Association of weight loss strategies with all-cause and specific-cause mortality: a prospective cohort study.

BACKGROUND: The health effects of different weight loss strategies vary greatly, and the relationship between weight loss strategies, especially the combination of multiple strategies, and death is still unclear. We aimed to examine the associations of various numbers and combinations of weight loss strategies with all-cause and specific-cause mortality and to further evaluate the associations of different total weight loss volumes with mortality. METHODS: Using data from NHANES (1999-2018) with 48,430 participants aged 20 and above, we collected fourteen self-reported weight loss strategies and identified five clusters using latent class analysis. Cox proportional hazards models were used to examine the association between the amounts and clusters of weight loss strategies and mortality. RESULTS: During a median follow-up of 9.1 years of 48,430 participants, 7,539 deaths were recorded (including 1,941 CVDs and 1,714 cancer). Participants who adopted 2, 3-4, and ≥ 5 weight loss strategies had a lower risk of all-cause mortality, with HRs of 0.88 (95% CI, 0.81 to 0.97), 0.89 (95% CI, 0.81 to 0.96) and 0.71 (95% CI, 0.61 to 0.82). Regardless of weight loss or weight gain categories, there was a significant trend toward reduced mortality as the number of weight loss strategies increased (P trend < 0.05). Participants who adopted cluster-1 (four strategies), cluster-2 (five strategies) and cluster-3 (three strategies) had a significantly lower risk of all-cause mortality, with HRs of 0.71 (95% CI, 0.60 to 0.84), 0.70 (95% CI, 0.55 to 0.89) and 0.81 (95% CI, 0.70 to 0.94). Among them, cluster-1 and cluster-2 are both characterized by eating less food, exercising, drinking plenty of water, lowering calories and eating less fat. Conversely, cluster-4 (five strategies) and cluster-5 (four strategies) had marginally significant effects, and they both had actual higher total energy intakes. Similar associations were observed for CVDs and cancer mortality. CONCLUSIONS: Employing two or more weight loss strategies was associated with a lower risk of death, even among those who gained weight. Eating less food, exercising, drinking plenty of water, lowering calories and eating less fat is a better combination of strategies. On this basis, limiting the actual intake of total energy is necessary.

Failure mechanical properties of lumbar intervertebral disc under high loading rate.

BACKGROUND: Lumbar disc herniation (LDH) is the main clinical cause of low back pain. The pathogenesis of lumbar disc herniation is still uncertain, while it is often accompanied by disc rupture. In order to explore relationship between loading rate and failure mechanics that may lead to lumbar disc herniation, the failure mechanical properties of the intervertebral disc under high rates of loading were analyzed. METHOD: Bend the lumbar motion segment of a healthy sheep by 5° and compress it to the ultimate strength point at a strain rate of 0.008/s, making a damaged sample. Within the normal strain range, the sample is subjected to quasi-static loading and high loading rate at different strain rates. RESULTS: For healthy samples, the stress-strain curve appears collapsed only at high rates of compression; for damaged samples, the stress-strain curves collapse both at quasi-static and high-rate compression. For damaged samples, the strengthening stage becomes significantly shorter as the strain rate increases, indicating that its ability to prevent the destruction is significantly reduced. For damaged intervertebral disc, when subjected to quasi-static or high rates loading until failure, the phenomenon of nucleus pulposus (NP) prolapse occurs, indicating the occurrence of herniation. When subjected to quasi-static loading, the AF moves away from the NP, and inner AF has the greatest displacement; when subjected to high rates loading, the AF moves closer to the NP, and outer AF has the greatest displacement. The Zhu-Wang-Tang (ZWT) nonlinear viscoelastic constitutive model was used to describe the mechanical behavior of the intervertebral disc, and the fitting results were in good agreement with the experimental curve. CONCLUSION: Experimental results show that, both damage and strain rate have a significant effect on the mechanical behavior of the disc fracture. The research work in this article has important theoretical guiding significance for preventing LDH in daily life.

