Coixol mitigates Toxoplasma gondii infection-induced liver injury by inhibiting the Toxoplasma gondii HSP70/TLR4/NF-κB signaling pathway in hepatic macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Coix seed, the dry mature seed kernel of the gramineous plant coix (Coix lacryma-jobi L. var. ma-yuen Stapf), is widely consumed as a traditional Chinese medicine and functional food in China and South Korea. We have previously demonstrated the protective effect of coixol, a polyphenolic compound extracted from coix, against Toxoplasma gondii (T. gondii) infection-induced lung injury. However, the protective effect of coixol on hepatic injury induced by T. gondii infection have not yet been elucidated. AIM OF THE STUDY: This study explores the impact of coixol on T. gondii infection-induced liver injury and elucidates the underlying molecular mechanisms. MATERIALS AND METHODS: Female BALB/c mice and Kupffer cells (KCs) were employed to establish an acute T. gondii infection model in vivo and an inflammation model in vitro. The study examined coixol's influence on the T. gondii-derived heat shock protein 70 (T.g.HSP70)/toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway in T. gondii-infected liver macrophages. Furthermore, a co-culture system of KCs and NCTC-1469 hepatocytes was developed to observe the impact of liver macrophages infected with T. gondii on hepatocyte injury. RESULTS: Coixol notably inhibited the proliferation of tachyzoites and the expression of T.g.HSP70 in mouse liver and KCs, and attenuated pathological liver injury. Moreover, coixol decreased the production of high mobility group box 1, tumor necrosis factor-α, and inducible nitric oxide synthase by suppressing the TLR4/NF-κB signaling pathway in vitro and in vivo. Coixol also mitigated KCs-mediated hepatocyte injury. CONCLUSIONS: Coixol protects against liver injury caused by T. gondii infection, potentially by diminishing hepatocyte injury through the suppression of the inflammatory cascade mediated by the T.g.HSP70/TLR4/NF-κB signaling pathway in KCs. These findings offer new perspectives for developing coixol as a lead compound for anti-T. gondii drugs.

Association between socioeconomic status and risk of chronic obstructive pulmonary disease in China: a prospective cohort study.

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.

Associations between perceived care quality, self-care behaviors, and glycemic control in Chinese adults with type 2 diabetes under the national essential public health services program.

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.

Trends in injury-related mortality among residents of Jiangsu Province from 2012 to 2021: an age-period-cohort analysis.

Objective: We investigated the temporal trends and examined age-, period-, and cohort-specific effects of injury-related deaths among residents in Jiangsu to provide evidence for future injury prevention. Methods: This study included 406,936 injury deaths from the Jiangsu provincial population death registration system. The average annual percent change (AAPC) in age-standardized mortality rates (ASMRs) was analyzed using joinpoint regression. Age-period-cohort models were generated to explore the effects of age, period, and birth cohort effects on mortality risk. Results: ASMRs for all injuries (AAPC = -2.3%), road traffic accidents (AAPC = -5.3%), suicide (AAPC = -3.8%), and drowning (AAPC = -3.9%) showed a downward trend during 2012-2021(all p < 0.05), while unintentional falls showed an upward trend (AAPC = 5.1%, p < 0.05). From 2012 to 2021, the age-standardized mortality rates (ASMRs) for four primary types of injuries consistently exhibited higher among males compared to females, with rural regions displaying higher ASMRs than urban areas. Trends in ASMRs for road traffic accidents, drowning, and unintentional falls by sex and urban/rural areas were consistent with overall trends. Significant age, cohort, and period effects were identified in the trends of injury-related deaths for both sexes in Jiangsu. The age effect showed that the highest age effect for injury-related deaths was for the ages of 85 years and above, except for suicide, which was for the ages 80-84 years. Between 2012 and 2021, the period effect on road traffic accidents declined, while that on accidental falls increased. Initially, the period effect on suicide decreased but then rose, peaking in 2012 with a Relative Risk (RR) of 1.11 (95% CI: 1.04-1.19). Similarly, the period effect on drowning initially declined before rising, with the highest effect observed in 2013, at an RR of 1.12 (95% CI: 1.07-1.19). The highest cohort effects for road traffic accidents were observed in the 1957-1961 group, for accidental falls in the 1952-1956 group, and for both drowning and suicide in the 1927-1931 group. Conclusion: The mortality rate of unintentional falls has been increasing. Older adults are at high risk for the four leading injuries. The improvements in mortality rates can be attributed to advancements in education, urbanization, and the promulgation and implementation of laws and policies.

