Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.

Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 µM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.

Greenness mitigate cause-specific mortality associated with air pollutants in ischemic and hemorrhagic stroke patients: An ecological health cohort study.

BACKGROUND: Air pollution is one of the most serious environmental risks to mortality of stroke. However, there exists a noteworthy knowledge gap concerning the different stroke subtypes, causes of death, the susceptibility of stroke patient, and the role of greenness in this context. METHODS: We analyzed data from an ecological health cohort, which included 334,261 patients aged ≥40 years with stroke (comprising 288,490 ischemic stroke and 45,771 hemorrhagic stroke) during the period 2013-2019. We used Cox proportional hazards models with time-varying exposure to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the associations of annual average fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) with both all-cause and cause-specific mortality. Additionally, we conducted analyses to examine the effect modification by greenness and identify potential susceptibility factors through subgroup analyses. RESULT: In multivariable-adjusted models, long-term exposure to PM2.5 and NO2 was associated with increased risk of all-cause mortality (HR: 1.038, 95% CI: 1.029-1.047 for PM2.5; HR: 1.055, 95% CI: 1.026-1.085 for NO2, per 10 µg/m3, for ischemic stroke patients; similar for hemorrhagic stroke patients). Gradually increasing effect sizes were shown for CVD mortality and stroke mortality. The HRs of mortality were slightly weaker with high versus low vegetation exposure. Cumulative exposures increased the HRs of pollutant-related mortality, and greater greenness decreased this risk. Two subtypes of stroke patients exhibited diverse patterns of benefit. CONCLUSION: Increasing residential greenness attenuates the increased risk of mortality with different patterns due to chronic air pollutants for ischemic and hemorrhagic stroke, offering valuable insights for precise tertiary stroke prevention strategies.

The combined effect of air pollution and non-optimal temperature on mortality in Shandong Province, China: establishment of air health index.

PURPOSE: The air health index (AHI) captures the combined effects of air pollution and non-optimal temperatures and helps assess the atmospheric environment's overall health risk. Shandong Province is a crucial industrial base in China, and the health effects of air pollution and non-optimal temperature cannot be ignored. To construct an AHI for Shandong Province and assess the district-level mortality burden due to AHI in the study area. METHODS: Daily district-specific mortality, meteorological, and air pollution data over 2013-2018 were collected in Shandong Province, China. The AHI construction eventually incorporated PM2.5 and NO2, O3, and non-optimal temperatures. Attributable fraction (AF) and attributable number (AN) were used to estimate the district-specific mortality burden attributable to AHI. RESULTS: The average AHI value observed in Shandong Province was 6. Our research revealed a positive association between the total AHI and total mortality, with an overall trend of a slow increase followed by a rapid increase. The exposure-response curves, when stratified by gender, age, and cause of death, were approximately consistent with the overall trend. The provincial attributable fraction (AF) was 5.31% (95% CI 4.58%, 5.91%), and the attributable number (AN) was 188,246 (95% CI 162,396, 209,533). Overall, higher ANs mainly appeared in the southwestern area, while higher values of AF were observed in the central-eastern and central-northern areas. CONCLUSIONS: The air health index performs well in predicting death burden and can convey health risks related to exposure to the ambient environment to the public.

Association of ambient ozone exposure and greenness exposure with hemorrhagic stroke mortality at different times: A cohort study in Shandong Province, China.

Evidence on the association between long-term ozone exposure and greenness exposure and hemorrhagic stroke (HS) is limited, with mixed results. One potential source of this inconsistency is the difference in exposure time metrics. This study aimed to investigate the association between long-term exposure to ambient ozone, greenness, and mortality from HS using exposure metrics at different times. We also examined whether greenness exposure modified the relationship between ozone exposure and mortality due to HS. The study population consisted of 45771 participants aged ≥40 y residing in 20 counties in Shandong Province who were followed up from 2013 to 2019. Ozone exposure metrics (annual mean and warm season) and the normalized difference a measure of greenness exposure, were calculated. The relationship between environmental exposures (ozone and greenness exposures) and mortality from HS was assessed using time-dependent Cox proportional hazards models, and the modification of greenness exposure was examined using stratified analysis with interaction terms. The person-years at the end of follow-up were 90,663. With full adjustments, the risk of death from hemorrhagic stroke increased by 5% per interquartile range increase in warm season ozone [hazard ratio =1.05; 95 % confidence interval: 1.01-1.08]. No clear association was observed between annual ozone and mortality HS. Both the annual and summer NDVI were found to reduce the risk of HS mortality. The relationships were influenced by age, sex, and residence (urban or rural). Furthermore, greenness exposure was shown to have a modifying effect on the relationship between ozone exposure and the occurrence of HS mortality (P for interaction = 0.001). Long-term exposure to warm season O3 was positively associated with HS mortality, while greenness exposure was inversely associated with HS mortality. Greenness exposure may mitigate the negative effects of warm season ozone exposure on HS mortality.

