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1.
Environ Pollut ; 297: 118791, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34998893

RESUMO

Tetrabromobisphenol A (TBBPA), which is the most widely employed brominated flame retardant, and its alternative tetrachlorobisphenol A (TCBPA) are widely distributed in aquatic environments. In the present study, the hepatotoxicity induced by TBBPA and TCBPA was investigated in Rana nigromaculata, and the potential mechanisms were investigated with a particular focus on ROS (reactive oxygen species) -dependent mitochondria-mediated apoptosis. Healthy adult frogs were exposed to 0, 0.001, 0.01, 0.1, and 1 mg/L waterborne TBBPA and TCBPA for 14 days. The results showed that liver weight was significantly increased by 51.52%-98.99% in the 0.01, 0.1, and 1 mg/L TBBPA and TCBPA groups relative to the control. Histological examination revealed that the structure of the liver, to some extent, was influenced by TBBPA and TCBPA with nuclear shrinkage and mitochondrial swelling. Meanwhile, TBBPA and TCBPA have significantly increased the alanine transaminase level in serum and the content of ROS, while inhibiting the activity of superoxide dismutase in the liver. In addition, DNA fragments were observed in the TBBPA and TCBPA groups relative to the control. Expression of Cytochrome C was significantly increased by 1.13-, 1.38-, 1.60-, and 2.46-fold in 0.001, 0.01, 0.1, and 1 mg/L TBBPA, and by 1.26-, 1.51-, 2.14-, and 2.98- fold in 0.001, 0.01, 0.1, and 1 mg/L TCBPA, respectively, which indicated that TCBPA may be more toxic than TBBPA. Similarly, the ratio of Bax/Bcl-2 was increased in a dose-dependent manner. These results indicated that apoptosis in the ROS-dependent mitochondrial pathway mediates hepatotoxicity caused by TBBPA and TCBPA. The present study will facilitate an understanding of the toxicity mechanism of flame retardants.

2.
J Hypertens ; 40(2): 264-273, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34992197

RESUMO

OBJECTIVE: We aimed to establish and validate a user-friendly and clinically practical nomogram for estimating the probability of echocardiographic left ventricular hypertrophy (echo-LVH) indexed to BSA among hypertensive patients from northern China. METHODS: A total of 4954 hypertensive patients were recruited from a population-based cohort study from January 2012 to August 2013. The dataset was randomly split into two sets: training (n = 3303) and validation (n = 1651). Three nomograms were initially constructed. That is the Cornell product nomogram, the non-ECG nomogram, and the integrated nomogram which integrated non-ECG risk factors and Cornell-voltage duration product. The least absolute shrinkage and selection operator strategies were employed to screen for non-ECG features. The performance of the nomograms was evaluated using discrimination, calibration, and decision curve analysis (DCA). The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were also calculated. RESULTS: The AUCs, NRIs, IDIs, and DCA curves of the nomograms demonstrated that the integrated nomogram performed best among all three nomograms. The integrated nomogram incorporated age, sex, educational level, hypertension duration, SBP, DBP, eGFR, sleep duration, tea consumption, and the Cornell-voltage duration product. The AUC was 0.758 and had a good calibration (Hosmer-Lemeshow test, P = 0.73). Internal validation showed an acceptable AUC of 0.735 and good calibration was preserved (Hosmer-Lemeshow test, P = 0.19). The integrated nomogram was clinically beneficial across a range of thresholds of 10-50%. CONCLUSION: The integrated nomogram is a convenient and reliable tool that enables early identification of hypertensive patients at high odds of LVH and can assist clinicians in their decision-making.

3.
Carbohydr Polym ; 276: 118798, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34823804

RESUMO

The medicinal fungus Sanghuangporus vaninii can be cultivated in large scale and has outstanding antitumour activity. In this study, water-soluble S. vaninii polysaccharides (SVPs) were extracted from fruiting bodies. Four polysaccharide sub-fractions (SVP-W, SVP-1, SVP-2 and SVP-3) were isolated, with molecular weights from 90.50 kDa to 261.70 kDa, and all inhibited the proliferation of non-small cell lung cancer cell lines A549, 95-D and NCI-H460, especially the acidic SVP-1. SVP-1 affected cell morphology and colony formation in NCI-H460 cells. It also promoted cell apoptosis following nuclear fluorescence staining and flow cytometry. Methylation and nuclear magnetic resonance analyses revealed that SVP-1 is a heteroglycan with the main chain →4)-ß-D-Glcp-(1 â†’ 6)-ß-D-Glcp-(1 â†’ 6)-α-D-Galp-(1 â†’ 6)-ß-D-Glcp-(1→, and the branched chain α-D-Manp-(1 â†’ 2)-α-D-Manp-(1 â†’ 3)-ß-D-Glcp-(1 â†’ 3,6)-ß-D-Glcp-(1→. The findings indicate that this natural acidic polysaccharide has potential for non-small cell lung cancer therapy.

