Trends in cancer mortality among the elderly in China, 2005-2035.

BACKGROUND: With the appearance and aggravation of the aging society, cancer has become one of the major problems that threaten the life and health of Chinese residents seriously. OBJECTIVE: To explore the cancer epidemiological characteristics among the elderly in China from 2005 to 2016, and to provide strategies for cancer prevention and treatment. METHODS: Stratified analysis was conducted on the cancer mortality data of the elderly aged ≥60 years in China, which were selected from the Chinese Cancer Registry Annual Report. Joinpoint regression model was used to calculted average annual percentage change (AAPC) to estimate the time trends. Age-period-cohort (APC) model was used to explore the age, period and birth cohort effect on the risk of cancer death. Bayesian age-period-cohort (BAPC) model was used to predict trends in cancer mortality among elderly by gender and region to 2035. RESULTS: 2005-2016, cancer mortality in the elderly in China showed a decreasing trend (AAPC = -1.2%, P<0.001). Cancer mortality in rural areas was higher than that in urban areas, but the urban-rural difference gradually narrowed (t = 6.1, P<0.01). The APC model showed that cancer mortality increased with age. The relative risk (RR) for the period effect decreased. RR was lower for the later- born cohort than that for the earlier-born cohort in rural areas. Lung cancer mortality ranked first in both male and female, and showed an increasing trend among female in the 60-64, 80-84 and ≥85 age groups (AAPC60-64 = 1.0%, AAPC80-84 = 0.8%, AAPC≥85 = 2.0%, all P<0.05). By 2035, cancer mortality for the elderly was predicted to decline nationally, by sex and in rural areas, while rising in urban areas. CONCLUSION: Cancer mortality in the elderly in China showed a decreasing trend from 2005 to 2016, but it was still higher than the world average. Early cancer screening is important, especially in the elderly male and in rural areas.

The status and influencing factors of lung ventilation function in employees exposed to dust in enterprises of the XPCC, China.

Background: Occupational health is closely related to harmful factors in the workplace. Dust is the primary contributing factor causing impaired lung ventilation function among employees with dust exposure, and their lung ventilation function may also be influenced by other factors. We aimed at assessing the status and influencing factors of lung ventilation function among employees exposed to dust in the enterprises of the Eighth Division located in the Xinjiang Production and Construction Corps (XPCC), China. Methods: Employees exposed to dust in enterprises of the Eighth Division located in the XPCC in 2023 were selected as the subjects of this cross-sectional study. Their lung ventilation function indicators were extracted from health examination records, and an on-site electronic questionnaire survey was conducted among them. Binary logistic regression analyses were conducted to evaluate the factors influencing lung ventilation function. Results: According to the fixed value criteria, the abnormal rates of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC were 31.6, 1.4, and 0.4%, respectively. The lower limit of normal (LLN) criteria could overestimate the rate of abnormal lung ventilation function. Several factors were related to impaired lung ventilation function, including gender, age, education level, marital status, body mass index (BMI), smoking status, physical activity, the type of dust, industry, enterprise scale, occupation, length of service, working shift, monthly income, and respiratory protection. Conclusions: A relatively low abnormal rate of lung ventilation function was observed among employees exposed to dust in enterprises of the Eighth Division, XPCC, and their lung ventilation function was associated with various factors. Effective measures should be taken urgently to reduce the effects of adverse factors on lung ventilation function, thereby further protecting the health of the occupational population.

Global, regional, and national burden of non-communicable diseases attributable to occupational asbestos exposure 1990-2019 and prediction to 2035: worsening or improving?

Understanding the burden associated with occupational asbestos exposure on a global and regional scale is necessary to implement coordinated prevention and control strategies. By the GBD Study 2019, we conducted a comprehensive assessment of the non-communicable diseases burden attributable to occupational asbestos exposure. In 2019, 239,330 deaths and 4,189,000 disability-adjusted life years (DALYs) worldwide due to occupational asbestos exposure occurred. 1990-2019, deaths and DALYs attributed to occupational asbestos exposure increased by 65.65% and 43.66%, respectively. Age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) decreased, with the most rapid declines in high Socio-Demographic Index (SDI) regions, with average annual percent change (AAPC) of - 1.05(95%CI: -1.2, -0.89) and -1.53(95%CI: -1.71, -1.36), respectively. Lung cancer, mesothelioma and ovarian cancer were the top three contributors to the increase in deaths and DALYs, accounting for more than 96%. AAPCs of ASMR and ASDR were positively associated with SDI. Global deaths from occupational asbestos exposure were predicted to increase and ASMR to decrease by 2035, mostly in males. Due consideration should be given to the susceptibility of the elderly, the lag of asbestos onset, and the regional differences, and constantly improve the prevention and control measures of occupational asbestos exposure and related diseases.