Hydroxycitric Acid Alleviated Lung Ischemia-Reperfusion Injury by Inhibiting Oxidative Stress and Ferroptosis through the Hif-1α Pathway.

Lung ischemia-reperfusion injury (LIRI) is a prevalent occurrence in various pulmonary diseases and surgical procedures, including lung resections and transplantation. LIRI can result in systemic hypoxemia and multi-organ failure. Hydroxycitric acid (HCA), the primary acid present in the peel of Garcinia cambogia, exhibits anti-inflammatory, antioxidant, and anticancer properties. However, the effects of HCA on LIRI remain unknown. To investigate the impact of HCA on LIRI in mice, the mice were randomly divided into four groups: the control group, the I/R model group, and the I/R + low- or high-dose HCA groups. Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia for 12 h followed by reoxygenation for 6 h to simulate in vitro LIRI. The results demonstrated that administration of HCA effectively attenuated lung injury, inflammation, and edema induced by ischemia reperfusion. Moreover, HCA treatment significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels while decreasing iron content and increasing superoxide dismutase (SOD) levels after ischemia-reperfusion insult. Mechanistically, HCA administration significantly inhibited Hif-1α and HO-1 upregulation both in vivo and in vitro. We found that HCA could also alleviate endothelial barrier damage in H/R-induced HUVECs in a concentration-dependent manner. In addition, overexpression of Hif-1α counteracted HCA-mediated inhibition of H/R-induced endothelial cell ferroptosis. In summary, these results indicate that HCA alleviated LIRI by inhibiting oxidative stress and ferroptosis through the Hif-1α pathway.

Systematic analysis of histone acetylation regulators across human cancers.

BACKGROUND: Histone acetylation (HA) is an important and common epigenetic pathway, which could be hijacked by tumor cells during carcinogenesis and cancer progression. However, the important role of HA across human cancers remains elusive. METHODS: In this study, we performed a comprehensive analysis at multiple levels, aiming to systematically describe the molecular characteristics and clinical relevance of HA regulators in more than 10000 tumor samples representing 33 cancer types. RESULTS: We found a highly heterogeneous genetic alteration landscape of HA regulators across different human cancer types. CNV alteration may be one of the major mechanisms leading to the expression perturbations in HA regulators. Furthermore, expression perturbations of HA regulators correlated with the activity of multiple hallmark oncogenic pathways. HA regulators were found to be potentially useful for the prognostic stratification of kidney renal clear cell carcinoma (KIRC). Additionally, we identified HDAC3 as a potential oncogene in lung adenocarcinoma (LUAD). CONCLUSION: Overall, our results highlights the importance of HA regulators in cancer development, which may contribute to the development of clinical strategies for cancer treatment.

Estimating future PM2.5-attributed acute myocardial infarction incident cases under climate mitigation and population change scenarios in Shandong Province, China.