Identification of prognostic genes for breast cancer related to systemic lupus erythematosus by integrated analysis and machine learning.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disease with multi-organ involvement, and some studies have found that SLE has a reduced risk of breast cancer (BRCA). So, we tried to find prognostic genes for BRCA related to SLE by integrated analysis and machine learning. METHOD: First, we downloaded 2 SLE datasets from Gene Expression Omnibus (GEO) and BRCA data from the Cancer Genome Atlas (TCGA). Subsequently, we performed differentially expressed genes (DEGs) and functional enrichment analysis by Metascape in SLE. Genes that were differentially expressed in both datasets were the validated DEGs. And after constructing PPI network, genes with nodes >30 were intersected with survival genes in BRCA to obtain candidate genes. Then, the candidate genes were validated by lasso regression in both training and validation sets to obtain prognostic genes. Afterwards, we investigated the diagnostic potential of prognostic genes for SLE and the predictive efficacy for BRCA prognosis. Moreover, GSEA analysis and immune infiltration were performed for SLE and BRCA. Finally, we constructed a prognostic gene-miRNAs network and did functional enrichment of the shared genes. RESULT: DEGs for SLE were mainly enriched with neutrophil degranulation and IFN pathways. After the lasso model of BRCA was established, IRF7, IFI35 and EIF2AK2, were identified as prognostic genes for BRCA related to SLE and had good predictive ability for the prognosis of BRCA. Prognostic genes had excellent diagnostic potential for SLE, with IFI35 and EIF2AK2 positively associated with SLE activity and IRF7 positively associated with IFI35. GSEA showed that both SLE and BRCA were associated with ubiquitinated degradation. Immune infiltrates suggest that plasma cells, dendritic cells (DC), neutrophils and monocyte were elevated in SLE. DC, NK and CD8+ T cells were elevated in the BRCA low-risk group. Finally, 5 shared miRNAs were confirmed, which were mainly enriched in the IFN pathway. CONCLUSION: IRF7, IFI35 and EIF2AK2, were identified as prognostic genes for BRCA related to SLE. IFN pathway played an important role in the etiology of SLE and the prognosis of BRCA.

Trends of Mortality in End-Stage Liver Disease - China, 2008-2020.

Introduction: Liver cancer and cirrhosis represent the most prevalent forms of end-stage liver diseases (ESLDs). Notably, in China, deaths attributed to ESLDs contribute significantly to the global mortality rate of these disorders. Enhanced comprehension of the mortality profile associated with ESLDs in China could provide crucial insights into intervention prioritization, which could in turn help reduce the overall global burden of these diseases. Methods: Data were obtained from China's Disease Surveillance Points system. The presentation includes both crude and age-standardized mortality rates, stratified by sex, residential location, and region. Using Joinpoint Regression, trends in annual mortality rates were estimated from the period of 2008 to 2020 and expressed as the average annual percentage change (AAPC). Results: In 2020, the gross mortality rate of ESLD stood at 30.08 cases per 100,000 individuals. A higher age-standardized ESLD mortality rate was observed in males and rural populations in comparison to their female and urban counterparts, respectively. Noticeably, the highest mortality rates associated with liver cancer and cirrhosis were reported in South and Southwest China, respectively. A positive correlation was noticed between age-specific ESLD mortality rates and advancing age. Interestingly, an annual decrease in the ESLD mortality rate was observed from 2008 to 2020. In urban contexts, the AAPC of cirrhosis was noted to be higher than that of liver cancer. Conclusions: The mortality rate associated with ESLDs in China decreased between 2008 and 2020. Nevertheless, the death burden attributable to ESLD continues to be alarmingly high. Future initiatives should prioritize the reduction of ESLD mortality in particular populations: males, elderly individuals, and those residing in rural regions of South and Southwest China. The emphasis of future interventions should be placed on antiviral therapy for adults diagnosed with viral hepatitis, and on the prevention of hepatitis B virus (HBV) infection across all demographics.

Genes associated with cellular senescence favor melanoma prognosis by stimulating immune responses in tumor microenvironment.

PURPOSE: Skin cutaneous melanoma (SKCM), a malignant tumor from melanocytes, is the fifth most prevalent tumor. Immune checkpoint inhibitor (ICI) immunotherapy improves prognosis of SKCM, but immune response varies for different populations. Cellular senescence in the tumor microenvironment (TME) promotes antitumor immunity, mediated by dendritic cells (DC) and CD8+ T cells. Therefore, we sought to explore the role of cellular senescence in the TME of SKCM through bioinformatics and machine learning. METHODS: First, we obtained 93 cellular senescence-prognosis genes (CSPGs) by univariate survival analysis. Thereafter, 23 optimal CSPGs were obtained by least absolute shrinkage and selection operator (lasso) analysis. Based on the riskscore obtained by lasso analysis and clinical information from multivariate cox, we obtained the nomogram of SKCM, which was validated in the validation cohort. Based on the riskscore, the patients were split into low- and high-risk groups. Functional differences between the two groups were analyzed using Metascape and GSEA, and immune infiltration differences were achieved by multiple algorithms. We obtained a risk prediction nomogram for the validated SKCM based on the lasso model by univariate and multivariate cox regression analysis. RESULTS: In the low-risk group, immune responses were in an active state. NK, CD8+ T, DC, macrophages, and neutrophils were significantly upregulated, and ICI-relevant genes were notably upregulated. With the differentially expressed genes (DEGs) and optimal CSPGs, we obtained the hub genes: NOX4, NTN4, PROX1, and TRPM8. The hub genes were mainly expressed by cancer-associated fibroblasts (CAFs) and endothelial cells by single cell analysis, which were mainly associated with angiogenesis. CONCLUSION: Genes associated with cellular senescence favor SKCM prognosis by stimulating immune responses in TME. Patients with high expression of cellular senescence associated genes in the TME might have better benefit from ICI immunotherapy. Cellular senescence functions as a pro-tumor agent in mesenchymal cells and needs further study.

