Associations between co-exposure to per- and polyfluoroalkyl substances and metabolic diseases: The mediating roles of inflammation and oxidative stress.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) pose potential risks to human health. In real-world settings, humans are exposed to various PFAS through numerous pathways. OBJECTIVES: This study evaluated the associations between co-exposure to PFAS and obesity and its comorbidities, along with the mediating roles of inflammation and oxidative stress. METHODS: We analyzed 11,090 participants from National Health and Nutrition Examination Survey (NHANES), 2003-2018. Linear regression, logistic regression, and generalized additive models were used to assess the individual effects of PFAS exposure on obesity and its comorbidities. The environmental risk score (ERS) was calculated using the adaptive elastic-net model to assess the co-exposure effects. Linear and logistic regression models explored the associations between ERS and obesity and its comorbidities. Mediation analyses explored the roles of inflammatory (neutrophils, lymphocytes, and alkaline phosphatase) and oxidative stress (gamma-glutamyl transferase, total bilirubin, and uric acid) markers in the associations between ERS and obesity and its comorbidities. RESULTS: For each unit increase in ERS, the odds of obesity and type 2 diabetes mellitus (T2DM) increased 3.60-fold (95 % CI: 2.03, 6.38) and 1.91-fold (95 % CI: 1.28, 2.86), respectively. For each unit increase in ERS, BMI increased by 2.36 (95 % CI: 1.24, 3.48) kg/m2, waist circumference increased by 6.47 (95 % CI: 3.56, 9.37) cm, and waist-to-height ratio increased by 0.04 (95 % CI: 0.02, 0.06). Lymphocytes, alkaline phosphatase, and total bilirubin were significantly associated with both ERS and obesity, with mediation proportions of 4.17 %, 3.62 %, and 7.37 %, respectively. Lymphocytes, alkaline phosphatase, total bilirubin, and uric acid were significantly associated with both ERS and T2DM, with the mediation proportions of 8.90 %, 8.74 %, 29.73 %, and 38.19 %, respectively. CONCLUSIONS: Co-exposure to PFAS was associated with obesity and T2DM, and these associations may be mediated by inflammation and oxidative stress. Further mechanistic and prospective studies are required to verify these associations.

The ROS Mediates MCUb in Mitochondria-Regulated Apoptosis of TM4 Cells Induced by Titanium Dioxide Nanoparticles.

Titanium dioxide nanoparticles (TiO2 NPs) can cause mitochondrial apoptosis of TM4 cells associated with reactive oxygen species (ROS) accumulation and Ca2+ overload, but the relations among these processes remain unclear. This study aimed to evaluate whether the accumulation of ROS caused by TiO2 NPs inhibits MCUb expression, leading to mitochondrial calcium overload and subsequent cell apoptosis through the mitochondrial pathway. TM4 cells were exposed to different concentrations of TiO2 NPs (0, 25, 50, 75, 100 µg/mL) for 24 h. We assessed cell viability, ROS level, MCUb and VDAC1 expression, mitochondrial and cytoplasmic Ca2+ levels, mitochondrial membrane potential (MMP), apoptosis rate, and key proteins related to mitochondrial apoptosis (Bcl-2, Bax, Caspase 3, Caspase 9, p53 and Cyt c). Additionally, the effect of N-acetylcysteine (NAC) on MCUb expression, calcium homeostasis, and cell apoptosis was evaluated. Compared to control group, TiO2 NPs significantly increased ROS level, downregulated MCUb expression, elevated Ca2+ levels in mitochondria and cytoplasm, and enhanced mitochondria-regulated apoptosis, starting from the 50 µg/mL TiO2 NPs group. However, NAC significantly increased MCUb expression, attenuated Ca2+ levels in mitochondria and cytoplasm, and reduced mitochondria-related apoptosis. In conclusion, TiO2 NPs induced ROS accumulation, which inhibited the expression of MCUb. The decreased MCUb level led to Ca2+ overload in mitochondria, causing TM4 cell apoptosis via the mitochondrial pathway. This research elucidates, for the first time, the role of MCUb and its relation with ROS in apoptosis of TM4 cells induced by TiO2 NPs, which supplementing the molecular mechanism of cell apoptosis caused by TiO2 NPs.