BACKGROUND: The effects of fine particulate matter (PM2.5) on acute myocardial infarction (AMI) have been widely recognized. However, no studies have comprehensively evaluated future PM2.5-attributed AMI burdens under different climate mitigation and population change scenarios. We aimed to quantify the PM2.5-AMI association and estimate the future change in PM2.5-attributed AMI incident cases under six integrated scenarios in 2030 and 2060 in Shandong Province, China. METHODS: Daily AMI incident cases and air pollutant data were collected from 136 districts/counties in Shandong Province from 2017 - 2019. A two-stage analysis with a distributed lag nonlinear model was conducted to quantify the baseline PM2.5-AMI association. The future change in PM2.5-attributed AMI incident cases was estimated by combining the fitted PM2.5-AMI association with the projected daily PM2.5 concentrations under six integrated scenarios. We further analyzed the factors driving changes in PM2.5-related AMI incidence using a decomposition method. RESULTS: Each 10 µg/m3 increase in PM2.5 exposure at lag05 was related to an excess risk of 1.3 % (95 % confidence intervals: 0.9 %, 1.7 %) for AMI incidence from 2017 - 2019 in Shandong Province. The estimated total PM2.5-attributed AMI incident cases would increase by 10.9-125.9 % and 6.4-244.6 % under Scenarios 1 - 3 in 2030 and 2060, whereas they would decrease by 0.9-5.2 % and 33.0-46.2 % under Scenarios 5 - 6 in 2030 and 2060, respectively. Furthermore, the percentage increases in PM2.5-attributed female cases (2030: -0.3 % to 135.1 %; 2060: -33.2 % to 321.5 %) and aging cases (2030: 15.2-171.8 %; 2060: -21.5 % to 394.2 %) would wholly exceed those in male cases (2030: -1.8 % to 133.2 %; 2060: -41.1 % to 264.3 %) and non-aging cases (2030: -41.0 % to 45.7 %; 2060: -89.5 % to -17.0 %) under six scenarios in 2030 and 2060. Population aging is the main driver of increased PM2.5-related AMI incidence under Scenarios 1 - 3 in 2030 and 2060, while improved air quality can offset these negative effects of population aging under the implementation of the carbon neutrality and 1.5 °C targets. CONCLUSION: The combination of ambitious climate policies (i.e., 1.5 °C warming limits and carbon neutrality targets) with stringent clean air policies is necessary to reduce the health impacts of air pollution in Shandong Province, China, regardless of population aging.

Uridine Alleviates Sepsis-Induced Acute Lung Injury by Inhibiting Ferroptosis of Macrophage.

Uridine metabolism is extensively reported to be involved in combating oxidative stress. Redox-imbalance-mediated ferroptosis plays a pivotal role in sepsis-induced acute lung injury (ALI). This study aims to explore the role of uridine metabolism in sepsis-induced ALI and the regulatory mechanism of uridine in ferroptosis. The Gene Expression Omnibus (GEO) datasets including lung tissues in lipopolysaccharides (LPS) -induced ALI model or human blood sample of sepsis were collected. In vivo and vitro, LPS was injected into mice or administered to THP-1 cells to generate sepsis or inflammatory models. We identified that uridine phosphorylase 1 (UPP1) was upregulated in lung tissues and septic blood samples and uridine significantly alleviated lung injury, inflammation, tissue iron level and lipid peroxidation. Nonetheless, the expression of ferroptosis biomarkers, including SLC7A11, GPX4 and HO-1, were upregulated, while lipid synthesis gene (ACSL4) expression was greatly restricted by uridine supplementation. Moreover, pretreatment of ferroptosis inducer (Erastin or Era) weakened while inhibitor (Ferrostatin-1 or Fer-1) strengthened the protective effects of uridine. Mechanistically, uridine inhibited macrophage ferroptosis by activating Nrf2 signaling pathway. In conclusion, uridine metabolism dysregulation is a novel accelerator for sepsis-induced ALI and uridine supplementation may offer a potential avenue for ameliorating sepsis-induced ALI by suppressing ferroptosis.

Quantifying substantial carcinogenesis of genetic and environmental factors from measurement error in the number of stem cell divisions.

BACKGROUND: The relative contributions of genetic and environmental factors versus unavoidable stochastic risk factors to the variation in cancer risk among tissues have become a widely-discussed topic. Some claim that the stochastic effects of DNA replication are mainly responsible, others believe that cancer risk is heavily affected by environmental and hereditary factors. Some of these studies made evidence from the correlation analysis between the lifetime number of stem cell divisions within each tissue and tissue-specific lifetime cancer risk. However, they did not consider the measurement error in the estimated number of stem cell divisions, which is caused by the exposure to different levels of genetic and environmental factors. This will obscure the authentic contribution of environmental or inherited factors. METHODS: In this study, we proposed two distinct modeling strategies, which integrate the measurement error model with the prevailing model of carcinogenesis to quantitatively evaluate the contribution of hereditary and environmental factors to cancer development. Then, we applied the proposed strategies to cancer data from 423 registries in 68 different countries (global-wide), 125 registries across China (national-wide of China), and 139 counties in Shandong province (Shandong provincial, China), respectively. RESULTS: The results suggest that the contribution of genetic and environmental factors is at least 92% to the variation in cancer risk among 17 tissues. Moreover, mutations occurring in progenitor cells and differentiated cells are less likely to be accumulated enough for cancer to occur, and the carcinogenesis is more likely to originate from stem cells. Except for medulloblastoma, the contribution of genetic and environmental factors to the risk of other 16 organ-specific cancers are all more than 60%. CONCLUSIONS: This work provides additional evidence that genetic and environmental factors play leading roles in cancer development. Therefore, the identification of modifiable environmental and hereditary risk factors for each cancer is highly recommended, and primary prevention in early life-course should be the major focus of cancer prevention.

