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1.
Int J Epidemiol ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33826715

RESUMO

BACKGROUND: Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond 1 month and the potential modifying effect of cardiovascular risk factors on such an association are less well established. METHODS: The China Kadoorie Biobank enrolled 512 726 participants aged 30-79 years from 10 areas across China during 2004-2008. By the end of 2017, a total of 5444 participants with new-onset ischaemic heart disease (IHD) and 4846 with ischaemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case-series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischaemic cardiovascular disease (CVD) after pneumonia. RESULTS: The risk of ischaemic CVD increased during days 1-3 after pneumonia hospitalization, with an RI (95% CI) of 4.24 (2.92-6.15) for IHD and 1.85 (1.02-3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92-365 for IHD (1.23, 1.12-1.35) and days 29-91 for IS (1.25, 1.05-1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischaemic CVD risks, such as chronic obstructive pulmonary disease for both IHD and IS, and diabetes and smoking for IHD (all Pinteraction < 0.05). Besides, the risk of ischaemic CVD was also higher among the participants aged ≥70 years (Pinteraction < 0.001 for IHD and 0.033 for IS). CONCLUSION: Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischaemic CVD risk for ≤1 year.

2.
Nutrients ; 13(4)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805392

RESUMO

A few prospective studies have suggested that tea, alcohol, and fruit consumption may reduce the risk of kidney stones. However, little is known whether such associations and their combined effect persist in Chinese adults, for whom the popular tea and alcohol drinks are different from those investigated in the aforementioned studies. The present study included 502,621 participants from the China Kadoorie Biobank (CKB). Information about tea, alcohol, and fruit consumption was self-reported at baseline. The first documented cases of kidney stones during follow-up were collected through linkage with the national health insurance system. Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). During a median of 11.1 years of follow-up, we collected 12,407 cases of kidney stones. After multivariable adjustment, tea, alcohol, and fruit consumption were found to be negatively associated with kidney stone risk, but the linear trend was only found in tea and fruit consumption. Compared with non-tea consumers, the HR (95% CI) for participants who drank ≥7 cups of tea per day was 0.73 (0.65-0.83). Compared with non-alcohol consumers, the HR (95% CI) was 0.79 (0.72-0.87) for participants who drank pure alcohol of 30.0-59.9 g per day but had no further decrease with a higher intake of alcohol. Compared with less-than-weekly consumers, the HR (95% CI) for daily fruit consumers was 0.81 (0.75-0.87). Even for those who did not drink alcohol excessively, increasing tea and fruit consumption could also independently reduce the stone risk. Among Chinese adults, tea, alcohol, and fruit consumption was associated with a lower risk of kidney stones.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33677664

RESUMO

This study aims to investigate the potential safety hazards and provide reference for improving the medical waste disposal procedure in SARS-CoV-2 testing laboratory. Our SARS-CoV-2 testing group detected the RNA residue on the surface of medical waste with Droplet Digital PCR, and held a meeting to discuss the risks in the laboratory medical waste disposal process. After effective autoclaving, SARS-CoV-2 contaminated on the surface of medical waste bags was killed, but the average concentration of viral RNA residues was still 0.85 copies/cm2. It would not pose a health risk, but might contaminate the laboratory and affect the test results. When the sterilized medical waste bags were transferred directly by the operators without hand disinfection, re-contamination would happen, which might cause the virus to leak out of the laboratory. Furthermore, we found that sterilization effect monitoring and cooperation among operators were also very important. In summary, we investigated and analyzed the potential safety hazards during the medical waste disposal process in SARS-CoV-2 testing laboratory, and provided reasonable suggestions to ensure the safety of medical waste disposal.