The trend of lymphoma incidence in China from 2005 to 2017 and lymphoma incidence trend prediction from 2018 to 2035: a log-linear regression and Bayesian age-period-cohort analysis.

Objectives: The aims of this study were to explore the incidence characteristics and trend prediction of lymphoma from 2005 to 2035, and to provide data basis for the prevention and control of lymphoma in China. Method: The data on lymphoma incidence in China from 2005 to 2017 were obtained from the Chinese Cancer Registry Annual Report. The Joinpoint regression model was used to calculate annual percentage change (APC) and average annual percentage change (AAPC) to reflect time trends. Age-period-cohort models were conducted to estimate age, period, and cohort effects on the lymphoma incidence. A Bayesian age-period-cohort model was used to predict lymphoma incidence trends from 2018 to 2035. Results: From 2005 to 2017, the incidence of lymphoma was 6.26/100,000, and the age-standardized incidence rate (ASIR) was 4.11/100,000, with an AAPC of 1.4% [95% confidence interval (CI): 0.3%, 2.5%]. The ASIR was higher in men and urban areas than in women and rural areas, respectively. The age effect showed that the incidence risk of lymphoma increased with age. In the period effect, the incidence risk of lymphoma in rural areas decreased first and then increased with 2010 as the cutoff point. The overall risk of lymphoma incidence was higher in the cohort before the 1970-1974 birth cohort than in the cohort after. From 2018 to 2035, the lymphoma incidence in men, women, and urban areas will show an upward trend. Conclusion: From 2005 to 2017, the incidence of lymphoma showed an increasing trend, and was different in regions, genders, and age groups in China. It will show an upward trend from 2018 to 2035. These results are helpful for the formulation and adjustment of lymphoma prevention, control, and management strategies, and have important reference significance for the treatment of lymphoma in China.

A Histopathologic Correlation Study Evaluating Glymphatic Function in Brain Tumors by Multiparametric MRI.

PURPOSE: This study aimed to elucidate the impact of brain tumors on cerebral edema and glymphatic drainage by leveraging advanced MRI techniques to explore the relationships among tumor characteristics, glymphatic function, and aquaporin-4 (AQP4) expression levels. EXPERIMENTAL DESIGN: In a prospective cohort from March 2022 to April 2023, patients with glioblastoma, brain metastases, and aggressive meningiomas, alongside age- and sex-matched healthy controls, underwent 3.0T MRI, including diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index and multiparametric MRI for quantitative brain mapping. Tumor and peritumor tissues were analyzed for AQP4 expression levels via immunofluorescence. Correlations among MRI parameters, glymphatic function (DTI-ALPS index), and AQP4 expression levels were statistically assessed. RESULTS: Among 84 patients (mean age: 55 ± 12 years; 38 males) and 59 controls (mean age: 54 ± 8 years; 23 males), patients with brain tumor exhibited significantly reduced glymphatic function (DTI-ALPS index: 2.315 vs. 2.879; P = 0.001) and increased cerebrospinal fluid volume (201.376 cm³ vs. 115.957 cm³; P = 0.001). A negative correlation was observed between tumor volume and the DTI-ALPS index (r: -0.715, P < 0.001), whereas AQP4 expression levels correlated positively with peritumoral brain edema volume (r: 0.989, P < 0.001) and negatively with proton density in peritumoral brain edema areas (ρ: -0.506, P < 0.001). CONCLUSIONS: Our findings highlight the interplay among tumor-induced compression, glymphatic dysfunction, and altered fluid dynamics, demonstrating the utility of DTI-ALPS and multiparametric MRI in understanding the pathophysiology of tumor-related cerebral edema. These insights provide a radiological foundation for further neuro-oncological investigations into the glymphatic system. See related commentary by Surov and Borggrefe, p. 4813.