Short-term effects of exposure to ambient PM1, PM2.5, and PM10 on ischemic and hemorrhagic stroke incidence in Shandong Province, China.

BACKGROUND: Short-term exposure to ambient PM2.5 and PM10 is associated with increased risk of mortality and hospital admissions for stroke. However, there is less evidence regarding the effect of exposure to PM1 on stroke incidence. We estimated the incidence risk of stroke and the attributable fractions related to short-term exposure to ambient PM1, PM2.5 and PM10 in China. METHODS: County-specific incidence of stroke was obtained from health statistics in years 2014-2019. We linked county-level mean daily concentrations of PM1, PM2.5 and PM10 with stroke incidence. We used the time stratified case-crossover design to estimate the associations between stroke incidence and exposure to PM1, PM2.5 and PM10. We also estimated the disease burden fractions attributable to PM1, PM2.5, and PM10. RESULTS: The study included a total of 2,193,954 stroke, from which 1,861,331 were ischemic and 332,623 were hemorrhagic stroke. PM1, PM2.5, and PM10 levels were associated with increased risks of total stroke and ischemic stroke at when assessing the associations in exposure at lag0-4 days. The increase of 10 µg/m3 in PM1, PM2.5, and PM10 was associated with total stroke, and the relative risks were 1.012 (95% confidence interval: 1.008, 1.015), 1.006 (1.004, 1.007) and 1.003 (1.002, 1.004), while the associations with ischemic stroke were 1.013 (1.010, 1.017), 1.006 (1.005, 1.008) and 1.003 (1.002, 1.004), respectively. There was no significant association between PM and risk of hemorrhagic stroke. The attributable fractions of total stroke were 6.9% (5.1%, 8.5%), 5.6% (4.2%, 6.8%) and 5.6% (3.9%, 7.1%) for PM1, PM2.5, and PM10, respectively. CONCLUSIONS: PM1 showed a stronger association with stroke, with a larger attributable fraction of outcomes, than PM2.5 and PM10. Clean air policies should target the whole scope of PM, including PM1.

CircC3P1 attenuated pro-inflammatory cytokine production and cell apoptosis in acute lung injury induced by sepsis through modulating miR-21.

Acute lung injury (ALI) induced by sepsis is characterized by an inflammatory process related to the up-regulation of inflammatory cytokines and chemokines. In the present study, we explored the role of circC3P1 in sepsis-induced ALI in vitro and in vivo. The caecal ligation and puncture (CLP)-induced sepsis model was established through CLP surgery. Forty adult male C57BL/6 mice were randomly assigned into sham, CLP, CLP + vector and CLP + circC3P1 (each n = 10). Primary murine pulmonary microvascular endothelial cells (MPVECs) were transfected with circC3P1 or empty vector 24 hours prior to LPS treatment via Lipofectamine 2000. The expressions of circC3P1, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß were evaluated after 6-h LPS treatment. Cell apoptosis was evaluated via flow cytometry. The CLP group demonstrated pulmonary morphological abnormalities, increased concentrations of TNF-α, IL-6 and IL-1ß in the lung tissue, compared with the sham group. MPVECs treated with LPS significantly elevated TNF-α, IL-6 and IL-1ß levels and increased cell apoptosis than that in the control group. The circC3P1 overexpression in sepsis-induced ALI mice attenuated pulmonary injury, inflammation and apoptosis. Besides, circC3P1 revealed anti-inflammatory and anti-apoptotic effect in MPVEC-treated LPS. CircC3P1 overexpression reduced cell apoptosis and pro-inflammatory cytokines levels via down-regulating miR-21. CircC3P1 attenuated pro-inflammatory cytokine production and cell apoptosis in ALI induced by sepsis through modulating miR-21, indicating that circC3P1 is a promising therapeutic biomarker for sepsis-induced ALI.