4.
Am J Clin Nutr ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33709113

RESUMO

BACKGROUND: Evidence from epidemiological studies remains inconsistent or limited about the associations of tea consumption with incident diabetes and risk of diabetic complications and death among patients with diabetes. OBJECTIVES: We aimed to investigate the associations of tea consumption with long-term risk of developing type 2 diabetes (T2D) and risks of diabetic complications and death among patients with diabetes. METHODS: This study included 482,425 diabetes-free participants and 30,300 patients with diabetes aged 30-79 y at study enrollment from the China Kadoorie Biobank. Tea consumption information was collected at baseline by interviewer-administered questionnaires. Incidences of diabetes, diabetic complications, and death were identified by linkages to the National Health Insurance system, disease registries, and death registries. Cox proportional hazard regression models were used to estimate HRs and 95% CIs. RESULTS: The mean ± SD age of participants free of diabetes was 51.2 ± 10.5 y and 41% were male. The mean ± SD age of patients with diabetes was 58.2 ± 9.6 y and 39% were male. Of all daily tea consumers, 85.8% preferred green tea. In the diabetes-free population, 17,434 participants developed incident T2D during 11.1 y of follow-up. Compared with participants who never consumed tea in the past year, the HR (95% CI) of T2D for daily consumers was 0.92 (0.88, 0.97). In patients with diabetes, we identified 6572 deaths, 12,677 diabetic macrovascular cases, and 2441 diabetic microvascular cases during follow-up. Compared with patients who never consumed tea in the past year, the HRs (95% CIs) of all-cause mortality and risk of microvascular complications for daily consumers were 0.90 (0.83, 0.97) and 0.88 (0.78, 1.00), respectively. Tea consumption was not associated with risk of macrovascular complications among patients with diabetes. With regard to tea consumed, the inverse associations between daily tea consumption and risks of T2D and all-cause mortality in patients with diabetes were only observed among daily green tea drinkers. CONCLUSIONS: In Chinese adults, daily green tea consumption was associated with a lower risk of incident T2D and a lower risk of all-cause mortality in patients with diabetes, but the associations for other types of tea were less clear. In addition, daily tea consumption was associated with a lower risk of diabetic microvascular complications, but not macrovascular complications.

5.
Int J Colorectal Dis ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33760952

RESUMO

PURPOSE: To investigate the association between KRAS mutation and prognosis in rectal cancer patients with neoadjuvant chemoradiotherapy. METHODS: Literature was searched in the databases including Cochrane Library, EMBASE (Ovid), and MEDLINE (PubMed) from inception to December 16, 2020. The keywords "rectal cancer" or "rectal carcinoma" or "rectal adenocarcinoma" and "KRAS" and "neoadjuvant" were used for preliminary literature retrieval. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated for the KRAS mutation and clinical outcomes including overall survival (OS), disease-free survival (DFS), pathologic complete remission (pCR), downstaging of T stages and tumor stages, as well as improvements in tumor regression grading (TRG). Publication bias was assessed by the funnel plots. RESULTS: A total of 16 articles were included for eligibility. The total number of patients was 3674 cases, with an incidence of KRAS gene mutation of 36.6% (1346/3674). Meta-analysis showed that the pooled OR for KRAS mutation on OS was 1.33 (95%CI: 113-1.56). Consistently, results also indicated that the KRAS mutant was related to the poor DFS (pooled OR=1.55, 95%CI: 1.19-2.02). However, KRAS mutation is not related to the PCR (pooled OR= 0.71, 95%CI: 0.44-1.14), downstaging in T stages (pooled OR= 0.66, 95%CI: 0.42-1.06), tumor stages (pooled OR= 1.18, 95%CI: 0.78-1.78, I2=12.9%), as well as improvement in TRG grades (pooled OR= 0.84, 95%CI: 0.59-1.20). CONCLUSION: KRAS mutation is a predictor for the poor prognosis of neoadjuvant chemoradiotherapy in patients with rectal cancer, but it is not related to the responses of tumors after treatment.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33782052

RESUMO

BACKGROUND: The relationship between educational attainment and ischaemic heart disease (IHD) is limited in evidence in middle-income countries like China. Exploring lifestyle-related mediators, which might be not universal between socioeconomic status and health outcomes in diverse regions, can contribute to interventions targeted at the Chinese to narrow the educational gap in IHD. METHODS: Based on the China Kadoorie Biobank of 489 594 participants aged 30-79 years who did not have heart disease or stroke at baseline, this study examined the association of educational attainment with IHD. Total IHD cases were further divided into acute myocardial infarction (AMI) cases and non-AMI cases. The Cox proportional hazard model was performed to estimate the HRs and 95% CIs for mortality and incidence of IHD. Logistic regression was used to estimate the ORs and 95% CIs for case fatality. RESULTS: During the median follow-up period of 11.1 years, this study documented 45 946 (6668) incident IHD (AMI) cases and 5948 (3689) deaths altogether. Lower educational attainment was associated with increased risk of incident AMI as well as death and fatality of total IHD including its subtypes (ptrend <0.001). Although the risk of incident non-AMI was greater for participants with higher levels of education in the whole population (ptrend <0.001), an inverse association of education with its incidence was found in participants from <50 years age group and rural areas. Smoking and dietary habits were the two most potent mediating factors in the associations of education with mortality and AMI incidence; whereas, physical activity was the major mediating factor for non-AMI incidence in the whole population. DISCUSSION: Interventions targeting unhealthy lifestyles are ideal ways to narrow the educational gap in IHD while solving 'upstream' causes of health behaviours might be the most fundamental ones.