Global burden of maternal disorders attributable to malnutrition from 1990 to 2019 and predictions to 2035: worsening or improving?

Background and aims: Maternal malnutrition is a major global public health problem that can lead to serious maternal diseases. This study aimed to analyze and predict the spatio-temporal trends in the burden of maternal disorders attributable to malnutrition, and to provide a basis for scientific improvement of maternal malnutrition and targeted prevention of maternal disorders. Methods: Data on maternal disorders attributable to malnutrition, including number of deaths, disability-adjusted life years (DALYs), population attributable fractions (PAFs), age-standardized mortality rates (ASMRs), and age-standardized DALY rates (ASDRs) were obtained from the Global Burden of Disease Study 2019 to describe their epidemiological characteristics by age, region, year, and type of disease. A log-linear regression model was used to calculate the annual percentage change (AAPC) of ASMR or ASDR to reflect their temporal trends. Bayesian age-period-cohort model was used to predict the number of deaths and mortality rates to 2035. Results: Global number of deaths and DALYs for maternal disorders attributable to malnutrition declined by 42.35 and 41.61% from 1990 to 2019, with an AAPC of -3.09 (95% CI: -3.31, -2.88) and -2.98 (95% CI: -3.20, -2.77) for ASMR and ASDR, respectively. The burden was higher among younger pregnant women (20-29 years) in low and low-middle socio-demographic index (SDI) regions, whereas it was higher among older pregnant women (30-39 years) in high SDI region. Both ASMR and ASDR showed a significant decreasing trend with increasing SDI. Maternal hemorrhage had the highest burden of all diseases. Global deaths are predicted to decline from 42,350 in 2019 to 38,461 in 2035, with the ASMR declining from 1.08 (95% UI: 0.38, 1.79) to 0.89 (95% UI: 0.47, 1.31). Conclusion: Maternal malnutrition is improving globally, but in the context of the global food crisis, attention needs to be paid to malnutrition in low SDI regions, especially among young pregnant women, and corresponding measures need to be taken to effectively reduce the burden of disease.

Titanium Dioxide Nanoparticles Induce Cell Cycle Arrest and Apoptosis through Inhibiting PI3K/AKT/mTOR Pathway in Spermatogonia.

Titanium dioxide nanoparticles (TiO2 NPs) can result in the reduction of sperm numbers, but the mechanisms have not been well elucidated. The purpose of this study was to investigate the effects of TiO2 NPs on cell cycle and apoptosis in spermatogonia and to explore the role of PI3K/AKT/mTOR signaling pathway in this process. The mouse spermatogonia cell line (GC-1) was treated with TiO2 NPs at different concentrations (0, 25, 50, 75 and 100 µg/mL) for 24 h to detect cell viability, cell cycle, apoptosis, and key proteins related to cell cycle and PI3K/AKT/mTOR signaling pathway. The agonist (IGF-1) and inhibitor (LY294002) of PI3K were used to verify the role of PI3K/AKT/mTOR signaling pathway in cell cycle and apoptosis. TiO2 NPs significantly inhibited cell proliferation, induced cell cycle arrest at G0/G1 phase and resulted in apoptosis. TiO2 NPs downregulated the levels of cyclin-dependent kinases (CDKs) and cyclins, including CDK4, CDK2, Cyclin D1 and Cyclin E1, while upregulated the levels of p21 and p53 proteins. Furthermore, TiO2 NPs inhibited the PI3K/AKT/mTOR signaling pathway by decreasing the levels of p-PI3K, p-AKT and p-mTOR. IGF-1 reversed the G0/G1 phase arrest and apoptosis caused by TiO2 NPs. However, LY294002 aggravated the G0/G1 phase arrest and apoptosis resulting from TiO2 NPs. Collectively, TiO2 NPs induced cell cycle arrest at G0/G1 phase and apoptosis through inhibiting the activation of PI3K/AKT/mTOR pathway, which could be the main reason for the reduction in sperm numbers caused by TiO2 NPs.