MiR-20a-containing exosomes from umbilical cord mesenchymal stem cells alleviates liver ischemia/reperfusion injury.

Mesenchymal stem cells (MSCs) have been proved to exert considerable therapeutic effects on ischemia-reperfusion (I/R)-induced injury, but the underlying mechanism remains unknown. In this study, we aimed to explore the potential molecular mechanism underlying the therapeutic effect of MSCs-derived exosome reinforced with miR-20a in reversing liver I/R injury. Quantitative real-time polymerase chain reaction, Western blot, and IHC were carried out to compare the differential expressions of miR-20a, Beclin-I, FAS, Caspase-3, mTOR and P62 in IR rats and normal rats. TUNEL was performed to assess IR-induced apoptosis in IR rats, and luciferase assay was used to confirm the inhibitory effect of miR-20a on Beclin-I and FAS expression. Among the 12 candidate microRNAs (miRNAs), miR-486, miR-25, miR-24, miR-20a,miR-466 and miR-433-3p were significantly downregulated in I/R. In particular, miR-20a, a miRNA highly expressed in umbilical cord-derived mesenchymal stem cells, was proved to bind to the 3' UTR of Beclin-I and FAS to exert an inhibitory effect on their expressions. Since Beclin-I and FAS were aberrantly upregulated in IR, exosomes separated from UC-MSCs showed therapeutic efficacy in reversing I/R induced apoptosis. In addition, exosomes reinforced with miR-20a and separated from UC-MSCs almost fully alleviated I/R injury. Furthermore, our results showed that miR-20a could alleviate the abnormal expression of genes related to apoptosis and autophagy, such as active Caspase-3, mTOR, P62, and LC3II. This study presented detailed evidence to clarify the mechanism underlying the therapeutic efficacy of UC-MSCs in the treatment of I/R injury.

Iodine nutritional status in the adult population of Shandong Province (China) prior to salt reduction program.

PURPOSE: Tremendous differences in iodine status and daily iodine intake persist across provinces of China. The objective of the present study was to evaluate the iodine status and dietary iodine intake of Shandong adults before the implementation of the salt reduction program and a new salt iodization standard. METHODS: Data from a baseline survey of the Shandong and Ministry of Health Action on Salt Reduction and Hypertension project (2011) were analyzed. The iodine contents of 1949 24-h urine samples and 136 drinking water samples were assayed. Daily urinary iodine excretion and daily iodine intake were calculated, analyzed, stratified by different analytical variables and compared with Chinese Dietary Reference Values. RESULTS: The median urinary iodine concentration and median daily iodine intake of Shandong adults were 248.5 µg/L and 368.2 µg/day, respectively. The median iodine intake of different groups was between the estimated average requirements and the upper limit, except group in water iodine >300 µg/L with median iodine intake of 1200.7 µg/L. Salt intake and iodine levels in drinking water related to iodine intake significantly. CONCLUSIONS: Shandong adults had more than adequate iodine nutrition, and the dietary iodine intake of the population was generally appropriate and safe except residents in high water iodine areas. In the context of the implementation of a salt reduction program and a new salt iodization standard, the iodine status of high water iodine areas may remain in the recommended level, but in low water iodine areas, the risk of inadequate iodine intake may increase, needing monitoring of urine iodine excretion, dietary iodine intake and iodized salt consumption regularly.

Are 24 h urinary sodium excretion and sodium:potassium independently associated with obesity in Chinese adults?

OBJECTIVE: To examine the association of 24 h urinary Na excretion and Na:K with obesity in Chinese adults. DESIGN: Population-based cross-sectional study using a four-stage stratified sampling strategy. SETTING: Shandong Province, China. SUBJECTS: Chinese adults (n 1906) aged 18-69 years who provided complete 24 h urine samples. RESULTS: Odds of obesity increased significantly across increasing quartiles of urinary Na excretion (1·00, 1·54, 1·69 and 2·52, respectively, for overweight; 1·00, 1·20, 1·50, and 2·03, respectively, for obesity; 1·00, 1·44, 1·85 and 2·53, respectively, for abdominal obesity (assessed by waist circumference); and 1·00, 1·28, 1·44 and 1·75, respectively, for abdominal obesity (assessed by waist-to-height ratio); P for linear trend <0·001 for all). In addition, odds of abdominal obesity, but not odds of overweight and obesity, increased significantly with successive Na:K quartiles. Additionally, for each increment in urinary Na excretion of 100 mmol, odds of overweight, obesity, abdominal obesity (by waist circumference) and abdominal obesity (by waist-to-height ratio) increased significantly by 46 %, 39 %, 55 % and 33 %, respectively. Similarly, with a 1 sd increase in Na:K, odds of abdominal obesity (by waist circumference) and abdominal obesity (by waist-to-height ratio) increased significantly by 12 % and 15 %, respectively. CONCLUSIONS: These findings suggest that 24 h urinary Na excretion and Na:K might be important risk factors for obesity in Chinese adults.

