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α-Solanine has been shown to exhibit anti-inflammatory and anti-tumour properties; however, its efficacy in treating osteoarthritis (OA) remains ambiguous. The study aimed to evaluate the therapeutic effects of α-solanine on OA development in a mouse OA model. The OA mice were subjected to varying concentrations of α-solanine, and various assessments were implemented to assess OA progression. We found that α-solanine significantly reduced osteophyte formation, subchondral sclerosis and OARSI score. And it decreased proteoglycan loss and calcification in articular cartilage. Specifically, α-solanine inhibited extracellular matrix degradation by downregulating collagen 10, matrix metalloproteinase 3 and 13, and upregulating collagen 2. Importantly, α-solanine reversed chondrocyte pyroptosis phenotype in articular cartilage of OA mice by inhibiting the elevated expressions of Caspase-1, Gsdmd and IL-1ß, while also mitigating aberrant angiogenesis and sensory innervation in subchondral bone. Mechanistically, α-solanine notably hindered the early stages of OA progression by reducing I-κB phosphorylation and nuclear translocation of p65, thereby inactivating NF-κB signalling. Our findings demonstrate the capability of α-solanine to disrupt chondrocyte pyroptosis and sensory innervation, thereby improving osteoarthritic pathological progress by inhibiting NF-κB signalling. These results suggest that α-solanine could serve as a promising therapeutic agent for OA treatment.
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FN-kappa B , Osteoartritis , Solanina , Ratones , Animales , FN-kappa B/metabolismo , Piroptosis , Condrocitos/metabolismo , Osteoartritis/metabolismo , Modelos Animales de Enfermedad , Colágeno/metabolismo , Interleucina-1beta/metabolismo , Inflamación/patologíaRESUMEN
AIM: To investigate the associations of individual and combined healthy lifestyle factors (HLS) with the risk of stroke in individuals with diabetes in China. METHODS: This prospective analysis included 41 314 individuals with diabetes [15 191 from the Comprehensive Research on the Prevention and Control of the Diabetes (CRPCD) project and 26 123 from the China Kadoorie Biobank (CKB) study]. Associations of lifestyle factors, including cigarette smoking, alcohol consumption, physical activity, diet, body shape and sleep duration, with the risk of stroke, intracerebral haemorrhage (ICH) and ischaemic stroke (IS) were assessed using Cox proportional hazard models. RESULTS: During median follow-up periods of 8.02 and 9.05 years, 2499 and 4578 cases of stroke, 2147 and 4024 of IS, and 160 and 728 of ICH were documented in individuals with diabetes in the CRPCD and CKB cohorts, respectively. In the CRPCD cohort, patients with ≥5 HLS had a 14% lower risk of stroke (hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.75-0.98) than those with ≤2 HLS. In the CKB cohort, the adjusted HR (95% CI) for patients with ≥5 HLS were 0.74 (0.66-0.83) for stroke, 0.74 (0.66-0.83) for IS, and 0.57 (0.42-0.78) for ICH compared with those with ≤2 HLS. The pooled adjusted HR (95% CI) comparing patients with ≥5 HLS versus ≤2 HLS was 0.79 (0.69-0.92) for stroke, 0.80 (0.68-0.93) for IS, and 0.60 (0.46-0.78) for ICH. CONCLUSIONS: Maintaining a healthy lifestyle was associated with a lower risk of stroke, IS and ICH among individuals with diabetes.
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Estilo de Vida , Accidente Cerebrovascular , Humanos , China/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Anciano , Factores de Riesgo , Estilo de Vida Saludable , Diabetes Mellitus/epidemiología , Ejercicio Físico , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Modelos de Riesgos Proporcionales , Hemorragia Cerebral/epidemiología , Estudios de CohortesRESUMEN
It is widely recognized that air pollution exerts substantial detrimental effects in human health and the economy. The potential for harm is closely linked to the concentrations of pollutants like nitrogen dioxide (NO2) and ozone (O3), as well as their collective oxidative potential (OX). Yet, due to the challenges of directly monitoring OX as an independent factor and the influences of different substances' varying ability to contain or convey OX, uncertainties persist regarding its actual impact. To provide further evidence to the association between short-term exposures to NO2, O3, and OX and mortality, this study conducted multi-county time-series analyses with over-dispersed generalized additive models and random-effects meta-analyses to estimate the mortality data from 2014 to 2020 in Jiangsu, China. The findings reveal that short-term exposures to these pollutants are linked to increased risks of all-cause, cardiovascular, and respiratory mortality, where NO2 demonstrates 2.11% (95% confidence interval: 1.79%, 2.42%), 2.28% (1.91%, 2.66%), and 2.91% (2.13%, 3.69%) respectively per every 10 ppb increase in concentration, and the effect of O3 is 1.11% (0.98%, 1.24%), 1.39% (1.19%, 1.59%), and 1.82% (1.39%, 2.26%), and OX is 1.77% (1.58%, 1.97%), 2.19% (1.90%, 2.48%), and 2.90% (2.29%, 3.52%). Notably, women and individuals aged over 75 years exhibit higher susceptibility to these pollutants, with NO2 showing a greater impact, especially during the warm seasons. The elevated mortality rates associated with NO2, O3, and OX underscore the significance of addressing air pollution as a pressing public health issue, especially in controlling NO2 and O3 together. Further research is needed to explore the underlying mechanisms and possible influential factors of these effects.