Validation of non-invasive indicators in the screening of metabolic dysfunction-associated fatty liver disease: a cross-sectional study among Uighurs in rural Xinjiang.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in China. Our study aimed to evaluate the screening value of the fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation product (LAP), visceral adiposity index (VAI), and Zhejiang University index (ZJU), as well as other single indicators for MAFLD. We aimed to find the optimal screening tool and its appropriate cut-off values for rural Uyghur adults. METHODS: We completed a survey of 14,321 Uyghur adults in 51 groups in Kashgar, Xinjiang, in 2016 using a typical sampling method, with 12,794 patients ultimately included in statistical analyses. Fatty liver was diagnosed using ultrasonography. RESULTS: The prevalence of fatty liver disease (FLD) and MAFLD was 16.73% and 16.55%, respectively, and the FLI, HSI, LAP, VAI, and ZJU were all independently associated with an increased risk of MAFLD. The areas under the receiver operating characteristic curves (AUCs) of the FLI for diagnosing MAFLD in men and women were 0.853 and 0.847, respectively. The AUCs of the body mass index (BMI) for diagnosing MAFLD in men and women were 0.850 and 0.852, respectively. Compared with other metabolic-related markers, FLI had the largest AUC. In men, the optimal cut-off values of FLI and BMI for diagnosing MAFLD were 45 (sensitivity 84.83%, specificity 69.57%) and 27.4 (sensitivity 78.47%, specificity 76.30%), respectively. In women, the optimal cut-off values of FLI and BMI for diagnosing MAFLD were 45 (sensitivity 80.11%, specificity 74.23%) and 28.0 (sensitivity 79.56%, specificity 75.41%), respectively. In men and women, an FLI score of < 30 ruled out MAFLD, while a score of ≥ 50 was a basis for diagnosis. CONCLUSION: FLI and BMI had good screening ability for MAFLD and were superior to HSI, LAP, VAI, and ZJU in both sexes.

Corrigendum: Global burden of non-communicable chronic diseases associated with a diet low in fruits from 1990 to 2019.

[This corrects the article DOI: 10.3389/fnut.2023.1202763.].

Speckle tracking tissue motion mitral annulus displacement to assess early changes in the left ventricle and its association with lung function in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the early changes in left ventricular (LV) in patients with chronic obstructive pulmonary disease (COPD) by measuring tissue motion mitral annulus displacement (TMAD) and three-dimensional (3D) parameters using speckle tracking imaging (STI), and to explore its correlation with lung function. METHODS: Forty two COPD patients (GOLD I, GOLD II, GOLD III) and 30 healthy individuals (control group) were included. STI was used to assess the changes in LV structure and systolic function. Receiver operating characteristic (ROC) curves were drawn, and correlations among TMAD parameters, LV systolic function, structural, pulmonary artery systolic pressure (PASP), and lung function were analyzed. RESULTS: Compared to the control group, COPD patients were able to undergo LV remodeling, with a decrease in the absolute value of global longitudinal strain (GLS) and TMAD, but no significant modification of LVEF. Correlation analysis showed that TMAD was positively related to the absolute value of GLS (r > 0.51, P < 0.01) and predicted forced expiratory volume in the first second (FEV1%) (r > 0.56, P < 0.01), and negatively to PASP (r < -0.52, P < 0.01). The LV posterior wall thickness (LVPWd), relative wall thickness (RWT), end-diastolic volume (LVEDV) and PASP negatively correlated with FEV1%. CONCLUSION: The LV geometric changes and systolic function impairment in COPD patients were found to correlate with airflow restriction (FEV1%). TMAD aided in detection of early changes in LV systolic function in COPD patients. It negatively correlated with PASP and positively with FEV1%. Moreover, it was more convenient than GLS.

