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1.
Nature ; 616(7955): 190-198, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36949198

RESUMEN

The membrane-integrated synthase FKS is involved in the biosynthesis of ß-1,3-glucan, the core component of the fungal cell wall1,2. FKS is the target of widely prescribed antifungal drugs, including echinocandin and ibrexafungerp3,4. Unfortunately, the mechanism of action of FKS remains enigmatic and this has hampered development of more effective medicines targeting the enzyme. Here we present the cryo-electron microscopy structures of Saccharomyces cerevisiae FKS1 and the echinocandin-resistant mutant FKS1(S643P). These structures reveal the active site of the enzyme at the membrane-cytoplasm interface and a glucan translocation path spanning the membrane bilayer. Multiple bound lipids and notable membrane distortions are observed in the FKS1 structures, suggesting active FKS1-membrane interactions. Echinocandin-resistant mutations are clustered at a region near TM5-6 and TM8 of FKS1. The structure of FKS1(S643P) reveals altered lipid arrangements in this region, suggesting a drug-resistant mechanism of the mutant enzyme. The structures, the catalytic mechanism and the molecular insights into drug-resistant mutations of FKS1 revealed in this study advance the mechanistic understanding of fungal ß-1,3-glucan biosynthesis and establish a foundation for developing new antifungal drugs by targeting FKS.


Asunto(s)
Microscopía por Crioelectrón , Glucosiltransferasas , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Antifúngicos/farmacología , beta-Glucanos/metabolismo , Dominio Catalítico , Membrana Celular/química , Membrana Celular/metabolismo , Farmacorresistencia Fúngica/efectos de los fármacos , Farmacorresistencia Fúngica/genética , Equinocandinas/farmacología , Glucosiltransferasas/antagonistas & inhibidores , Glucosiltransferasas/química , Glucosiltransferasas/genética , Glucosiltransferasas/metabolismo , Glucosiltransferasas/ultraestructura , Pruebas de Sensibilidad Microbiana , Mutación , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/enzimología , Proteínas de Saccharomyces cerevisiae/antagonistas & inhibidores , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/ultraestructura
2.
Nat Methods ; 20(3): 459-468, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36823335

RESUMEN

Single-molecule localization microscopy in a typical wide-field setup has been widely used for investigating subcellular structures with super resolution; however, field-dependent aberrations restrict the field of view (FOV) to only tens of micrometers. Here, we present a deep-learning method for precise localization of spatially variant point emitters (FD-DeepLoc) over a large FOV covering the full chip of a modern sCMOS camera. Using a graphic processing unit-based vectorial point spread function (PSF) fitter, we can fast and accurately model the spatially variant PSF of a high numerical aperture objective in the entire FOV. Combined with deformable mirror-based optimal PSF engineering, we demonstrate high-accuracy three-dimensional single-molecule localization microscopy over a volume of ~180 × 180 × 5 µm3, allowing us to image mitochondria and nuclear pore complexes in entire cells in a single imaging cycle without hardware scanning; a 100-fold increase in throughput compared to the state of the art.


Asunto(s)
Aprendizaje Profundo , Imagenología Tridimensional/métodos , Imagen Individual de Molécula/métodos
3.
Clin Immunol ; 259: 109871, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38101498

RESUMEN

To clarify the role of the C5a/C5aR (C5a receptor) and C5b-9 pathways in macrovascular thrombosis (MAT) and renal microthrombosis (MIT), 73 renal biopsy-proven complement-mediated thrombotic microangiopathy (C-TMA) patients were enrolled; 9 patients with pure MAT and 13 patients with pure MIT were selected for further study. Twenty-five external C-TMA patients were selected as the validation cohort. Plasma C5a and sC5b-9 (soluble C5b-9) levels were significantly higher in patients with MAT than in those with MIT (P = 0.008, P = 0.041, respectively). The mean optical density of C5aR1 in the kidney was significantly higher in MAT patients than in those with MIT (P < 0.001). Both urinary sC5b-9 levels (MIT: P < 0.001, MAT: P = 0.004) and renal deposition of C5b-9 (MIT: P < 0.001, MAT: P = 0.001) were significantly higher in C-TMA patients compared to normal control, but were similar between MAT and MIT groups. In the correlation analysis within 22C-TMA patients, urinary sC5b-9 levels and renal deposition of C5b-9 were positively correlated to renal MIT formation (P = 0.009 and P = 0.031, respectively). Furthermore, the renal citrullinated histone H3 (CitH3)- and neutrophil elastase (NE)-positive area ratios were both significantly higher in the MAT group than in the MIT group (P = 0.006 and P = 0.020, respectively). Therefore, the local C5b-9 and C5a/C5aR1 pathways might have differential contributions to MIT and MAT formation in the disease.