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Ambientales , Ozono , Humanos , Femenino , Anciano , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Dióxido de Nitrógeno/toxicidad , Dióxido de Nitrógeno/análisis , Factores de Tiempo , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Ozono/toxicidad , Ozono/análisis , Contaminantes Ambientales/análisis , Estrés Oxidativo , Material Particulado/análisisRESUMEN
BACKGROUND: The rising prevalence of Type 2 diabetes (T2D) in China poses a critical health challenge, necessitating effective management strategies. The National Essential Public Health Services Program (NEPHSP), initiated in 2009, focuses on equitable access to health services, including T2D management. This study investigates the associations between perceived care quality, self-care behaviors, and glycemic control in Chinese adults with T2D under NEPHSP, particularly examining the mediating role of self-care behaviors. METHODS: Conducted from April to November 2020 in Huai'an City, Jiangsu Province, this study involved 1,577 T2D patients enrolled in NEPHSP. We assessed perceived care quality using the Patient Assessment of Chronic Illness Care (PACIC) scale and developed a comprehensive self-care behavior score, covering nine essential health practices. Glycemic control was evaluated using HbA1c levels. Linear regression models were used to explore these associations, adjusting for demographic and clinical factors, while causal mediation analyses examined the role of intermediate variables. RESULTS: Higher PACIC scores significantly correlated with improved self-care behaviors (ß = 0.294, 95% CI: 0.233 to 0.354) and were negatively associated with HbA1c levels (ß=-0.109, 95% CI: -0.192 to -0.026). The self-care behavior score inversely related to HbA1c levels (ß=-0.197, 95% CI: -0.263 to -0.132). Notably, self-care behaviors mediated 50.41% (P < 0.05) of the effect of perceived care quality on HbA1c levels. CONCLUSIONS: This study demonstrates a substantial association between perceived care quality and better glycemic control in Chinese adults with T2D under NEPHSP, with self-care behaviors playing a crucial mediating role. These findings suggest that patient-centered care and comprehensive self-care practices are essential for effective T2D management within NEPHSP.
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Diabetes Mellitus Tipo 2 , Control Glucémico , Calidad de la Atención de Salud , Autocuidado , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/psicología , Masculino , Femenino , Persona de Mediana Edad , China , Anciano , Adulto , Hemoglobina Glucada/análisis , Estudios Transversales , Pueblos del Este de AsiaRESUMEN
OBJECTIVE: Socioeconomic status (SES) has been proven to be associated with chronic obstructive pulmonary disease (COPD) in Western populations, but the evidence is very limited in China. This study aimed to investigate the association between SES and the risk of COPD incident. METHODS: This study was based on the China Kadoorie Biobank (CKB) project in Wuzhong District, Suzhou. A total of 45,484 adults aged 30-79 were included in the analysis during 2004-2008. We used Cox proportional hazard models to investigate the association between SES and the risk of COPD. Household income, education, private property and consumption potential was used to measure SES. Incident COPD cases were ascertained using hospitalization records, death certificates, and active follow-up. RESULTS: A total of 524 COPD cases were identified during a median follow-up of 11.2 years. Household income was inversely associated with the risk of COPD (Ptrend<0.005). The adjusted hazard ratios (95% confidence intervals) for incident COPD were 0.88 (0.69-1.14), 0.77 (0.60-0.99), and 0.42 (0.31-0.57) for participants with annual household income of 10,000 ~ 19,999 yuan, 20,000 ~ 34,999 yuan and ≥ 35,000 yuan respectively, in comparison to participants with an annual household income < 10,000 yuan. Furthermore, we found that education level, refrigerator use, private toilet, private phone, and motor vehicle were adversely associated with COPD risk, while ownership of newly renovated flats was positively correlated with COPD incident. CONCLUSIONS: This prospective study suggests that SES is associated with the risk of COPD in Chinese adults. Population-based COPD prevention strategies tailored for people with different SES could help reduce the burden of COPD in Chinese.
