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The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility.
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Pontos de Checagem da Fase M do Ciclo Celular , Meiose , Animais , Feminino , Camundongos , Ciclossomo-Complexo Promotor de Anáfase/genética , Ciclossomo-Complexo Promotor de Anáfase/metabolismo , Oócitos/metabolismo , Ubiquitinas/metabolismoRESUMO
BACKGROUND: Colorectal juvenile polyps are rare and generally considered benign in adults. Carcinogenesis or neoplastic changes are rarely mentioned in the literature. We systematically evaluated the characteristics and potential malignancy of colorectal juvenile polyps in adults. METHODS: We retrospectively reviewed the medical records of 103 adults diagnosed with colorectal juvenile polyps from September 2007 to May 2020 at our hospital. The characteristics, endoscopic findings, occurrence of intraepithelial neoplasia, carcinogenesis and diagnostic value of chicken skin mucosa (CSM) were analyzed. RESULTS: The average age of patients with juvenile polyps was 43.2 years (range, 19 to 78 years). A total of 101 patients (101/103, 98.1%) had a single juvenile polyp, and two patients had multiple polyps (107 polyps in total). Polyp sizes ranged from 0.5 to 5 cm. One (1/107, 0.9%) juvenile polyp was cancerous, and 7 (7/107, 6.5%) developed low-grade intraepithelial neoplasia. Neoplasia and cancerization did not appear in the two patients with multiple polyps. A 27-year-old female had a 2-cm polyp with well-differentiated adenocarcinoma in the mucosa in the sigmoid colon with erosion on the surface. CSM was observed adjacent to 17 polyps, which were all located in the rectum and sigmoid colon, and one polyp showed low-grade intraepithelial neoplasia. CONCLUSIONS: Colorectal juvenile polyps occur in a wide range of locations and in variable sizes and numbers. These polyps are solitary in most patients and have neoplastic potential. CSM is not a tumorigenic marker in colorectal juvenile polyps and usually occurs in the distant colorectum. Colorectal juvenile polyps in adults may progress from low-grade intraepithelial neoplasia to high-grade intraepithelial neoplasia and then to carcinoma and should be treated when discovered and regularly followed as colorectal adenomas.
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Adenoma , Pólipos do Colo , Neoplasias Colorretais , Adenoma/diagnóstico , Adulto , Idoso , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Sichuan is a province located in southwestern China, which have a higher incidence of tuberculosis (TB). This study aimed to analyze the epidemiological and clinical characteristics, as well as drug resistance in culture-confirmed children with Tuberculosis meningitis (TBM) in Southwest of China. METHODS: We performed a retrospective study on children (< 14 years old) with cerebrospinal fluid (CSF) culture-confirmed TBM between January 2013 and December 2018 at Public Health Clinical Center of Chengdu (PHCCC). Mycobacterium tuberculosis (MTB) drug sensitivity testing (DST) was performed using the MicroDST™ method. The age, gender, family history of tuberculosis, status of Bacillus Calmette-Guérin (BCG) vaccination, residential areas information, clinical, laboratory, and radiological features were recorded. Data were analyzed using SPSS Statistics Client 25.0, and the change in drug resistance rate was examined using the Cruskal-Wallis test. RESULTS: Among 319 patients clinically diagnosed with TBM, 42 (13.2%) were Mycobacterial culture positive. Their median age was nine years, and the distribution was equal among female and male patients. Among 42 patients who were enrolled in the study, 1/42 (2.38%) passed away. Children with TBM were concentrated in the minority areas of western Sichuan, where 34/42 (81.0%) patients with TBM belonged to ethnic minorities, and only 2/42 (4.76%) received BCG vaccination in the past. Chest X-rays changes were observed in all patients. Fever and headache were the most common presenting symptom. Thirty-five (83.3%) patients suffered from neck stiffness, and 30/42 (71.4%) had high CSF pressure. DST results showed that the resistance rate was high; resistance to any anti-tuberculosis drug (ATD) was observed in 13 (31.0%) patient isolates, while multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) were found in 2 (4.8%) and 1 (2.4%) patients, respectively. CONCLUSIONS: TBM among children in Southwest China was mainly concentrated in the minority areas of western Sichuan and more than 95% of patients did not receive BCG vaccination at birth. The most common symptoms were fever, headache, and neck stiffness and all patients had positive chest X-ray findings. In addition, high rates of drug resistance were found.