Global burden of non-communicable chronic diseases associated with a diet low in fruits from 1990 to 2019.

Background: The aim of this study was to assess the global burden of disease from non-communicable chronic diseases (NCD) due to diet low in fruits from 1990 to 2019. Methods: Based on data from the Global Burden of Disease (GBD) 2019, the global burden of disease due to diet low in fruits was analyzed for each country or region, disaggregated by disease type, age, sex, and year. The number of deaths and disability-adjusted life years (DALYs), population attributable fraction (PAF), age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) were calculated, and the average annual percentage change (AAPC) was calculated to describe trends in ASMR and ASDR from 1990 to 2019. Results: From 1990 to 2019, the number of deaths and DALYs due to diet low in fruits increased by 31.5 and 27.4%, respectively. Among the tertiary diseases, ischemic heart disease, stroke, and diabetes and kidney disease were the top three contributors to the global increase in deaths and DALYs. However, both ASMR and ASDR showed a decreasing trend. The fastest decline in ASMR and ASDR was in stroke, with AAPC of -2.13 (95% CI: -2.22, -2.05, p < 0.05) and -0.56 (95% CI: -0.62, -0.51, p < 0.05), respectively. For GBD regions, high PAF occurred mainly in South Asia, Oceania, and sub-Saharan Africa. Age-specific PAF for stroke and ischemic heart disease death attributable to diet low in fruits was significantly negatively associated with age. Diet low in fruits related ASMR and ASDR showed an M-shaped relationship with the socio-demographic index (SDI), but with an overall decreasing trend. Conclusion: The number of deaths and DALYs due to diet low in fruits continues to increase. Therefore, early nutritional interventions should be implemented by the relevant authorities to reduce the burden of diseases caused by diet low in fruits.

Epidemiological characteristics of leukemia in China, 2005-2017: a log-linear regression and age-period-cohort analysis.

BACKGROUND: Leukemia is a threat to human health, and there are relatively few studies on the incidence, mortality and disease burden analysis of leukemia in China. This study aimed to analyze the incidence and mortality rates of leukemia in China from 2005 to 2017 and estimate their age-period-cohort effects, it is an important prerequisite for effective prevention and control of leukemia. METHODS: Leukemia incidence and mortality data from 2005 to 2017 were collected from the Chinese Cancer Registry Annual Report. Joinpoint regression model was used to estimate the average annual percentage change (AAPC) and annual percentage change (APC) response time trend. Age-period-cohort model was constructed to analyze the effects of age, period and cohort. RESULTS: The age-standardized incidence rate of leukemia was 4.54/100,000 from 2005 to 2017, showed an increasing trend with AAPC of 1.9% (95% CI: 1.3%, 2.5%). The age-standardized mortality rate was 2.91/100,000, showed an increasing trend from 2005 to 2012 with APC of 2.1% (95%CI: 0.4%, 3.9%) and then a decreasing trend from 2012 to 2017 with APC of -2.5% (95%CI: -5.3%, 0.3%). The age-standardized incidence (mortality) rates of leukemia were not only higher in males than that in females, but also increased more rapidly. The incidence of leukemia in rural areas was lower than in urban areas, but the AAPC was 2.2 times higher than urban areas. Children aged 0-4 years were at higher risk of leukemia. The risk of leukemia incidence and mortality increased with age. The period effect of leukemia mortality risk showed a decreasing trend, while the cohort effect showed an increasing and then decreasing trend with the turning point of 1955-1959. CONCLUSIONS: The age-standardized incidence rate of leukemia in China showed an increasing trend from 2005 to 2017, while the age-standardized mortality rate increased first and then decreased in 2012 as a turning point. Differences existed by gender and region. The risk of leukemia incidence and mortality increased accordingly with age. The risk of mortality due to leukemia gradually decreased from 2005 to 2017. Leukemia remains a public health problem that requires continuous attention.

Patterns of global burden of 13 diseases attributable to lead exposure, 1990-2019.