Impaired long-term anti-HBs responses in choronic hepatitis C patients: Results from a five-year follow-up study with healthy control.

Although hepatitis B virus (HBV) vaccination is recommended for hepatitis C virus (HCV)-infected individuals to avoid HBV superinfection, the persistence of their humoral and cell-mediated immunity responses to HBV vaccination is still under investigation. Patients with chronic hepatitis C (CHC) and matched healthy controls, who completed three doses of hepatitis B vaccine (HepB) in 2014, were followed up five years later. One booster dose of HepB was given to those with antibody against hepatitis B surface antigen (anti-HBs) lower than 10mIU/mL. Anti-HBs was tested at follow-up and on the 14th day after the booster dose, as well as HBsAg specific spot-forming cells of interferon γ and interleukin (IL) 2, 4, 5, and 6. At five years, only 56.58% of the CHC patients had sero-protective titers (≥10mIU/mL) of anti-HBs, compared to 70.83% in the controls (P < .05). Similarly, the geometric mean concentration (GMC) of anti-HBs in CHC patients was significantly lower than that in controls (16.95 vs 37.34 mIU/mL, P < .05). After the booster, both GMC and the rate of anamnestic response increased to a very high level in the two groups and the difference between them disappeared (P > .05). Multivariable analysis showed that HCV infection was an independent predictor factor to anti-HBs level at follow-up. HBsAg specific IL-6 was stronger in the CHC patients compared to the controls (P < .05). The data indicate that the durability of protective anti-HBs is poorer in CHC patients compared to healthy individuals, and impaired long-term anti-HBs responses might be associated with the increased HBsAg specific IL-6 responses.

Global, Regional, and National Burden of Cancer in Children Younger Than 5 Years, 1990-2019: Analysis of the Global Burden of Disease Study 2019.

Objectives: To quantify the burden and variation trends of cancers in children under 5 years at the global, regional, and national levels from 1990 to 2019. Methods: Epidemiological data for children under 5 years who were diagnosed with any one childhood cancer were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) from 1990 to 2019. The outcomes were the absolute numbers and rates of incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for different types of cancer. Results: In 2019, 8,774,979.1 incident cases (95% uncertainty interval [UI]: 6,243,599.2 to11,737,568.5) and 8,956,583.8 (6,446,323.9 to 12,364,520.8) prevalent cases of cancer in children under 5 years were identified worldwide; these cancers resulted in 44,451.6 (36,198.7 to 53,905.9) deaths and 3,918,014.8 (3,196,454.9 to 4,751,304.2) DALYs. From 1990 to 2019, although the numbers of incident and prevalent cases only decreased by -4.6% (-7.0 to -2.2) and -8.3% (-12.6 to -3.4), respectively, the numbers of deaths and DALYs clearly declined by -47.8% (-60.7 to -26.4) and -47.7% (-60.7 to -26.2), respectively. In 2019, the middle sociodemographic index (SDI) regions had the highest incidence and prevalence, whereas the low SDI regions had the most mortality and DALYs. Although all of the SDI regions displayed a steady drop in deaths and DALYs between 1990 and 2019, the low-middle and low SDI regions showed increasing trends of incidence and prevalence. Leukemia remained the most common cancer globally in 2019. From 1990 to 2019, the burdens of leukemia, liver cancer, and Hodgkin's lymphoma declined, whereas the incidence and prevalence of other cancers grew, particularly testicular cancer. Conclusions: The global childhood cancer burden in young children has been steadily decreasing over the past three decades. However, the burdens and other characteristics have varied across different regions and types of cancers. This highlights the need to reorient current treatment strategies and establish effective prevention methods to reduce the global burden of childhood cancer.

