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1.
Eur Respir J ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764183

RESUMO

BACKGROUND: Enlarging tuberculosis (TB) preventive treatment among at-risk populations is a critical component of the End TB Strategy. It is urgently needed to develop suitable latent tuberculosis infection (LTBI) testing and treatment tools according to local TB epidemic and available resources in worldwide. METHODS: Based on an open-labeled randomised controlled trial conducted since 2015 among rural residents aged 50-70 years with LTBI, the protective efficacy of the 6-week twice-weekly regimen of rifapentine plus isoniazid was further evaluated in a 5-year follow-up survey. RESULTS: A total of 1298 treated participants and 1151 untreated controls were included in the 5-year protective efficacy analysis. In the per-protocol analysis, the incidence rate was 0.49/100 person-years (95% confidence interval (CI): 0.30-0.67) in the untreated control group and 0.19/100 person-years (95% CI: 0.07-0.32) in the treated group, the protection rate was 61.22%. Subgroup analysis showed that the protection rate was 76.82% in the per-protocol analysis among participants with baseline IFN-γ levels in the highest quartile (≥3.25 IU·mL-1). The multiple logistic regression analysis indicated that participants with baseline BMI <18.5 kg·m-2 and with pulmonary fibrotic lesions had increased hazard of developing active disease with an adjusted hazard ratio (aHR) of 3.64 (95% CI: 1.20-11.00) and 5.99 (95% CI: 2.20-16.27), respectively. In addition, individuals with higher baseline IFN-γ levels showed an increased risk of TB occurrence (aHR 2.27, 95% CI 1.13-4.58). CONCLUSIONS: Our findings suggested the 6-week twice-weekly regimen of rifapentine plus isoniazid for LTBI treatment might be an optional tool for TB control in Chinese population.

2.
IUBMB Life ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34773437

RESUMO

Posttranslational modifications (PTMs) could influence many aspects of protein behavior and function in organisms. Protein glycosylation is one of the major PTMs observed in bacteria, which is crucial for functional regulations of many prokaryotic and eukaryotic organisms. Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine has been recognized as an indispensable tool in the global fight against tuberculosis (TB) worldwide over several decades. Nevertheless, analysis of glycoprotein profiles of BCG has not been clearly investigated. In this study, we performed O-mannosylated protein analysis in BCG bacteria using gel-based and gel-free approaches. In total, 1,670 hexosylated peptides derived from 754 mannosylated proteins were identified. Furthermore, 20 novel protein products supported by 78 unique peptides not annotated in the BCG database were detected. Additionally, the translational start sites of 384 proteins were confirmed, and 78 proteins were validated through the extension of translational start sites based on N-terminus-derived peptides. The bioinformatic analysis of the O-mannosylated proteins was performed and the expression profiles of four randomly selected proteins were validated through Western blotting. A number of proteins involved in metabolic pathways, including the tricarboxylic acid cycle, glycolysis, oxidative phosphorylation, and two-component system, are discussed. Taken together, these results offer the first O-mannosylated protein analysis of a member of mycobacteria reported to date by using complementary gel-based and gel-free approaches. Some of the proteins identified in this study have important roles involved in metabolic pathways, which could provide insight into the immune molecular mechanisms of this recognized vaccine strain.

3.
BMC Pulm Med ; 21(1): 378, 2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34802431

RESUMO

OBJECTIVE: Obstructive sleep apnoea (OSA) is one cause of pulmonary hypertension (PH) and can also emerge along with PH. The clinical diagnosis and treatment of OSA in patients with PH are still controversial. The purpose of this clinical observation study was to observe and summarize the incidence and clinical characteristics of OSA in patients with PH and to explore possible predictors of PH combined with OSA. METHODS: Patients with PH diagnosed by right heart catheterization who underwent overnight cardiorespiratory monitoring from December 2018 to December 2020 were enrolled. OSA was defined as an apnoea-hypopnoea index of ≥ 5/h with ≥ 50% of apnoeic events being obstructive. Baseline clinical characteristics and parameters were collected to compare PH patients with and without OSA. Logistic regression analysis was run to determine the risk factors for OSA in PH patients. RESULTS: A total of 35 (25%) of 140 patients had OSA. OSA is relatively frequent in patients with PH, especially in patients with chronic thromboembolic pulmonary hypertension and patients with lung disease- or hypoxia-associated PH. The patients who had OSA were mostly male and had a higher age and a lower daytime arterial oxygen pressure. Logistic regression analysis found that older age, male sex, and lower daytime arterial blood oxygen pressure correlated with OSA in PH patients. CONCLUSION: OSA is common in patients with PH. Lower daytime arterial oxygen pressure is a risk factor for OSA in older male patients with PH.