Asunto(s)
Trombosis , Microangiopatías Trombóticas , Humanos , Activación de Complemento , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Proteínas del Sistema Complemento , Receptor de Anafilatoxina C5a , Complemento C5b
4.
Small ; : e2401972, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38770749

RESUMEN

Due to the chemical stability of graphene, synthesis of carboxylated graphene still remains challenging during the electrochemical exfoliation of graphite. In this work, a spatially confined radical addition reaction which occurs in the sub-nanometer scaled interlayers of the expanded graphene sheets for the electrochemical synthesis of highly stable carboxylated graphene is reported. Here, formate anions act as both intercalation ions and co-reactant acid for the confinement of electro-generated carboxylic radical (●COOH) in the sub-nanometer scaled interlayers, which facilitates the radical addition reaction on graphene sheets. The controllable carboxylation of graphene is realized by tuning the concentration of formate anions in the electrolyte solution. The high crystallinity of the obtained product indicates the occurrence of spatially confined ●COOH addition reaction between the sub-nanometer interlayers of expanded graphite. In addition, the carboxylated graphene have been used for water desalination and hydrogen/oxygen reduction reaction. Therefore, this work provides a new method for the in situ preparation of functionalized graphene through the electrolysis and its applications in water desalination and hydrogen/oxygen reduction reactions.

5.
Chemistry ; 30(2): e202302934, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-37842799

RESUMEN

It is highly challenging to activate the basal plane and minimize the π-π stacking of MoS2 sheets, thus enhancing its catalytic performance. Here, we display an approach for making well-dispersed MoS2 . By using the N-doped multi-walled carbon nanotubes (NMWCNTs) as an isolation unit, the aggregation of MoS2 sheets was effectively reduced, favoring the dispersion of Pt nanoparticles (noted as Pt/NMWCNTs-isolated-MoS2 ). Excellent bifunctional catalytic performance for methanol oxidation and oxygen reduction reaction (MOR/ORR) were demonstrated by the produced Pt/NMWCNTs-isolated-MoS2 . In comparison to Pt nanoparticles supported on MoS2 (Pt/MoS2 ), the MOR activity (2314.14 mA mgpt -1 ) and stability (317.69 mA mgpt -1 after 2 h of operation) on Pt/NMWCNTs-isolatedMoS2 were 24 and 232 times higher, respectively. As for ORR, Pt/NMWCNTs-isolated-MoS2 holds large half-wave potential (0.88 V) and high stability (92.71 % after 22 h of operation). This work presents a tactic for activating the basal planes and reducing the π-π stacking of 2D materials to satisfy their applications in electrocatalysis. In addition, the proposed sheet-isolation method can be used for fabricating other 2D materials to promote the dispersion of nanoparticles, which assist its application in other fields of energy as well as the environment.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39191526

RESUMEN

BACKGROUND: The concurrence of monoclonal gammopathy and TMA was suggested in a few studies. However, the complement activation was not fully studied in previous cases. In this study, we aimed to determine the complement activation in these group of patients and the association with clinical, laboratory and pathological features. METHODS: Between 2007 to 2020, 20 patients with biopsy-proven renal TMA patients and monoclonal gammopathy in Peking University First Hospital were included in the study. Complement activation was tested by enzyme-linked immunosorbent assay. Associations with clinical features, pathological data, and laboratory findings were further investigated. RESULTS: Among renal TMA patients beyond 50 years of age, the prevalence of monoclonal gammopathy was 16.51% (18/109) which is almost 4-fold greater than the expected rate in population (4.2%). Eleven patients had acute kidney injury, and two patients required dialysis. Hematological diagnosis was consistent with monoclonal gammopathy of undetermined significance (n = 10), unconfirmed MGUS (n = 3), POEMS syndromes (n = 4), Castleman's disease (n = 2), and chronic lymphocytic leukemia (n = 1). A majority of patients (84.2%) showed the activation of complement classical pathway. 15% (3/20) of patients received conservative therapy, 5% one patient received steroid only, 30% (6/20) received with immunosuppression, and 50% (10/20) received with clone-targeted chemotherapy. During 56 months Of median follow-up, ESRD developed in 2 patients, and 5 patients died mainly because of hematological progression. CONCLUSION: This study found the dysregulation of complement activation, especially the classical pathway, involved in the pathogenesis of biopsy-proven renal TMA and monoclonal gammopathy.