7.
Eur Respir J ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33766948

RESUMO

Lung function is a heritable complex phenotype with obesity being one of its important risk factors. However, the knowledge of their shared genetic basis is limited. Most genome-wide association studies (GWASs) for lung function have been based on European populations, limiting the generalisability across populations. Large-scale lung function GWAS in other populations are lacking.We included 100 285 subjects from China Kadoorie Biobank (CKB). To identify novel loci for lung function, single-trait GWAS were performed on FEV1, FVC, FEV1/FVC in CKB. We then performed genome-wide cross-trait analysis between the lung function and obesity traits (body mass index [BMI], BMI-adjusted waist-to-hip ratio, and BMI-adjusted waist circumference) to investigate the shared genetic effects in CKB. Finally, polygenic risk scores (PRSs) of lung function were developed in CKB and its interaction with BMI's association on lung function were examined. We also conducted cross-trait analysis in parallel with CKB using 457 756 subjects from UK Biobank (UKB) for replication and investigation of ancestry specific effect.We identified 9 genome-wide significant novel loci for FEV1, 6 for FVC and 3 for FEV1/FVC in CKB. FEV1 and FVC showed significant negative genetic correlation with obesity traits in both CKB and UKB. Genetic loci shared between lung function and obesity traits highlighted important pathways, including cell proliferation, embryo and tissue development. Mendelian randomisation analysis suggested significant negative causal effect of BMI on FEV1 and on FVC in both CKB and UKB. Lung function PRSs significantly modified the effect of change-in-BMI on change-in-lung function during an average follow-up of 8 years.This large-scale GWAS of lung function identified novel loci and shared genetic etiology between lung function and obesity. Change-in-BMI might affect change-in-lung function differently according to a subject's polygenic background. These findings may open new avenue for the development of molecular-targeted therapies for obesity and lung function improvement.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33671018

RESUMO

Objective: To assess the incidence and risk factors of hyperuricemia among Chinese adults in 2017-2018. Methods: A total of 2,015,847 adults (mean age 41.2 ± 12.7, 53.1% men) with serum uric acid concentrations assayed on at least two separate days in routine health examinations during 2017-2018 were analyzed. Hyperuricemia was defined as fasting serum urate concentration >420 µmol/L in men and >360 µmol/L in women. The overall and sex-specific incidence rate were stratified according to age, urban population size, geographical region, annual average temperature and certain diseases. Logistic regression analyses were performed to explore risk factors associated with hyperuricemia. Results: 225,240 adults were newly diagnosed with hyperuricemia. The age- and sex-standardized incidence rate per 100 person-years was 11.1 (95%CI: 11.0-11.1) (15.2 for men and 6.80 for women). The risk of hyperuricemia was positively associated with younger age, being male, larger urban population size, higher annual temperature, higher body mass index, lower estimate glomerular filtration rate, hypertension, dyslipidemia and fat liver. Conclusions: The incidence of hyperuricemia was substantial and exhibited a rising trend among younger adults, especially among men. Socioeconomic and geographic variation in incidence were observed. The risk of hyperuricemia was associated with estimate glomerular filtration rate, fat liver and metabolic factors.