4.
Int J Gen Med ; 14: 7337-7348, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737628

RESUMO

Objective: Coronavirus disease 2019 (COVID-19) was associated with a higher risk of arrhythmia in infected patients. However, there are no reports about the effect of the ongoing pandemic on arrhythmias in the non-infected population. We measured the arrhythmia burden in a non-infected population with cardiac implantable devices. Methods: The arrhythmia burden during the COVID-19 pandemic was compared to a 6-month interval in the pre-COVID-19 period. The COVID-19 pandemic was divided into high-risk (17 January 2020 to 16 March 2020) and low-risk periods (17 March 2020 to 17 July 2020) according to whether there were locally infected patients. Arrhythmia burdens were compared among the pre-COVID-19, high-risk, and low-risk periods. Results: A total of 219 patients with 1859 episodes were included. We observed a larger proportion of patients with atrial fibrillation (AF) during the COVID-19 pandemic (38.36% vs 26.03%, p = 0.006). There was not significantly more ventricular arrhythmia during the COVID period than the pre-COVID-19 period (p > 0.05). During the high-risk period, daily frequency of non-sustained ventricular tachycardia (NSVT) (0.0172, 0.0475 vs 0.0109, 0.0164, p < 0.05), atrial tachycardia (AT) (0.0345, 0.0518 vs 0.0164, 0.0219 p < 0.05) and AF (0.0345, 0.0432 vs 0.0164, 0.0186, p < 0.05) and daily duration of NSVT (0.1982, 0.2845 vs 0.0538, 0.1640 p < 0.05) were higher and longer than those in the pre-COVID-19 period. Regression modeling showed that the impact of COVID-19 pandemic lead to an increased onset of AF (odds ratio 2.465; p < 0.01). Patients with paroxysmal AF who had undergone a previous radiofrequency ablation had a lower burden of AF (incidence 21.43% vs 55.00%, P = 0.049, daily frequency 0.0000, 0.0027 vs 0.0000, 241.7978, P = 0.020) during the pandemic. Conclusion: The COVID-19 pandemic contributed to a higher burden of arrhythmias in non-infected patients. Patients would experience a lower burden of AF following radiofrequency ablation treatment, and this effect persisted during the pandemic.

5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(6): 948-953, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34841760

RESUMO

Objective: To study the effect of outer membrane vesicles (OMVs) derived from Salmonella typhimurium (ST) on the ultrastructural features and immune function of dendritic cells (DC). Methods: Mice bone marrow cells were collected aseptically, and myeloid DC were generated by the combined induction and amplification with recombinant mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant mouse interleukin-4 (rm IL-4). Cell morphology was observed under inverted phase contrast microscope and the phenotype was identified with flow cytometry. ST-OMVs were isolated through ultracentrifugation. The survival rate of DC was assessed with CCK-8 assay, and the stimulus concentration of OMVs was henceforth determined. The ultrastructural characteristics of DC loaded with OMVs were observed with transmission electron microscopy. The cytokine secretion, surface molecule expression and phagocytic capacity of DC were examined with flow cytometry. Results: The DC induced and amplified in vitro displayed typical DC phenotype in morphological analysis and the purity of DC exceeded 85%. Transmission electron microscopy showed that there were large numbers of protrusions on the cell surface. After stimulation with ST-OMVs, it was observed that the dendritic structures on the surface of DC were reduced and a large number of phagolysosomes were found in the cytoplasm. In addition, increased numbers of mitochondria, swelling and typical apoptosis were observed. After treatment with ST-OMVs at 5 µg/mL and 10 µg/mL, the secretion of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) of DC increased significantly ( P<0.05). Furthermore, the immature DC could differentiate into mature DCs after stimulation with ST-OMVs, which were characterized by a decrease in phagocytic capacity ( P<0.05) and an upregulation of phenotypic markers ( P<0.05). Conclusion: ST-OMVs can stimulate DC to produce TNF-α and IL-1ß and promote DC maturation and antigen presentation.