7.
Eur J Epidemiol ; 39(6): 679-689, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38703249

RESUMEN

The Chinese keratoconus (CKC) cohort study is a population-based longitudinal prospective cohort study in the Chinese population involving a clinical database and biobanks. This ongoing study focuses on the prevention of KC progression and is the first to involve the effect of gene‒environment interactions on KC progression. The CKC cohort is hospital-based and dynamic and was established in Zhengzhou, China; KC patients (n = 1114) from a large geographical area were enrolled from January 2019 to June 2023, with a mean age of 22.23 years (6‒57 years). Demographic details, socioeconomic characteristics, lifestyle, disease history, surgical history, family history, and visual and social function data are being collected using questionnaires. General physical examination, eye examination, biological specimen collection, and first-degree relative data were collected and analyzed in the present study. The primary focus of the present study was placed on gene, environment and the effect of gene‒environment interactions on KC progression. The follow-up of the CKC cohort study is expected to include data collection at 3 months, 6 months, and 1 year after the initial examination and then at the annual follow-up examinations. The first follow-up of the CKC cohort study was recorded. A total of 918 patients completed the follow-up by June 1, 2023, with a response rate of 82.40%. Aside from the younger age of patients who were followed up, no significant differences were found between patients who were followed up and patients who were not.


Asunto(s)
Interacción Gen-Ambiente , Queratocono , Humanos , Queratocono/genética , Queratocono/epidemiología , Femenino , Masculino , Adulto , China/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Adolescente , Adulto Joven , Estudios Longitudinales , Niño , Progresión de la Enfermedad , Estudios de Cohortes , Encuestas y Cuestionarios , Pueblo Asiatico/genética , Pueblo Asiatico/estadística & datos numéricos , Pueblos del Este de Asia
8.
Sleep Breath ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225721

RESUMEN

PURPOSE: To investigate the separate and joint association between snoring and total sleep duration with the risk of type 2 diabetes mellitus (T2DM) in both genders within Chinese rural community. METHODS: The Henan Rural Cohort Study included a total of 28093 participants. Data on snoring and total sleep duration were obtained through the Pittsburgh Sleep Quality Index (PSQI). Binary logistic regression was employed to assess the correlation between snoring and total sleep duration with T2DM. RESULTS: The prevalences of T2DM were 8.53% in males and 9.27% in females. Males exhibited a higher prevalence of snoring (34.90%) compared to females (22.42%), and the median of total sleep duration was also longer in males (8.83 h) than in females (8.67 h), respectively (P < 0.001). Females who snored had an adjusted odds ratio (OR) and 95% confidence interval (CI) for T2DM of 1.19 (1.06, 1.35) when contrasted with non-snorers. Compared with optimal total sleep duration (6-8 h), longer total sleep duration (≥ 8 h) increased the prevalence of T2DM by 17% (95%CI: 3%, 32%) in females. Additionally, the participants with shorter total sleep duration (< 6 h) and snoring have the highest risk of T2DM, with an increase of 91% (95%CI: 20%, 204%) than those with optimal total sleep duration and non-snorers in females. These significant associations were not found in males. CONCLUSIONS: Snoring and longer total sleep duration independently elevated the prevalence of T2DM. Meantime, a synergistic relationship was observed between snoring and total sleep duration with a higher prevalence of T2DM. These associations exhibited gender-specific differences.