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Enfermedad Pulmonar Obstructiva Crónica , Clase Social , Humanos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , China/epidemiología , Persona de Mediana Edad , Masculino , Femenino , Estudios Prospectivos , Adulto , Anciano , Factores de Riesgo , Modelos de Riesgos Proporcionales , IncidenciaRESUMEN
BACKGROUND & AIMS: Mild and moderate dysplasia are major premalignant lesions of esophageal squamous cell carcinoma (ESCC); however, evidence of the progression risk in patients with these conditions is extremely limited. We aimed to assess the incidence and risk factors for advanced neoplasia in patients with mild-moderate dysplasia. METHODS: This prospective cohort study included patients with mild-moderate dysplasia from 9 regions in rural China. These patients were identified from a community-based ESCC screening program conducted between 2010 and 2016 and were offered endoscopic surveillance until December 2021. We estimated the incidence of advanced esophageal neoplasia, including severe dysplasia, carcinoma in situ, or ESCC, and identified potential risk factors using the Cox regression model. RESULTS: The 1183 patients with mild-moderate dysplasia were followed up over a period of 6.95 years. During follow-up evaluation, 88 patients progressed to advanced neoplasia (7.44%), with an incidence rate of 10.44 per 1000 person-years. The median interval from the progression of mild-moderate dysplasia to advanced neoplasia was 2.39 years (interquartile range, 1.58-4.32 y). A total of 74.47% of patients with mild-moderate dysplasia experienced regression to nondysplasia, and 18.09% showed no lesion progression. Patients with mild-moderate dysplasia who had a family history of esophageal cancer and were age 55 years and older showed 97% higher advanced neoplasia yields than all patients with mild-moderate dysplasia. CONCLUSIONS: In a country with a high incidence of ESCC, patients with mild-moderate dysplasia showed an overall risk of advanced neoplasia progression of 1.04% per year. Patients with mild-moderate dysplasia would be recommended for endoscopic surveillance during the first 2 to 3 years.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Lesiones Precancerosas , Humanos , Persona de Mediana Edad , Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas/patología , Estudios Prospectivos , Lesiones Precancerosas/patología , Esofagoscopía , HiperplasiaRESUMEN
AIMS: To investigate the association between glycated haemoglobin (HbA1c) levels and chronic obstructive pulmonary disease (COPD) incidents in the general population, and the association between HbA1c levels and mortality in patients with COPD. MATERIALS AND METHODS: We investigated the association of HbA1c levels with COPD risk in the general population in the UK Biobank, using data from 420 065 participants. Survival analysis was conducted for 18 854 patients with COPD. We used restricted cubic spline analysis to assess the dose-response relationship between HbA1c levels and COPD risk and survival. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12.3 years, 11 556 COPD cases were recorded. HbA1c had a non-linear relationship with COPD risk (p for non-linearity < .05). Compared with the quintile 2 (32.2-<34.3 mmol/mol), those with HbA1c levels above 38.7 mmol/mol (quintile 5) had a 22% (HR, 1.22, 95% CI: 1.15-1.30) higher risk of COPD. Compared with the HbA1c decile 2 (30.5-<32.2 mmol/mol), the HRs (95% CI) of COPD risk were 1.16 (1.03-1.30) and 1.36 (1.24-1.50) in the lowest HbA1c decile (<30.5 mmol/mol) and highest decile (≥41.0 mmol/mol), respectively. The increased COPD risk associated with HbA1c was more pronounced in younger, current smokers, passive smokers, and participants with a higher Townsend deprivation index (all p for interaction < .05). Among patients with COPD, 4569 COPD cases died (488 because of COPD) during a median follow-up of 5.4 years. Regarding COPD survival, HbA1c had a non-linear relationship with all-cause death (p for non-linearity < .05). Those with HbA1c quintile 5 (≥38.7 mmol/mol) had a 23% (HR, 1.23, 95% CI: 1.10-1.37) higher risk of all-cause death compared with the quintile 2 (32.2-<34.3 mmol/mol). Compared with the HbA1c decile 4 (33.3-<34.3 mmol/mol), those in the lowest HbA1c decile (<30.5 mmol/mol) and highest HbA1c decile (≥41.0 mmol/mol) had 22% (HR, 1.22; 95% CI: 1.01-1.47) and 28% (HR, 1.28; 95% CI: 1.11-1.48) higher risk for overall death. However, no significant association was observed between HbA1c levels and the risk of COPD-specific death. CONCLUSIONS: Our findings indicated that lower and higher HbA1c levels were associated with a higher risk of COPD. In COPD cases, lower and higher HbA1c levels were associated with a higher COPD all-cause death risk.
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Bancos de Muestras Biológicas , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Hemoglobina Glucada , Estudios Prospectivos , Incidencia , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Reino Unido/epidemiología , Factores de RiesgoRESUMEN
AIM: To investigate the associations of diabetes, prediabetes and diabetes duration with chronic obstructive pulmonary disease (COPD) risk and survival in the UK Biobank. MATERIALS AND METHODS: We conducted a prospective analysis among 452 680 participants without COPD at baseline using UK Biobank data. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox regression models. The dose-response relationship was explored using restricted cubic splines. A separate survival analysis was conducted for 12 595 patients with incident COPD. RESULTS: Over a median follow-up of 12.3 years, 12 595 cases of COPD were documented. Compared with the reference group, those with prediabetes and diabetes were associated with an 18% (HR 1.18 [95% CI: 1.13-1.24]) and 35% (HR 1.35 [95% CI: 1.24-1.47]) higher risk of COPD, respectively. Diabetes duration was associated with COPD risk, with multivariable HRs (95% CIs) of 1.23 (1.05-1.44), 1.20 (1.04-1.39) and 1.18 (1.01-1.37) for diabetes duration of 7 years or longer, 3 to less than 7 years, and 1 to less than 3 years versus less than 1 year, respectively. Dose-response analysis revealed a non-linear relationship between diabetes duration and COPD risk. Regarding COPD survival, COPD patients with prediabetes and diabetes had a 9% (HR 1.09 [95% CI: 1.00-1.19]) and 21% (HR 1.21 [95% CI: 1.05-1.41]) higher risk of overall death, respectively. Compared with the cases with a diabetes duration of less than 1 year, those with a diabetes duration of 7 years or longer were associated with a 46% higher risk of overall death (HR 1.46 [95% CI: 1.11-1.92]). CONCLUSIONS: Our findings indicate that diabetes, prediabetes and a longer diabetes duration are associated with a higher risk of and worse survival for COPD. Future studies are warranted to determine the optimal way of diabetes control that might reduce COPD risk.