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Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/epidemiologia , Adolescente , Antituberculosos/uso terapêutico , Vacina BCG , Criança , Pré-Escolar , China/epidemiologia , Tuberculose Extensivamente Resistente a Medicamentos/líquido cefalorraquidiano , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Feminino , Humanos , Incidência , Lactente , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/tratamento farmacológico , VacinaçãoRESUMO
The clinical treatment of joint contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca2+-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-ß1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.
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Contratura/etiologia , Imobilização/efeitos adversos , Articulações , Músculo Esquelético , Transdução de Sinais/fisiologia , Atrofia , Autofagia , Cálcio/metabolismo , Caspases/metabolismo , Tecido Conjuntivo/metabolismo , Tecido Conjuntivo/patologia , Contratura/metabolismo , Contratura/patologia , Contratura/terapia , Fibrose , Humanos , Lisossomos/metabolismo , Metaloproteinases da Matriz/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Fator de Crescimento Transformador beta1/metabolismo , Ubiquitina/metabolismoRESUMO
An efficient synthesis of (E)-cinnamaldehydes by a metal-free DDQ-mediated oxidative transformation of allylarenes was developed. The protocol provides a practical method to prepare diverse (E)-cinnamaldehydes with broad functional group tolerance in good to excellent yields, including easy access to natural products randainal and geranyloxy sinapyl aldehyde from plant extracts. Finally, the mechanism of a single-electron transfer process was proposed.
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BACKGROUND: We compared the diagnostic utility of procalcitonin (PCT), C-reactive protein (CRP), and hematological markers, including white blood cell count (WBC), neutrophils (NEU), percentage of neutrophils (NEU%), lymphocytes (LYM), neutrophil-lymphocyte count ratio (NLCR), and platelet count (PLT) for predicting bloodstream infection (BSI), which was confirmed by blood culture (BC). METHODS: A retrospective analysis was conducted for 1807 inpatients. The level of PCT, CRP, blood cells, and blood culture results were compared between the positive blood culture group and negative blood culture group; each indicator was analyzed in the performance of bacterial BSI diagnosis by drawing ROC curves. RESULTS: Blood cultures were positive in 230 patients; hence, the prevalence of bacteremia was 12.7%. There were significant differences in the median value for each marker between positive group BCs and negative group BCs (p < 0.05). The areas under the receiver operating characteristic curves (ROC-AUCs) of PCT, CRP, WBC, NEU, NUE%, LYM, NLCR, and PLT for discriminating positive BCs from negative BCs were 0.811, 0.654, 0.612, 0.634, 0.684, 0.595, 0.682, and 0.633 respectively. PCT concentrations of gram-negative (14.94 ng/mL, IQR 2.93 ï¾ 48.76) were significantly higher than gram-positive (4.74 ng/mL, IQR 1.22 ï¾ 17.5) and fungal (1.47 ng/mL, IQR 0.66 ï¾ 35.34). CONCLUSIONS: PCT proved to be the most reliable predictor of BSI, second were NEU% and NLCR. A higher PCT level was found in patients with a gram-negative BSI compared to gram-positive BSI and fungal BSI.