Cancer incidence and mortality in Shandong province, 2012.

OBJECTIVE: Population-based cancer registration data in 2012 from all available cancer registries in Shandong province were collected by Shandong Center for Disease Control and Prevention (SDCDC). SDCDC estimated the numbers of new cancer cases and cancer deaths in Shandong province with compiled cancer incidence and mortality rates. METHODS: In 2015, there were 21 cancer registries submitted data of cancer incidence and deaths occurred in 2012. All the data were checked and evaluated based on the National Central Cancer Registry (NCCR) criteria of data quality. Qualified data from 15 registries were used for cancer statistics analysis as provincial estimation. The pooled data were stratified by area (urban/rural), gender, age group (0, 1.4, 5.9, 10.14, …, 85+ years) and cancer type. New cancer cases and deaths were estimated using age-specific rates and corresponding provincial population in 2012. The Chinese census data in 2000 and Segi's population were applied for age-standardized rates. All the rates were expressed per 100,000 person-year. RESULTS: Qualified 15 cancer registries (4 urban and 11 rural registries) covered 17,189,988 populations (7,486,039 in urban and 9,703,949 in rural areas). The percentage of cases morphologically verified (MV%) and death certificate-only cases (DCO%) were 66.12% and 2.93%, respectively, and the mortality to incidence rate ratio (M/I) was 0.60. A total of 253,060 new cancer cases and 157,750 cancer deaths were estimated in Shandong province in 2012. The incidence rate was 263.86/100,000 (303.29/100,000 in males, 223.23/100,000 in females), the age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 192.42/100,000 and 189.50/100,000 with the cumulative incidence rate (0.74 years old) of 22.07%. The cancer incidence, ASIRC and ASIRW in urban areas were 267.64/100,000, 195.27/100,000 and 192.02/100,000 compared to 262.32/100,000, 191.26/100,000 and 188.48/100,000 in rural areas, respectively. The cancer mortality was 164.47/100,000 (207.42/100,000 in males, 120.23/100,000 in females), the age-standardized incidence rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 117.54/100,000 and 116.90/100,000, and the cumulative mortality rate (0.74 years old) was 13.53%. The cancer mortality, ASMRC and ASMRW were 141.59/100,000, 101.17/100,000 and 100.33/100,000 in urban areas, and 173.79/100,000, 124.20/100,000 and 123.64/100,000 in rural areas, respectively. Cancers of the lung, stomach, liver, esophagus, colorectum, female breast, brain, leukemia, bladder and pancreas were the most common cancers, accounting for about 82.12% of all cancer new cases. Lung cancer, stomach cancer, liver cancer, esophageal cancer, colorectal cancer, female breast cancer, pancreatic cancer, brain tumor, leukemia and lymphoma were the leading causes of cancer death, accounting for about 89.01% of all cancer deaths. The cancer spectrum showed difference between urban and rural, males and females both in incidence and mortality rates. CONCLUSIONS: Cancer surveillance information in Shandong province is making great progress with the increasing number of cancer registries, population coverage and the improving data quality. Cancer registration plays a fundamental role in cancer control by providing basic information on population-based cancer incidence, mortality, survival and time trend. The disease burden of cancer is serious in Shandong province, and so cancer prevention and control in Shandong province should be enhanced including health education, health promotion, cancer screening and cancer care services.

Association between 24 h urinary sodium and potassium excretion and the metabolic syndrome in Chinese adults: the Shandong and Ministry of Health Action on Salt and Hypertension (SMASH) study.