Exploration of the molecular mechanisms, shared gene signatures, and MicroRNAs between systemic lupus erythematosus and diffuse large B cell lymphoma by bioinformatics analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex heterogeneous systemic autoimmune disease. Previous studies have shown that SLE may be related to diffuse large B cell lymphoma (DLBCL), but the mechanism of their relationship is still unclear. The present study aimed to explore the common genetic molecular mechanisms, core shared genes, and miRNAs between SLE and DLBCL as well as to investigate the diagnostic markers of DLBCL. METHODS: The SLE and DLBCL microarray data were downloaded from the comprehensive Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules. Four core shared genes were screened out by various algorithms and validated in other cohorts. Finally, we constructed a common core gene-miRNA network using the human microRNA disease database (HMDD) and TarBase. RESULTS: Using WGCNA, four modules were identified as important modules for SLE and DLBCL. Enrichment analysis of the shared genes showed that the highly activated NF-κB pathway was a common feature of the pathophysiology. Four core shared genes, namely, PSMB10, PSMB4, TAF10, and NFΚBIA, were screened out. These core shared genes were significantly upregulated in both diseases, and they may be potential diagnostic markers of DLBCL. The core gene-miRNA network showed that miR-155-5p, regulating the shared NF-κB pathway, may play an important role in the susceptibility of SLE patients to DLBCL. CONCLUSION: The present study revealed that NF-κB pathway in SLE may be a crucial susceptible factor for DLBCL. In addition, we identified PSMB10, PSMB4, TAF10, NFΚBIA and miR-155 involved in the common pathogenesis as potential biomarkers and therapeutic targets for DLBCL.

CircRNA circFADS2 is under-expressed in sepsis and protects lung cells from LPS-induced apoptosis by downregulating miR-133a.

BACKGROUND: It has been reported that hsa_circRNA_100833 (identified as circFADS2) and miR-133a play opposite roles in LPS-induced cell apoptosis, which contributes to the development of sepsis. This study was carried out to explore the interaction between circFADS2 and miR-133a in sepsis. METHODS: Expression of circFADS2 and miR-133a in plasma from both sepsis patients (n=62) and healthy controls (n=62) was studied by RT-qPCR. Pearson's correlation coefficient analysis was utilized to analyze the correlation between circFADS2 and miR-133a levels across plasma samples from sepsis patients. Cell viability and apoptosis, levels of proteins associated with apoptosis (cleaved caspase-3 and cleaved caspase-9), and expression of pro-inflammatory cytokines in LPS-treated HBEpCs were detected by MTT assay, cell apoptosis assay, western blot, and ELISA, respectively. In addition, a dual-luciferase reporter assay was performed to verify the interaction between circFADS2 and miR-133a. RESULTS: CircFADS2 was under-expressed (0.56-fold vs. control) in sepsis, and miR-133a was highly expressed (2.05-fold vs. control) in sepsis. An inverse correlation between circFADS2 and miR-133a was observed across sepsis samples. LPS decreased cell viability, increased cell apoptosis, and elevated productions of tumor necrosis factor (TNF)-α, interleukins (IL)-1ß, IL-6, and IL-8 in HBEpCs in a dose-dependent manner. In addition, circFADS2 was identified as a target gene of miR-133a. The further experiment revealed that circFADS2 overexpression and miR-133a inhibition prominently promoted cell viability (1.71-fold vs. pcDNA3.1; 1.65-fold vs. NC miRNA) and decreased apoptosis of LPS-treated HBEpCs (0.44-fold vs. pcDNA3.1; 0.47-fold vs. NC miRNA). Moreover, circFADS2 knockdown and miR-133a overexpression inhibited viability (0.36-fold vs. pcDNA3.1; 0.37-fold vs. NC miRNA) and increased apoptosis (1.54-fold vs. pcDNA3.1; 1.51-fold vs. NC miRNA) of LPS-treated HBEpCs. Notably, circFADS2 overexpression reduced the effects of miR-133a on LPS-treated HBEpCs. CONCLUSIONS: CircFADS2 is under-expressed in sepsis and may protect lung cells from LPS-induced apoptosis by downregulating miR-133a.

Immunogenicity and persistence of high-dose recombinant hepatitis B vaccine in adults infected with human immunodeficiency virus in China: A randomized, double-blind, parallel controlled trial.

