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The association between serum 25-hydroxy vitamin D (25(OH)D) concentrations and mortality remains unclear among patients with metabolic dysfunction-associated fatty liver disease (MAFLD) or non-alcoholic fatty liver disease (NAFLD).To evaluate the association between serum 25(OH)D concentrations and mortality among individuals with MAFLD/NAFLD.The study included 4651 individuals with fatty liver disease (FLD) (3964 had MAFLD and 3968 had NAFLD) from the Third National Health and Nutrition Examination Survey. Fatty liver disease was identified by ultrasonographic detection of hepatic steatosis. Mortality was ascertained by linkage to the National Death Index up to 31 December 2019. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment of potential confounders.Of 4651 individuals with FLD, 3427 individuals (69.7%) had both MAFLD and NAFLD. During median follow-ups of 25.8 and 26.1 years, we identified 1809 and 1665 deaths among 3964 participants with MAFLD and 3968 participants with NAFLD, respectively. Compared with participants with serum 25(OH)D concentrations ≤30.0 nmol/L, the multivariable-adjusted HR and 95% CI of all-cause mortality were 0.62 (0.43, 0.89) for participants with MAFLD having serum 25(OH)D75.0 nmol/L (P-trend = 0.001), and 0.63 (0.42, 0.95) for participants with NAFLD having serum 25(OH)D75.0 nmol/L (P-trend = 0.002). A nonlinearly inverse association was observed between serum 25(OH)D concentrations and all-cause mortality among participants with MAFLD (Poverall0.001; Pnonlinear = 0.003) or NAFLD (Poverall0.001; Pnonlinear = 0.009), with a threshold effect at around 50.0 nmol/L. The inverse association was stronger among participants with MAFLD aged60 years (P-interaction = 0.001).This study suggested a nonlinearly inverse association between serum 25(OH)D concentrations and all-cause mortality among patients with MAFLD/NAFLD, with a threshold effect at around 50.0 nmol/L of serum 25(OH)D.

Cancer has contributed to an increasing proportion of diabetes-related deaths, while lifestyle management is the cornerstone of both diabetes care and cancer prevention. We aimed to evaluate the associations of combined healthy lifestyles with total and site-specific cancer risks among individuals with diabetes.We included 92,239 individuals with diabetes but without cancer at baseline from five population-based cohorts in the USA (National Health and Nutrition Examination Survey and National Institutes of Health [NIH]-AARP Diet and Health Study), the UK (UK Biobank study) and China (Dongfeng-Tongji cohort and Kailuan study). Healthy lifestyle scores (range 0-5) were constructed based on current nonsmoking, low-to-moderate alcohol drinking, adequate physical activity, healthy diet and optimal bodyweight. Cox regressions were used to calculate HRs for cancer morbidity and mortality, adjusting for sociodemographic, medical and diabetes-related factors.During 376,354 person-years of follow-up from UK Biobank and the two Chinese cohorts, 3229 incident cancer cases were documented, and 6682 cancer deaths were documented during 1,089,987 person-years of follow-up in the five cohorts. The pooled multivariable-adjusted HRs (95% CIs) comparing participants with 4-5 vs 0-1 healthy lifestyle factors were 0.73 (0.61, 0.88) for incident cancer and 0.55 (0.46, 0.67) for cancer mortality, and ranged between 0.41 and 0.63 for oesophagus, lung, liver, colorectum, breast and kidney cancers. Findings remained consistent across different cohorts and subgroups.This international cohort study found that adherence to combined healthy lifestyles was associated with lower risks of total cancer morbidity and mortality as well as several subtypes (oesophagus, lung, liver, colorectum, breast and kidney cancers) among individuals with diabetes.