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Bacteriemia/diagnóstico , Calcitonina/sangue , Fungemia/diagnóstico , Adulto , Idoso , Área Sob a Curva , Bacteriemia/sangue , Bacteriemia/microbiologia , Técnicas Bacteriológicas , Biomarcadores/sangue , Proteína C-Reativa/análise , Feminino , Fungemia/sangue , Fungemia/microbiologia , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
Efflux pump systems are one of the most important mechanisms conferring multidrug resistance in Pseudomonas aeruginosa. MexAB-OprM efflux pump is one of the largest multi-drug resistant efflux pumps with high-level expression, which is controlled by regulatory genes mexR, nalC, and nalD. This study investigated the role of efflux pump MexAB-OprM in 75 strains of carbapenem-resistant P. aeruginosa and evaluated the influence of point mutation of the regulatory genes. The minimum inhibitory concentrations of imipenem and meropenem, with or without MC207110, an efflux pump inhibitor, were determined by agar dilution method to select the positive strains for an overexpressed active efflux pump. Carba NP test and EDTA-disk synergy test were used for the detection of carbapenemase and metallo-ß-lactamases, respectively. The gene mexA, responsible for the fusion protein structure, and the reference gene rpoD of the MexAB-OprM pump were amplified by real-time PCR. The quantity of relative mRNA expression was determined simultaneously. By PCR method, the efflux regulatory genes mexR, nalC, and nalD and outer membrane protein OprD2 were amplified for the strains showing overexpression of MexAB-OprM and subsequently analyzed by BLAST. Among the 75 P. aeruginosa strains, the prevalence of efflux pump-positive phenotype was 17.3 % (13/75). Carba NP test and EDTA-disk synergy test were all negative in the 13 strains. PCR assay results showed that ten strains overexpressed the MexAB-OprM efflux pump and were all positive for the regulatory genes mexR, nalC, and nalD. Sequence analysis indicated that of the ten isolates, nine had a mutation (Gly â Glu) at 71st amino acid position in NalC, and eight also had a mutation (Ser â Arg) at 209th position in NalC. Only one strain had a mutation (Thr â Ile) at the 158th amino acid position in NalD, whereas eight isolates had mutations in MexR. In conclusion, overexpression of efflux pump MexAB-OprM plays an important role in carbapenem-resistant P. aeruginosa. The mutations of regulatory genes may be a main factor contributing to overexpression of MexAB-OprM.
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Antibacterianos/farmacologia , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/metabolismo , Carbapenêmicos/farmacologia , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Pseudomonas aeruginosa/genética , beta-Lactamases/metabolismo , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Genes Reguladores/genética , Humanos , Meropeném , Testes de Sensibilidade Microbiana , Mutação , Fenótipo , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Repressoras/genética , Tienamicinas/farmacologia , beta-Lactamases/genéticaRESUMO
Fangchinoline (FA) is an alkaloid derived from the traditional Chinese medicine Fangji. Numerous studies have shown that FA has a toxic effect on various cancer cells, but little is known about its toxic effects on germ cells, especially oocytes. In this study, we investigated the effects of FA on mouse oocyte maturation and its potential mechanisms. Our results showed that FA did not affect meiosis resumption but inhibited the first polar body extrusion. This inhibition is not due to abnormalities at the organelle level, such as chromosomes and mitochondrial, which was proved by detection of DNA damage and reactive oxygen species. Further studies revealed that FA arrested the oocyte at the metaphase I stage, and this arrest was not caused by abnormal kinetochore-microtubule attachment or spindle assembly checkpoint activation. Instead, FA inhibits the activity of anaphase-promoting complexes (APC/C), as evidenced by the inhibition of CCNB1 degeneration. The decreased activity of APC/C may be due to a reduction in CDC25B activity as indicated by the high phosphorylation level of CDC25B (Ser323). This may further enhance Maturation-Promoting Factor (MPF) activity, which plays a critical role in meiosis. In conclusion, our study suggests that the metaphase I arrest caused by FA may be due to abnormalities in MPF and APC/C activity.