OBJECTIVES: To explore the immunogenicity and persistence of the 60 µg hepatitis B vaccine in adults infected with human immunodeficiency virus (HIV). METHODS: We conducted a randomised controlled trial for adults infected with HIV. A total of 182 patients were randomly allocated to receive 20 µg (IM20 group) or 60 µg (IM60 group) of recombinant hepatitis B vaccine at months 0, 1, and 6 to assess the immunogenicity and were followed-up from month 7 to 42 to assess long-term immunogenicity. RESULTS: Our data showed that the response rate and geometric mean concentration (GMC) of antibodies to hepatitis B surface antigen (anti-HBs) in the IM60 group at month 7 were higher than those in the IM20 group (P > 0.05). The GMC of anti-HBs among the two groups decreased rapidly during the follow-up period (P > 0.05). Survival analysis showed that 25% of patients with anti-HBs ≥ 10 mIU/mL were 20 months in the IM60 group and 9.3 months in the IM20 group. CONCLUSION: The three-dose 60 µg hepatitis B vaccine showed partially better immunogenicity and persistence than the three-dose 20 µg vaccine. TRIAL REGISTRATION: The trial was registered on clinicaltrials.gov, NCT03316807.

High Risk Thyroid Nodule Discrimination and Management by Modified TI-RADS.

OBJECTIVE: Thyroid cancer is the most common primary malignant disorder of the thyroid. We aimed to illustrate the modified TI-RADS report system for differentiating malignant thyroid nodules from benign ones, and especially its role in the management of high risk nodules. METHODS: In this retrospective study, 5,162 healthy individuals who underwent thyroid ultrasound according to modified TI-RADS from January 2014 to December 2014 were enrolled and followed up during the whole 5 years, and the medical data were investigated and reviewed. RESULTS: The total detection rate of thyroid nodules was 39.40%. The total detection rate of thyroid cancer was 0.66%. Most thyroid cancers were single-shot, located at unilateral, at early clinical stages, without lymph node metastases, and with low recurrence risk. All patients had thyroid papillary carcinoma, except one thyroid medullary carcinoma. Based on modified TI-RADS classification, at the end of 5 years follow-up, more changes of thyroid nodules grade status were observed in grades 4a and above. The higher the grade status, the more malignant advances were occurred. The modified TI-RADS report system played an instructional role in adding medical treatment choice and decision for clinicians. CONCLUSION: The modified TI-RADS report system plays an important role in thyroid benign and malignant nodule identification and management.

Long-term durability of immunogenicity induced by standard and triple-dose hepatitis B vaccine in patients receiving methadone maintenance treatment.

OBJECTIVES: We explored the long-term immunogenicity induced by 60 µg and 20 µg hepatitis B vaccines among patients receiving methadone maintenance treatment (MMT). METHODS: In initial study, a randomized controlled trial was conducted, in which patients receiving MMT were administered 20 µg (IM20 group) or 60 µg (IM60 group) hepatitis B vaccines at months 0, 1, and 6. In this study, the responders at month 7 were followed-up at months 18, 30, and 42 to estimate long-term immunogenicity. RESULTS: The response rate decreased from 78.0% (39/50) to 31.1% (14/45) in the IM20 group, and from 86.0% (43/50) to 50.0% (20/40) in the IM60 group from month 7 to 42. Vaccine-induced responses in 75% of patients were observed for 14.2 months in the IM20 group and for 20.0 months in the IM60 group, and differences between these two groups were non-significant (P > 0.05). CONCLUSION: The three-dose 20 µg and 60 µg hepatitis B vaccines showed similar rapid hepatitis B surface antibody decreases. Abbreviations: HBV, hepatitis B virus; MMT, methadone maintenance treatment; HCC, hepatocellular carcinoma; HBsAg, hepatitis B surface antigen; anti-HBs, hepatitis B surface antibody; HR, hazard ratio; CI, confidence interval; IQR, interquartile range; GEE, generalized estimated equation.

Self-motivated medical care-seeking behaviors and disease progression in a community-based cohort of chronic hepatitis B virus-infected patients in China.