9.
PLoS Med ; 18(3): e1003545, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33705376

RESUMO

BACKGROUND: Suicide is a leading cause of death in China and accounts for about one-sixth of all suicides worldwide. The objective of this study was to examine the recent distribution of suicide and risk factors for death by suicide. Identifying underlying risk factors could benefit development of evidence-based prevention and intervention programs. METHODS AND FINDINGS: We conducted a prospective study, the China Kadoorie Biobank, of 512,715 individuals (41% men, mean age 52 years) from 10 (5 urban, 5 rural) areas which are diverse across China in geographic locations, social economic developmental stages, and prevalence of disease patterns. After the baseline measurements of risk factors during 2004 to 2008, participants were followed up for suicide outcomes including suicide and possible suicide deaths. Risk factors, such as sociodemographic factors and physical and mental health status, were assessed by semistructured interviews and self-report questionnaires. Suicide and possible suicide deaths were identified through linkage to the local death registries using ICD-10 codes. We conducted Cox regression to calculate hazard ratios (HRs) for suicide and for possible suicide in sensitivity analyses. During an average follow-up period of 9.9 years, 520 (101 per 100,000) people died from suicide (51.3% male), and 79.8% of them lived in rural areas. Sociodemographic factors associated with increased suicide risk were male gender (adjusted hazard ratios [aHR] = 1.6 [95% CI 1.4 to 2.0], p < 0.001), older age (1.3 [1.2 to 1.5] by each 10-yr increase, p < 0.001), rural residence (2.6 [2.1 to 3.3], p < 0.001), and single status (1.7 [1.4 to 2.2], p < 0.001). Increased hazards were found for family-related stressful life events (aHR = 1.8 [1.2 to 1.9], p < 0.001) and for major physical illnesses (1.5 [1.3 to 1.9], p < 0.001). There were strong associations of suicide with a history of lifetime mental disorders (aHR = 9.6 [5.9 to 15.6], p < 0.001) and lifetime schizophrenia-spectrum disorders (11.0 [7.1 to 17.0], p < 0.001). Links between suicide risk and depressive disorders (aHR = 2.6 [1.4 to 4.8], p = 0.002) and generalized anxiety disorders (2.6 [1.0 to 7.1], p = 0.056) in the last 12 months, and sleep disorders (1.4 [1.2 to 1.7], p < 0.001) in the past month were also found. All HRs were adjusted for sociodemographic factors including gender, age, residence, single status, education, and income. The associations with possible suicide deaths were mostly similar to those with suicide deaths, although there was no clear link between possible suicide deaths and psychiatric factors such as depression and generalized anxiety disorders. A limitation of the study is that there is likely underreporting of mental disorders due to the use of self-report information for some diagnostic categories. CONCLUSIONS: In this study, we observed that a range of sociodemographic, lifestyle, stressful life events, physical, and mental health factors were associated with suicide in China. High-risk groups identified were elderly men in rural settings and individuals with mental disorders. These findings could form the basis of targeted approaches to reduce suicide mortality in China.

10.
Br J Cancer ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33772150

RESUMO

BACKGROUND: Gallstone disease (GSD) is associated with a higher risk of gastrointestinal (GI) cancer. However, it is unclear whether the associations are causal. METHODS: The prospective China Kadoorie Biobank (CKB) recorded 17,598 cases of GI cancer among 510,137 participants without cancer at baseline during 10 years of follow-up. Cox regression was used to estimate hazard ratios (HRs) for specific cancer by GSD status and duration. Mendelian randomisation was conducted to assess the genetic associations of GSD with specific cancer. RESULTS: Overall 6% of participants had symptomatic GSD at baseline. Compared with those without GSD, individuals with symptomatic GSD had adjusted HRs of 1.13 (1.01-1.29) for colorectal, 2.01 (1.78-2.26) for liver, 3.70 (2.88-4.87) for gallbladder, 2.31 (1.78-3.07) for biliary tract, and 1.38 (1.18-1.74) for pancreatic cancer. Compared with participants without GSD, the risks of colorectal, liver, gallbladder, biliary tract, and pancreatic cancer were highest during 0 to <5 years following disease diagnosis. There was evidence of genetic associations of GSD with these cancers, with odds ratios per 1-SD genetic score of 1.08 (1.05-1.11) for colorectal, 1.22 (1.19-1.25) for liver, 1.56 (1.49-1.64) for gallbladder, 1.39 (1.31-1.46) for biliary tract, and 1.16 (1.10-1.22) for pancreatic cancer. When meta-analysing the genetic estimates in CKB and UK Biobank, there was evidence of causal associations of GSD with colon cancer, gallbladder and biliary tract cancer (GBTC), and total GI cancer (RR per 1-SD: 1.05 [0.99-1.11], 2.00 [1.91-2.09], and 1.09 [1.05-1.13]). CONCLUSIONS: GSD was associated with higher risks of several GI cancers, warranting future studies on the underlying mechanisms.