Temporal change in multimorbidity prevalence, clustering patterns, and the association with mortality: findings from the China Kadoorie Biobank study in Jiangsu Province.

Objectives: The characteristics of multimorbidity in the Chinese population are currently unclear. We aimed to determine the temporal change in multimorbidity prevalence, clustering patterns, and the association of multimorbidity with mortality from all causes and four major chronic diseases. Methods: This study analyzed data from the China Kadoorie Biobank study performed in Wuzhong District, Jiangsu Province. A total of 53,269 participants aged 30-79 years were recruited between 2004 and 2008. New diagnoses of 15 chronic diseases and death events were collected during the mean follow-up of 10.9 years. Yule's Q cluster analysis method was used to determine the clustering patterns of multimorbidity. A Cox proportional hazards model was used to estimate the associations of multimorbidity with mortalities. Results: The overall multimorbidity prevalence rate was 21.1% at baseline and 27.7% at the end of follow-up. Multimorbidity increased more rapidly during the follow-up in individuals who had a higher risk at baseline. Three main multimorbidity patterns were identified: (i) cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), (ii) respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), and (iii) mental, kidney and arthritis multimorbidity (neurasthenia, psychiatric disorders, chronic kidney disease, and rheumatoid arthritis). There were 3,433 deaths during the follow-up. The mortality risk increased by 24% with each additional disease [hazard ratio (HR) = 1.24, 95% confidence interval (CI) = 1.20-1.29]. Compared with those without multimorbidity at baseline, both cardiometabolic multimorbidity and respiratory multimorbidity were associated with increased mortality from all causes and four major chronic diseases. Cardiometabolic multimorbidity was additionally associated with mortality from cardiovascular diseases and diabetes, with HRs of 2.64 (95% CI = 2.19-3.19) and 28.19 (95% CI = 14.85-53.51), respectively. Respiratory multimorbidity was associated with respiratory disease mortality, with an HR of 9.76 (95% CI = 6.22-15.31). Conclusion: The prevalence of multimorbidity has increased substantially over the past decade. This study has revealed that cardiometabolic multimorbidity and respiratory multimorbidity have significantly increased mortality rates. These findings indicate the need to consider high-risk populations and to provide local evidence for intervention strategies and health management in economically developed regions.

The short-term effects of individual and mixed ambient air pollutants on suicide mortality: A case-crossover study.

It is critical to explore intervenable environmental factors in suicide mortality. Based on 30,688 suicide cases obtained from the Mortality Surveillance System of the Jiangsu Provincial Centre for Disease Control and Prevention, we utilized a case-crossover design, and found that the OR of suicide deaths increased by a maximum of 0.71 % (95 % CI: 0.09 %, 1.32 %), 0.68 % (95 % CI: 0.12 %, 1.25 %), 0.77 % (95 % CI: 0.19 %, 1.37 %), 2.95 % (95 % CI: 1.62 %, 4.29 %), 4.18 % (95 % CI: 1.55 %, 6.88 %), and 0.93 % (95 % CI: 0.10 %, 1.77 %), respectively, for per 10 µg/m3 increase in the particulate matter (PM) with diameters ≤ 2.5 µm (PM2.5), PM with diameters ≤ 10 µm (PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and per 0.1 mg/m3 increase in carbon monoxide (CO) concentrations with the conditional logistic regression analysis. People living in county-level cities were more susceptible. Particularly, a significant positive association was found between air pollutant mixture exposure and suicide deaths (OR=1.04,95 % CI: 1.01, 1.06). The excess fraction of suicide deaths due to air pollution reached a maximum of 8.07 %. In conclusion, we found associations between individual and mixed ambient air pollutants and suicide deaths, informing the development of integrated air pollution management and targeted measures for suicide prevention and intervention. ENVIRONMENTAL IMPLICATION: As a major contributor to the global burden of disease, air pollution was confirmed by accumulating studies to have adverse impact on mental health, and potentially lead to suicide deaths. However, systematic studies on the association between air pollution and suicide mortality are lacking. We explored the associations of multiple air pollutants and pollution mixtures with suicide deaths and assessed excess suicide mortality due to air pollution, emphasizing the importance of air pollution control on suicide prevention. Our study provides evidence to support mechanistic studies on the association between air pollution and suicide, and informs comprehensive air pollution management.