BACKGROUND: To determine the treatment behaviors among a community-based cohort of chronic hepatitis B virus (HBV)-infected persons and to examine the disease progression among non-antiviral-treated HBV-infected cases after 5 years of follow-up. METHODS: We conducted a community-based prospective study on people with chronic HBV infection in mainland China from 2009 to 2014. In 2009, we recruited participants who were identified as HBV infected in 2006 in a national sero-survey. A face-to-face follow-up investigation was completed in 2014, and the personal information, the clinical diagnosis provided at the last hospital visit, the HBV antiviral treatment history, and the insurance type was collected for each patient for analysis. Multivariable logistic regression was used to identify factors that are associated with active medical care- seeking and antiviral treatments. RESULTS: Among the 2422 chronic HBV-infected patients recruited in 2009, 1784 (73.7%) were followed-up to 2014, and 638 (35.8%) had sought medical care in hospitals; among them, 140 (21.9%) received antiviral treatments. The lowest medical care-seeking rate (26%) was in participants over 50-year old. We determined that the frequency of medical care-seeking was higher among those participants living in urban areas (aRR = 1.3, 95% CI:1.0-1.6), those in 0-19-year old (aRR = 1.5, 95% CI:1.1-2.1), 20-39-year old (aRR = 2.2, 95% CI:1.7-3.0) and 40-49-year old (aRR = 1.5, 95% CI:1.1-2.0), and persons with insurance of the type Urban residents' basic medical insurance (URBMI) or Commercial health insurance (CHI) (aRR = 2.5, 95% CI:1.7-3.6) and New Rural Cooperative Medical System (NRCMS) (aRR = 1.9, 95% CI:1.4-2.6). Patients were more likely to receive antiviral treatment if they were 20-39-year old (aRR = 0.4, 95% CI:0.3-0.7), had insurance of the type URBMI or CHI (aRR = 2.6, 95% CI:1.1-6.3) or NRCMS (aRR = 3.0, 95% CI:1.3-6.9) and were treated at prefecture and above-level hospitals (aRR = 2.0, 95% CI:1.4-3.0). Among non-antiviral-treated HBV-infected cases, we found the annual rates for HBsAg sero-clearance, progress to cirrhosis and HCC were 1.0, 0.6 and 0.2%, respectively. CONCLUSION: The rates of medical care-seeking and antiviral treatment were low among community-based chronic HBV-infected persons, thus we recommend improving the insurance policies for HBV-infected persons to increase the antiviral treatment rate, and conducting extensive education to promote HBV-infected patients actively seeking medical care from hospitals.

Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Public health is a priority for the Chinese Government. Evidence-based decision making for health at the province level in China, which is home to a fifth of the global population, is of paramount importance. This analysis uses data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to help inform decision making and monitor progress on health at the province level. METHODS: We used the methods in GBD 2017 to analyse health patterns in the 34 province-level administrative units in China from 1990 to 2017. We estimated all-cause and cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), summary exposure values (SEVs), and attributable risk. We compared the observed results with expected values estimated based on the Socio-demographic Index (SDI). FINDINGS: Stroke and ischaemic heart disease were the leading causes of death and DALYs at the national level in China in 2017. Age-standardised DALYs per 100 000 population decreased by 33·1% (95% uncertainty interval [UI] 29·8 to 37·4) for stroke and increased by 4·6% (-3·3 to 10·7) for ischaemic heart disease from 1990 to 2017. Age-standardised stroke, ischaemic heart disease, lung cancer, chronic obstructive pulmonary disease, and liver cancer were the five leading causes of YLLs in 2017. Musculoskeletal disorders, mental health disorders, and sense organ diseases were the three leading causes of YLDs in 2017, and high systolic blood pressure, smoking, high-sodium diet, and ambient particulate matter pollution were among the leading four risk factors contributing to deaths and DALYs. All provinces had higher than expected DALYs per 100 000 population for liver cancer, with the observed to expected ratio ranging from 2·04 to 6·88. The all-cause age-standardised DALYs per 100 000 population were lower than expected in all provinces in 2017, and among the top 20 level 3 causes were lower than expected for ischaemic heart disease, Alzheimer's disease, headache disorder, and low back pain. The largest percentage change at the national level in age-standardised SEVs among the top ten leading risk factors was in high body-mass index (185%, 95% UI 113·1 to 247·7]), followed by ambient particulate matter pollution (88·5%, 66·4 to 116·4). INTERPRETATION: China has made substantial progress in reducing the burden of many diseases and disabilities. Strategies targeting chronic diseases, particularly in the elderly, should be prioritised in the expanding Chinese health-care system. FUNDING: China National Key Research and Development Program and Bill & Melinda Gates Foundation.

Personal ultraviolet Radiation exposure in a cohort of Chinese mother and child pairs: the Chinese families and children study.