The association of 24 h urinary Na and potassium excretion with the risk of the metabolic syndrome (MetS) has not been studied in China. The aim of the present study was to examine this association by analysing the data from 1906 study participants living in north China. To this end, 24 h urine samples were collected. Of the 1906 participants, 471 (24·7 %) had the MetS. The mean urinary Na and K excretion was 228·7 and 40·8 mmol/d, respectively. After multivariate adjustment, the odds of the MetS significantly increased across the increasing tertiles of urinary Na excretion (1·00, 1·40 and 1·54, respectively). For the components of the MetS, the odds of central obesity, elevated blood pressure and elevated TAG, but not the odds of low HDL-cholesterol and elevated fasting glucose, significantly increased with the successive tertiles of urinary Na excretion. Furthermore, for every 100 mmol/d increase in urinary Na excretion, the odds of the MetS, central obesity, elevated blood pressure and elevated TAG was significantly increased by 29, 63, 22 and 21 %, respectively. However, urinary K excretion was not significantly associated with the risk of the MetS. These findings suggest that high Na intake might be an important risk factor for the MetS in Chinese adults.

Urinary albumin excretion and prevalence of microalbuminuria in a general Chinese population: a cross-sectional study.

BACKGROUND: Microalbuminuria has been shown to be a risk factor for cardiovascular and renal disease in patients with hypertension and diabetes as well as in the general population. Urinary albumin excretion over 24 h is considered a 'gold standard' to detect microalbuminuria. Few studies have used 24-h urinary albumin excretion to analyze the prevalence of and related factors for microalbuminuira in a general Chinese population. METHODS: This study included 1980 adults aged 18-69 years from the Shandong-Ministry of Health Action on Salt and Hypertension (SMASH) Project 2011 survey. Blood pressure, height, weight and waist circumference were measured, and a venous blood and timed 24-h urine samples were collected from each participant. Linear and logistic regression analyses were used to test associations between established cardiovascular risk factors and microalbuminuria. RESULTS: The median (25th-75th percentile) of 24-h urinary albumin excretion was 6.1 mg/d (4.5-8.7 mg/d) for all adults, 6.0 mg/d (4.4-8.5 mg/d) for men and 6.2 mg/d (4.6-8.9 mg/d) for women. The overall prevalence of microalbuminuria was 4.1% (95% confidence interval [CI]: 3.2-5.0%), 3.7% (95% CI: 2.9-4.5%) for men and 4.6% (95% CI: 3.7-5.5%) for women. Microalbuminuria was present in 8.1% (95% CI: 6.9-9.3%) of individuals with hypertension, 11.4% (95% CI: 10.0-12.8%) of those with diabetes and 15.6% (95% CI: 14.0-17.2%) of those with both. Multiple logistic regression analysis indicated that systolic blood pressure (odds ratio [OR] 1.02; 95% CI: 1.01-1.03) and fasting blood glucose (OR 1.19; 95% CI: 1.05-1.35) were the independent risk factors for microalbuminuria. CONCLUSIONS: Adults in the general population of Shandong Province have a moderate prevalence of microalbuminuria. Those with hypertension and diabetes are at high risk of having microalbuminuria, suggesting the need for screening and early intervention for microalbuminuria among these individuals.

Prevalence of overweight and obesity and their associations with blood pressure among children and adolescents in Shandong, China.

BACKGROUND: Obesity and high blood pressure (BP) are public health problems all over the world. Some studies have reported a positive association between them in children and adolescents. The purpose of this study was to assess the prevalence of overweight and obesity and their associations with BP among school children and adolescents in Shandong, an important province in eastern China. METHODS: In 2011, we conducted a cross-sectional population-representative survey in Shandong, China. A total of 4 898 children and adolescents aged 6-17 years were randomly selected from 140 counties/districts using a multistage random cluster sampling. Weight, height and BP were measured by a trained physician or pediatrician, and information about age, gender and place of residence was obtained using questionnaires. Obesity and high BP were defined according to age- and gender-specific Chinese reference data for children. RESULTS: A total of 4 898 (100%) children and adolescents provided complete information. The prevalence of overweight, obesity and overweight plus obesity were 10.9%, 8.7% and 19.6%, respectively. Boys were more likely to be overweight or obese than girls (P < 0.05 for overweight; P < 0.001 for obesity). The prevalence of overweight plus obesity was highest among children aged 6-11 years (22.3%). BP and the prevalence of high BP increased with increasing body mass index (BMI). With age and sex adjusted, odds ratios (ORs) for high BP were [OR 2.2;95% CI 1.7-2.8) in overweight and [OR 3.6;95% CI 2.6-4.9] in obese children. CONCLUSION: The representative survey confirms high prevalence of overweight and obesity among children and adolescents in Shandong. Childhood obesity is a strong risk factor for high BP. Intervention programs should be implemented to combat the growing obesity epidemic.