OBJECTIVES: Understanding the spatio-temporal patterns of the global burden of various diseases resulting from lead exposure is critical for controlling lead pollution and disease prevention. METHODS: Based on the 2019 Global Burden of Disease (GBD) framework and methodology, the global, regional, and national burden of 13 level-three diseases attributable to lead exposure were analyzed by disease type, patient age and sex, and year of occurrence. Population attributable fraction (PAF), deaths and disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) obtained from the GBD 2019 database were used as descriptive indicators, and the average annual percentage change (AAPC) was estimated by a log-linear regression model to reflect the time trend. RESULTS AND CONCLUSIONS: From 1990 to 2019, the number of deaths and DALYs resulting from lead exposure increased by 70.19% and 35.26%, respectively; however, the ASMR and ASDR decreased by 20.66% and 29.23%, respectively. Ischemic heart disease (IHD), stroke, and hypertensive heart disease (HHD) showed the highest increases in deaths; IHD, stroke, and diabetes and kidney disease (DKD) had the fastest-growing DALYs. The fastest decline in ASMR and ASDR was seen in stroke, with AAPCs of -1.25 (95% CI [95% confidence interval]: -1.36, -1.14) and -1.66 (95% CI: -1.76, -1.57), respectively. High PAFs occurred mainly in South Asia, East Asia, the Middle East, and North Africa. Age-specific PAFs of DKD resulting from lead exposure were positively correlated with age, whereas the opposite was true for mental disorders (MD), with the burden of lead-induced MD concentrated in children aged 0-6 years. The AAPCs of ASMR and ASDR showed a strong negative correlation with the socio-demographic index. Our findings showed that the global impact of lead exposure and its burden increased from 1990 to 2019 and varied significantly according to age, sex, region, and resulting disease. Effective public health measures and policies should be adopted to prevent and control lead exposure.

Fatal, non-fatal burden of cancer in the elderly in China, 2005-2016: a nationwide registry-based study.

BACKGROUND: As populations age, cancer burden becomes increasingly conspicuous. This study quantified the cancer burden of the elderly (≥ 60 years) in China, based on the China Cancer Registry Annual Report to provide epidemiological evidence for cancer prevention and control. METHODS: Data on cancer cases and deaths among the elderly aged ≥ 60 years were collected from the China Cancer Registry Annual Report, 2008-2019. Potential years of life lost (PYLL) and disability-adjusted life years (DALY) were calculated to analyze fatalities and the non-fatal burden. The time trend was analyzed using the Joinpoint model. RESULTS: From 2005 to 2016, the PYLL rate of cancer in the elderly was stable between 45.34‰ and 47.62‰, but the DALY rate for cancer decreased at an average annual rate of 1.18% (95% CI: 0.84-1.52%). The non-fatal cancer burden in the rural elderly was higher than that of the urban elderly. Lung, gastric, liver, esophageal, and colorectal cancers were the main cancers causing the cancer burden in the elderly, and accounted for 74.3% of DALYs. The DALY rate of lung cancer in females in the 60-64 age group increased (annual percentage change [APC] = 1.14%, 95% CI: 0.10-1.82%). Female breast cancer was one of the top five cancers in the 60-64 age group, with DALY rates that also increased (APC = 2.17%, 95% CI: 1.35-3.01%). With increasing age, the burden of liver cancer decreased, while that of colorectal cancer rose. CONCLUSIONS: From 2005 to 2016, the cancer burden in the elderly in China decreased, mainly reflected in the non-fatal burden. Female breast and liver cancer were a more serious burden in the younger elderly, while colorectal cancer burden was mainly observed in the older elderly.

Trends of cancer incidence among Chinese older adults from 2005 to 2016: A log-linear regression and age-period-cohort analysis.