Association of lifestyle with reduced stroke risk in 41 314 individuals with diabetes: Two prospective cohort studies in China.

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.

Prognostic value of tumor deposits and positive lymph node ratio in stage III colorectal cancer: a retrospective cohort study.

BACKGROUND: In colorectal cancer (CRC), tumor deposits (TD) have been used to guide the N staging only in node-negative patients. It remains unknown about the prognostic value of TD in combination with positive lymph node ratio (LNR) in stage III CRC. PATIENTS AND METHODS: The authors analyzed data from 31 139 eligible patients diagnosed with stage III CRC, including 30 230 from the Surveillance, Epidemiology, and End Results (SEER) database as a training set and 909 from two Chinese hospitals as a validation set. The associations of TD and LNR with cancer-specific survival (CSS) and overall survival (OS) were evaluated using the Kaplan-Meier method and Cox regression models. RESULTS: Both TD-positive and high LNR (value ≥0.4) were associated with worse CSS in the training [multivariable hazard ratio (HR), 1.50; 95% CI: 1.43-1.58 and HR, 1.74; 95% CI: 1.62-1.86, respectively] and validation sets (HR, 1.90; 95% CI: 1.41-2.54 and HR, 2.01; 95% CI: 1.29-3.15, respectively). Compared to patients with TD-negative and low LNR (value<0.4), those with TD-positive and high LNR had a 4.09-fold risk of CRC-specific death in the training set (HR, 4.09; 95% CI: 3.54-4.72) and 4.60-fold risk in the validation set (HR, 4.60; 95% CI: 2.88-7.35). Patients with TD-positive/H-LNR CRC on the right side had the worst prognosis ( P <0.001). The combined variable of TD and LNR contributed the most to CSS prediction in the training (24.26%) and validation (32.31%) sets. A nomogram including TD and LNR showed satisfactory discriminative ability, and calibration curves indicated favorable consistency in both the training and validation sets. CONCLUSIONS: TD and LNR represent independent prognostic predictors for stage III CRC. A combination of TD and LNR could be used to identify those at high-risk of CRC deaths.

Phenotypic and genotypic analysis of a patient with Miyoshi myopathy caused by truncated protein.

Dysferlin protein deficiency can cause neuromuscular dysfunction, resulting in autosomal recessive dysferlinopathy, which is caused by DYSF gene mutation. Dysferlin proteins belongs to the Ferlin1-like protein family and are associated with muscle membrane repair and regeneration. In China, pathogenic mutations of the protein often result in two clinical phenotypes of Miyoshi muscular or limb band muscular dystrophy type 2B. It is clinically characterized by progressive muscle weakness and elevated serum creatine kinase. The data of the child were collected, blood samples of the child and his family members were collected, and whole exome sequencing (WES) was performed. The recombinant expression vector was constructed, the function of the mutation was verified by minigene, and the pathogenicity of the mutation was further analyzed by combining with biological information analysis. The patient initially presented with asymptomatic elevation of serum creatine kinase（CK）. Then progressive lower limb weakness, mainly distal limb weakness. Large amounts of scattered necrosis, myogenic lesions, and complete deletion of dysferlin protein were observed under muscle biopsy, which further improved genetic detection. Whole exome sequencing showed compound mutations (c.1397 + 1_1397 + 3del and c.1375dup p.M459Nfs*15) in DYSF gene. c.1375dup p.M459Nfs*15 have been reported. The other mutation is the deletion of c.1397 + 1_1397 + 3 in Intron15, which is an intron mutation that may affect splicing and the pathogenesis is still unknown. Minigene splicing assay verified that c.1397 + 1_1397 + 3del resulted in exon15 skipping and produced a premature termination codon. We report a novel pathogenic mutation in DYSF gene with Miyoshi myopathy and demonstrate this variant causes skipping of exon15 by minigene splicing assay. We point out the need of conducting functional analysis to verify the pathogenicity of intronic mutation. The finding enriches the mutation spectrum of DYSF gene and laid a foundation for future studies on the correlation between genotype and phenotype.