4.
J Pharm Biomed Anal ; 209: 114498, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34952293

RESUMO

Conventional strategies for screening of protein binders cannot be used for complicated samples such as ligand libraries created by combinatorial chemistry or from natural product extracts. In the current study, we developed a novel method in a competitive binding configuration for screening protein binders from complicated samples by a combination of streptavidin-coated 96-well plate format in conjunction with ultra-high-performance liquid chromatography coupled with Orbitrap mass spectrometry (UHPLC-Orbitrap-MS). The concanavalin A (Con A) modified 96-well plate and lysozyme modified 96-well plate (as control) were incubated with oligosaccharide standards respectively, and the compounds with the decreased peak areas in experimental group compared to those in the control group were detected as binders by UHPLC-ESI-MS. The factors such as incubation time, incubation temperature, and buffer, which might affect the binding affinity and reproducibility were optimized. The potential of the approach is examined using the extracts of Radix ginseng cruda and American ginseng. The relative binding degrees (RBDs) of the detected disaccharides were relatively high in the extracts of Radix ginseng cruda, and those of the trisaccharides were similar in the extracts of the two kinds of ginseng. To our knowledge, it's the first time to reveal the differences and analogies in lectin peanut agglutinin (PNA)-binding capabilities of oligosaccharides between the extracts of radix ginseng cruda and American ginseng, indicating the efficiency of the method for analysis of complicated samples.


Assuntos
Panax , Cromatografia Líquida de Alta Pressão , Ensaios de Triagem em Larga Escala , Espectrometria de Massas , Reprodutibilidade dos Testes
5.
Front Biosci (Landmark Ed) ; 26(11): 1176-1190, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34856762

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is considered the second most common urogenital tract carcinoma, plaguing patients worldwide due to its high incidence and resistance to treatment. Thus, it is urgent to screen new biomarkers and decipher their molecular mechanisms to support early clinical diagnosis and targeted therapy of ccRCC. It is reported that epithelial membrane protein 3 (EMP3) acts as a tumor-promoting or suppressing factor in a variety of malignant tumors, but its relationship with ccRCC remains to be explored. Methods: The Cancer Genome Atlas (TCGA) and Oncomine database were utilized to screen the differentially expressed genes in ccRCC. Western blot and qPCR were used to verify the expression of our subject of interest, EMP3 in ccRCC tissues and cell lines. Next, a series of functional experiments were conducted to explore the biological functions of EMP3 in tumor cells, including cell counting kit-8, transwell, wound healing assays, Oil red O staining and triglyceride determination. Western blotting was used to explore the potential mechanism of EMP3 induced ccRCC deterioration. Finally, the TIMER2.0 database was used to explore the effect of EMP3 on tumor immune infiltration and its relationship with multiple immune checkpoints. Results: In this study, we uncovered that EMP3 was more prominently expressed in ccRCC and its expression level had a significant positive correlation with the clinical stage and histopathological grade of tumor patients. Based on the TCGA database, the Receiver operating characteristic (ROC) curves showed that EMP3 could be potentially utilized as a specific biomarker in diagnosing ccRCC patients. Meanwhile, six independent prognostic factors were determined and integrated into our nomogram, with an OS concordance index (C-index) of 0.760 (95% CI: 0.689-0.831). Furthermore, in vitro depletion of EMP3 could alleviate the proliferation, migration, invasion, and lipid storage in ccRCC cells. Mechanistically, EMP3 was shown to enhance the malignant potential of tumor cells by promoting epithelial-mesenchymal transition (EMT) and lipid accumulation. In addition, the expression of EMP3 was closely related to the infiltration of a variety of immune cells, and was positively related to PD-L1, suggesting that it may be a tight connection with tumor immune escape. Conclusions: Our results revealed that EMP3 might be a candidate biomarker and independent prognostic indicator, and related to EMT process, lipid accumulation, as well as immune infiltration in ccRCC. Targeted EMP3 therapy might be a promising and effective treatment strategy for ccRCC patients.