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Benzilisoquinolinas , Fator Promotor de Maturação , Meiose , Mesotelina , Oócitos , Animais , Meiose/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Feminino , Benzilisoquinolinas/farmacologia , Fator Promotor de Maturação/metabolismo , Camundongos , Fosfatases cdc25/metabolismo , Fosfatases cdc25/genética , Ciclossomo-Complexo Promotor de Anáfase/metabolismo , Camundongos Endogâmicos ICR , Espécies Reativas de Oxigênio/metabolismo , Dano ao DNA/efeitos dos fármacos , Ciclina B1/metabolismo , Ciclina B1/genéticaRESUMO
As one of food-borne parasitic diseases, toxoplasmosis entails the risk of developing reactivation in immunocompromised patients. The synthetic dipeptide pidotimod is a potent immunostimulating agent that improves the immunodefenses in immunodepression. To investigate the efficacy of pidotimod as a preventive treatment, we used a murine model of reactivated toxoplasmosis with cyclophosphamide (CY)-induced immunosuppression. Pidotimod administration significantly restored the body weight and spleen organ index, increased survival time (from 70 to 90%), and decreased the parasitemia (from 80 to 35%) of CY-induced mice with reactivated toxoplasmosis. Cytokine profiles and CD4(+) T cells subpopulation analyses by Cytometric Bead Array and flow cytometry demonstrated that pidotimod treatment resulted in a significant upregulation of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2) and Th1 cells (from 3.73 ± 0.39 to 5.88 ± 0.46%) after CY induction in infected mice. Additionally, histological findings and parasite DNA quantification revealed that mice administered with pidotimod had a remarkable reduction of parasite burden (two-log) and amelioration of histopathology in the brains. The in vitro studies showed that pidotimod significantly restored concanavalin A-induced splenocyte proliferation and pro-inflammatory cytokines in the supernatants of splenocyte culture. It could be concluded that the administration of pidotimod in immunocompromised mice significantly increases the Th1-biased immune response, prolongs survival time, and ameliorates the load of parasites in the blood. This is the first report of the preventive effect of pidotimod on reactivated toxoplasmosis.
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Fatores Imunológicos/uso terapêutico , Ácido Pirrolidonocarboxílico/análogos & derivados , Tiazolidinas/uso terapêutico , Toxoplasmose Animal/prevenção & controle , Animais , Ciclofosfamida/farmacologia , Citocinas/genética , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Imunossupressores/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Parasitemia , Ácido Pirrolidonocarboxílico/uso terapêutico , Organismos Livres de Patógenos Específicos , Baço/citologia , Baço/efeitos dos fármacos , Toxoplasmose Animal/imunologiaRESUMO
Objectives: This study summarizes the epidemiological characteristics, species distribution, and drug sensitivity of clinical nontuberculous mycobacteria (NTM) isolates at the Public Health Clinical Center of Chengdu, China, from January 2017 to December 2022. Methods: We retrospectively analyzed data from patients with clinically isolated NTM strains. Chi-square analysis assessed the rate of Mycobacterium strain isolation over 6 years. Results: The number of samples tested for Mycobacterium tuberculosis (MTB) and/or NTM increased each year, while MTB detection decreased and NTM detection rose significantly each year (P=0.03). The average age of NTM patients was 51 ± 17.53 years, with a 14.1% HIV infection rate. The predominant isolates were Mycobacterium avium-intracellulare (MAC) and M. chelonae/M. abscessus, with 96.4% of cases being of Han ethnicity. Amikacin, moxifloxacin, and clarithromycin were effective against M. avium and M. intracellulare; linezolid, amikacin, and cefoxitin were effective against M. chelonae/M. abscessus. Over 90% of NTM cases originated from the respiratory tract. Conclusion: The NTM isolation rate in Southwest China has risen in recent years, primarily among elderly patients with a high HIV co-infection rate. The main NTM isolates were MAC and M. chelonae/M. abscessus. Amikacin, moxifloxacin, clarithromycin, and linezolid exhibited strong antibacterial activity against SGM, while amikacin and linezolid displayed relatively better antibacterial activity against RGM. The prevalence of NTM infection may be positively associated with regional economic development and health conditions.