9.
Ecotoxicol Environ Saf ; 283: 116778, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39067072

RESUMEN

BACKGROUND AND AIMS: There is no evidence on the longitudinal and causal associations between multiple pesticides and the incidence of type 2 diabetes mellitus (T2DM) in the Chinese rural population, and whether physical activity (PA) modified these associations remains unclear. Here, we aimed to investigate the longitudinal and causal associations between pesticides mixture and T2DM, and determine whether PA modified these associations. METHODS: A total of 925 subjects with normal glucose and 925 subjects with impaired fasting glucose (IFG) were enrolled in this case-cohort study. A total of 51 targeted pesticides were quantified at baseline. Logistic regression, quantile g-computation, and Bayesian kernel machine regression (BKMR) were used to assess the individual and combined effects of pesticides on IFG and T2DM. Mendelian randomization (MR) analysis was employed to obtain the causal association between pesticides and T2DM. RESULTS: After 3-year follow-up, one-unit increment in ln-isofenphos, ln-malathion, and ln-deltamethrin were associated with an increase conversion of IFG to T2DM (FDR-P<0.05). One quartile increment in organochlorine pesticides (OCPs), organophosphorus pesticides (OPs), herbicides and pyrethroids mixtures were related to a higher incidence of T2DM among IFG patients (P<0.05). The BKMR results showed a positive trend between exposure to pesticides mixture and T2DM. The MR analysis indicated a positive association between exposure to pesticides and T2DM risk (P<0.05). No any significant association was found between pesticides and IFG. In addition, compared to subjects with high levels of PA, those with low levels of PA were related to increased risk of T2DM with the increased levels of pesticides among IFG patients. CONCLUSIONS: Individual and combined exposure to pesticides increased the incidence of T2DM among IFG patients. MR analysis further supported the causal association of pesticides exposure with T2DM risk. Our study furtherly indicated that high levels of PA attenuated the diabetogenic effect of pesticides exposure.


Asunto(s)
Diabetes Mellitus Tipo 2 , Ejercicio Físico , Análisis de la Aleatorización Mendeliana , Plaguicidas , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Persona de Mediana Edad , Femenino , China/epidemiología , Estudios de Cohortes , Adulto , Incidencia , Piretrinas/toxicidad , Exposición a Riesgos Ambientales , Estudios de Casos y Controles , Anciano , Glucemia/análisis , Contaminantes Ambientales
10.
Clin Immunol ; 247: 109221, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36610524

RESUMEN

The current study was initiated to comprehensively evaluate renal NLRP3 inflammasome pathway activation in lupus nephritis (LN) patients and their clinicopathological significances based on a Chinese LN cohort. We found that the expressions of NLRP3, ASC, caspase-1, IL-1ß and IL-18 were all significantly higher in the kidneys of LN patients and were predominantly expressed in glomerular mesangial cells, podocytes, renal tubular epithelial cells and macrophages. The expressions of NLRP3, ASC, caspase-1 and IL-1ß were positively correlated to SLEDAI scores and several renal pathological activity indices, while the expression of NLRP3 was negatively associated with chronicity scores. Moreover, the foot process width was positively correlated with glomerular caspase-1 levels, and several podocyte injury markers were decreased significantly in LN patients with higher caspase-1 expression compared with those with lower expression. Our findings indicated that renal NLRP3 inflammasome was activated in LN patients and correlated with disease activity, which needs further explorations.


Asunto(s)
Nefritis Lúpica , Humanos , Nefritis Lúpica/patología , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Riñón/patología , Caspasa 1/metabolismo
11.
Eur J Nutr ; 62(7): 2929-2938, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37405440

RESUMEN

PURPOSE: Insufficient evidence currently exists regarding the relationship between eating frequency and arteriosclerotic cardiovascular disease (ASCVD). Thus, the objective of this study was to explore the association of at-home eating (AHE) and out-of-home eating (OHE) frequency with 10-year ASCVD risk. METHODS: A total of 23,014 participants were included from the Henan Rural Cohort Study. A face-to-face questionnaire was used to acquire data on the frequency of OHE and AHE. The relationship of OHE and AHE frequency with 10-year ASCVD risk was evaluated by logistic regression. Mediation analysis was conducted to evaluate whether BMI mediated the association of OHE and AHE frequency with 10-year ASCVD risk. RESULTS: The adjusted OR and 95% CI of 10-year ASCVD risk for participants who ate out 7 or more times a week was 2.012 (1.666, 2.429) compared with participants who had OHE 0 times. Compared to those who had AHE ≤ 11 times, the adjusted OR and 95% CI for the participants eating every meal at home (21 times) was 0.611 (0.486, 0.769). The relationship of OHE and AHE frequency with 10-year ASCVD risk was mediated by BMI, and the proportion of BMI explained was 25.3% and 36.6%. CONCLUSIONS: The OHE frequency was associated with increased 10-year ASCVD risk, while AHE was related to decreased 10-year ASCVD risk, and BMI may play a partial mediating role in the relationship. Implementing health promotion strategies that promote AHE and discourage frequent OHE may prove to be an effective approach to preventing and controlling ASCVD. TRIAL REGISTRATION NUMBER: ChiCTR-OOC-15006699 (2015-07-06).