Hypertension prevalence, awareness, treatment, and control and sodium intake in Shandong Province, China: baseline results from Shandong-Ministry of Health Action on Salt Reduction and Hypertension (SMASH), 2011.

INTRODUCTION: In China, population-based blood pressure levels and prevalence of hypertension are increasing. Meanwhile, sodium intake, a major risk factor for hypertension, is high. In 2011, to develop intervention priorities for a salt reduction and hypertension control project in Shandong Province (population 96 million), a cross-sectional survey was conducted to collect information on sodium intake and hypertension prevalence, awareness, treatment, and control. METHODS: Complex, multistage sampling methods were used to select a provincial-representative adult sample. Blood pressure was measured and a survey conducted among all participants; condiments were weighed in the household, a 24-hour dietary recall was conducted, and urine was collected. Hypertension was determined by blood pressure measured on a single occasion and self-reported use of antihypertension medications. RESULTS: Overall, 23.4% (95% confidence interval [CI], 20.9%-26.0%) of adults in Shandong were estimated to have hypertension. Among those classified as having hypertension, approximately one-third (34.5%) reported having hypertension, approximately one-fourth (27.5%) reported taking medications, and one-seventh (14.9%) had their blood pressure controlled (<140/<90 mm Hg). Estimated total average daily dietary sodium intake was 5,745 mg (95% CI, 5,428 mg-6,063 mg). Most dietary sodium (80.8%) came from salt and high-salt condiments added during cooking: a sodium intake of 4,640 mg (95% CI, 4,360 mg-4,920 mg). The average daily urinary sodium excretion was 5,398 mg (95% CI, 5,112 mg-5,683 mg). CONCLUSION: Hypertension and excessive sodium intake in adults are major public health problems in Shandong Province, China.

[Comparison of dietary survey, frequency and 24 hour urinary Na methods in evaluation of salt intake in the population].

OBJECTIVE: To compare the difference and correlation between dietary salt intakes assessed by 24 hours urinary Na method, food weighted record method and food frequency questionnaire method. METHODS: All 2 184 subjects aged 18 to 69 were selected by multi stage stratified cluster random sampling method in Shandong province in June to September, 2011. Dietary salt intakes were measured by 24 hours urinary Na method, food weighted record method and food frequency questionnaire method. The information on gender, age, dining locations and labour intensity of members dining at home for 3 days were recorded. And the dietary habits were surveyed by questionnaire. RESULTS: Salt intakes were 14.0, 12.0 and 10.5 g/d assessed by 24 hours urinary Na method, food weighted record method and food frequency questionnaire, respectively. Comparing with 24 hours urinary Na method, salt intakes assessed by food weighted record method and food frequency questionnaire method were 2.0 g (14.3% undervalued) and 3.4 g (24.3% undervalued) less, respectively. Comparing with 24 hours urinary Na method, the proportion of individuals with salt intake over-reported and under-reported were 42.4% (856/2 020) and 55.3% (1 117/2 020) by food weighted record method, and were 20.7% (418/2 020) and 16.3% (329/2 020) by food frequency questionnaire method, respectively; the proportion of individuals with salt intakes within ± 25% of 24 hours urinary Na method were 36.9% (745/2 020) and 28.4% (574/2 020), respectively. Salt intakes assessed by 24 hours urinary method correlated significantly with both salt intakes assessed by food weighted record method and food frequency questionnaire method; the correlation coefficients were 0.13 and 0.07, respectively. With the increasing of salt intakes by subjects' self-judgment, salt intakes were all rising significantly using three survey methods. Salt intakes of three group population of light, moderate and partial taste salty were 13.6, 13.6 and 14.7 g/d by 24 hours urinary Na method (F = 0.47, P < 0.05); 11.0, 12.0 and 12.7 g/d by food weighted record method (F = 5.83, P < 0.05), and 9.3, 10.2 and 11.9 g/d by food frequency questionnaire method (F = 5.83, P < 0.05), respectively. CONCLUSION: Comparing with 24 hours urinary method, food weighted record method and food frequency questionnaire method would undervalue dietary salt intake. Salt intake status can be more accurately assessed by adjusting the underestimation rate.