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Infecções por HIV , Infecções por Mycobacterium não Tuberculosas , Tuberculose , Humanos , Idoso , Adulto , Pessoa de Meia-Idade , Micobactérias não Tuberculosas , Claritromicina/farmacologia , Amicacina/farmacologia , Linezolida/farmacologia , Linezolida/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Moxifloxacina/farmacologia , Estudos Retrospectivos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Tuberculose/epidemiologia , China/epidemiologia , Testes de Sensibilidade MicrobianaRESUMO
Purpose: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a serious medical condition with a high short-term mortality rate, making accurate prognostic assessment essential for informed clinical decision-making. In this study, we aimed to develop a simple and effective prognostic model for predicting short-term mortality in patients with HBV-ACLF. Patients and Methods: To achieve our objective, we enrolled both a cross-sectional cohort (n = 291) and a retrospective cohort (n = 185) in this study. We collected laboratory and clinical data from these cohorts and performed univariate and multivariate logistic regression analyses to identify independent predictors of short-term mortality. Subsequently, we developed a novel prognostic score for HBV-ACLF, which was validated and assessed using receiver operating characteristic (ROC) curve analysis to determine its performance. Results: Our analysis revealed that the admission prealbumin (PAB) level was a robust independent predictor of 30-day mortality, with an area under the receiver operating characteristic (AUROC) of 0.760. Moreover, we developed the HIAPP score, a prognostic-score model based on PAB. The HIAPP score was significantly lower in survivors compared to non-survivors (-2.80±0.21 vs 0.97±0.41, P < 0.001). The HIAPP score's AUROC value was 0.899, which was found to be superior to the MELD score (AUROC = 0.795) and the CLIF-C ACLF score (AUC =0.781) and comparable to the COSSH-ACLF II score (AUC =0.825) for predicting 30-day mortality. These findings were also validated in a separate cohort, further supporting the utility of the HIAPP score as a prognostic tool for HBV-ACLF patients. Conclusion: Our study identifies the admission PAB level as a simple and valuable predictive index for 30-day mortality in HBV-ACLF patients. Furthermore, the HIAPP score, which incorporates PAB, PLT, INR, HE, and age, is an easy-to-use and pragmatic prognostic score in predicting short-term mortality.
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OBJECTIVES: There are few reports on extrapulmonary tuberculosis/human immunodeficiency virus (EPTB/HIV) co-infection patients, especially the resistance profile of culture-confirmed EPTB. The purpose of our study was to analyse the clinical characteristics, common sites and drug resistance profile of culture-confirmed EPTB/HIV co-infection patients in Southwest China (2017-2020). METHODS: A total of 201 EPTB/HIV co-infection cases were selected for this study. Patient demographics and clinical characteristics were collected. Mycobacterium tuberculosis drug susceptibility testing (DST) was performed by the microporous plate method. RESULTS: Among 2884 culture-confirmed EPTB cases, patients were predominantly male (1921/2884; 66.6%) and the mean age was 31 years. There were 201 patients (7.0%) with EPTB/HIV co-infection, among which 170 (84.6%) were male and the mean age was 42 years (range 13-86 years). During the 7-year study period, the mean number of EPTB/HIV co-infection cases was 29 per year (range 12-49 per year) at the studied institution. Diarrhoea, headache and fever were the most common presenting symptoms. DST showed resistance to any anti-TB drug in 62 isolates (30.8%), while multidrug-resistant TB and extensively drug-resistant TB were found in 14 (7.0%) and 10 (5.0%) cases, respectively. The distribution of EPTB tissue type was mainly meningeal and lymphatic, but varied between the sexes. CONCLUSION: The immune level of EPTB/HIV co-infected patients was low and most were in advanced-stage AIDS. Patients were mainly young males and the site of EPTB was mainly meningeal and lymphatic. The most common symptoms were diarrhoea, headache and fever. High rates of drug resistance were found.