6.
Front Microbiol ; 12: 765269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34938278

RESUMO

The plant microbiome is a key determinant of health and productivity. However, it is still difficult to understand the structural composition of the bacterial and fungal microbiomes of diseased and healthy plants, especially the spatial dynamics and phylogenies of endophytic and rhizosphere microbial communities. We studied the differentiation and variability in the rhizosphere and endosphere microbiomes of healthy and diseased cotton from north and south of the Tianshan Mountains using the methods of PCR-based high-throughput sequencing and real-time quantitative PCR. The endophytic and rhizosphere bacterial abundances in the diseased plants were greater than those of healthy plants. The numbers of endophytic and rhizosphere fungi associated with diseased plants were greater than those associated healthy plants (p < 0.05). Endophytic and rhizosphere bacteria did not share common OTUs. The dominant rhizosphere bacteria were Proteobacteria (29.70%), Acidobacteria (23.14%), Gemmatimonadetes (15.17%), Actinobacteria (8.31%), Chloroflexi (7.99%), and Bacteroidetes (5.15%). The dominant rhizosphere fungi were Ascomycota (83.52%), Mortierellomycota (7.67%), Basidiomycota (2.13%), Chytridiomycota (0.39%), and Olpidiomycota (0.08%). The distribution of dominant bacteria in different cotton rhizosphere soils and roots differed, with the dominant bacteria Pseudomonas (15.54%) and Pantoea (9.19%), and the dominant fungi Alternaria (16.15%) and Cephalotrichum (9.10%) being present in the greatest numbers. At sampling points in different ecological regions, the total numbers of cotton endophytic and rhizosphere microbiome OTUs from southern to northern Xinjiang showed an increasing trend. There were significant differences in the composition and diversity of rhizosphere microbes and endophytes during the entire cotton growth period and in representative ecological regions (p < 0.01), whereas rhizosphere microbes and endophytes showed no significant differences among the four growth periods and in representative ecological regions. RB41, H16, Nitrospira, and Sphingomonas play important roles in the microbial ecology of cotton rhizosphere soil. Pseudomonas accounted for a large proportion of the microbes in the cotton rhizosphere soil. This study provides an in-depth understanding of the complex microbial composition and diversity associated with cotton north and south of the Tianshan Mountains.

7.
BMJ Open ; 11(12): e050907, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34916312

RESUMO

OBJECTIVES: This study aimed to reveal the association between metabolic score for insulin resistance (MetS-IR) and the risk of mildly decreased estimated glomerular filtration rate (eGFR), and explore the evaluation effect of MetS-IR on the progress of eGFR decline. STUDY DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: A total of 11 956 rural participants (aged ≥35 years) from northeastern China were enrolled in the study. After excluding the subjects whose data were not integrated or who met the exclusion criteria, we finally obtained 11 042 participants in the present study. MAIN OUTCOME MEASURES: Mildly decreased eGFR was defined as 60-90 mL/min/1.73 m2. RESULTS: The prevalence of mildly decreased eGFR in the general population was 36.9%. After adjustment of covariates, each SD increment of MetS-IR could bring 26.3% additional risk of mildly decreased eGFR (OR: 1.263, 95% CI: 1.066 to 1.497, p=0.007). When MetS-IR was classified into four levels by quartile, we observed participants in the top level had 3.032-fold risk of mildly decreased eGFR (OR: 3.032, 95% CI: 1.841 to 4.991, p<0.001) compared with those from the bottom level. Further, we found the participants with higher MetS-IR score were more likely to aggravate into a worse renal state which presented as higher risk of accelerated decline of eGFR, by additional 28.3% risk in whole participants (OR: 1.283, 95% CI: 1.150 to 1.430, p<0.001) and 41.9% in men (OR: 1.419, 95% CI: 1.183 to 1.701, p<0.001). CONCLUSION: High MetS-IR was associated with high risk of mildly reduced eGFR and often accompanied by a high risk of accelerated decline in eGFR. Hence, we believed MetS-IR was a suitable indicator to evaluate the risk of early-stage renal dysfunction.