The therapeutic effect of anti-CD19 antibody on DHEA-induced PCOS mice.

Immune dysregulation has been summarized as a critical factor in the occurrence and development of Polycystic ovary syndrome (PCOS), but potential mediators and mechanisms remain unclear. Our previous study showed that CD19+ B cells were involved in the pathogenesis of dehydroepiandrosterone (DHEA)-induced PCOS mice. Here, we studied the therapeutic potential of anti-CD19 antibody (aCD19 Ab) on DHEA-induced PCOS mice. The results showed that aCD19 Ab treatment improved ovarian pathological structure and function of PCOS mice, manifested by an increased number of corpus luteum, a decreased number of cystic follicles and atretic follicles, and regular estrus cycles. The aCD19 Ab treatment reduced the proportion of splenic CD21+ CD23low marginal zone B cells as well as the level of serum IgM and decreased the percentage of peripheral blood and splenic neutrophils. In particular, aCD19 Ab treatment reduced the apoptosis of granulosa cells and macrophage infiltration in ovarian secondary follicles of PCOS mice, as well as the expression of TNF-α in ovarian tissue and serum TNF-α levels. Moreover, we confirmed that TNF-α induced the apoptosis of human ovarian granulosa tumor cell line cells in vitro. Thus, our work demonstrates that aCD19 Ab treatment improves ovarian pathological phenotype and function by reducing local and systemic inflammation in PCOS mice, which may provide a novel insight into PCOS therapy.

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.

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.].

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.

Adverse associations between maternal deoxynivalenol exposure and birth outcomes: a prospective cohort study in China.

BACKGROUND: Deoxynivalenol (DON), one of the most prevalent mycotoxins, has been found to cause fetal growth retardation in animals. However, limited evidence exists regarding its effects on pregnant women. METHODS: Maternal urinary concentration of total DON (tDON) and free DON (fDON) in the second trimester was measured using liquid chromatography with tandem mass spectrometry. Provisional daily intake (PDI) of DON was calculated based on tDON concentration. Linear and logistic regression models were used to evaluate the association between DON exposure levels and birth weight, birth length, and the risk of small for gestational age (SGA). RESULTS: Among 1538 subjects, the median concentrations of tDON and fDON were 12.1 ng/mL and 5.1 ng/mL, respectively. The PDI values revealed that the median DON intake was 0.7 µg/kg bw, and 35.9% of the total population exceeded the provisional maximum tolerable daily intake (PMTDI) of 1 µg/kg bw. Compared with the lowest tertile, birth weight decreased by 81.11 g (95% CI: -127.00, -35.23) for tDON (P-trend < 0.001) and 63.02 g (95% CI: -108.72, -17.32) for fDON (P-trend = 0.004) in the highest tertile. Each unit increase in Ln-tDON and Ln-fDON was also inversely associated with birth weight. Furthermore, compared to those who did not exceed PMTDI, pregnant women whose PDI exceeded PMTDI had lower birth weight (ß = -79.79 g; 95% CI: -119.09, -40.49) and birth length (ß = -0.21 cm; 95% CI: -0.34, -0.07), and a higher risk of SGA (OR = 1.48; 95% CI: 1.02, 2.15) in their offspring. Similar associations with birth weight, birth length, and SGA were found when comparing the highest tertile of PDI to the lowest tertile (all P-trend < 0.05). CONCLUSIONS: Maternal DON exposure is related to decreased birth weight. Our findings implicate that DON exposure during pregnancy may cause fetal growth faltering, and measures should be taken to reduce DON exposure in pregnant women.

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.

Association of H-Type Hypertension with miR-21, miR-29, and miR-199 in Kazahks of Xinjiang, China.