Assuntos
Apresentação do Antígeno , Medula Óssea , Animais , Células da Medula Óssea , Diferenciação Celular , Células Dendríticas , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Camundongos , Salmonella
6.
Biomed Pharmacother ; : 112147, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34810050

RESUMO

As one of the important treatments of health care and anti-aging in traditional Chinese medicine (TCM), moxibustion has been proved to have the effects of scavenging free radicals, anti-oxidation, reducing inflammatory reaction, regulating immunity and so on. Recent studies have shown that intestinal microbiota affect the process of aging. The relationship between aging, moxibustion and intestinal microbiota is still unclear. In this study, we explored the effects of moxibustion at Guanyuan (RN4) acupoint on intestinal microbiota, short-chain fatty acids and immunological characteristics of young and elder female Wistar rats to explore the relationship between aging, moxibustion and intestinal microbiota. Six 12-week-old female Wistar rats were young group (Y), and twelve 36-week-old female Wistar rats were randomly divided into elder group (C) and moxibustion group (M). The rats in M group were received mild moxibustion at Guanyuan (RN4) acupoint, 20 min/d for 40 days. The rats in Y group and C group were not given any therapeutic intervention. The results showed that moxibustion increased the abundance of intestinal probiotics (mainly Lactobacillus) and the level of short chain fatty acids, the microcirculation blood flow around Guanyuan (RN4) acupoint was also significantly improved in elder rats. In addition, the expression of MyD88, MAPK, TRAF6, NF-κB in intestinal tissue was down-regulated, and the levels of inflammatory cytokines in intestinal were decreased.

7.
Cardiovasc Diagn Ther ; 11(5): 1047-1057, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34815955

RESUMO

Background: In the 6th World Symposium on Pulmonary Hypertension (PH), the hemodynamic definition of PH was reduced from a mean pulmonary artery pressure (mPAP) ≥25 to >20 mmHg. This study aimed to evaluate the impact of the revised hemodynamic definition on the diagnosis of precapillary PH. Methods: We retrospectively enrolled patients who underwent right heart catheterization from January 2012 to December 2018. All included patients were reassessed according to the revised hemodynamic definition. Results: A total of 1,251 patients were included for analysis, of whom 1,044 patients had precapillary PH and 182 patients had mPAP <25 mmHg. After applying the revised definition, 33 (18.1%) of 182 patients with mPAP <25 mmHg were reclassified as having PH. However, only 7 of these 33 patients had a pulmonary vascular resistance ≥3 wood units and could be considered to have precapillary PH, accounting for 0.7% of the existing precapillary PH population. More importantly, 12 patients with mPAP ≥25 mmHg were delisted from precapillary PH for pulmonary vascular resistance <3 wood units (5 patients from Group III, 4 patients from Group IV, 3 patients from Group V). Overall, there was a net 0.5% decrease [(12-7)/1044×100%] in the population with precapillary PH. Conclusions: The revised hemodynamic definition had a minor impact on the diagnosis of precapillary PH. It should be noted that the revised definition would influence not only patients with mPAP =21-24 mmHg, but also patients with mPAP ≥25 mmHg.