8.
Cancer Cell Int ; 21(1): 627, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34838029

RESUMO

BACKGROUND: Cancer cachexia is a wasting disorder characterized by significant weight loss, and is attributed to skeletal muscle weakness. In the process of cancer development, microRNAs act as oncogenes or tumor suppressors. Moreover, they are implicated in muscle development and wasting. This study sought to explore the mechanisms and correlation between miR-29c and muscle wasting in lung cancer cachexia. METHODS: Data for expression analysis were retrieved from the Cancer Genome Atlas (TCGA) database. qRT-PCR analyses were performed to explore the expression levels of miR-29c and Leukemia Inhibitory Factor (LIF). Lewis lung carcinoma (LLC) cell line was used to establish a cachexia model to explore the functions of miR-29c and LIF in lung cancer cachexia. Furthermore, in vitro (in C2C12 myotubes) and in vivo (in LLC tumor-bearing mice) experiments were performed to explore the mechanisms of miR-29c and LIF in lung cachexia. RESULTS: Analysis of the lung cancer cachexia model showed that miR-29c was down-regulated, and its expression was negatively correlated with muscle catabolic activity. Overexpression of miR-29c mitigated the cachectic phenotype. Mechanistic studies showed that LIF was a direct target gene of miR-29c, and LIF was upregulated in vitro and in vivo. Analysis showed that LIF promoted muscle wasting through the JAK/STAT and MAP-kinase pathways. CONCLUSIONS: The findings indicated that miR-29c was negatively correlated with the cachectic phenotype, and the miR-29c-LIF axis is a potential therapeutic target for cancer cachexia.

9.
Clin Transl Med ; 11(11): e592, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34841698

RESUMO

BACKGROUND: The key role of hypoxia-inducible factor 2alpha (HIF2α) in the process of renal cancer has been confirmed. In the field of tumour research, oxidative stress is also considered to be an important influencing factor. However, the relationship and biological benefits of oxidative stress and HIF2α in ccRCC remain unclear. This research attempts to explore the effect of oxidative stress on the cancer-promoting effect of HIF2α in ccRCC and reveal its mechanism of action. METHODS: The bioinformatics analysis for ccRCC is based on whole transcriptome sequencing and TCGA database. The detection of the expression level of related molecules is realised by western blot and PCR. The expression of Nucleoside diphosphate-linked moiety X-type motif 1 (NUDT1) was knocked down by lentiviral infection technology. The functional role of NUDT1 were further investigated by CCK8 assays, transwell assays and cell oxidative stress indicator detection. The exploration of related molecular mechanisms is realised by Luciferase assays and Chromatin immunoprecipitation (ChIP) assays. RESULTS: Molecular screening based on knockdown HIF2α sequencing data and oxidative stress related data sets showed that NUDT1 is considered to be an important molecule for the interaction of HIF2α with oxidative stress. Subsequent experimental results showed that NUDT1 can cooperate with HIF2α to promote the progression of ccRCC. And this biological effect was found to be caused by the oxidative stress regulated by NUDT1. Mechanistically, HIF2α transcription activates the expression of NUDT1, thereby inhibiting oxidative stress and promoting the progression of ccRCC. CONCLUSIONS: This research clarified a novel mechanism by which HIF2α stabilises sirtuin 3 (SIRT3) through direct transcriptional activation of NUDT1, thereby inhibiting oxidative stress to promote the development of ccRCC. It provided the possibility for the selection of new therapeutic targets for ccRCC and the study of combination medication regimens.

10.
J Agric Food Chem ; 69(46): 13933-13941, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34756022

RESUMO

The effects of the deacetylation degree (DD) of chitosan on heterocyclic aromatic amine formation were investigated in chemical models and beef patties. The results in model systems showed that at lower addition levels (10 mg), chitosan with 85% DD showed the strongest inhibitory effect against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formation, while chitosan with a higher DD (95%) or a lower DD (72 and 50%) did not show any significantly inhibitory effect. Further mechanism study showed that chitosan addition reduced the content of Maillard reaction intermediates including phenylacetaldehyde and the aldol condensation product but increased the PhIP precursor creatinine residue in the chemical model, indicating that chitosan at least partially competed with creatinine to react with phenylacetaldehyde to inhibit PhIP formation. In roast beef patties, 0.15% (w/w) chitosan (85% DD) significantly reduced the formation of PhIP, MeIQx, 4,8-DiMeIQx, Harman, and Norharman by 56.21, 33.32, 31.35, 25.14, and 28.12%, respectively. Moreover, chitosan significantly inhibited the formation of aldehydes in roast beef patties, further confirming the above-mentioned inhibition mechanism. However, the addition of chitosan might promote fatty acid oxidation. In addition, chitosan addition below 0.15% (w/w) had no significant effect on the textural properties of the roast samples.