Objective: This study aims to analyze the expressions of miR-21, miR-29, and miR-199 in the serum of the patients with H-type hypertension among Kazakhs. Then, we analyzed the effect of MTHFR 677C > T polymorphism on the association between the above miRNA and H-type hypertension. Method: In this study, the expression of miR-21, miR-29, and miR-199 was quantitatively measured in 120 serum samples and then stratified according to the C677T polymorphism to analyze the relationship between target miRNAs and HHcy. Results: The expression of miR-21/-29 in the hypertension group was higher than the normal group (P < 0.001). And the expression of miR-199 was higher in the hcy group than in the normal group (P < 0.001). In the CC and CT genotypes of MTHFR 677C > T, the expression of miR-21 was lower in the HHcy patients than in the normal individuals (P = 0.005 and P = 0.001) and miR-199 was significantly higher in the HHcy patients than in the normal ones (P = 0.002 and P = 0.048). No such difference was found in the TT genotype. Logistic regression analysis showed that after adjusting for sex, age, BMI, systolic blood pressure, diastolic blood pressure, and MTHFRC677 T gene polymorphism, miR-21 was negatively correlated with hcy (OR = 0.222, 95% CI (0.101-0.485), P < 0.001) and miR-199 was positively correlated with hcy (OR = 1.823,95%CI (1.272∼2.614), P = 0.001). Conclusion: miR-21, miR-29, and miR-199 are associated with H-type hypertension in the Kazakhs, especially hyperhomocysteinemia. And these three miRNAs may serve as biomarkers to provide clues to the potential pathogenesis of H-type hypertension.

Association of three insulin resistance indices with hypertension and body weight among Uyghur adults in rural areas of Xinjiang, China.

Obesity and insulin resistance are significant contributors to hypertension. There is a high prevalence of obesity among Uyghurs in the rural areas of Xinjiang, China. Therefore, this study aimed to explore the association between insulin resistance indices and hypertension according to different body weights in rural Uyghur residents of Xinjiang, China. A total of 12 813 local Uyghur residents were recruited for the study. Excluding those with incomplete data and those using antihypertensive, lipid-lowering, or glycemic drugs, 9577 permanent residents were eligible for the study. Three insulin resistance indicators were calculated: triglyceride to high-density lipoprotein cholesterol ratio, product of fasting triglyceride and glucose (TYG), and metabolic score for insulin resistance. Multivariate logistic regression analysis was performed to estimate the association between the three non-insulin-based insulin resistance indices and the risk of hypertension for different body weights. TYG was significantly associated with hypertension in the normal-weight group, particularly in women. In the obese group that was obese, all three indicators were associated with hypertension. Since TYG was associated with hypertension in the groups with normal weight and obesity, it may be useful as a reference indicator for insulin resistance. This indicator may provide a basis for the identification and management of hypertension risk among adults in the Uyghur population.

Updating Framingham CVD risk score using waist circumference and estimated cardiopulmonary function: a cohort study based on a southern Xinjiang population.

PURPOSE: To explore the association between waist circumference (WC), estimated cardiopulmonary function (eCRF), and cardiovascular disease (CVD) risk in southern Xinjiang. Update the Framingham model to make it more suitable for the southern Xinjiang population. METHODS: Data were collected from 7705 subjects aged 30-74 years old in Tumushuke City, the 51st Regiment of Xinjiang Production and Construction Corps. CVD was defined as an individual's first diagnosis of non-fatal acute myocardial infarction, death from coronary heart disease, and fatal or non-fatal stroke. The Cox proportional hazards regression analysis was used to analyze the association between WC, eCRF and CVD risk. Restricted cubic spline plots were drawn to describe the association of the two indicators with CVD risk. We update the model by incorporating the new variables into the Framingham model and re-estimating the coefficients. The discrimination of the model is evaluated using AUC, NRI, and IDI metrics. Model calibration is evaluated using pseudo R2 values. RESULTS: WC was an independent risk factor for CVD (multivariate HR: 1.603 (1.323, 1.942)), eCRF was an independent protective factor for CVD (multivariate HR: 0.499 (0.369, 0.674)). There was a nonlinear relationship between WC and CVD risk (nonlinear χ2 = 12.43, P = 0.002). There was a linear association between eCRF and CVD risk (non-linear χ2 = 0.27, P = 0.6027). In the male, the best risk prediction effect was obtained when WC and eCRF were added to the model (AUC = 0.763((0.734,0.792)); pseudo R2 = 0.069). In the female, the best risk prediction effect was obtained by adding eCRF to the model (AUC = 0.757 (0.734,0.779); pseudo R2 = 0.107). CONCLUSION: In southern Xinjiang, WC is an independent risk factor for CVD. eCRF is an independent protective factor for CVD. We recommended adding WC and eCRF in the male model and only eCRF in the female model for better risk prediction.