8.
Front Nutr ; 8: 690428, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616762

RESUMO

Background: Dietary patterns promoting hyperinsulinemia and chronic inflammation, including the empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP), have been shown to strongly influence risk of weight gain, type 2 diabetes, cardiovascular disease, and cancer. EDIH was developed using plasma C-peptide, whereas EDIP was based on plasma C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha receptor 2 (TNF-αR2). We investigated whether these dietary patterns were associated with a broader range of relevant biomarkers not previously tested. Methods: In this cross-sectional study, we included 35,360 women aged 50-79 years from the Women's Health Initiative with baseline (1993-1998) fasting blood samples. We calculated EDIH and EDIP scores from baseline food frequency questionnaire data and tested their associations with 40 circulating biomarkers of insulin response/insulin-like growth factor (IGF) system, chronic systemic inflammation, endothelial dysfunction, lipids, and lipid particle size. Multivariable-adjusted linear regression was used to estimate the percent difference in biomarker concentrations per 1 standard deviation increment in dietary index. FDR-adjusted p < 0.05 was considered statistically significant. Results: Empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) were significantly associated with altered concentrations of 25 of the 40 biomarkers examined. For EDIH, the percent change in biomarker concentration in the insulin-related biomarkers ranged from +1.3% (glucose) to +8% (homeostatic model assessment for insulin resistance) and -9.7% for IGF-binding protein-1. EDIH impacted inflammation and endothelial dysfunction biomarkers from +1.1% (TNF-αR2) to +7.8% (CRP) and reduced adiponectin by 2.4%; and for lipid biomarkers: +0.3% (total cholesterol) to +3% (triglycerides/total cholesterol ratio) while reducing high-density lipoprotein cholesterol by 2.4%. EDIP showed a similar trend of associations with most biomarkers, although the magnitude of association was slightly weaker for the insulin-related biomarkers and stronger for lipids and lipid particle size. Conclusions: Dietary patterns with high potential to contribute to insulin hypersecretion and to chronic systemic inflammation, based on higher EDIH and EDIP scores, were associated with an unfavorable profile of circulating biomarkers of glucose-insulin dysregulation, chronic systemic inflammation, endothelial dysfunction and dyslipidemia. The broad range of biomarkers further validates EDIH and EDIP as mechanisms-based dietary patterns for use in clinical and population-based studies of metabolic and inflammatory diseases.

9.
Pulm Circ ; 11(4): 20458940211051292, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659741

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important and major player in the pathophysiology of hypercholesterolemia and atherosclerosis. Recently, PCSK9 has been implicated in the pathogenesis of inflammatory diseases. Whether PCSK9 is involved in idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to investigate the relationship between PCSK9 and IPAH. Serum PCSK9, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 ß (IL-1ß), and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme linked immunosorbent assay. Transthoracic echocardiography was performed among 40 IPAH patients and 20 control subjects. Hemodynamic data were collected via right heart catheterization in patients with IPAH. Serum PCSK9, TNF-α, IL-6, IL-1ß, and MCP-1 levels were significantly higher in IPAH patients than in control subjects (p < 0.001). Among enrolled IPAH patients, PCSK9 levels were higher in WHO-FC III/IV patients compared with those in WHO-FC I/II (p < 0.05), and were positively correlated with TNF-α, IL-6, MCP-1, N-Terminal pro-brain natriuretic peptide, pulmonary arterial systolic pressure (r = 0.653, p < 0.001), pulmonary arterial diastolic pressure (r = 0.466, p = 0.002), mean pulmonary arterial pressure (mPAP, r = 0.730, <0.001), pulmonary vascular resistance (r = 0.488, p = 0.001), and right ventricle diameter (r = 0.563, p < 0.001). In multiple regression analysis, mPAP was strongly associated with serum PCSK9 (ß = 0.694, p < 0.001), independent of other variables. Receiver operating characteristic curve analysis showed the optimal cutoff value of serum PCSK9 concentration for predicting IPAH was 90.67 ng/ml, with a sensitivity of 90.0% and a specificity of 85.0%. In conclusion, IPAH patients had elevated serum PCSK9 levels which correlated the presence and severity of pulmonary hypertension. PCSK9 may be a novel potential therapeutic target.

11.
Oncoimmunology ; 10(1): 1996000, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712513

RESUMO

Multimodality treatment provides modest survival benefits for patients with locally advanced (stage III) non-small-cell lung cancer (NSCLC). Nevertheless, preoperative immunotherapy has continuously been shown to be promising in treating resectable NSCLC.This phase 2 trial enrolled patients with AJCC-defined stage IIIA or T3-4N2 IIIB NSCLC deemed surgically resectable. Patients received three cycles of neoadjuvant treatment with intravenous PD-1 inhibitor toripalimab (240 mg), carboplatin (area under the curve 5), and pemetrexed (500 mg/m2 for adenocarcinoma) or nab-paclitaxel (260 mg/m2 for other subtypes) on day 1 of each 21-day cycle. Surgical resection was performed 4-5 weeks afterward. The primary endpoint was major pathological response (MPR), defined as less than 10% residual tumor remaining at the time of surgery.Thirty-three patients were enrolled, of whom 13 (39.4%) had T3-4N2 stage IIIB disease. Thirty (90.9%) patients underwent resection and all except one (96.7%) achieved R0 resection. Twenty patients (60.6%) in the intention-to-treat population achieved an MPR, including 15 patients (45.5%) who achieved a pathological complete response (pCR). The MPR and pCR rates in the per-protocol population were 66.7% and 50.0%, respectively. The surgical complications included three cases of arrhythmias, one case of a prolonged air leak, and one case of chylothorax. The most common grade 3 treatment-related adverse event (TRAE) was anemia (2, [6.1%]). Severe TRAEs included one (3.0%) case of grade 3 peripheral neuropathy that resulted in surgical cancellation.Toripalimab plus platinum-based doublet chemotherapy yields a high MPR rate, manageable toxicity, and feasible resection in stage III NSCLC.Trial ClinicalTrials.gov (NCT04304248).