Background: To study the corresponding strategies for controlling cancer in older adults aged 60 and above in China, a comprehensive assessment of disease burden is required. Therefore, we will introduce the cancer epidemiological characteristics of older adults in China over a recent 12 year period. Methods: The age-period-cohort model was constructed using the cancer incidence data from the Chinese Cancer Registry Annual Report published in 2008-2019. The annual change percentage (APC) was estimated by log-linear regression to reflect the time trend. The data from the GLOBOCAN 2020 database was selected for worldwide comparative analysis. Results: The cancer incidence in older adults aged 60 and above in China showed a decreasing trend (APC = -0.73%, P = 0.009). The urban/rural ratio of cancer incidence increased from 0.94 to 1.07 (t = 3.52, P < 0.05), while the sex ratio (male/female) showed a significant decreasing trend only in rural areas (t = -6.77, P < 0.05), and the ratio decreased from 2.02 to 1.72. The results of the age-period-cohort model showed that the cancer incidence increased with age in both males and females, urban and rural areas. The RR of period effect increased from 2005 to 2010, then decreased from 2010 to 2015, and the downward trend was more obvious. The RR of the later-born cohort was lower than that of the earlier-born cohort in rural areas. Lung, gastric, colorectal, esophageal, liver, and breast cancers were common cancers in Chinese older adults. Lung cancer incidence ranked first in males, and it decreased with time in the 75-79 and 80-84 age groups (APC75 - 79 = -1.10%, APC80 - 84 = -0.88%, all P < 0.05). Breast cancer incidence ranked first among female in the 60-64 age group and showed an increasing trend (APC60 - 64 = 1.52%, P < 0.05). Conclusions: The cancer incidence in Chinese older adults aged 60 and above showed a decreasing trend, but it was still at a relatively high level. The key targets of prevention and treatment should be males, urban areas, younger people, older adults aged 60-69, lung, gastrointestinal, and breast cancers in the future.

Burden of cardiovascular disease attributable to dietary lead exposure in adolescents and adults in China.

Lead is a naturally occurring metal with a range of industrial applications; however, it can cause adverse health effects upon human exposure. Even if blood lead levels (BLLs) in the human body are in the acceptable range, it is independently associated with cardiovascular disease (CVD), which is the leading cause of death in China. However, the role of lead exposure in CVD outcomes has not been quantified well. A top-down approach was adopted in this study to calculate the population attribution fraction (PAF) by combining pooled BLLs in the Chinese population reported between 2001 and 2022 with the relative risk (RR) of lead-induced CVD. Subsequently, the disease burden (DB) of lead-induced CVD was estimated and expressed in disability-adjusted life years (DALYs), and the attribution analysis about various sources of lead exposure was performed. Among Chinese adolescents and adults, BLLs of 5.50 ±â€¯2.45 µg/dL resulted in an estimated total DB (×106 DALYs) of 2.21 (2.07-2.32) for CVD, including 1.18 (1.12-1.25), 0.71 (0.69-0.74), 0.23 (0.15-0.26), and 0.02 (0.02-0.02) for stroke, and ischemic, hypertensive, and rheumatic heart diseases, respectively. Dietary lead intake was a major contributor to the DB (68.1%), and lead ingested through food was responsible for 15.1 × 105 DALYs of the CVD burden. Guangxi, Hunan, and Yunnan regions in China reported higher BLLs in adolescents and adults, and the DB of lead-induced CVD was higher in Hunan, Henan, and Sichuan. Lead is a risk factor for CVD that can cause significant DB. Further practical and cost-effective efforts to reduce lead exposure are urgently needed.

Genotoxicity evaluation of silica nanoparticles in murine: a systematic review and meta-analysis.

Silica nanoparticles (SiNPs) have been widely used in nanotechnology, and more attention has been paid to their safety evaluation. However, there are still inconsistent conclusions about the genotoxicity of SiNPs. A systematic review was conducted to explore whether SiNPs have genotoxicity followed by a meta-analysis of in vivo and in vitro murine genotoxicity tests. A total of 26 eligible studies were identified in this meta-analysis through a detailed process of inclusion and exclusion, which included 9 in vivo studies, 15 in vitro studies, and 2 in both. The results of in vitro studies showed that SiNPs exposure significantly increased the indicators of the comet assay, such as tail DNA content (T DNA%), tail length (TL), and olive tail moment (OTM). Indicators of mutagenicity had not been affected in vitro studies, such as mutation frequency (MF) and micronucleus (MN) frequency. There was a significant increase in MN frequency, but there was no influence on T DNA% in vivo. Results of subgroup analysis indicated that size and treatment time of SiNPs were the associated factors in vitro genotoxicity. The size of SiNPs, <21 nm, induced more DNA damage than larger sized SiNPs. It could induce MN formation when the treatment time of SiNPs was <12 h, and even more DNA damage when the exposure time over 12 h. SiNPs can induce genotoxicity both in vivo and in vitro. Comet assay may be more sensitive to detect in vitro genotoxicity, and MN frequency may be more suitable to detect in vivo genotoxicity.