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Coinfecção , Tuberculose Extensivamente Resistente a Medicamentos , Infecções por HIV , Mycobacterium tuberculosis , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Coinfecção/epidemiologia , Diarreia/epidemiologia , Resistência a Medicamentos , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Cefaleia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Influenza A virus (IAV) triggers acute exacerbation of chronic obstructive pulmonary disease (AECOPD), but the molecular mechanisms remain unclear. In this study, we investigated the role of IAV induced NLRP3 inflammasome activation to increase airway inflammation response in the progression of AECOPD. METHODS: Human bronchial epithelial cells were isolated and cultured from normal and COPD bronchial tissues and co-cultured with IAV. The NLRP3 inflammasome associated genes were identified using RNA sequencing, and the expressions of NLRP3 inflammasome components were measured using qRT-PCR and western blot after cells were transfected with siRNA and treated with MCC950. Moreover, IAV-induced COPD rat models were established to confirm the results; 37 AECOPD patients were included to measure the serum and bronchoalveolar lavage fluid (BALF) of interleukin (IL)-18 and IL-1ß. RESULTS: Increased levels of NLRP3 inflammasome components were not seen until 6 h post-inoculation in normal cells. However, both cell groups reached peak NLRP3 level at 12 h post-inoculation and maintained it for up to 24 h. ASC, Caspase-1, IL-1ß and IL-18 were also elevated in a similar time-dependent pattern in both cell groups. The mRNA and protein expression of the NLRP3 inflammasome components were decreased when COPD cells treated with siRNA and MCC950. In COPD rats, the NLRP3 inflammasome components were elevated by IAV. MCC950 alleviated lung damage, improved survival time, and reduced NLRP3 inflammasome components expression in COPD rats. Additionally, the serum and BALF levels of IL-1ß and IL-18 were increased in AECOPD patients. CONCLUSIONS: NLRP3 inflammasome is activated in COPD patients as a pre-existing condition that is further exacerbated by IAV infection.
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Objective: To develop effective alternatives to natural enzymes, it is crucial to develop nanozymes that are economical, resource efficient, and environmentally conscious. Carbon nanomaterials that have enzyme-like activities have been extensively developed as substitutes for traditional enzymes. Methods: Carbide-derived carbons (CDCs) were directly synthesized via a one-step electrochemical method from a MAX precursor using an ammonium bifluoride electrolyte at ambient conditions. The CDCs were characterized by systematic techniques. Results: CDCs showed bienzyme-like activities similar to that of peroxidase and superoxide dismutase. We systematically studied the dependence of CDC enzyme-like activity on different electrolytes and electrolysis times to confirm activity dependence on CDC content. Additionally, the synthesis mechanism and CDC applicability were elaborated and demonstrated, respectively. Conclusion: The demonstrated synthesis strategy eliminates tedious intercalation and delamination centrifugation steps and avoids using high concentrations of HF, high temperatures, and halogen gases. This study paves the way for designing two-dimensional material-based nanocatalysts for nanoenzyme and other applications.
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Compostos de Amônio/síntese química , Carbono/química , Técnicas Eletroquímicas , Enzimas , Fluoretos/síntese química , Nanoestruturas , Oxirredução , HumanosRESUMO
With rapid and efficient drug release, few side effects and excellent biodegradable properties, the reduction-sensitive carriers is not only the new hot point in the field of pharmaceutical research, but also the most promising intelligent drug carrier on clinical application. This paper reviews the latest research of reduction-sensitive drug and gene carriers, including the mechanisms of drug release and the synthesis of the reduction-sensitive conjugates, reduction-sensitive nano polymer micelles, nano vesicles, nano hollow microspheres, nano liposomes, as well as the characteristics and advantages of various kinds of carrier system. It will provide a theoretical basis for its further application.