12.
Future Med Chem ; 13(24): 2153-2166, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34608806

RESUMO

Dyslipidemia has been associated with the development of osteoarthritis. Our previous study found that 5,7,3',4'-tetramethoxyflavone (TMF) exhibited protective activities against the pathological changes of osteoarthritis. Aim: To investigate the roles of TMF in regulating ABCA1-mediated cholesterol metabolism. Methods: Knockdown and overexpression were employed to study gene functions. Protein-protein interaction was investigated by co-immunoprecipitation, and the subcellular locations of proteins were studied by immunofluorescence. Results: IL-1ß decreased ABCA1 expression and induced apoptosis. Therapeutically, TMF ameliorated the effects of IL-1ß. FOXO3a knockdown expression abrogated the effects of TMF, and FOXO3a overexpression increased ABCA1 expression by interacting with LXRα. TMF promoted FOXO3a nuclear translocation by activating SIRT1 expression. Conclusions: TMF ameliorates cholesterol dysregulation by increasing the expression of FOXO3a/LXRα/ABCA1 signaling through SIRT1 in C28/I2 cells.

13.
Angew Chem Int Ed Engl ; 60(49): 25793-25798, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34676649

RESUMO

Mn-based oxides have sparked extensive scientific interest for aqueous Zn-ion batteries due to the rich abundance, plentiful oxidation states, and high output voltage. However, the further development of Mn-based oxides is severely hindered by the rapid capacity decay during cycling. Herein, a two-step metal-organic framework (MOF)-engaged templating strategy has been developed to rationally synthesize heterostructured Mn2 O3 -ZnMn2 O4 hollow octahedrons (MO-ZMO HOs) for stable zinc ion storage. The distinctive composition and hollow heterostructure endow MO-ZMO HOs with abundant active sites, enhanced electric conductivity, and superior structural stability. By virtue of these advantages, the MO-ZMO HOs electrode shows high reversible capacity, impressive rate performance, and outstanding electrochemical stability. Furthermore, ex situ characterizations reveal that the charge storage of MO-ZMO HOs mainly originates from the highly reversible Zn2+ insertion/extraction reactions.

14.
Front Microbiol ; 12: 716900, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484159

RESUMO

Objectives: Exploring biomarkers monitoring latent tuberculosis infection (LTBI) treatment effectiveness would benefit optimizing the therapeutic regimen. This study aims to identify potential mycobacteria-specific antigen-induced cytokines associated with host responses to preventive treatment. Methods: Based on a randomized controlled trial on LTBI treatment among individuals with chest radiography abnormalities suggestive of prior tuberculosis (TB), the dynamically changed cytokine levels in QuantiFERON-TB Gold In-Tube (QFT) supernatants were estimated during the treatment by bead-based multiplex assays and enzyme-linked immunosorbent assay. Results: In total, 63 treated participants and 32 untreated controls were included in the study. The levels of 13 background-corrected mycobacteria-specific antigen-stimulated cytokines [basic fibroblast growth factor (FGF), growth-regulated oncogene (GRO)-α, interleukin (IL)-1α, IL-1ra, IL-12 (p70), stem cell factor (SCF), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), IL-8, interferon (IFN)-α2, IL-5, IL-12 (p40), leukemia inhibitory factor (LIF), and IL-17A] were found to be statistically different between before and after treatment in treated participants, while no statistically differences were observed in untreated controls. Among these 13 cytokines, the level of IL-8 was significantly lower in the QFT reversed group than that in the non-reversed group (p = 0.028) among treated participants, while such a difference was not found for untreated controls (p = 0.292). Conclusion: Our results suggested that the lower level of mycobacteria-specific antigen-induced IL-8 might be associated with the host's positive response to LTBI treatment.