Asunto(s)
Enfermedades Cardiovasculares , Humanos , Estudios de Cohortes , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Población Rural , Promoción de la Salud , Comidas , Factores de Riesgo
12.
Environ Res ; 237(Pt 1): 116862, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37574100

RESUMEN

BACKGROUND: Ambient air pollution was linked to elevated risks of adverse cardiovascular events, and alterations in electrophysiological properties of the heart might be potential pathways. However, there is still lacking research exploring the associations between PM1 exposure and cardiac conduction parameters. Additionally, the interactive effects of PM1 and residential greenness on cardiac conduction parameters in resource-limited areas remain unknown. METHODS: A total of 27483 individuals were enrolled from the Henan Rural Cohort study. Cardiac conduction parameters were tested by 12-lead electrocardiograms. Concentrations of PM1 were evaluated by satellite-based spatiotemporal models. Levels of residential greenness were assessed using Enhanced Vegetation Index (EVI) and Normalized difference vegetation index (NDVI). Logistic regression models and restricted cubic splines were fitted to explore the associations of PM1 and residential greenness exposure with cardiac conduction abnormalities risk, and the interaction plot method was performed to visualize their interaction effects. RESULTS: The 3-year median concentration of PM1 was 56.47 (2.55) µg/m3, the adjusted odds rate (ORs) and 95% confidence intervals (CIs) for abnormal HR, PR, QRS, and QTc interval risk in response to 1 µg/m3 increase in PM1 were 1.064 (1.044, 1.085), 1.037 (1.002, 1.074), 1.061 (1.044, 1.077) and 1.046 (1.028, 1.065), respectively. Participants exposure to higher levels of PM1 had increased risks of abnormal HR (OR = 1.221, 95%CI: 1.144, 1.303), PR (OR = 1.061, 95%CI: 0.940, 1.196), QRS (OR = 1.225, 95%CI: 1.161, 1.294) and QTc interval (OR = 1.193, 95%CI: 1.121, 1.271) compared with lower levels of PM1. Negative interactive effects of exposure to PM1 and residential greenness on abnormal HR, QRS, and QTc intervals were observed (Pfor interaction < 0.05). CONCLUSION: Long-term PM1 exposure was associated with elevated cardiac conduction abnormalities risks, and this adverse association might be mitigated by residential greenness to some extent. These findings emphasize that controlling PM1 pollution and increasing greenness levels might be effective strategies to reduce cardiovascular disease burdens in resource-limited areas.

13.
Nutr Metab Cardiovasc Dis ; 33(12): 2334-2343, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37788950

RESUMEN

BACKGROUNDS AND AIMS: Evidence on the association between habitual snoring, excessive daytime sleepiness (EDS), and cardiovascular diseases (CVDs) remains uncertain and limited. The study aimed to explore the independent and joint association between habitual snoring, EDS, and CVDs in rural Chinese adults. METHODS AND RESULTS: A total of 28,140 participants from the Henan rural cohort study were included. Sleep status information was obtained by self-reported. Based on their sleep status, the participants were classified into four groups: "no snoring and no EDS (NSNS) (reference group)", "snoring and no EDS (SNS)", "no snoring and EDS (NSS)", "snoring and EDS (SS)." The logistic regression models were used to calculate independent and joint odds ratios (OR) and 95% confidence intervals (CI) between the snoring, EDS status and stroke, CHD, and CVD. Of the 28,140 participants, 740 subjects reported snoring and sleepiness. The ORs and (95% CIs) for CVDs in the adjusted model were 1.31 (1.20-1.43) for participants who snored frequently and 2.44 (1.76-3.39) for frequent sleepiness compared with no snoring and no sleepiness. Individuals with both snoring and sleepiness had higher odds of CVDs compared with no snoring and no sleepiness (OR: 2.18, 95%CI: 1.80-2.62). CONCLUSION: Habitual snoring and excessive daytime sleepiness were independently and jointly associated with CVDs in the Chinese rural population. More studies are needed to explore the mechanisms of the relationship. CLINICAL TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 2015-52 07-06. http://www.chictr.org.cn/showproj.aspx?proj=11375.