Assuntos
Quitosana , Modelos Químicos , Animais , Bovinos , Culinária , Imidazóis , Carne/análise , Piridinas
11.
Front Cardiovasc Med ; 8: 685072, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631809

RESUMO

Background: The latest guidelines recommend the use of proton pump inhibitors (PPIs) to minimize gastrointestinal bleeding (GIB) in patients receiving dual antiplatelet therapy (DAPT), even though this co-administration may increase the risk of ischemia due to drug interactions. We have noticed that there are few studies conducted on patients with a lower risk of GIB. Therefore, we investigated the clinical effect of co-administration of PPI on DAPT patients with low GIB risk. Methods and Results: From January 2013 to September 2014, a total of 17,274 consecutive patients on DAPT from 108 hospitals with low risk for GIB in the China Acute Myocardial Infarction (CAMI) registry were analyzed. The primary endpoints were GIB and major adverse cardiovascular and cerebrovascular events (MACCE). Multivariate logistic regression analysis and Cox proportional hazard models were used to assess the effect of PPIs use. Of the analyzed patients, 66.6% (n = 11,487) were treated with PPIs. PPI use did not show an extra gastrointestinal protective effect in patients with low risk for GIB who were hospitalized and on follow-up after 2 years. Moreover, it was associated with an increased risk of stroke during the 2-year follow-up [hazard ratio (HR) 2.072, 95% confidence interval (CI) 1.388-3.091, p = 0.0003] and an increased risk of MI after 6 months (HR 1.580, 95% CI 1.102-2.265, p = 0.0119). We found the same results after propensity score matching. Conclusion: PPI use is prevalent in DAPT patients with low GIB risk. PPIs did not show an extra gastrointestinal protective effect, while an increased risk of stroke was observed during the 2-year follow-up. Clinical Trial Registration:www.clinicaltrials.gov, identifier NCT01874691.

12.
J Transl Med ; 19(1): 417, 2021 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627268

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney. New and reliable biomarkers are in urgent need for ccRCC diagnosis and prognosis. The CENP family is overexpressed in many types of cancers, but its functions in ccRCC have not been fully clarified. In this paper, we found that several CENP family members were highly expressed in ccRCC tissues. Also, CENPA expression level was related to clinicopathological grade and prognosis by weighted gene co-expression network analysis (WGCNA). CENPA served as a representative CENP family member as a ccRCC biomarker. Further in vitro experiments verified that overexpression of CENPA promoted ccRCC proliferation and metastasis by accelerating the cell cycle and activating the Wnt/ß-catenin signaling pathway. The elevated ß-catenin led by CENPA overexpression translocated to nucleus for downstream effect. Functional recovery experiment confirmed that Wnt/ß-catenin pathway was essential for ccRCC progression and metastasis. Developing selective drugs targeting CENPA may be a promising direction for cancer treatment.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Prognóstico , Via de Sinalização Wnt
13.
Artigo em Inglês | MEDLINE | ID: mdl-34670959