16.
Cell Biol Toxicol ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508303

RESUMO

BACKGROUND: Osteosarcomas (OS) are frequent primary sarcomas of the bone in children and adolescents. The long non-coding RNAs (lncRNAs) can affect the progression of many cancers by their sense transcripts. The present study was designed to probe the role of ZMIZ1-AS1 and the downstream pathway in OS progression. METHODS: Cell proliferation, invasion, and migration were detected by colony formation, transwell, and wound healing assays. The binding of SOX2 or MYC protein with ZMIZ1-AS1 promoter was explored by ChIP assay and dual-luciferase reporter assay. Interaction between PTBP1 protein and ZMIZ1-AS1 (or ZMIZ1 mRNA) was detected by RIP assay. RESULTS: SOX2 and MYC are the downstream effectors of the Hippo pathway and transcriptionally activated ZMIZ1-AS1. Compared to the controls, OS tissues and cells contained higher ZMIZ1-AS1 expression. Silencing of ZMIZ1-AS1 repressed OS cell viability, proliferation, migration, and invasion. Our findings further showed that ZMIZ1-AS1 recruits RNA-binding protein PTBP1 to stabilize ZMIZ1 mRNA. PTBP1 or ZMIZ1 overexpression rescues the suppressive effects of silenced ZMIZ1-AS1 on OS cellular processes. Importantly, ZMIZ1-AS1 promotes OS growth in vivo by stabilization of ZMIZ1. CONCLUSIONS: Long non-coding RNA ZMIZ1-AS1 promotes OS progression by stabilization of ZMIZ1. The Hippo pathway is inactivated in osteosarcoma. Transcriptional factors SOX2 and MYC downstream the Hippo pathway induce the upregulation of ZMIZ1-AS1 in osteosarcoma. ZMIZ1-AS1 recruits RNA binding protein PTBP1 that stabilizes ZMIZ1, the sense transcript of ZMIZ1-AS1. ZMIZ1-AS1 promotes osteosarcoma cell viability, proliferation, migration, and invasion by ZMIZ1 in a PTBP1 dependent manner.

17.
Front Cardiovasc Med ; 8: 722908, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458345

RESUMO

Background: Cardiac hypertrophy was accompanied by various cardiovascular diseases (CVDs), and due to the high global incidence and mortality of CVDs, it has become increasingly critical to characterize the pathogenesis of cardiac hypertrophy. We aimed to determine the metabolic roles of fatty acid binding protein 3 (FABP3) on transverse aortic constriction (TAC)-induced cardiac hypertrophy. Methods and Results: Transverse aortic constriction or Ang II treatment markedly upregulated Fabp3 expression. Notably, Fabp3 ablation aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction. Multi-omics analysis revealed that Fabp3-deficient hearts exhibited disrupted metabolic signatures characterized by increased glycolysis, toxic lipid accumulation, and compromised fatty acid oxidation and ATP production under hypertrophic stimuli. Mechanistically, FABP3 mediated metabolic reprogramming by directly interacting with PPARα, which prevented its degradation and synergistically modulated its transcriptional activity on Mlycd and Gck. Finally, treatment with the PPARα agonist, fenofibrate, rescued the pro-hypertrophic effects of Fabp3 deficiency. Conclusions: Collectively, these findings reveal the indispensable roles of the FABP3-PPARα axis on metabolic homeostasis and the development of hypertrophy, which sheds new light on the treatment of hypertrophy.