Comparison of the Incidence of Cardiovascular Diseases in Weight Groups with Healthy and Unhealthy Metabolism.

BACKGROUND: We aimed to identify the relationship between metabolically healthy obesity (MHO), a special subtype of obesity, and the incidence of cardiovascular disease (CVD) in rural Xinjiang. METHODS: Body mass index (BMI) and the Joint Interim Statement criteria were utilized to define obesity and metabolic status, respectively. A baseline survey was conducted between 2010 and 2012. The cohort was followed-up until 2017, including 5059 participants (2953 Uyghurs and 2106 Kazakhs) in the analysis. RESULTS: During 6.78 years of follow-up, 471 individuals developed CVD, 10.8% (n=545) of whom were obese, and the prevalence of MHO and MHNW was 5.2% and 54.5%, respectively. Compared with metabolically healthy normal weight subjects, the subjects with MHO had an increased risk of CVD (hazard ratio [HR]=1.76, 95% confidence interval [CI]: 1.23-2.51), while the metabolically unhealthy obesity (MUO) group had an even higher risk (HR=3.80, 95% CI: 2.87-5.03). Additionally, there were sex differences in the relationship between BMI-metabolic status and incident CVD (P interaction =0.027). Compared with the subjects with MHO, those with MUO had an increased risk of CVD (HR=1.84, 95% CI: 1.26-2.71). CONCLUSION: MHO was associated with a high risk of CVD among adults in rural Xinjiang. In each BMI category, metabolically unhealthy subjects had a higher risk of developing CVD than did metabolically healthy subjects.

The Association of Metabolic Syndrome with the development of cardiovascular disease among Kazakhs in remote rural areas of Xinjiang, China: a cohort study.

BACKGROUND: Metabolic syndrome (MS) can promote the development of cardiovascular disease (CVD). The objective of this study was to examine the association of MS and its components with CVD, to further prevent and control CVD in Kazakhs. METHODS: In the cohort study, a total of 2644 participants completed the baseline survey between April 2010 and December 2012.The follow-up survey was conducted from April 2016 to December 2016 and was completed by 2286 participants (86.46% follow-up rate). Cox regression was used to evaluate the association of each component and the number of combinations of MS components on the development of CVD. RESULTS: A total of 278 CVD patients were enrolled from rural residents of Xinjiang. The average age of the MS and non-MS groups was 46.33 and 38.71 years, respectively. Independent associations with CVD were found for elevated blood pressure (BP) (adjusted hazard ratio (HR) [aHR] = 1.50,95%confidence interval [CI]: 1.08-2.08), elevated waist circumference (WC) (aHR = 1.60, 95%CI: 1.19-2.15), and elevated triglycerides (TG) (aHR = 1.44, 95%CI: 1.04-2.01). Participants with one to 5 MS components had an increased HR for developing CVD, from 1.82to 8.59 (P for trend < 0.001), compared with those with no MS components. The risk of developing CVD increased when TG and WC coexisted (aHR = 2.16, 95%CI: 1.54-3.04)), when TG and BP coexisted ((aHR = 1.92, 95%CI: 1.32-2.79), and when WC and BP coexisted (aHR = 1.93, 95%CI: 1.33-2.82)). However, no significant interactions were found between BP, WC, and TG. CONCLUSIONS: Elevations of BP, WC, and TG were independent risk factors for CVD in Kazakhs. Control of these factors is important to prevent CVD in this population.

Effect of Nano-Titanium Dioxide on Blood-Testis Barrier and MAPK Signaling Pathway in Male Mice.