Green tea consumption and incidence of cardiovascular disease in type 2 diabetic patients with overweight/obesity: a community-based cohort study.

BACKGROUND: Green tea has been reported to be potentially protective against the development of cardiovascular disease (CVD). This study aimed to investigate the association between green tea consumption and incident CVD in type 2 diabetes (T2D) patients with overweight/obesity. METHODS: A total of 4756 Chinese overweight/obese T2D patients were recruited and followed up for 6.27 years. Information on green tea consumption was collected at baseline using interviewer-administered questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD according to green tea consumption were estimated using the Cox proportional hazards model. RESULTS: Compared with non-habitual consumers, participants who consumed > 5 g/day of green tea leaves reduced the risk of CVD by 29% (95%CI: 0.55-0.92), stroke by 30% (95%CI: 0.51-0.95) and coronary heart disease (CHD) by 40% (95%CI: 0.40-0.89). Similarly, participants who consumed green tea for ≥ 40 years reduced the risk of CVD by 31% (95%CI: 0.54-0.88), stroke by 33% (95%CI: 0.50-0.90) and CHD by 39% (95%CI: 0.42-0.88). Among participants with < 5-year history of T2D, > 5 g/day of tea leaves and > 40 years of tea consumption were associated with 59% (95%CI: 0.23-0.72) and 57% (95%CI: 0.26-0.74) reduced risk of stroke, respectively. However, among participants with ≥ 5-year history of T2D, > 5 g/day of tea leaves and > 40 years of tea consumption were associated with a 50% (95%CI: 0.30-0.82) and 46% (95%CI: 0.35-0.85) reduced risk of CHD, respectively. CONCLUSIONS: Green tea consumption is associated with reduced risk of CVD, stroke, and CHD in overweight/obese T2D patients.

α-Solanine attenuates chondrocyte pyroptosis to improve osteoarthritis via suppressing NF-κB pathway.

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.

The impact of short-term exposures to ambient NO2, O3, and their combined oxidative potential on daily mortality.

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.

Association of Short-Term Co-Exposure to Particulate Matter and Ozone with Mortality Risk.

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.

Phosphorylated Hsp27 promotes adriamycin resistance in breast cancer cells through regulating dual phosphorylation of c-Myc.

Chemotherapy resistance of breast cancer cells is one of the major factors affecting patient survival rate. Heat shock protein 27 (Hsp27) is a member of the small heat shock protein family that has been reported to be associated with chemotherapy resistance in tumor cells, but the exact mechanism is not fully understood. Here, we explored the regulation of Hsp27 in adriamycin-resistant pathological conditions of breast cancer in vitro and in vivo. We found that overexpression of Hsp27 in MCF-7 breast cancer cells reversed DNA damage induced by adriamycin, and thereby reduced subsequent cell apoptosis. Non-phosphorylated Hsp27 accelerated ubiquitin-mediated degradation of c-Myc under normal physiological conditions. After stimulation with adriamycin, Hsp27 was phosphorylated and translocated from the cytoplasm into the nucleus, where phosphorylated Hsp27 upregulated c-Myc and Nijmegen breakage syndrome 1 (NBS1) protein levels thus leading to ATM activation. We further showed that phosphorylated Hsp27 promoted c-Myc nuclear import and stabilization by regulating T58/S62 phosphorylation of c-Myc through a protein phosphatase 2A (PP2A)-dependent mechanism. Collectively, the data presented in this study demonstrate that Hsp27, in its phosphorylation state, plays a critical role in adriamycin-resistant pathological conditions of breast cancer cells.

Long-term esophageal cancer risk and distinct surveillance intervals after a single endoscopy screening: a multicentre population-based cohort study.