11.
J Bone Miner Res ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33784428

RESUMO

Uncovering additional causal clinical traits and exposure variables is important when studying osteoporosis mechanisms and for the prevention of osteoporosis. Until recently, the causal relationship between anthropometric measurements and osteoporosis had not been fully revealed. In the present study, we utilized several state-of-the-art Mendelian randomization (MR) methods to investigate whether height, body mass index (BMI), waist-to-hip ratio (WHR), hip circumference (HC), and waist circumference (WC) are causally associated with two major characteristics of osteoporosis, bone mineral density (BMD) and fractures. Genomewide significant (p ≤ 5 × 10-8 ) single-nucleotide polymorphisms (SNPs) associated with the five anthropometric variables were obtained from previous large-scale genomewide association studies (GWAS) and were utilized as instrumental variables. Summary-level data of estimated bone mineral density (eBMD) and fractures were obtained from a large-scale UK Biobank GWAS. Of the MR methods utilized, the inverse-variance weighted method was the primary method used for analysis, and the weighted-median, MR-Egger, mode-based estimate, and MR pleiotropy residual sum and outlier methods were utilized for sensitivity analyses. The results of the present study indicated that each increase in height equal to a single standard deviation (SD) was associated with a 9.9% increase in risk of fracture (odds ratio [OR] = 1.099; 95% confidence interval [CI] 1.067-1.133; p = 8.793 × 10-10 ) and a 0.080 SD decrease of estimated bone mineral density (95% CI -0.106-(-0.054); p = 2.322 × 10-9 ). We also found that BMI was causally associated with eBMD (beta = 0.129, 95% CI 0.065-0.194; p = 8.113 × 10-5 ) but not associated with fracture. The WHR adjusted for BMI, HC adjusted for BMI, and WC adjusted for BMI were not found to be related to fracture occurrence or eBMD. In conclusion, the present study provided genetic evidence for certain causal relationships between anthropometric measurements and bone mineral density or fracture risk. © 2021 American Society for Bone and Mineral Research (ASBMR).

12.
Eur J Cancer ; 148: 1-13, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33691262

RESUMO

BACKGROUND: GLS-010, a novel engineered fully human immunoglobin G4 monoclonal antibody, can specially block the PD-1/PD-L1/2 axis and reactivate the antitumor immunity. AIM: This phase Ia/Ib study was carried out to evaluate the safety, recommended phase II dose (R2PD), and primary antitumor effects of GLS-010 in patients with advanced, refractory lymphoma and solid tumors. METHODS: In phase Ia study, patients with refractory solid tumors and lymphoma enrolled and received GLS-010 at a dose of 1, 4, or 10 mg/kg Q2W; 240 mg Q3W or Q2W. The primary objective was to assess the dose-limiting toxicity (DLT). In phase Ib study, doses were expanded in 9 specific tumors to ensure the R2PD and explore the efficacy. Tumor mutation burden level and PD-L1 expression were also assessed with whole-exome sequencing and immunohistochemistry (SP263), respectively. RESULTS: Up to April 18, 2020, a total of 289 patients (n = 24, phase Ia; n = 265, phase Ib) were enrolled. DLT was not observed in phase Ia part. The T1/2, CLss, and Vd were similar among all dose groups and different tumors. The most common treatment-emergent adverse events (TEAEs) were anemia, leukopenia, elevated alanine aminotransaminase/asparate aminotransferase (ALT/AST), and elevated bilirubin. And hypothyroidism was the most common immune-related adverse event (irAE). The incidence of grade ≥3 TEAE was 39.8%, while grade ≥3 irAE was only 4.5%. Based on safety studies, pharmacokinetics/pharmacodynamics, and preclinical data, 240-mg Q2W was recommended as the expansion dose. The overall objective response rate was 23.6%, with 10 patients achieving complete response. Patients with a high PD-L1 expression level (31.3% Versus. 13.7%, p = 0.012) or t-issue tumor mutation burden level (31.3% Versus. 5.6%, p = 0.009) showed a significantly better response. CONCLUSION: GLS-010 showed acceptable safety profile and favorable clinical response. The dose of 240 mg Q2W was an optimal recommended dose as monotherapy.