Asunto(s)
Enfermedades Cardiovasculares , Trastornos de Somnolencia Excesiva , Humanos , Adulto , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Ronquido/diagnóstico , Ronquido/epidemiología , Estudios de Cohortes , Población Rural , Somnolencia , Pueblos del Este de Asia , Trastornos de Somnolencia Excesiva/diagnóstico , Trastornos de Somnolencia Excesiva/epidemiología
14.
Qual Life Res ; 32(1): 81-92, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35972617

RESUMEN

PURPOSE: This study aimed to investigate the associations between overall lifestyles and HRQoL, as well as the variations in age, sex, education level, and income. METHODS: A total of 23,402 participants from the Henan rural cohort were included. The healthy lifestyle score (HLS) consists of five lifestyle factors: smoking, alcohol drinking, physical activity, diet, and body mass index. HRQoL was assessed by the EQ-5D-5L questionnaire. The general linear model and Tobit regression model were utilized to assess the associations of HLS with visual analogue score (VAS) and utility index. RESULTS: Compared with participants with an HLS of 0-2, the corresponding regression coefficients (ß) and 95% confidence intervals (CI) of participants with an HLS of 3, 4, and 5 for VAS score were 1.09 (0.59, 1.59), 1.92 (1.38, 2.46), and 2.60 (1.83, 3.37); the corresponding ß and 95% CI for utility index were 0.02 (0.01, 0.03), 0.05 (0.03, 0.06), and 0.06 (0.04, 0.07). Notably, these positive associations were greater among the elderly, female, and those with lower education level and average monthly income (p for interaction < 0.05). For instance, the corresponding ß and 95% CI of individuals with an HLS of 5 for utility index in average monthly income < 500 RMB, 500-999 RMB, and ≥ 1000 RMB groups were 0.08 (0.05, 0.11), 0.06 (0.03, 0.09), and 0.02 (- 0.00, 0.05). CONCLUSION: Engaging in healthier lifestyle habits was associated with a higher level of HRQoL, especially in the elderly, females, and those with low education level and average monthly income.


Asunto(s)
Pueblos del Este de Asia , Calidad de Vida , Humanos , Adulto , Femenino , Anciano , Calidad de Vida/psicología , Estudios Transversales , Encuestas y Cuestionarios , Escolaridad , Estilo de Vida Saludable
15.
Int J Med Sci ; 20(8): 1097-1113, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37484807

RESUMEN

Purpose: Endometrial carcinoma (EC) is one of the three most common female genital tract cancers, and it contributes to the leading deaths of gynecologic cancer. MTHFD2 was reported up-regulated and associated with poor prognosis in many malignancies. However, its biological functions and mechanisms in EC are unclear. The present study aimed to identify the biological functions and potential molecular mechanisms of MTHFD2 in EC. Methods: The gene expression and information of patients used in this study were derived from TCGA, GEO and HPA databases. KM survival analysis was used to explore the clinical outcomes of EC patients and correlation analysis was applied to find the correction between MTHFD2 expression level and immune infiltration in EC. We used GO and GSEA analysis to explore the biological functions and mechanisms of MTHFD2. The CCK8 assay, the colony formation assay and the transwell migration assay were conducted to validate the function of MTHFD2 in EC cells. We applied STRING to find the protein that interacted with MTHFD2. Finally, ENCORI was used to explore the potential upstream regulation of MTHFD2 in EC and it was validated in EC cells. Results: In the present study, we found that MTHFD2 was up-regulated in EC and its high expression level was associated with patients' poor prognosis and adverse clinical parameters. MTHFD2 level was shown to be correlated with immune infiltration. Knockdown of MTHFD2 inhibited the malignant phenotype of HEC-1A and Ishikawa cells, including proliferation, colony formation and migration. Furthermore, we found the SNHG3/hsa-miR-455-5p axis as the potential upstream of MTHFD2. Conclusion: SNHG3/hsa-miR-455-5p axis-mediated high expression of MTHFD2, and the MTHFD2 expression level was associated with tumor immune infiltration and endometrial carcinoma progression. Knockdown of MTHFD2 significantly inhibited the malignant phenotype of EC cells. MTHFD2 may be a valuable predictive biomarker, and targeting MTHFD2 may be an effective way to improve the therapeutic effect in EC.


Asunto(s)
Neoplasias Endometriales , MicroARNs , Femenino , Humanos , Línea Celular Tumoral , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , MicroARNs/genética , MicroARNs/metabolismo
16.
Neurol Sci ; 44(5): 1687-1694, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36653543