Background: Endoscopy surveillance is recommended for mild-moderate dysplasia and negative endoscopy findings every 3 years and 5 years, respectively, but evidence is limited. This study aimed to assess long-term esophageal cancer (EC) incidence and mortality after a single endoscopy screening. Methods: We included individuals at high risk of EC aged 40-69 years who underwent endoscopy screening in 2007-2012 at six centres in rural China and had a baseline diagnosis of negative endoscopy findings, mild dysplasia, or moderate dysplasia. Participants were followed up for EC incidence and mortality. Cumulative incidence and mortality rates of EC were estimated by Kaplan-Meier analyses. Cox regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between baseline endoscopy diagnosis and the risk of EC incidence and mortality. EC incidence and mortality after a single endoscopy screening were compared with those of the population in rural China by the standardized incidence ratio (SIR) and standardized mortality ratio (SMR). Findings: A total of 42,827 participants (40,977 with negative endoscopy findings, 1562 with mild dysplasia, and 288 with moderate dysplasia) were included; 268 EC cases and 128 EC deaths were identified during a median follow-up of 10.62 years. The cumulative EC incidence at 10 years was 0.45% (0.38-0.52) in the group with negative endoscopy findings, 2.39% (1.62-3.16) in the mild dysplasia group, and 8.90% (5.57-12.24) in the moderate dysplasia group, and the cumulative EC mortality at 10 years was 0.23% (0.18-0.27), 0.96% (0.46-1.46), and 2.50% (0.67-4.33), respectively. Compared with individuals with negative endoscopy findings, the HRs for EC incidence and mortality in the mild dysplasia group were 3.52 (2.49-4.97) and 2.43 (1.41-4.19), and those in the moderate dysplasia group were 13.18 (8.78-19.76) and 6.46 (3.13-13.29), respectively. The SIR was 0.53 (0.40-0.70) for the group with negative endoscopy findings, 1.95 (1.69-2.24) for the mild dysplasia group, and 6.75 (6.25-7.28) for the moderate dysplasia group, with the SMRs of 0.43 (0.31-0.58), 1.07 (0.88-1.29) and 2.67 (2.36-3.01), respectively. Interpretation: Individuals with negative endoscopy findings after a single endoscopy screening had a lower EC risk than the general population for up to 10.62 years, while those with mild-moderate dysplasia had an elevated risk. Our results support endoscopy surveillance for mild-moderate dysplasia every 3 years and suggest extending the interval to 10 years after a negative endoscopy finding. Funding: National Key R&D Programme of China, Special Project of Beijing-Tianjin-Hebei Basic Research Cooperation, and Sanming Project of Medicine in Shenzhen.

Performance and effectiveness of hepatocellular carcinoma screening in individuals with HBsAg seropositivity in China: a multicenter prospective study.

Current guidelines recommend hepatocellular carcinoma (HCC) surveillance for at-risk individuals, including individuals with hepatitis B virus infection. However, the performance and survival benefits of annual screening have not been evaluated through multicenter prospective studies in a Chinese population. Between 2017 and 2021, we included 14,426 participants with hepatitis B surface antigen seropositivity in an annual HCC screening study in China using a multicenter prospective design with ultrasonography and serum alpha-fetoprotein. After four rounds of screening and follow-up, the adjusted hazard ratios of death after correction for lead-time and length-time biases for screen-detected cancers at the prevalent and incident rounds were 0.74 (95% confidence interval = 0.60-0.91) and 0.52 (95% confidence interval = 0.40-0.68), respectively. A meta-analysis demonstrated that HCC screening was associated with improved survival after adjusting for lead-time bias. Our findings highlight the 'real-world' feasibility and effectiveness of annual HCC screening in community settings for the early detection of HCC and to improve survival.

Association of Serum Calcium with the Risk of Chronic Obstructive Pulmonary Disease: A Prospective Study from UK Biobank.