18.
J Clin Tuberc Other Mycobact Dis ; 25: 100266, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34458591

RESUMO

Background: In China, rural doctors played a crucial role in TB cases referral and management. The current study aimed to evaluate the effect of WeChat-based training program on improving the rural doctors' knowledge on TB management. Methods: A One-year WeChat-based training was conducted among registered rural doctors from Zhongmu County, located in middle China, by means of releasing original contents (in forms of text, poster, video or cartoon) through WeChat subscription account (WeChat SA) once a week. Pre-and-post-training offline tests were hold using the same self-administered questionnaire to evaluate the training effect. Results: A total of 467 rural doctor were included in the study. During the training, 60 original articles were posted through WeChat SA. With respect to the two tests, the median score increased from 50 (40.0-60.0) to 60 (53.0-70.0) (p < 0.001) after training. As compared with posters, the median readings were significantly higher for released contents in forms of text, video and cartoon (p < 0.001). Female's test performance improved better than male's. In addition, a positive relation was observed between education level and the test performance regardless of training. Conclusions: Our results indicated that WeChat-based training improved the knowledge of rural doctors on TB management to a certain extent. It is worthy to explore more effective new media-based training methods to promote TB control in rural China.

19.
BMC Infect Dis ; 21(1): 815, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388985

RESUMO

BACKGROUND: Identifying and prioritizing at-risk populations is critical for pediatric tuberculosis control. We aimed to identify a latent tuberculosis infection (LTBI) screening strategy that is appropriate for the Chinese context among children with different TB exposure levels and to explore its clinical importance. METHODS: During 2013-2015, we enrolled hospitalized children with suspected respiratory infectious disease (RID) for LTBI screening using the tuberculin skin test (TST) and interferon-γ release assay (IGRA) T-SPOT.TB as part of a work up for their RID. Participants with confirmed diagnosis were classified into three subgroups according to level of exposure to TB: no reported contact risk, with household contact risk, and with non-household contact risk. RESULTS: A total 6202 children (median age: 4.76 years; interquartile range: 1.0-8.0 years) were enrolled. Children with no reported contact risk had the lowest proportions of positive results for the IGRA (0.7%) and TST (3.3%). The proportion of positive results for each test was higher for household contacts than non-household contacts. The TST positive proportion was much higher than that for the IGRA in all three groups. Children with IGRA+/TST+ results had larger indurations than those with IGRA- /TST+ results (15 mm vs. 13 mm, P = 0.02). For IGRA, older age (> 5 years) and non-household or household contact risk were associated with a positive result. CONCLUSIONS: Positive IGRA results in children with a contact risk can serve as a critical reference for LTBI management. IGRA can be used, in preference to TST, for Chinese children with a TB exposure risk.


Assuntos
Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Programas de Rastreamento/métodos , Teste Tuberculínico/métodos , Criança , Pré-Escolar , Busca de Comunicante/métodos , Feminino , Hospitais , Humanos , Interferon gama/metabolismo , Tuberculose Latente/epidemiologia , Masculino , Tuberculose/diagnóstico , Tuberculose/epidemiologia
20.
Front Cardiovasc Med ; 8: 699904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34355032

RESUMO

Background: Emerging evidence has showed that serum carbohydrate antigen 125 (CA 125) levels are associated with the severity and prognosis of heart failure. However, its role in pulmonary hypertension remains unclear. This study aimed to investigate the clinical, echocardiographic, hemodynamic, and prognostic associations of CA 125 in pulmonary hypertension. Methods and Results: We conducted a retrospective cohort study of all idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients receiving CA 125 measurement in Fuwai Hospital (January 1, 2014-December 31, 2018). The primary end-point was cumulative 1-year clinical worsening-free survival rate. Linear regression was performed to assess the association between CA 125 and clinical, echocardiographic, and hemodynamic parameters. Cox proportional hazards models were used to assess the association between CA 125 and clinical worsening events. Receiver operating characteristic (ROC) curve analysis was performed to determine the predictive performance of CA 125. A total of 231 patients were included. After adjustment, CA 125 still positively correlated with World Health Organization functional class, NT-proBNP, right ventricular end-diastolic diameter, pericardial effusion, mean right atrial pressure and pulmonary arterial wedge pressure; negatively correlated with 6-min walk distance, left ventricular end-diastolic diameter, mixed venous oxygen saturation, and cardiac index. After adjustment, CA 125 > 35 U/ml was associated with over 2 folds increased risk of 1-year clinical worsening. Further, ROC analysis showed that CA 125 provided additional predictive value in addition to the established pulmonary hypertension biomarker NT-proBNP. Conclusion: CA 125 was associated with functional status, echocardiography, hemodynamics and prognosis of pulmonary hypertension.

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