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Portadores de Fármacos/química , Nanopartículas , Preparações Farmacêuticas/química , Polímeros/química , Portadores de Fármacos/administração & dosagem , Micelas , Microesferas , Oxirredução , Preparações Farmacêuticas/administração & dosagem , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: To investigate caries status and its impact factors in preschool children in plateau and to provide reference for caries prevention in highlands. METHODS: Examination of caries was performed on 1 597 children aged 3-5 years old in 11 kindergartens in Changdu, Xizang, in accordance with the 4th National Oral Health Survey standards and methods. Their parents were surveyed with the questionnaire regarding oral hygiene habit and consciousness about oral health and related factors. All the data were collected and analyzed. RESULTS: The prevalence of caries among children aged 3-5 years old in Changdu was 52.85%, with dmft index of 2.44. The caries rate and dmft of children aged 3 years old were lower than those of children aged 4 and 5 years old (P<0.05). No significant difference was observed in the caries rate between males and females (P>0.05). Single-factor analysis showed that the frequency of brushing teeth more than twice a day, low frequency of eating sweets, high frequency of drinking butter tea, and regular oral examination can reduce the rate of caries (P<0.05). Multivariate logistic analysis showed that the frequency of eating sweets, drinking butter tea, and oral examination are related impact factors of caries. CONCLUSIONS: The prevalence of ca-ries in children aged 3-5 years old in Changdu increases with aging. Good oral hygiene and eating habits and regular oral examination can reduce the rate of caries.
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Cárie Dentária , Pré-Escolar , Estudos Transversais , Índice CPO , Cárie Dentária/epidemiologia , Cárie Dentária/prevenção & controle , Suscetibilidade à Cárie Dentária , Feminino , Humanos , Masculino , Saúde Bucal , Higiene Bucal , PrevalênciaRESUMO
The ongoing coronavirus disease 2019 (COVID-19) pandemic represents one of the most exigent threats of our lifetime to global public health and economy. As part of the pandemic, from January 10 to March 10, 2020, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) began to spread in Hefei (Anhui Province, China) with a total of 174 confirmed cases of COVID-19. During this period, we were able to gather critical information on the transmission and evolution of pathogens through genomic surveillance. Particularly, the objective of our study was to track putative variants of SARS-CoV-2 circulating in Hefei for the first time and contribute to the global effort toward elucidating the molecular epidemic profile of the virus. Patients who showed symptoms of COVID-19 were routinely tested for SARS-CoV-2 infections via RT-PCR at the First Affiliated Hospital of Anhui Medical University. Whole-genome sequencing was performed on 97 clinical samples collected from 29 confirmed COVID-19 patients. As a result, we identified a local novel single-nucleotide polymorphism site (10,380) harboring a G â T mutation (Gly â Val) in Hefei. Further phylogenetic network analysis with all the sequences of SARS-CoV-2 deposited in GenBank collected in East and Southeast Asia revealed a local subtype of S-type SARS-CoV-2 (a1) harboring a C â T synonymous mutation (Leu) at position 18,060 of ORF1b, likely representing a local SARS-CoV-2 mutation site that is obviously concentrated in Hefei and the Yangtze River Delta region. Moreover, clinical investigation on the inflammatory cytokine profile of the patients suggested that mutations at positions 18,060 (the shared variable site of subtype a1) and 28,253(harboring a C â T synonymous mutation, Phe) were associated with milder immune responses in the patients.
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OBJECTIVE: To investigate the diagnosis and treatment of macrocystic serous adenoma of the pancreas (MSAP). METHODS: The clinical data of 5 patients with MSAP treated from October 1999 to October 2009 were retrospectively analyzed. There were 5 female and 1 male. RESULTS: Of the 5 patients, 3 patients presented with abdominal pain and fullness, 1 patient with jaundice, 1 patient with asymptomatic. Ultrasonography and CT could manifest macrocystic lesion of the pancreas; all the lesion showed a well-defined border, internal septations, enhanced cyst walls, with no intramural (mural) nodule and papillary projections; the wall was smooth and thin in 4 cases; irregular lobulation could be observed in 3 cases, round or oval in 2 cases; 2 cases had pancreatic duct dilatation, 1 case had biliary duct dilatation. The tumors located in the pancreatic body and tail in 3 cases, the tumors located the pancreatic head in 2 cases. The sizes of the tumors ranged from 6.5 cm to 13.0 cm (mean, 8.8 cm). Five patients all accepted surgical intervention. The main postoperative complication was pancreatic fistula (2 cases); all the fistula was cured. Recurrence or metastasis were not found in 5 patient followed up postoperatively from 8 to 35 months. CONCLUSIONS: MSAP has no specific symptoms. The imaging appearance of MSAP is similar to mucinous cystic neoplasm of the pancreas. The tumor can gradually grow up and produce compression symptoms. MSAP can be cured by complete resection.