13.
Int J Cancer ; 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33521941

RESUMO

China has made rapid progress in reducing the incidence of HBV infection in the past three decades, along with a rapidly changing lifestyle and aging population. We aimed to develop and validate an up-to-date liver cancer risk prediction model with routinely available predictors and evaluate its applicability for screening guidance. Using data from the China Kadoorie Biobank, we included 486 285 participants in this analysis. Fifteen risk factors were included in the model. Flexible parametric survival models were used to estimate the 10-year absolute risk of liver cancer. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. A total of 2706 participants occurred liver cancer over the 4 814 320 person-years of follow-up. Excellent discrimination of the model was observed in both development and validation datasets, with c-statistics (95% CI) of 0.80 (0.79-0.81) and 0.80 (0.78-0.82) respectively, as well as excellent calibration of observed and predicted risks. Decision curve analysis revealed that use of the model in selecting participants for screening improved benefit at a threshold of 2% 10-year risk, compared to current guideline of screening all HBsAg carriers. Our model was more sensitive than current guideline for cancer screening (28.17% vs 25.96%). We developed and validated a CKB-PLR (Prediction for Liver cancer Risk Based on the China Kadoorie Biobank Study) model to predict the absolute risk of liver cancer for both HBsAg seropositive and seronegative populations. Application of the model is beneficial for precisely identifying the high-risk groups among the general population.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33596318

RESUMO

BACKGROUND: Observational studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels were associated with favorable serum lipids and related metabolites. However, if such observations reflect causality remains unclear. OBJECTIVE: We aimed to investigate the causal effect of elevated 25(OH)D with the detailed systemic metabolite profile in Chinese adults. METHODS: A total of 225 lipid and other metabolites were quantified in 4,662 individuals in China Kadoorie Biobank. Instrumental variable analyses were performed to test the causal associations of plasma 25(OH)D with the lipids and metabolites. RESULTS: Higher plasma 25(OH)D was related to favorable lipid profiles in observational analyses. The genetic risk score was robustly correlated with observed 25(OH)D (beta[SE]= 3.54 [0.32]; P<1×10 -5, F-statistic =122.3) and explained 8.4% of the variation in 25(OH)D in the Chinese population. For all individual metabolites, the causal estimates were not significant for at the threshold P<5×10 -4 (multiple testing corrected). However, the MR estimate showed that per 1-SD increase in genetically determined 25(OH)D was suggestive associated with decreased levels of cholesterol, lipoprotein particle, phospholipids within very small very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) (P≤0.05, nominal significance). For amino acids, fatty acids, ketone bodies, glycoprotein acetyls, fatty acids and other traits, we did not observe any significant causal association. CONCLUSIONS: The MR analysis of metabolic data based a population-based cohort suggested a potential causal association of plasma 25(OH)D with cholesterol, lipoprotein particle, phospholipids concentrations and total lipids within very small VLDL and IDL. Our findings highlight long-term effect of 25(OH)D levels in maintaining healthy lipid metabolism.

15.
J Nat Prod ; 84(2): 436-443, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33560122

RESUMO

A new axial chiral binaphtoquinone, hypocrellone (1), and a new perylenequinone, hypomycin F (2), were isolated from the stromata of Hypocrella bambusae, together with five known compounds, 3-7. The structures of 1 and 2 were assigned by spectroscopic and HRESIMS data analyses. The axial chirality of 1 was determined by electronic circular dichroism data analysis, and the absolute configurations of 2 and 3 were determined by X-ray crystallography. The axial chirality of 7 was determined by UV-induced photooxidation from 4. Compounds 1, 4, and 5 showed inhibitory activity against pseudotyped SARS-CoV-2 infection in 293T-ACE2 cells with IC50 values of 0.17, 0.038, and 0.12 µM. Compounds 4 and 5 were also active against live SARS-CoV-2 infection with EC50 values of 0.22 and 0.21 µM, respectively. Further cell-cell fusion assays, surface plasmon resonance assays, and molecular docking studies revealed that 4 and 5 could bind with the receptor-binding domain of SARS-CoV-2 S protein to prevent its interaction with human angiotensin-converting enzyme II receptor. Our results revealed that 4 and 5 are potential SARS-CoV-2 entry inhibitors.