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Diabetes Mellitus , Estado Prediabético , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Estado Prediabético/complicaciones , Estado Prediabético/epidemiología , Bancos de Muestras Biológicas , Diabetes Mellitus/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Reino Unido/epidemiología , Factores de RiesgoRESUMEN
OBJECTIVE: To explore the molecular mechanism of γ-glutamylcysteine (γ-GC) in response to inflammation in vivo and in vitro on regulating the polarization of macrophages. METHODS: The expressions of gene or protein were assessed by qPCR and Western blot assays, respectively. Cell viability was investigated by CCK-8 assay. Eight-week-old male BALB/c mice were established to examine the therapeutic effects of γ-GC in vivo. The release of TNF-α and IL-4 was determined by ELISA assay. Macrophages polarization was identified by flow cytometry assay. RESULTS: Our data showed that γ-GC treatment significantly improved the survival, weight loss, and colon tissue damage of IBD mice. Furthermore, we established M1- and M2-polarized macrophages, respectively, and our findings provided evidence that γ-GC switched M1/M2-polarized macrophages through activating AMPK/SIRT1 axis and inhibiting inflammation-related signaling pathway. CONCLUSION: Collectively, both in vivo and in vitro experiments suggested that γ-GC has the potential to become a promising novel therapeutic dipeptide for the treatment of IBD, which provide new ideas for the treatment of inflammatory diseases in the future.
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Enfermedades Inflamatorias del Intestino , Masculino , Animales , Ratones , Enfermedades Inflamatorias del Intestino/inducido químicamente , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , Macrófagos/metabolismo , Inflamación/metabolismo , Dipéptidos/farmacología , Dipéptidos/uso terapéutico , Dipéptidos/metabolismoRESUMEN
A complex regional air pollution problem dominated by particulate matter (PM) and ozone (O3) needs drastic attention since the levels of O3 and PM are not decreasing in many parts of the world. Limited evidence is currently available regarding the association between co-exposure to PM and O3 and mortality. A multicounty time-series study was used to investigate the associations of short-term exposure to PM1, PM2.5, PM10, and O3 with daily mortality from different causes, which was based on data obtained from the Mortality Surveillance System managed by the Jiangsu Province Center for Disease Control and Prevention of China and analyzed via overdispersed generalized additive models with random-effects meta-analysis. We investigated the interactions of PM and O3 on daily mortality and calculated the mortality fractions attributable to PM and O3. Our results showed that PM1 is more strongly associated with daily mortality than PM2.5, PM10, and O3, and percent increases in daily all-cause nonaccidental, cardiovascular, and respiratory mortality were 1.37% (95% confidence interval (CI), 1.22-1.52%), 1.44% (95% CI, 1.25-1.63%), and 1.63% (95% CI, 1.25-2.01%), respectively, for a 10 µg/m3 increase in the 2 day average PM1 concentration. We found multiplicative and additive interactions of short-term co-exposure to PM and O3 on daily mortality. The risk of mortality was greatest among those with higher levels of exposure to both PM (especially PM1) and O3. Moreover, excess total and cardiovascular mortality due to PM1 exposure is highest in populations with higher O3 exposure levels. Our results highlight the importance of the collaborative governance of PM and O3, providing a scientific foundation for pertinent standards and regulatory interventions.