BACKGROUND: Although intracellular calcium had been demonstrated to involve in the pathogenesis of chronic obstructive pulmonary disease (COPD), the association between serum calcium and COPD risk remains unclear. METHODS: We included 386,844 participants with serum calcium measurements and without airway obstruction at the baseline from UK Biobank. The restricted cubic splines were used to assess the dose-response relationship. Multivariable cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of albumin-corrected calcium concentrations with the risk of COPD incidence and mortality. RESULTS: During a median of 12.3 years of follow-up, 10,582 incident COPD cases were documented. A linear positive association was observed between serum calcium concentrations and the risk of COPD incidence. Compared to participants with normal serum calcium (2.19-2.56 mmol/L), a 14% higher risk of COPD was observed in hypercalcemic participants (≥2.56 mmol/L, HR = 1.14; 95% CI: 1.02-1.27). No significant effect modifications were observed in stratified variables. In survival analysis, 215 COPD-specific deaths were documented after a median survival time of 3.8 years. Compared to participants with normal serum calcium, hypercalcemic participants had a 109% (HR = 2.09, 95% CI: 1.15-3.81) increased risk for COPD-specific mortality. CONCLUSION: Our study indicated that hypercalcemia was associated with an elevated risk of COPD incidence and mortality in the European population, and suggested that serum calcium may have a potential impact on the progression of COPD.

Association between glycated haemoglobin and the risk of chronic obstructive pulmonary disease: A prospective cohort study in UK biobank.

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.

Trends in the rate of regular exercise among adults: results from chronic disease and risk factor surveillance from 2010 to 2018 in Jiangsu, China.

Objective: The aims of this study were to estimate the rates of regular exercise and its trends among the adult population in Jiangsu, from 2010 to 2018, China, and to assess associations with sociodemographic factors. Methods: Chronic disease and risk factor surveillance data from adults aged ≥18 years were gathered in Jiangsu Province from 2010 to 2018. Rates of regular exercise were calculated after post-stratification weighting, and time trends were compared among participants with different characteristics, including gender, age, urban-rural region, educational level, occupation, annual household income, body mass index (BMI), baseline self-reported chronic diseases, smoking status, alcohol consumption, and region. Multivariable logistic regression analyses were performed to assess the associations of sociodemographic characteristics with regular exercise. Results: A total of 33,448 participants aged 54.05 ± 14.62 years and 55.4% female (8,374 in 2010, 8,302 in 2013, 8,372 in 2015, and 8,400 in 2018) were included in this study. The weighted rate of regular exercise was 12.28% (95% confidence interval [CI]: 9.11-15.45%) in 2010 and 21.47% (95% CI, 17.26-25.69%) in 2018, showing an overall increasing trend (P for trend = 0.009). Nevertheless, stratification analysis showed that the regular exercise rate decreased from 33.79% in 2010 to 29.78% in 2018 among retired adults. Significant associations were observed between regular exercise and age >45 years (45- < 60 years, odds ratio [OR]: 1.24, 95% CI: 1.14-1.34; ≥60 years, OR: 1.20, 95% CI: 1.08-1.34), urban residence (OR: 1.43, 95% CI: 1.32-1.54), higher education (primary, OR: 1.30, 95% CI: 1.16-1.46; secondary, OR: 2.00, 95% CI: 1.79-2.25; college or higher, OR: 3.21, 95% CI: 2.77-3.72), occupation (manual work, OR: 1.52, 95% CI: 1.33-1.73; non-manual work, OR: 1.69, 95% CI: 1.54-1.85; not working, OR: 1.22, 95% CI: 1.03-1.44; retired, OR: 2.94, 95% CI: 2.61-3.30), higher income (¥30,000- < ¥60,000, OR: 1.16, 95% CI: 1.06-1.28; ≥¥60,000, OR: 1.20, 95% CI: 1.10-1.32), higher BMI (overweight, OR: 1.12, 95% CI: 1.05-1.20), self-reported chronic disease at baseline (OR: 1.24, 95% CI:1.16-1.33), former smoking (OR: 1.15, 95% CI: 1.01-1.31) and ever (30 days ago) drinking (OR: 1.20, 95% CI: 1.11-1.29). Conclusion: The rate of regular exercise among adults in Jiangsu Province was low, but this rate increased by 9.17% from 2010 to 2018, showing an upward trend. There were differences in the rate of regular exercise among different sociodemographic factors.