BACKGROUND: Few studies in China have examined personal ultraviolet radiation (UVR) exposure using polysulfone dosimetry. METHODS: In this study, 93 mother and adolescent child pairs (N = 186) from two locations in China, one rural (higher latitude) and one urban (lower latitude), completed 3 days of personal UVR dosimetry and a sun/clothing diary, as part of a larger pilot study. RESULTS: The average daily ambient UVR in each location as measured by dosimetry was 20.24 Minimal Erythemal Doses (MED) in the rural location and 20.53 MED in the urban location. Rural mothers had more average daily time outdoors than urban mothers (5.5 h, compared with 1.5 h, in urban mothers) and a much higher daily average personal UVR exposure (4.50 MED, compared with 0.78 MED in urban mothers). Amongst adolescents, rural males had the highest average daily personal UVR exposure, followed by rural females, urban females and urban males (average 2.16, 1.05, 0.81, and 0.48 MED, respectively). CONCLUSIONS: Although based on small numbers, our findings show the importance of geographic location, age, work/school responsibilities, and sex of the adolescents in determining personal UVR exposure in China. These results suggest that latitude of residence may not be a good proxy for personal UVR exposure in all circumstances.

The 20 Most Important and Most Preventable Health Problems of China: A Delphi Consultation of Chinese Experts.

OBJECTIVES: To identify the 20 most important and most preventable health problems that should be addressed in the next 20 years in China. METHODS: In 2015, we applied a modified electronic Delphi technique to reach consensus from a panel of top Chinese health experts (n = 70), who were requested to identify 20 health problems that, in their judgment, were most important and preventable. We also compared the results with evidences from epidemiological studies on disease-specific mortalities and disability-adjusted life years. RESULTS: Consensus was reached after the second-round survey. The final agreed-upon 20 most important and most preventable health problems included 9 noncommunicable diseases, 4 communicable diseases, 2 unhealthy behaviors, and 2 forms of environmental pollution, plus depression, road injury, and contamination of food with pesticides, antibiotics, and hormone residues. The results are supported by relevant epidemiological studies in China. CONCLUSIONS: The 20 most important and most preventable health problems in China for the next 20 years, agreed upon by a panel of top Chinese health experts, should be taken into consideration in national policymaking.

[Meta-analysis on association between genetic polymorphisms of cytochrome P450 2E1 and susceptibility to Chinese gastric cancer].

OBJECTIVE: To conduct a comprehensive quantitative analysis about the association between genetic polymorphisms of CYP 2E1 and susceptibility to Chinese gastric cancer in order to offer evidence-based evidence for the etiology of gastric cancer. METHODS: Using the keywords and entry terms of cytochrom P450 2E1, cytochrome P450, CYP 2E1, stomach neoplasms, individual susceptibility, gene polymorphism, risk factors in English and Chinese, we searched medical literature databases, such as Pub Med, Embase, CBM, VIP, CNKI, China Info, published from January 1 th, 1997 to December 31 th, 2016, the Chines population was selected as the research object. Metaanalysis was performed using Stata 14. 0 in literature that selected quality studies of original literatures of more than 6 stars. RESULTS: There were 10 high-quality original articles covering high, middle and low incidence areas of gastric cancer in our country, with 832 cases and 1018 controls were included, which fit the HWE test. The population with CYP 2E1 C1C2 genotype have a lower risk of developing gastric cancer than the population with CYP 2E1 C1C1 genotype( OR = 0. 650, P < 0. 001, 95% CI 0. 515-0. 821); Subgroup-analysis result reveals that, in smaller sample size population with CYP 2E1 C1C1 genotype have a gastric cancer risk of 2. 02 times the risk of having gastric cancer with CYP 2E1 C1C2 and C2C2 genotypes( P < 0. 001, 95% CI 1. 55-2. 64), in bigger sample size population with CYP 2E1 C1C1 genotype have a gastric cancer risk of0. 93 times the risk of having gastric cancer with CYP 2E1 C1C2 and C2C2 genotypes( P = 0. 586, 95% CI 0. 71-1. 22), in overall sample size population with CYP 2E1 C1C1 genotype have a gastric cancer risk of 1. 50 times the risk of having gastric cancer with CYP 2E1 C1C2 and C2C2 genotypes( P = 0. 006, 95% CI 1. 12-2. 00). CONCLUSION: The size of the sample is an important factor affecting the result. The small sample size of the study tends to get positive result. Whether CYP 2E1 C1C1 genotype of the population is a risk factor for gastric cancer remains to be further studied.

Prospective investigation of folic acid supplements before and during early pregnancy and paediatric and adult cancers in the Chinese children and families cohort: a pilot study in a sample of rural and urban families.