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Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Material Particulado/análisis , Ozono/análisis , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , China/epidemiología , Exposición a Riesgos Ambientales/análisis , MortalidadRESUMEN
PURPOSE: Perampanel (PER) and lacosamide (LCM) are the new third-generation anti-seizure medications (ASMs) that were approved for the monotherapy of focal epilepsy in children over four years of age in China, in 2021. Very few studies have analyzed the application of PER monotherapy among pediatric patients aged ≥four years, and no study compared the efficacy and tolerability of PER monotherapy with LCM monotherapy in pediatric patients with focal epilepsy. The present study aimed to investigate the efficacy, tolerability, and effect on behavior and emotion of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy, which is beneficial for clinicians to have more choices to treat pediatric patients with focal epilepsy. METHODS: This was a prospective, single-center, observational study that involved pediatric patients (disease onset age ≥four years) with newly diagnosed focal epilepsy treated with PER or LCM as primary monotherapy. Outcomes included retention, being responders, and seizure-free rates after 3, 6, and 12 months. Adverse events (AEs) were noticed throughout the follow-up period. Behavioral outcomes were evaluated with Achenbach Child Behavior Checklist (CBCL/4-16) at baseline and after three and six months. RESULTS: Using randomization, 60 patients receiving PER (31 females, 29 males, median age: 7.79 [5.34, 10.16] years, median dose: 3.0 [2.0, 4.0] mg/day) and 60 patients receiving LCM (25 females, 35 males, median age: 7.72 [5.91, 10.72] years, median dose: 150.0 [100.0, 200.0] mg/day) were enrolled in the study. At the 12-month follow-up, the retention rates in the PER and LCM groups, both were 90.4%, and the responder rates were 65.4% and 71.2%, while seizure-free rates were 57.7% and 67.3%, respectively. There were no significant differences in the retention, responder and seizure-free rates between the two groups (P > 0.05). There were no significant differences in the responder rates between patients with BECTS, abnormal brain magnetic resonance imaging (MRI), or types of seizure in the two groups (P > 0.05). In the PER group, 28.8% (15/52) of patients experienced AEs, of which the most frequently reported were irritability (n = 7; 13.5%), dizziness (n = 5; 9.6%), somnolence (n = 3; 5.8%), ataxia (n = 1; 1.9%), headache (n = 1; 1.9%), and rash (n = 1; 1.9%). In the LCM group, 15.4% (8/52) of the patients had AEs, including headache (n = 4; 7.5%), dizziness (n = 4; 7.5%), nausea (n = 2; 3.8%), somnolence (n = 2; 3.8%), irritability (n = 1; 1.9%), stomach ache (n = 1; 1.9%), and vomiting (n = 1; 1.9%). The incidence of irritability was significantly higher in the PER group than in the LCM group (13.5% vs. 1.9%, P = 0.031), which occurred mainly within eight weeks after drug administration. Patients with irritability were not dangerous to surrounding people by the assessment of parental observation in the life. And the symptoms were relieved spontaneously within a few months. The outcomes of total scores, internalizing scores, and externalizing scores of the CBCL did not show statistically significant differences in the PER and LCM groups between baseline and three and six months. Characteristics of behavior and emotion did not have substantial changes in patients treated with PER and LCM monotherapy. CONCLUSIONS: The present study documented similar good effectiveness and good tolerance of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy and showed no behavioral or emotional impact, as assessed by the CBCL. Though the incidence of irritability with PER monotherapy may be higher than that with LCM monotherapy soon after medication initiation, this side effect appears to resolve spontaneously within a few months. At present, this study was the first research about PER and LCM monotherapy in pediatric patients with newly diagnosed focal epilepsy evaluating efficacy, tolerability, and behavior in China.
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Anticonvulsivantes , Epilepsia Rolándica , Masculino , Femenino , Humanos , Niño , Preescolar , Lacosamida/uso terapéutico , Estudios Prospectivos , Anticonvulsivantes/efectos adversos , Mareo/inducido químicamente , Somnolencia , Estudios Retrospectivos , Resultado del Tratamiento , Genio Irritable , Epilepsia Rolándica/tratamiento farmacológico , Cefalea/inducido químicamenteRESUMEN
BACKGROUND: The participation and results for liver cancer screening are rarely reported. The aim of this study was to determine the participation rates and factors affecting participation rates as well as to report the detection rate for liver cancer in an organized screening program. METHODS: The organized screening program for liver cancer was conducted in 12 rural sites. The risk of developing liver cancer was initially evaluated for each participant. High-risk individuals were offered α-fetoprotein measurement and ultrasonography examination. Potential risk factors associated with the participation rate were screened by fitted generalized linear mixed logistic regression models through reporting odds ratios (ORs) with 95% CIs. RESULTS: A total of 358,662 eligible participants completed the basic surveys, and 54,745 were evaluated to be at high risk of liver cancer. Of these high-risk individuals, 40,543 accepted the screening services. Determinants of participation for screening behavior included older age, being female, being positive for hepatitis B surface antigen, having a family history of liver cancer, chronic depression, and low income. The detection rate for liver cancer was estimated to be 0.41% (95% CI, 0.35-0.48). CONCLUSIONS: This study reported several significant factors associated with the screening behaviors for liver cancer. LAY SUMMARY: Participation rate and results for liver cancer screening in rural areas are rarely reported. The determinants associated with adherence rates and early detection rate of liver cancer in an organized screening program for liver cancer were assessed. A possible positive correlation between the participation rates and the early detection rate was observed among attendees of screening. These new finds could be beneficial to increasing the participation rate of screening.