Some studies have found that nano-sized titanium dioxide (nano-TiO2) has adverse effects on the male reproductive system. Blood-testis barrier (BTB), as one of the tightest blood-tissue restriction, is crucial to the male reproductive system. However, the potential effects on BTB and signaling pathway changes in testis tissue induced by nano-TiO2 remain poorly understood. Therefore, in this study, 60 Institute of Cancer Research mice were divided randomly into four groups (per group = 15). The mice of four groups were intragastrically administered with 0, 10, 50, and 100 mg/kg BW nano-TiO2 respectively for 30 days to analyze the changes of BTB structure, BTB-related proteins, and MAPK signal pathways. Besides, testosterone level, estradiol level, and sperm parameter (sperm count, sperm motility, and sperm malformation rate) changes were also studied in this research. The results indicated that nano-TiO2 could induce the BTB structural damage and accompanied by the BTB main protein (ZO-1, Claudin-11, and F-actin) elevation of irritability. Nano-TiO2 could also activate the MAPK signaling pathways (p38, JNK, and ERK) of mice testis tissue. The testosterone and estradiol levels in serum reduced. Besides when the mice were administered with nano-TiO2, we also found the sperm motility rate decreased, and sperm malformation increased. The above changes may be associated with BTB damage and the activation of MAPK signaling pathways, thereby causing male reproductive dysfunction.

Genotoxicity Evaluation of Titanium Dioxide Nanoparticles In Vitro: a Systematic Review of the Literature and Meta-analysis.

With the wide use of titanium dioxide nanoparticles (TiO2-NPs), the genotoxicity of TiO2-NPs, which is a factor for safety assessment, has attracted people's attention. However, their genotoxic effects in vitro remain controversial due to inconsistent reports. Therefore, a systematic review was conducted followed by a meta-analysis to reveal whether TiO2-NPs cause genotoxicity in vitro. A total of 59 studies were identified in this review through exhaustive database retrieval and exclusion. Meta-analysis results were presented based on different evaluation methods. The results showed that TiO2-NP exposure considerably increased the percentage of DNA in tail and olive tail moment in comet assay. Gene mutation assay revealed that TiO2-NPs could also induce gene mutation. However, TiO2-NP exposure had no effect on micronucleus (MN) formation in the MN assay. Subgroup analysis showed that normal cells were more vulnerable to toxicity induced by TiO2-NPs. Moreover, mixed form and small particles of TiO2-NPs increased the percentage of DNA in tail. In addition, short-term exposure could detect more DNA damage. The size, coating, duration, and concentration of TiO2-NPs influenced MN formation. This study presented that TiO2-NP exposure could cause genotoxicity in vitro. The physicochemical properties of TiO2-NPs and experimental protocols influence the genotoxic effects in vitro. Comet and gene mutation assays may be more sensitive to the detection of TiO2-NP genotoxic effects.

CSN6 aggravates Ang II-induced cardiomyocyte hypertrophy via inhibiting SIRT2.

The constitutive photomorphogenic 9 (COP9) signalosome complex subunit 6 (COPS6/CSN6) is crucial for structural integrity of the COP9 signalosome complex. CSN6 participates in various aspects of cancer progression, but its role in hypertrophic cardiomyopathy is not clear. Here, we found that the expression of CSN6 was increased in Angiotensin II (Ang II)-induced hypertrophic mice hearts and neonatal rat cardiomyocytes (NRCMs). Inhibition of CSN6 decreased the cardiomyocyte size and fetal genes' expression in Ang II-induced hypertrophic NRCMs, while overexpression of CSN6 aggravated Ang II-induced myocardial hypertrophy. Moreover, we demonstrated that the pro-hypertrophic function of CSN6 was mediated by SIRT2, which acts as a cardioprotective factor in pathological cardiac hypertrophy. CSN6 inhibited the expression of SIRT2, and re-expression of SIRT2 attenuated the myocardial hypertrophy caused by CSN6 overexpression. Further investigation discovered that CSN6 suppressed the expression of SIRT2 via up-regulating Nkx2.2, a transcription suppressor of SIRT2. Mechanistically, CSN6 blocked the ubiquitin proteasome system-mediated degradation of Nkx2.2 protein by interacting with it and inhibiting its ubiquitination directly in cardiomyocytes. Finally, our data showed that CSN6 was partially dependent on the stabilization of Nkx2.2 protein to inhibit SIRT2 and promote myocardial hypertrophy. Overall, our study identified CSN6 as a pro-hypertrophic deubiquitinase, and CSN6 inhibition may be a potential treatment strategy for heart failure.