RESUMEN

BACKGROUND: Limited studies have focused on the risk assessment of stroke in rural regions. Moreover, the application of artificial intelligence in stroke risk scoring system is still insufficient. This study aims to develop a simplified and visualized risk score with good performance and convenience for rural stroke risk assessment, which is combined with a machine learning (ML) algorithm. METHODS: Participants of the Henan Rural Cohort were enrolled in this study. The total participants (n = 38,322) were randomly split into a train set and a test set in the ratio of 7:3. An ML algorithm was used to select variables and the logistic regression was then applied to construct the scoring system. The C-statistic and the Brier score (BS) were used to evaluate the discrimination and calibration. The Framingham stroke risk profile (FSRP) and the self-reported stroke risk function (SRSRF) were chosen to be compared. RESULTS: The Rural Stroke Risk Score (RSRS) was produced in this study, including age, drinking status, triglyceride, type 2 diabetes mellitus, hypertension, waist circumference, and family history of stroke. On validation, the C-statistic was 0.757 (95% CI 0.749-0.765) and the BS was 0.058 in the test set. In addition, the discrimination of RSRS was 6.02% and 7.34% higher than that of the FSRP and SRSRF, respectively. CONCLUSIONS: A well-performed scoring system for assessing stroke risk in rural residents was developed in this study. This risk score would facilitate stroke screening and the prevention of cardiovascular disease in economically underdeveloped areas.


Asunto(s)
Diabetes Mellitus Tipo 2 , Accidente Cerebrovascular , Humanos , Inteligencia Artificial , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control
17.
Public Health Nutr ; 26(6): 1254-1263, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36788680

RESUMEN

OBJECTIVE: This study aimed to evaluate the recent prevalence and the distributions of morphological subtypes of anaemia in the rural population. DESIGN: Anaemia was defined according to the WHO and the Chinese criteria, and the morphological subtypes of anaemia were classified based on the erythrocyte parameters. The age-standardised prevalence was calculated according to the data of the Population Census 2010 in China. SETTING: A cross-sectional study in Henan Province. PARTICIPANTS: 33 585 subjects aged 18-79 years old. RESULTS: The standardised prevalence of anaemia across the WHO and the Chinese definitions was 13·63 % and 5·45 %, respectively. Regardless of which criteria was used, the standardised prevalence of anaemia was higher among women than among men and that increased with age in men, while markedly decreased after menopause in women. There were shifts in morphological patterns of anaemia using the WHO and the Chinese criteria that the standardised prevalence of microcytic anaemia was 3·74 % and 2·97 %, normocytic anaemia was 9·20 % and 2·34 %, and macrocytic anaemia was 0·75 % and 0·14 %, respectively. Besides, there were differences in the influencing factors of anaemia according to different criteria or gender. However, age, education level and renal damage were consistently significantly associated with anaemia in all participants. CONCLUSIONS: Anaemia may still be a serious health problem in rural China. It is necessary to reformulate prevention and management strategies to reduce the disease burden of anaemia.


Asunto(s)
Anemia , Población Rural , Masculino , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Prevalencia , Estudios Transversales , Pueblos del Este de Asia , Anemia/epidemiología , China/epidemiología , Factores de Riesgo
18.
Sleep Breath ; 27(1): 265-274, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35469369

RESUMEN

BACKGROUND: Inappropriate sleep duration is a potential cause of stroke. But the effect of napping on stroke risk remains controversial and the interaction between night sleep and napping duration remains unclear. The objective of this study was to examine the independent and combined effects of napping and nocturnal sleep duration on stroke. METHODS: Subjects were derived from a rural cohort study in Henan. The Pittsburgh Sleep Quality Index (PSQI) was applied to identify nap duration and nocturnal sleep duration. Binary logistic regression was employed to indicate the dose-response relationships between naps, nocturnal sleep, total 24-h sleep duration, and stroke. RESULTS: Among the 37,341 participants (14,485 men), 2600 suffered from a stroke. The odds ratios (ORs) and 95% confidence level (CI) for stroke in the fully adjusted model were 1.37 (1.13-1.65) for men nappers compared to non-nappers. Compared to 7-8 h of sleep per day, night sleep durations < 6 h and ≥ 9 h and 24-h sleep duration ≥ 10 h were linked to increased odds of stroke in men. The ORs (95%CI) were 1.34 (1.06-1.69) in nocturnal sleep duration < 6 h, 1.30 (1.06-1.59) in nocturnal sleep duration ≥ 9 h, and 1.40 (1.15-1.71) in 24-h sleep duration ≥ 10 h in men. In addition, long naps and prolonged nocturnal sleep duration have a joint effect on stroke in the fully adjusted model. CONCLUSION: The napping duration and nocturnal sleep duration have independently and jointly effects on stroke in rural populations. More research is required to explore the underlying mechanisms for this relationship. CLINICAL TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered on the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699) ( http://www.chictr.org.cn/showproj.aspx?proj=11375 ).