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Detección Precoz del Cáncer , Neoplasias Hepáticas , Estudios Transversales , Femenino , Antígenos de Superficie de la Hepatitis B , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Masculino , Tamizaje Masivo , Factores de Riesgo , alfa-FetoproteínasRESUMEN
Vibrio vulnificus is a pathogenic bacterium that causes disease in marine fish, affecting fish farming and human health worldwide. In May 2021, in the Bohai Bay region, a disease broke out in commercially farmed pearl gentian grouper (âEpinephelus fuscoguttatus × âEpinephelus lanceolatus), causing huge economic losses. The diseased fish had skin lesions, water accumulation in their abdomens, and showed tissue and organ damage. V. vulnificus biotype 2 has been reported in eels and other marine fish, but it is less reported in pearl gentian grouper. In this study, the pathogenic strain isolated from diseased fish was identified as V. vulnificus EPL 0201 biotype 2 on the basis of physiological and biochemical characteristics and the results of 16S rRNA gene and gyrB sequencing, virulence gene detection, and recursive infection experiments. To gain a comprehensive understanding of the pathogenicity and drug resistance of this strain, whole-genome sequencing was performed. Whole-genome analysis showed that the gene map of this strain was complete. The Virulence Factor Database annotation results showed that this strain had the key virulence factor genes vvhA and rtxA, which cause host disease. In addition, this strain had genes conferring resistance against cephalosporins, aminoglycosides, tetracyclines, and sulfonamides. Antimicrobial susceptibility testing confirmed the presence of these resistance genes identified in the genome. The results of this study show that V. vulnificus EPL 0201 biotype 2 is a multi-drug resistant strain with high pathogenicity.
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Lubina , Vibriosis , Vibrio vulnificus , Vibrio , Animales , Antibacterianos/farmacología , Anguilas/genética , Anguilas/microbiología , Humanos , ARN Ribosómico 16S/genética , Vibrio/genética , Vibriosis/microbiología , Vibriosis/veterinaria , Vibrio vulnificus/genética , Factores de Virulencia/genéticaRESUMEN
BACKGROUND: Lung cancer is currently the most frequent cancer in Jiangsu Province, China, and the features of cancer distribution have changed continuously in the last decade. The aim of this study was to analyse the trend of the incidence of lung cancer in Jiangsu from 2009 to 2018 and predict the incidence from 2019 to 2030. METHODS: Data on lung cancer incidence in Jiangsu from 2009 to 2018 were retrieved from the Jiangsu Cancer Registry. The average annual percentage change (AAPC) was used to quantify the trend of the lung cancer age-standardized rate (ASR) using Joinpoint software. Bayesian age-period-cohort models were used to predict lung cancer incidence up to 2030. RESULTS: In Jiangsu, the lung cancer crude rate increased from 45.73 per 100,000 in 2009 to 69.93 per 100,000 in 2018. The lung cancer ASR increased from 29.03 per 100,000 to 34.22 per 100,000 during the same period (AAPC = 2.17%, 95% confidence interval [CI], 1.54%, 2.80%). Between 2019 and 2030, the lung cancer ASR is predicted to decrease slightly to 32.14 per 100,000 (95% highest density interval [HDI], 24.99, 40.22). Meanwhile, the ASR showed a downward trend in males and rural regions while remaining stable in females and urban regions. CONCLUSION: We predict that the incidence of lung cancer in Jiangsu will decrease in the next 12 years, mainly due to the decrease in males and rural areas. Therefore, future lung cancer prevention and control efforts should be focused on females and urban regions.
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Neoplasias Pulmonares , Población Rural , Masculino , Femenino , Humanos , Incidencia , Población Urbana , Teorema de Bayes , China/epidemiología , Sistema de Registros , Neoplasias Pulmonares/epidemiologíaRESUMEN
BACKGROUND: In China, the quantity of physical activity differs from that in Western countries. Substantial uncertainty remains about the relevance of physical activity for cancer subtypes among Chinese adults. OBJECTIVE: This study aimed to investigate the association between total daily physical activity and the incidence of common types of cancer. METHODS: A total of 53,269 participants aged 30-79 years were derived from the Wuzhong subcohort of the China Kadoorie Biobank study during 2004-2008. We included 52,938 cancer-free participants in the final analysis. Incident cancers were identified through linkage with the health insurance system and death registries. Cox proportional hazard models were introduced to assess the associations of total daily physical activity with the incidence of 6 common types of cancer. RESULTS: During a follow-up of 10.1 years, 3,674 cases of cancer were identified, including 794 (21.6%) from stomach cancer, 722 (19.7%) from lung cancer, 458 (12.5%) from colorectal cancer, 338 (9.2%) from liver cancer, 250 (6.8%) from breast cancer, and 231 (6.3%) from oesophageal cancer. Compared to the participants in the lowest quartile of physical activity levels, those in the highest quartile had an 11% lower risk for total cancer incidence (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.81-0.99), 25% lower risk for lung cancer incidence (HR: 0.75, 95% CI: 0.60-0.94), and 26% lower risk for colorectal cancer incidence (HR: 0.74, 95% CI: 0.55-1.00). There were significant interactions of physical activity with sex and smoking on total cancer (both P for interaction < 0.005), showing a lower risk for females and never smokers (HR: 0.92, 95% CI: 0.87-0.98 and HR: 0.93, 95% CI: 0.87-0.98, respectively). CONCLUSIONS: Higher physical activity levels are associated with a reduced risk of total, lung, and colorectal cancer.