Assuntos
Hypocreales/química , Naftoquinonas/farmacologia , Perileno/análogos & derivados , Quinonas/farmacologia , Internalização do Vírus/efeitos dos fármacos , Naftoquinonas/química , Perileno/química , Perileno/farmacologia , Quinonas/química , /fisiologia
16.
Int J Cancer ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33634874

RESUMO

Alcohol drinking is associated with increased risks of several site-specific cancers, but its role in many other cancers remains inconclusive. Evidence is more limited from China, where cancer rates, drinking patterns and alcohol tolerability differ importantly from Western populations. The prospective China Kadoorie Biobank recruited >512 000 adults aged 30 to 79 years from 10 diverse areas during 2004 to 2008, recording alcohol consumption patterns by a standardised questionnaire. Self-reported alcohol consumption was estimated as grams of pure alcohol per week based on beverage type, amount consumed per occasion and drinking frequency. After 10 years of follow-up, 26 961 individuals developed cancer. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) relating alcohol consumption to incidence of site-specific cancers. Overall, 33% (n = 69 734) of men drank alcohol regularly (ie, ≥weekly) at baseline. Among male current regular drinkers, alcohol intake showed positive dose-response associations with risks of cancers in the oesophagus (655 events; HR = 1.98 [95%CI 1.79-2.18], per 280 g/wk), mouth and throat (236; 1.74 [1.48-2.05]), liver (573; 1.52 [1.31-1.76]), colon-rectum (575; 1.19 [1.00-1.43]), gallbladder (107; 1.60 [1.16-2.22]) and lung (1017; 1.25 [1.10-1.42]), similarly among never- and ever-regular smokers. After adjustment for total alcohol intake, there were greater risks of oesophageal cancer in daily drinkers than nondaily drinkers and of liver cancer when drinking without meals. The risks of oesophageal cancer and lung cancer were greater in men reporting flushing after drinking than not. In this male population, alcohol drinking accounted for 7% of cancer cases. Among women, only 2% drank regularly, with no clear associations between alcohol consumption and cancer risk. Among Chinese men, alcohol drinking is associated with increased risks of cancer at multiple sites, with certain drinking patterns (eg, daily, drinking without meals) and low alcohol tolerance further exacerbating the risks.

17.
Elife ; 102021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33558007

RESUMO

Adherence to healthy lifestyles is associated with reduced risk of coronary heart disease (CHD), but uncertainty persists about the underlying lipid pathway. In a case-control study of 4681 participants nested in the prospective China Kadoorie Biobank, 61 lipidomic markers in baseline plasma were measured by targeted nuclear magnetic resonance spectroscopy. Baseline lifestyles included smoking, alcohol consumption, dietary habit, physical activity, and adiposity levels. Genetic instrument was used to mimic the lipid-lowering effect of statins. We found that 35 lipid metabolites showed statistically significant mediation effects in the pathway from healthy lifestyles to CHD reduction, including very low-density lipoprotein (VLDL) particles and their cholesterol, large-sized high-density lipoprotein (HDL) particle and its cholesterol, and triglyceride in almost all lipoprotein subfractions. The statins genetic score was associated with reduced intermediate- and low-density lipoprotein, but weak or no association with VLDL and HDL. Lifestyle interventions and statins may improve different components of the lipid profile.