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Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To discuss the proper surgical management of pancreatic benign and low-grade malignant potential neoplasm. METHODS: The experience of 72 cases who accepted organ preserving pancreatectomy from January 1990 to May 2010 was analyzed retrospectively. There were 24 male and 48 female, aged from 15 to 68 years with mean age of 46 years. There were 9 cases underwent duodenum-preserving resection of the head of the pancreas, 29 cases underwent spleen-preserving distal pancreatectomy, 11 cases underwent middle segmental pancreatectomy, 23 cases underwent tumor extirpation of huge pancreatic cancer in pancreatic head and body. RESULTS: Pancreatic fistula and biliary fistula in 1 case respectively were cured among who accepted duodenum-preserving resection of the head of the pancreas. Pancreatic fistula was found in 3 cases who accepted spleen-preserving distal pancreatectomy. Pancreaticobiliary anastomotic bleeding in 1 case was cured among who accepted middle segmental pancreatectomy. Pancreatic fistula was found in 5 cases among who accepted tumor extirpation of huge pancreatic cancer in pancreatic head and body, and liver metastasis was found in 3 cases at 6, 12, 16 months after surgery respectively. CONCLUSIONS: Organ preserving pancreatectomy can obviously reduce operative injury to patients, its therapeutic effect is similar to that of classical operation, it is the first option of benign and low-grade malignant potential neoplasm.
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Pancreatectomia/métodos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an important clinical disease, and its global prevalence and mortality rates are high. It is meaningful to investigate the efficacy of integrative respiratory rehabilitation training in quality of life and respiratory physiology of COPD patients in stable phase. OBJECTIVE: To observe the efficacy of integrative respiratory rehabilitation training in exercise ability and quality of life of COPD patients in stable phase. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Eighty outpatients and inpatients with COPD from Department of Respiratory Medicine, Taihe Hospital, Yunyang Medical College were randomly divided into 4 groups, with 20 patients in each group. The patients in group A only received drug therapy, the patients in group B received traditional qigong training, the patients in group C received modern rehabilitation training, and the patients in group D received integrative respiratory rehabilitation training. MAIN OUTCOME MEASURES: Chronic respiratory questionnaire (CRQ), 6-minute walking distance and Borg score in each group were examined before and after one-, three-, and six-month and one-year treatment. RESULTS: The 6-minute walking distance, Borg score and CRQ score in group A had no significant changes after treatment (P>0.05). After one-month treatment, there were no significant differences in 6-minute walking distance and Borg score in groups B, C and D as compared with those before treatment (P<0.05). After three-month treatment, 6-minute walking distance and Borg score were improved in groups B, C and D (P<0.05). After six-month and one-year treatment, 6-minute walking distance, Borg score and CRQ score in groups B, C and D were improved as compared with those before treatment (P<0.05), and there were significant differences between group D and any of groups A, B and C (P<0.05). CONCLUSION: Modern rehabilitation training, traditional qigong training and integrative respiratory rehabilitation training programs all can improve the quality of life and exercise ability of COPD patients, and integrative respiratory rehabilitation training program is better than modern rehabilitation training and traditional qigong training programs. The efficacy of respiratory rehabilitation training is time-dependent, and need long-time adherence to the therapy.