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Neoplasias de la Mama , Neoplasias Colorrectales , Neoplasias Pulmonares , Adulto , Femenino , Humanos , Estudios Prospectivos , Factores de Riesgo , Pueblos del Este de Asia , Incidencia , China/epidemiología , Modelos de Riesgos Proporcionales , Ejercicio Físico , Neoplasias de la Mama/epidemiología , Neoplasias Pulmonares/epidemiología , Neoplasias Colorrectales/epidemiologíaRESUMEN
BACKGROUND AND AIMS: We explored the associations among fruit consumption, physical activity, and their dose-response relationship with all-cause and cardiovascular disease (CVD) mortality in type 2 diabetic patients. METHODS AND RESULTS: We prospectively followed 20,340 community-dwelling type 2 diabetic patients aged 21-94 years. Information on diets and physical activity was collected using standardized questionnaires. All-cause and CVD mortality were assessed. Hazard ratios (HRs) for all-cause mortality were estimated with Cox regression models, and HRs for CVD mortality were derived from a competing risk model. Restricted cubic spline regression was used to analyze dose-response relationships. We identified 1362 deaths during 79,844 person-years. Compared to non-consumption, fruit consumption >42.9 g/d was inversely associated with all-cause mortality (HR 0.76; 95% CI 0.64-0.88), CVD mortality (HR 0.69, 0.51-0.94) and stroke mortality (HR 0.57, 0.36-0.89), but not with heart disease mortality (HR 0.93, 0.56-1.52). The HRs comparing the top vs bottom physical activity quartiles were 0.44 (0.37-0.53) for all-cause mortality, 0.46 (0.33-0.64) for CVD mortality, 0.46 (0.29-0.74) for stroke mortality and 0.51 (0.29-0.88) for heart disease mortality. Lower fruit consumption combined with a lower physical activity level was associated with a greater mortality risk. A nonlinear threshold of 80 g fruit/day was identified; all-cause mortality risk was reduced by approximately 24% at this value. A physical activity threshold of eight metabolic equivalents (MET) h/day was also identified, after which the risk of mortality did not decrease. CONCLUSIONS: Fruit consumption and physical activity may reduce all-cause, CVD, and stroke mortality in type 2 diabetic patients.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Cardiopatías , Accidente Cerebrovascular , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Ejercicio Físico , Estudios de Seguimiento , Frutas , Humanos , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND/AIM: The number of coronavirus disease 2019 deaths and cases continues to increase globally. Novel therapies are urgently needed to treat patients with coronavirus disease 2019. We sought to provide a critical review of trials designed during the coronavirus disease 2019 pandemic. Our primary goal was to provide a critical review of the landscape of clinical trials designed to address the coronavirus disease 2019 pandemic. Specifically, we were interested in assessing the design of phase II/III and phase III interventional trials. METHODS: We utilized the ClinicalTrials.gov database to include trials registered between 1 December 2019 and 11 April 2021 to survey the current landscape of clinical trials for coronavirus disease 2019. Variables extracted included: National Clinical Trial number, title, location, sponsor, study type, start date, completion date, gender group, age group, primary outcome, secondary outcome, overall status, and associated references. RESULTS: About 57% of studies were interventional, 14.5% were phase III trials, and the majority of the therapeutic trials included hospitalized patients. There were 52 primary composite outcomes and 285 unique interventions spanning 10 drug classes. The outcomes, disease severity, and comparators varied substantially across trials, and the trials were often too small to be definitive. CONCLUSION: These findings are relevant as we strongly advocate for global coordination of efforts through the use of common platforms that enable harmonizing of endpoints, collection of common key variables and clear definition of disease severity to have clinically meaningful results from clinical trials.
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COVID-19 , Humanos , Pandemias , Proyectos de Investigación , SARS-CoV-2 , Índice de Severidad de la EnfermedadRESUMEN
Glutathione S-transferase pi (GSTpi) is an important phase II detoxifying enzyme that participates in various physiological processes, such as antioxidant, detoxification, and signal transduction. The high expression level of GSTpi has been reported to be related to drug-resistant and anti-inflammatory and it functioned via its non-catalytic ligandin. However, the previous protection mechanism of GSTpi in DNA damage has not been addressed so far. Nijmegen breakage syndrome 1 (NBS1) is one of the most important sensor proteins to detect damaged DNA. Here, we investigated the interaction between GSTpi and NBS1 in HEK-293 T cells and human breast adenocarcinoma cells during DNA damage. Our results showed that overexpression of GSTpi in cells by transfecting DNA vector decreased the DNA damage level after methyl methanesulfonate (MMS) or adriamycin (ADR) treatment. We found that cytosolic GSTpi could increase NBS1 ubiquitin-mediated degradation in unstimulated cells, which suggested that GSTpi could maintain the basal level of NBS1 during normal conditions. In response to DNA damage, GSTpi can be phosphorylated in Ser184 and inhibit the ubiquitination degradation of NBS1 mediated by Skp2 to recover NBS1 protein level. Phosphorylated GSTpi can further enhance NBS1 nuclear translocation to activate the ATM-Chk2-p53 signaling pathway. Finally, GSTpi blocked the cell cycle in the G2/M phase to allow more time for DNA damage repair. Thus, our finding revealed the novel mechanism of GSTpi via its Ser184 phosphorylation to protect cells from cell death during DNA damage and it enriches the function of GSTpi in drug resistance.