RESUMO

BACKGROUND: Regionalization of emergency general surgery (EGS) has primarily focused on expediting care of high acuity patients through interfacility transfers. In contrast, triaging low-risk patients to a non-designated trauma facility has not been evaluated. This study evaluates a 16-month experience of a five-surgeon team triaging EGS patients at a tertiary care, Level 1 Trauma Center (TC) to an affiliated community hospital 1.3 miles away. METHODS: All EGS patients who presented to the Level 1 TC emergency department (ED) from January 2020-April 2021 were analyzed. Patients were screened by EGS surgeons covering both facilities for transfer appropriateness including hemodynamics, resource need, and comorbidities. Patients were retrospectively evaluated for disposition, diagnosis, comorbidities, length of stay (LOS), surgical intervention, and 30-day mortality and readmission. RESULTS: Of 987 patients reviewed, 31.5% were transferred to the affiliated community hospital, 16.1% were discharged home from the ED, and 52.4 % were admitted to the Level 1 TC. Common diagnoses were biliary disease (16.8%), bowel obstruction (15.7%), and appendicitis (14.3%). Compared to Level I TC admissions, Charlson Comorbidity Index was lower (1.89 vs. 4.45, p < 0.001) and LOS was shorter (2.23 vs. 5.49 days, p < 0.001) for transfers. Transfers had a higher rate of surgery (67.5% vs. 50.1%, p < 0.001) and lower readmission and mortality (8.4% vs. 15.3%, p = 0.004; 0.6% vs. 5.0%, p < 0.001). Reasons not to transfer were emergency evaluation, comorbidity burden, OR availability, and established care. No transfers required transfer back to higher care (under-triage). Bed days saved at the Level 1 TC were 693 (591 inpatient). Total operating room minutes saved were 24,008 (16,919 between 0700-1700). CONCLUSIONS: Transfer of appropriate patients maintains high quality care and outcomes, while improving OR and bed capacity and resource utilization at a tertiary care, Level 1 TC. EGS regionalization should consider triage of both high-risk and low-risk patients. LEVEL OF EVIDENCE: Level II Evidence.

14.
Front Pharmacol ; 12: 738590, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497527

RESUMO

Perioperative neurocognitive disorder (PND) leads to progressive deterioration of cognitive function, especially in aged patients. Demyelination is closely associated with cognitive dysfunction. However, the relationship between PND and demyelination remains unclear. Here we showed that demyelination was related to the pathogenesis of PND. Clemastine, an antihistamine with potency in remyelination, was predicted to have a potential therapeutic effect on PND by next-generation sequencing and bioinformatics in our previous study. In the present study, it was given at 10 mg/kg per day for 2 weeks to evaluate the effects on PND in aged mice. We found that clemastine ameliorated PND and reduced the expression levels of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß). Further investigation suggested clemastine increased the expression of oligodendrocyte transcription factor 2 (OLIG2) and myelin basic protein (MBP) to enhance remyelination by inhibiting the overactivation of the WNT/ß-catenin pathway. At the same time, the expression of post-synaptic density protein 95 (PSD95, or DLG4), brain-derived neurotrophic factor (BDNF), synaptosomal-associated protein 25 (SNAP25) and neuronal nuclei (NEUN) were also improved. Our results suggested that clemastine might be a therapy for PND caused by anesthetic and surgical factors in aged patients.

15.
Front Immunol ; 12: 728669, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566986

RESUMO

CD8 T cell memory offers critical antiviral protection, even in the absence of neutralizing antibodies. The paradigm is that CD8 T cell memory within the lung tissue consists of a mix of circulating TEM cells and non-circulating TRM cells. However, based on our analysis, the heterogeneity within the tissue is much higher, identifying TCM, TEM, TRM, and a multitude of populations which do not perfectly fit these classifications. Further interrogation of the populations shows that TRM cells that express CD49a, both with and without CD103, have increased and diverse effector potential compared with CD49a negative populations. These populations function as a one-man band, displaying antiviral activity, chemokine production, release of GM-CSF, and the ability to kill specific targets in vitro with delayed kinetics compared with effector CD8 T cells. Together, this study establishes that CD49a defines multiple polyfunctional CD8 memory subsets after clearance of influenza infection, which act to eliminate virus in the absence of direct killing, recruit and mature innate immune cells, and destroy infected cells if the virus persists.