A Cardiovascular Disease Prediction Model Based on Routine Physical Examination Indicators Using Machine Learning Methods: A Cohort Study.

Background: Cardiovascular diseases (CVD) are currently the leading cause of premature death worldwide. Model-based early detection of high-risk populations for CVD is the key to CVD prevention. Thus, this research aimed to use machine learning (ML) algorithms to establish a CVD prediction model based on routine physical examination indicators suitable for the Xinjiang rural population. Method: The research cohort data collection was divided into two stages. The first stage involved a baseline survey from 2010 to 2012, with follow-up ending in December 2017. The second-phase baseline survey was conducted from September to December 2016, and follow-up ended in August 2021. A total of 12,692 participants (10,407 Uyghur and 2,285 Kazak) were included in the study. Screening predictors and establishing variable subsets were based on least absolute shrinkage and selection operator (Lasso) regression, logistic regression forward partial likelihood estimation (FLR), random forest (RF) feature importance, and RF variable importance. The selected subset of variables was compared with L1 regularized logistic regression (L1-LR), RF, support vector machine (SVM), and AdaBoost algorithm to establish a CVD prediction model suitable for this population. The incidence of CVD in this population was then analyzed. Result: After 4.94 years of follow-up, a total of 1,176 people were diagnosed with CVD (cumulative incidence: 9.27%). In the comparison of discrimination and calibration, the prediction performance of the subset of variables selected based on FLR was better than that of other models. Combining the results of discrimination, calibration, and clinical validity, the prediction model based on L1-LR had the best prediction performance. Age, systolic blood pressure, low-density lipoprotein-L/high-density lipoproteins-C, triglyceride blood glucose index, body mass index, and body adiposity index were all important predictors of the onset of CVD in the Xinjiang rural population. Conclusion: In the Xinjiang rural population, the prediction model based on L1-LR had the best prediction performance.

Exposure assessment of urinary deoxynivalenol in pregnant women in Wuhan, China.

Deoxynivalenol (DON) is a ubiquitous trichothecene mycotoxin in food. DON and its modified forms can cross the placental barrier and influence the foetus' health. Limited information is available on exposure of dietary DON intake of pregnant women in China recently. We estimated the exposure of dietary DON intake of pregnant women in a large sample size (n = 2534) from China. The total DON (tDON) and free DON (fDON) biomarkers in urine were detected by liquid chromatography-tandem mass spectrometry. The mean concentration of tDON was 34.8 ng/mg creatinine, and the fDON was 15.9 ng/mg creatinine. The estimated exposure of dietary DON intake was 0.96-1.91 µg/kg bw/day, and the difference in exposure of DON between the first and second trimesters was statistically insignificant. Approximately 26%-60% of individuals exceeded the provisional maximum tolerable daily intake (PMTDI). The age, pre-pregnancy BMI, and the sampling seasons may be the risk factor for the occurrence of exceeding PMTDI. This survey is the first exposure biomarker for DON in a large sample size from pregnant women in China. We found that the dietary DON exposure in pregnant women was relatively high and particular concern should be paid to the DON exposure during pregnancy.