and MPO were significantly elevated in NA nebulized mice in different time frame. CONCLUSION: A murine BO model was established by NA aerosol inhalation. It provides an easy, economic, and reproducible mice model for BO research.
Assuntos
Bronquiolite Obliterante/induzido quimicamente , Modelos Animais de Doenças , Ácido Nítrico/toxicidade , Aerossóis/administração & dosagem , Animais , Bronquiolite Obliterante/metabolismo , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Inalação , Metaloendopeptidases/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ácido Nítrico/administração & dosagem , Peroxidase/metabolismo , Reprodutibilidade dos Testes , Fatores de Tempo , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
BACKGROUND We aimed to predict the abnormal LDL level by using TG, TC, HDL, and non-HDL in this study. MATERIAL AND METHODS Triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) data were obtained from the Laboratory Information System (LIS) for 4 years (Oct 1, 2013 to Sept 30, 2017) from among 34 270 healthy Chinese patients at Shuyang People's Hospital. TG, TC, HDL, and LDL (direct clearance method) were measured using a TBA2000FR biochemical analyzer. The non-HDL was calculated as TC minus HDL. Correlations between TG, TC, non-HDL, and LDL were analyzed using Spearman's rank correlation. Receiver operating characteristics (ROC) curve analysis was used to evaluate the predictive utility of TG, TC, and non-HDL for the abnormal LDL level (<130 mg/dL). RESULTS Both TC (r=0.870) and non-HDL (r=0.893) were significantly positively correlated with LDL. The area under curve of TC and non-HDL can be used to predict abnormal LDL levels. Optimal thresholds were 182.5 mg/Dl (4.72 mmol/L) for TC and 135.3 mg/Dl (3.50 mmol/L) for non-HDL. Based on these optimal thresholds, less than 0.5% and 0.4% of tests with elevated LDL were missed using TC and non-HDL, respectively, but the value of these missed LDL levels was not very high (<147.3 mg/dL). CONCLUSIONS If the value of non-HDL is less than 135.3 mg/Dl (3.50 mmol/L) and/or TC is less than 182.5 mg/Dl (4.72 mmol/L) for the apparently healthy populations, the LDL level will be less than 130 mg/Dl (3.36 mmol/L). TC and non-HDL can be used to predict the abnormal LDL level in apparently healthy populations.