16.
Eur J Prev Cardiol ; 28(11): 1250-1258, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34551085

RESUMO

BACKGROUND: Recent studies have investigated the association of transitions in metabolic health and obesity status over time with the risk of cardiovascular disease, focusing on the subgroup demonstrating metabolically healthy obesity. However, these studies have produced inconsistent results. This study evaluates the relation in a general Chinese population. METHODS: We conducted a prospective cohort study in a general population in Northeast China, with examinations of cardiovascular health from 2012-2015 and follow-up for incident cardiovascular disease until 2018. Cox proportional hazards and logistic regression models were used to investigate the association of baseline metabolic health and obesity status and transitions in those statuses with cardiovascular disease risk. RESULTS: A total of 7472 participants aged ≥35 years who were free of cardiovascular disease at baseline were included in this analysis. Over a median follow-up of 4.66 years, a total of 344 cardiovascular disease events occurred. Among the 3380 participants who were obese at baseline, 37.1% were metabolically healthy. Metabolically healthy obesity was associated with a 48% increased risk of cardiovascular disease (hazard ratio: 1.48; 95% confidence interval: 1.07-2.06) compared with the metabolically healthy non-obese group at baseline. Transition from metabolically healthy obesity to metabolically unhealthy obesity was associated with elevated cardiovascular disease risk with an odds ratio of 1.82 (95% confidence interval: 1.06-3.14) compared with metabolically healthy non-obesity throughout after adjustment. Even maintaining metabolically healthy obesity over time was associated with a higher risk of cardiovascular disease (odds ratio: 1.72; 95% confidence interval: 1.00-2.97). CONCLUSIONS: Weight control and management of existing metabolic disorders should be prioritized in all obese population.

17.
BMC Geriatr ; 21(1): 505, 2021 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563137

RESUMO

BACKGROUND: This study aimed to estimate whether metabolic syndrome (MetS) and its components could be used to predict cardiovascular disease (CVD) in a longitudinal analysis in a rural elderly Chinese population. METHOD: At baseline during 2012-2013, a total of 2486 elderly from rural Chinese were enrolled and were followed up during 2015-2017. Stroke and coronary heart disease (CHD) were included in CVD and were diagnosed by clinicians. The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF) criteria were used to define MetS separately. RESULT: Hazard ratios adjusting for CHD, stroke and CVD in those with MetS using the NCEP ATP III criteria in females were 1.27 (95 % CI 0.73, 2.21), 1.54 (95 % CI 0.99, 2.40) and 1.45 (95 % CI 1.00, 2.10), respectively; 1.33 (95 % CI 0.77, 2.32), 1.44 (95 % CI 0.92, 2.25) and 1.36 (95 % CI 0.94, 1.97), respectively, with the AHA/NHLBI criteria; and 1.10 (95 % CI 0.89,1.36), 1.62 (95 % CI 1.03, 2.55) and 1.36 (95 % CI 0.93, 1.97), respectively, with the IDF criteria. Additionally, abdominal obesity using the AHA/NHLBI criteria was significantly associated with the incidence of stroke (HR: 1.60; 95 % CI 1.01, 2.52). However, among rural elderly males, neither MetS nor its components predicted new-onset CVD. CONCLUSIONS: MetS is correlated with high incidence of CVD among rural elderly female, and only using the NCEP ATP III criteria to define MetS could make the incidence of CVD obvious difference. In order to reduce rural elderly CVD, effective measures to prevent, diagnose, and treat MetS should be enacted in a timely manner, especially among females.


Assuntos
Doenças Cardiovasculares , Síndrome Metabólica , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Prevalência , Fatores de Risco
18.
BMJ Open ; 11(9): e044117, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493500

RESUMO

OBJECTIVE: To investigate the incidence of gastrointestinal bleeding (GIB) in patients with acute myocardial infarction (AMI), clarify the association between adverse clinical outcomes and GIB and identify risk factors for in-hospital GIB after AMI. DESIGN: Retrospective cohort study. SETTING: 108 hospitals across three levels in China. PARTICIPANTS: From 1 January 2013 to 31 August 2014, after excluding 2659 patients because of incorrect age and missing GIB data, 23 794 patients with AMI from 108 hospitals enrolled in the China Acute Myocardial Infarction Registry were divided into GIB-positive (n=282) and GIB-negative (n=23 512) groups and were compared. PRIMARY AND SECONDARY OUTCOME MEASURES: Major adverse cardiovascular and cerebrovascular events (MACCEs) are a composite of all-cause death, reinfarction and stroke. The association between GIB and endpoints was examined using multivariate logistic regression and Cox proportional hazards models. Independent risk factors associated with GIB were identified using multivariate logistic regression analysis. RESULTS: The incidence of in-hospital GIB in patients with AMI was 1.19%. GIB was significantly associated with an increased risk of MACCEs both in-hospital (OR 2.314; p<0.001) and at 2-year follow-up (HR 1.407; p=0.0008). Glycoprotein IIb/IIIa (GPIIb/IIIa) receptor inhibitor, percutaneous coronary intervention (PCI) and thrombolysis were novel independent risk factors for GIB identified in the Chinese AMI population (p<0.05). CONCLUSIONS: GIB is associated with both in-hospital and follow-up MACCEs. Gastrointestinal prophylactic treatment should be administered to patients with AMI who receive primary PCI, thrombolytic therapy or GPIIb/IIIa receptor inhibitor. TRIAL REGISTRATION NUMBER: NCT01874691.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , China/epidemiologia , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/etiologia , Hospitais , Humanos , Incidência , Infarto do Miocárdio/complicações , Infarto do Miocárdio/epidemiologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
19.
BMJ Open ; 11(9): e051172, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475185