18.
Environ Pollut ; 273: 116517, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33508629

RESUMO

Nicosulfuron is a sulfonylurea family herbicide which is commonly applied together with the triazine herbicide atrazine in agricultural practice. However, whether nicosulfuron can influence the biodegradation of atrazine is unclear. Therefore, the influence of nicosulfuron on atrazine removal as well as on cell viability and transcription of atrazine chlorohydrolase gene (trzN) in Arthrobacter sp. DNS10 was investigated in this study. Our results demonstrated that 76.0% of atrazine was degraded in the absence of nicosulfuron after 48h of culture, whereas 63.9, 49.1 and 42.6% was degraded in the presence of 1, 5, and 10 mg/L of nicosulfuron, respectively. Nicosulfuron also induced an increase in the level of intracellular reactive oxygen species (ROS), thereby damaging the cell membrane integrity and inhibiting the growth of the strain DNS10. Flow cytometry analysis revealed that the cell viability of strain DNS10 decreased with an increase in nicosulfuron concentration. The transcription of trzN in strain DNS10 exposed to the three described levels of nicosulfuron was 0.99, 0.72 and 0.52 times, respectively, that without nicosulfuron. In brief, nicosulfuron could inhibit atrazine removal efficiency by strain DNS10 by inducing the over-production of ROS which ultimately enhances the population of membrane-damaged cells, as well as reducing cell viability and trzN transcription. The outcomes of the present study provide new insights into the mechanism of nicosulfuron inhibition on atrazine biodegradation by strain DNS10.

19.
Int J Epidemiol ; 50(1): 199-211, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33484129

RESUMO

BACKGROUND: Previous case-control studies have reported positive associations of spicy food consumption with risks of certain gastrointestinal-tract (GI) cancers. However, there is no prospective evidence on such associations, particularly from China, where there are high incidence rates of GI cancers and spicy food is widely consumed. METHODS: The prospective China Kadoorie Biobank study recruited >512 000 adults aged 30-79 years from 10 areas in China during 2004-2008; 2350 oesophageal, 3350 stomach and 3061 colorectal incident cancer cases were recorded by 1 January 2017, after a median of 10.1 years of follow-up. Cox regression yielded adjusted hazard ratios (HRs) for each cancer associated with spicy food intake. RESULTS: Overall, 30% of participants reported daily spicy food consumption at baseline. Spicy food consumption was inversely associated with oesophageal cancer risk, with adjusted HRs of 1.00, 0.88, 0.76, 0.84 and 0.81 for those who never/rarely consumed (reference) and consumed monthly, 1-2 days/week, 3-5 days/week and 6-7 days/week, respectively (ptrend < 0.002). The association remained similar after excluding the first 3 years of follow-up but appeared stronger in participants who did not smoke or drink alcohol regularly (ptrend < 0.0001). The corresponding HRs for stomach cancer were 1.00, 0.97, 0.95, 0.92 and 0.89 (ptrend = 0.04), with the association disappearing after excluding the first 3 years of follow-up. For colorectal cancer, the HRs were 1.00, 1.00, 0.95, 0.87 and 0.90, respectively (ptrend = 0.04) and the inverse association appeared to be restricted to rectal rather than colon cancer (pheterogeneity = 0.004). The types and strength of spice used showed little additional effects on these associations. CONCLUSION: In Chinese adults, higher spicy food consumption was associated with lower risks of certain GI cancers, particularly among individuals who never smoked or drank alcohol regularly.

20.
Clin Infect Dis ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33395488

RESUMO

BACKGROUND: Few safety and effectiveness results have been published regarding the administration of tenofovir alafenamide fumarate (TAF) during pregnancy for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: In this multicenter prospective observational study, pregnant women with HBV DNA levels higher than 200,000 IU/ml who received TAF or tenofovir disoproxil fumarate (TDF) from gestational weeks 24-35 to delivery were 1:1 enrolled and followed until postpartum month 6. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoint was the hepatitis B surface antigen (HBsAg)-positive rate at 7 months for infants. RESULTS: In total, 116 and 116 mothers were enrolled, and 117 and 116 infants were born, in the TAF and TDF groups, respectively. TAF was well tolerated during a mean treatment duration of 11.0 weeks. The most common maternal adverse event was nausea (19.0%). One (0.9%), 3 (2.6%), and 9 (7.8%) mothers had abnormal alanine aminotransferase levels at delivery and at postpartum months 3 and 6, respectively. The TDF group had safety profiles that were comparable to those of the TAF group. No infants had birth defects in either group. The infants' physical and neurological development at birth and at 7 months in the TAF group were comparable with those in the TDF group. The HBsAg positive rate was 0% at 7 months in all 233 infants. CONCLUSION: Antiviral prophylaxis with TAF was determined to be generally safe for both mothers and infants and reduced the MTCT rate to 0%.

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