Asunto(s)
Duración del Sueño , Accidente Cerebrovascular , Adulto , Humanos , Masculino , Estudios de Cohortes , Pueblos del Este de Asia , Población Rural , Femenino
19.
J Hum Nutr Diet ; 36(4): 1349-1358, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36919869

RESUMEN

BACKGROUND: The present study aimed to explore the effect of modification of socioeconomic status (SES) on the association between famine exposure in early life and osteoporosis in adulthood via the baseline data from the Henan Rural cohort study. METHODS: A total of 2669 exposed to famine participants were selected from the Henan Rural cohort, and the questionnaires, physical examination and bone mineral density measurement were completed. Specific birth years were used to define five groups: the fetal exposed group, early-childhood exposed group, mid-childhood exposed group, late-childhood exposed group and unexposed group. And the age-matched control group was a combination of the unexposed group and late-childhood exposed group. Multivariable logistic regression models were utilised to analyse the association of famine exposure in early life with osteoporosis in adulthood. RESULTS: The prevalence rates of osteoporosis of participants exposed to famine during the fetal period, early-childhood, mid-childhood and the age-matched group were 21.67%, 25.76%, 23.90% and 18.14%, respectively. The adjusted odds ratios (95% confidence interval) of participants suffering from famine during the fetal period, early-childhood and mid-childhood versus age-matched group were 1.19 (0.82-1.73), 1.40 (1.04-1.88) and 1.57 (1.16-2.13), respectively. The female participants yielded consistent results. The risk of osteoporosis was higher in more severe famine eara. Moreover, an attenuated effect of early life famine exposure on osteoporosis was observed in female participants with high SES. CONCLUSIONS: Exposure to famine in early life showed a sex-specific association with an increased risk of osteoporosis in adulthood and the severity of famine may exacerbate this association. In addition, the risk could be modified by SES.


Asunto(s)
Osteoporosis , Efectos Tardíos de la Exposición Prenatal , Inanición , Masculino , Humanos , Femenino , Niño , Hambruna , Estudios de Cohortes , Inanición/complicaciones , Inanición/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Osteoporosis/epidemiología , Osteoporosis/etiología , China/epidemiología , Factores de Riesgo
20.
Ecotoxicol Environ Saf ; 265: 115524, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37776820

RESUMEN

BACKGROUND: Plasma polybrominated diphenyl ethers (PBDE) were used as flame retardants widely, however, epidemiological evidence for the association between PBDEs and type 2 diabetes mellitus (T2DM) is inconsistent. Moreover, the combined effects of PBDEs and blood lipid indicators on impaired fasting glucose (IFG) and T2DM remains largely unknown in rural areas lacking good waste recycling infrastructure. METHODS: In this study, a total of 2607 subjects aged 18-79 years were included from the Henan Rural Cohort. Generalized linear and logistic regression models were applied to evaluate the associations of various PBDE pollutants on IFG and T2DM. Quantile g-computation regression and PBDE pollution score created by the adaptive elastic net were applied to evaluate the impact of PBDEs mixtures on IFG and T2DM. Interaction effects of individual PBDE pollutants and blood lipid indicators on IFG and T2DM were assessed by using Interaction plots. RESULTS: The geometric mean concentrations (detection rates) were 0.09 ng/mL (100.0%), 0.12 ng/mL (97.8%), 0.22 ng/mL (94.7%), 0.16 ng/mL (99.2%) and 0.28 ng/mL (100.0%) for PBDE-28, PBDE-47, PBDE-99, and PBDE-153 respectively. However, PBDE-28, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 1.14 (1.06, 1.23), 1.16 (1.04, 1.29), 1.25 (1.14, 1.37), and 1.27 (1.08, 1.50)). Similarly, PBDE-28, PBDE-47, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with T2DM (ORs (95% CIs): 1.30 (1.10, 1.54), 1.13 (1.06, 1.22), 1.27 (1.13, 1.43), 1.27 (1.15, 1.40), and 1.30 (1.10, 1.54)). Moreover, five PBDE mixtures or jointly as PBDE pollution score, were significantly associated with an increased risk of T2DM (P < 0.05 for all). In addition, the harmful effect of PBDE exposure on T2DM was decreased with accompanying high-density lipoprotein cholesterol (HDL-C) levels increased. CONCLUSIONS: Our findings highlight the importance of managing PBDEs contamination and suggest that HDL-C may be a novel way to prevent T2DM.

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