RESUMO

OBJECTIVES: The sensitivity of ECG for detecting left ventricular hypertrophy (LVH) is low. The aim of this study was to explore a better ECG criterion for screening LVH in a large general Chinese population. DESIGN: Case-control study. SETTING: China Medical University in Shenyang, China. PARTICIPANTS: All permanent residents in Dawa, Zhangwu and Liaoyang aged 35 years or older were invited. Participants with unqualified data, pacemaker rhythm, frequent premature ventricular beats, Wolff-Parkinson-White syndrome, complete bundle branch block, myocardial infarction or hypertrophic cardiomyopathy were excluded. A total of 10 360 subjects (4630 males) were recruited. INTERVENTIONS: A novel ECG criterion (Northeast China Rural Cardiovascular Health Study (NCRCHS)) composed of different ratios of maximum R wave in lead V5 or V6 (RV5/V6), S wave in lead V3 (SV3) and R wave in lead aVL (RaVL) was proposed and validated using multiple linear regression. Receiver-operating characteristic curves were used to compare the NCRCHS criterion with traditional criteria for LVH detection. RESULTS: An optimised model (15*RaVL+8*SV3+7*RV5/V6) was constructed (R2 0.192, p<0.001) with the cut-off values of 36.8 mV for males and 26.1 mV for females. The maximum area under the curve was obtained using the NCRCHS criterion (male 0.74, 95% CI 0.73 to 0.75; female 0.73, 95% CI 0.72 to 0.75), followed by Cornell voltage criterion, Sokolow-Lyon criterion, Peguero-Lo Presti criterion, multi-ethnic study of atherosclerosis (MESA)-specific criterion and Syst-Eur voltage criterion. Compared with the Cornell voltage criterion, the NCRCHS criterion had a significantly higher sensitivity for detecting LVH at the same level of specificity (p<0.05). CONCLUSIONS: The NCRCHS criterion significantly improved sensitivity for LVH detection in a general Chinese population, with cut-off values of 36.8 and 26.1 mV for males and females, respectively. This criterion can detect LVH earlier and better and may prevent subsequent cardiovascular diseases.


Assuntos
Hipertensão , Hipertrofia Ventricular Esquerda , Bloqueio de Ramo , Estudos de Casos e Controles , China/epidemiologia , Estudos Transversais , Eletrocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico , Masculino
20.
Am J Transl Res ; 13(8): 9152-9159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540030

RESUMO

OBJECTIVE: To explore the application effect of Trinity new model home nursing in postoperative management of children with Hirschsprung's disease (HD). METHODS: A retrospective control research was designed, including 80 HD children underwent surgical treatment. According to the nursing model, the children were divided into control group (n=40) and observation group (n=40). They received conventional nursing and Trinity home nursing intervention respectively. The defecation function and quality of life, scores of self-rating anxiety scale (SAS) and family caregiver task inventory (FCTI), incidence of complications and nursing satisfaction before surgery, 3 and 6 months after surgery between the two groups were compared. RESULTS: Compared with the control group, the children in the observation group had lower Wexner constipation and fecal incontinence scores at 3 and 6 months after surgery (both P<0.001), while the children's quality of life generic core scale (PedsQLTM4.0) scores at 6 months after operation were higher than those in the control group (P<0.001). The SAS and FCTI scores of family members in the observation group were lower than those in the control group after intervention (all P<0.001). Compared with the control group, the observation group had lower total incidence of complications and higher nursing satisfaction (all P<0.05). CONCLUSION: Trinity new model home nursing can effectively increase the intestinal management quality of children undergoing HD surgery, improve their defecation function and quality of life, and reduce the risk of complications.

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