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Proteínas de Ciclo Celular/metabolismo , Daño del ADN , Gutatión-S-Transferasa pi/fisiología , Síndrome de Nijmegen/metabolismo , Proteínas Nucleares/metabolismo , Células HEK293 , Humanos , Células MCF-7 , Fosforilación , UbiquitinaciónRESUMEN
BACKGROUND: Ultraviolet (UV) radiation-induced oxidative stress is the main cause of photodamage to the skin. Glutathione (GSH) serves important physiological functions, including scavenging oxygen-free radicals and maintaining intracellular redox balance. γ-glutamylcysteine (γ-GC), as an immediate precursor of GSH and harboring antioxidant and anti-inflammatory properties, represents an unexplored option for skin photodamage treatment. PURPOSE: The purpose of this study was to investigate whether γ-GC can reduce UVB-induced NIH-3T3 cell damage. METHODS: The experimental groups were as follows: control, UVB radiation, UVB radiation after pretreatment with γ-GC. Cell counting kit-8 (CCK-8) assays were used to measure cell proliferation, flow cytometry, and immunoblotting to detect the apoptosis rate and apoptosis-associated proteins. The levels of Reactive Oxygen Species (ROS), Superoxide Dismutase (SOD), and GSH/GSSG (oxidized GSH) were measured to assess oxidative stress. Immunoblotting and immunofluorescence were used to detect DNA damage. The members of the MAPK signaling pathways were detected by immunoblotting. RESULTS: UVB irradiation significantly reduced cell viability and destroyed the oxidative defense system. Pretreatment with γ-GC reduced UVB-induced cytotoxicity, restored the oxidation defense system, and inhibited activation of the MAPK pathway. It also reduced the apoptosis rate, downregulated the levels of cleaved caspase 3 and cleaved PARP. Furthermore, pretreatment with γ-GC reduced the accumulation of γH2AX after UVB radiation exposure, indicating that γ-GC could protect cells from DNA damage. CONCLUSION: γ-GC protected NIH-3T3 from damage caused by UVB irradiation. The photoprotective effect of γ-GC is mediated via strengthening the endogenous antioxidant defense system, which prevents DNA damage and inhibits the activation of the MAPK pathway.
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Estrés Oxidativo , Rayos Ultravioleta , Humanos , Ratones , Animales , Células 3T3 NIH , Rayos Ultravioleta/efectos adversos , Dipéptidos/metabolismo , Dipéptidos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Glutatión/metabolismo , ApoptosisRESUMEN
BACKGROUND: Decreased physical activity had been reported to be a common causal and modifiable risk factor for major vascular events. However, the relationship of physical activity and sedentary leisure time with carotid atherosclerosis in population with high risk for cardiovascular diseases (CVDs) is still inconclusive. We aimed to evaluate the association of physical activity and sedentary leisure time with the risk of carotid atherosclerosis, and investigate any possible effect modifiers in population with high risk for CVDs. METHODS: The study population was drawn from the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project-Jiangsu project, which is a population-based screening project that included permanent residents aged 35-75 years from 6 surveillance cities in Jiangsu Province. Linear regression models were used to evaluate the association of physical activity and sedentary leisure time with carotid intima-media thickness (CIMT). The risks of abnormal carotid artery and carotid plaque (CP) were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. RESULTS: Overall, a total of 10,920 participants were enrolled in the final analysis. There was a significant inverse association of physical activity level with CIMT (per SD increase: ß=-0.0103; 95%CI: -0.0154, -0.0053). The risk of abnormal carotid artery and CP decreased significantly with the increase of physical activity level (per SD increase: OR=0.908, 95%CI: 0.869-0.948; OR=0.900, 95%CI: 0.857-0.945, respectively). When physical activity level was categorized as quartiles, a significantly lower risk of abnormal carotid artery and CP was found in quartiles 2-4 with quartile 1 as reference (P<0.05 for all). Furthermore, the inverse association were stronger in participants with age ≥60 years (vs. <60 years, Pinteraction<0.001 for both). However, there were no significant association of sedentary leisure time with CIMT, abnormal carotid artery and CP. CONCLUSIONS: In population with high risk for CVDs, physical activity was inversely associated with CIMT, abnormal carotid artery and CP, particularly among the elders. Sedentary leisure time was not associated with them. These results suggested that physical activity is important for carotid vascular health, and perhaps especially in elder population.