OBJECTIVE: To determine the feasibility of long-term prospective follow-up and ascertainment of cancer in offspring and mothers from the 1993-1995 Chinese Community Intervention Program that provided folic acid supplements before and during early pregnancy to reduce neural tube defects. DESIGN: Feasibility pilot study for a prospective cohort study. SETTING: Families residing during 2012-2013 in one rural and one urban county from 21 counties in 3 provinces in China included in the Community Intervention Program campaign. PARTICIPANTS: The feasibility study targeted 560 families, including 280 from the rural and 280 from the urban county included in the large original study; about half of mothers in each group had taken and half had not taken folic acid supplements. INTERVENTION: The planned new study is observational. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary: incidence of paediatric cancers in offspring; secondary: other chronic diseases in offspring and chronic diseases in mothers RESULTS: Only 3.4% of pilot study families could not be found, 3.9% had moved out of the study area and 8.8% refused to participate. Interviews were completed by 82% of mothers, 79% of fathers and 83% of offspring in the 560 families. Almost all mothers and offspring who were interviewed also participated in anthropometric measurements. We found notable urban-rural differences in sociodemographic and lifestyle characteristics of the parents, but fewer differences among the offspring. In eight catchment area hospitals, we identified a broad range of paediatric cancers diagnosed during 1994-2013, although paediatric brain tumours, lymphomas and rarer cancers were likely under-represented. CONCLUSIONS: Overall, 20 years after the original Community Intervention Program, the pilot study achieved high levels of follow-up and family member interview participation, and identified substantial numbers of paediatric malignancies during 1994-2013 in catchment area hospitals. Next steps and strategies for overcoming limitations are described.

Ultrasound features of extranodal extension in the metastatic cervical lymph nodes of papillary thyroid cancer: a case-control study.

OBJECTIVE: Extranodal extension in cervical lymph nodes is an important risk factor for the progression and prognosis of papillary thyroid cancer. The purpose of this study was to identify the common and characteristic preoperative ultrasonography features that are associated with the pathologic extranodal extension of metastatic papillary thyroid carcinoma. METHODS: We retrospectively assessed and compared clinicopathologic and ultrasound features between 60 papillary thyroid cancer patients with extranodal extension and 120 control patients with papillary thyroid cancer without extranodal extension. RESULTS: With respect to the pathological N stage and clinicopathologic features, N1b stage papillary thyroid carcinomas were more frequently found in patients who were extranodal extension-positive, in comparison with those who were extranodal extension-negative (78.3% vs. 63.3%, P=0.043). Extranodal extension was detected most frequently in level VI cervical lymph nodes (48.7%). In our univariate analysis of patients with papillary thyroid carcinoma, cervical lymph nodes with extranodal extension showed higher incidences of node matting, microcalcification, cystic area, aspect ratio <2, and larger diameter than those without extranodal extension (all P<0.05). Our multivariate analysis demonstrated that node matting and cystic area were independent risk factors for the presence of extranodal extension [odds ratio (OR): 4.751, 95% confidence interval (CI): 1.212~18.626, P=0.025; OR: 2.707, 95% CI: 1.127~6.502, P=0.026]. CONCLUSIONS: Common ultrasound features may indicate the presence of extranodal extension in patients with metastatic cervical lymph nodes of papillary thyroid carcinoma.

Evaluation of antioxidant activities of ethanol extract from Ligusticum subjected to in-vitro gastrointestinal digestion.

The Rhizome of Ligusticum chuanxiong Hort, a traditional Chinese medicine, is widely used to treat cardiovascular diseases and attenuate oxidative stress. The main bioactive compounds including tetramethylpyrazine (TMP), polyphenols, ferulic acid have been reported to be responsible for these effects. This study was to evaluate the influence of Ligusticum chuanxiong extraction (LCE) in mimic gastrointestinal tract on antioxidant activity. The effects of gastric digestion group metabolic liquid on free radical scavenging followed as DPPH > ·O2- > ·OH, while the clearance effects of intestine digestion group expressed as ·O2-> ·OH > DPPH. Furthermore, the digested extraction promoted lower cellular antioxidant activity (CAA) with dose-response correlations. Gastrointestinal digestion increased the release of bound ferulic acids and polyphenols. Content of ferulic acid in gastric and intestinal metabolic solution increased from 6.07 mg/g to 9.33 mg/g and 14.17 mg/g. The free phenolic before and after digestion were 177.38 mg/g, 179.69 mg/g and 194.99 mg/g, respectively. The simulated gastrointestinal digestion of LCE promoted a significant increase in the free phenolic acids content, antioxidant activity and CAA.