Background socioeconomic inequity in mortality and life expectancy remains inconclusive in low- and middle-income countries, and to what extent the associations are mediated or modified by lifestyles remains debatable. Methods we included 21,133 adults from China Health and Nutrition Survey (1991–2011) and constructed three parameters to reflect participants’ overall individual- (synthesising income, education and occupation) and area-level (urbanisation index) socioeconomic status (SES) and lifestyles (counting the number of smoking, physical inactivity and unhealthy diet and bodyweight). HRs for mortality and life expectancy were estimated by time-dependent Cox model and life table method, respectively. Results during a median follow-up of 15.2 years, 1,352 deaths were recorded. HRs (95% CIs) for mortality comparing low versus high individual- and area-level SES were 2.38 (1.75–3.24) and 1.84 (1.51–2.24), respectively, corresponding to 5.7 (2.7–8.6) and 5.0 (3.6–6.3) life-year lost at age 50. Lifestyles explained ≤11.5% of socioeconomic disparity in mortality. Higher lifestyle risk scores were associated with higher mortality across all socioeconomic groups. HR (95% CI) for mortality comparing adults with low individual-level SES and 3–4 lifestyle risk factors versus those with high SES and 0–1 lifestyle risk factors was 7.06 (3.47–14.36), corresponding to 19.1 (2.6–35.7) life-year lost at age 50. Conclusion this is the first nationwide cohort study reporting that disadvantaged SES was associated with higher mortality and shorter life expectancy in China, which was slightly mediated by lifestyles. Risk lifestyles were related to higher mortality across all socioeconomic groups, and those with risk lifestyles and disadvantaged SES had much higher mortality risks.

There is now a relatively large body of evidence suggesting a relationship between dysfunction of myelin and oligodendrocytes and the etiology of several neuropsychiatric disorders, including depression and schizophrenia, and also suggesting that ultrasound methods may alleviate some of the symptoms of depression. We have applied low-intensity pulsed ultrasound (LIPUS) to the brains of mice treated with the demyelinating drug cuprizone, a drug that has been used as the basis for a rodent model relevant to a number of psychiatric and neurologic disorders including depression, schizophrenia, and multiple sclerosis. Prior to conducting the studies in mice, preliminary studies were carried out on the effects of LIPUS in vitro in neuron-like SH-SY5Y cells and primary glial cells. In subsequent studies in mice, female C57BL/6 mice were restrained in plastic tubes for 20 min daily with the ultrasound transducer near the end of the tube directly above the mouse's head. LIPUS was used at an intensity of 25 mW/cm2 once daily for 22 days in control mice and in mice undergoing daily repetitive restraint stress (RRS). Behavioral or neurochemical studies were done on the mice or the brain tissue obtained from them. The studies in vitro indicated that LIPUS stimulation at an intensity of 15 mW/cm2 delivered for 5 min daily for 3 days in an enclosed sterile cell culture plate in an incubator increased the viability of SH-SY5Y and primary glial cells. In the studies in mice, LIPUS elevated levels of doublecortin, a marker for neurogenesis, in the cortex compared to levels in the RRS mice and caused a trend in elevation of brain levels of brain-derived neurotrophic factor in the hippocampus relative to control levels. LIPUS also increased sucrose preference (a measure of the attenuation of anhedonia, a common symptom of several psychiatric disorders) in the RRS model in mice. The ability of LIPUS administered daily to rescue damaged myelin and oligodendrocytes was studied in mice treated chronically with cuprizone for 35 days. LIPUS increased cortex and corpus callosum levels of myelin basic protein, a protein marker for mature oligodendrocytes, and neural/glial antigen 2, a protein marker for oligodendrocyte precursor cells, relative to levels in the cuprizone + sham animals. These results of this exploratory study suggest that future comprehensive time-related studies with LIPUS on brain chemistry and behavior related to neuropsychiatric disorders are warranted. Exploratory Study on Neurochemical Effects of Low Intensity Pulsed Ultrasound in Brains of Mice. Upper part of figure: LIPUS device and in-vitro cell experimental set-up. The center image is the LIPUS generating box; the image in the upper left shows the cell experiment set-up; the image in the upper right shows a zoomed-in sketch for the cell experiment; the image in the lower left shows the set-up of repetitive restraint stress (RRS) with a mouse; the image in the lower middle shows the set-up of LIPUS treatment of a mouse; the image in the lower right shows a zoomed-in sketch for the LIPUS treatment of a mouse.

Sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) intakes have been reported to be associated with mortality; however, conclusions have been inconsistent. This review synthesized the evidence on the associations of SSB and ASB intakes with mortality from all causes, cardiovascular disease (CVD), and cancer among all populations (including general, diseased, or occupational populations, etc.). PubMed, EMBASE, Web of Science, Cochrane Library, ProQuest, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searched up to March 2020. Fifteen studies including 17 cohorts were included in meta-analyses. Each serving (12 fluid ounces or 355 mL) increase in daily SSB consumption was associated with higher risks of all-cause (HR: 1.08; 95% CI: 1.04, 1.12; 11 cohorts with 965,851 participants) and CVD (HR: 1.08; 95% CI: 1.04, 1.12; 13 cohorts with 898,005 participants) mortality. The associations of ASB intakes with all-cause and CVD mortality were J-shaped, and HRs (95% CI) across different doses (0, 1, 1.5, 2, and 2.5 servings/d) were 1.00, 1.01 (0.99, 1.03), 1.04 (1.02, 1.07), 1.08 (1.05, 1.11), and 1.13 (1.09, 1.18) for all-cause mortality and 1.00, 1.01 (0.96, 1.07), 1.07 (1.01, 1.13), 1.15 (1.08, 1.23), and 1.25 (1.14, 1.37) for CVD mortality. No significant association was found for cancer mortality. According to the NutriGrade scoring system, the quality of evidence on the associations of SSB intakes with all-cause and CVD mortality was high, and the quality of evidence on other associations was low to moderate. In summary, higher SSB and ASB intakes were associated with higher risks of all-cause mortality and CVD mortality. Given the limited evidence, future studies should further investigate the association between ASB intakes and cause-specific mortality.

ImportanceImproved understanding of trends in the proportion of individuals with metabolically healthy obesity (MHO) may facilitate stratification and management of obesity and inform policy efforts.ObjectivesTo characterize trends in the prevalence of MHO among US adults with obesity, overall and by sociodemographic subgroups.Design, Setting, and ParticipantsThis survey study included 20 430 adult participants from 10 National Health and Nutrition Examination Survey (NHANES) cycles between 1999-2000 and 2017-2018. The NHANES is a series of cross-sectional and nationally representative surveys of the US population conducted continuously in 2-year cycles. Data were analyzed from November 2021 to August 2022.ExposuresNational Health and Nutrition Examination Survey cycles from 1999-2000 to 2017-2018.Main Outcomes and MeasuresMetabolically healthy obesity was defined as a body mass index of 30.0 (calculated as weight in kilograms divided by height in meters squared) without any metabolic disorders in blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), or triglycerides based on established cutoffs. Trends in the age-standardized prevalence of MHO were estimated using logistic regression analysis.ResultsThis study included 20 430 participants. Their weighted mean (SE) age was 47.1 (0.2) years; 50.8% were women, and 68.8% self-reported their race and ethnicity as non-Hispanic White. The age-standardized prevalence (95% CI) of MHO increased from 3.2% (2.6%-3.8%) in the 1999-2002 cycles to 6.6% (5.3%-7.9%) in the 2015-2018 cycles (P < .001 for trend). There were 7386 adults with obesity. Their weighted mean (SE) age was 48.0 (0.3) years, and 53.5% were women. The age-standardized proportion (95% CI) of MHO among these 7386 adults increased from 10.6% (8.8%-12.5%) in the 1999-2002 cycles to 15.0% (12.4%-17.6%) in the 2015-2018 cycles (P = .02 for trend). Substantial increases in the proportion of MHO were observed for adults aged 60 years or older, men, non-Hispanic White individuals, and those with higher income, private insurance, or class I obesity. In addition, there were significant decreases in the age-standardized prevalence (95% CI) of elevated triglycerides (from 44.9% [40.9%-48.9%] to 29.0% [25.7%-32.4%]; P < .001 for trend) and reduced HDL-C (from 51.1% [47.6%-54.6%] to 39.6% [36.3%-43.0%]; P = .006 for trend). There was also a significant increase in elevated FPG (from 49.7% [95% CI, 46.3%-53.0%] to 58.0% [54.8%-61.3%]; P < .001 for trend) but no significant change in elevated blood pressure (from 57.3% [53.9%-60.7%] to 54.0% [50.9%-57.1%]; P = .28 for trend).Conclusions and RelevanceThe findings of this cross-sectional study suggest that the age-standardized proportion of MHO increased among US adults from 1999 to 2018, but differences in trends existed across sociodemographic subgroups. Effective strategies are needed to improve metabolic health status and prevent obesity-related complications in adults with obesity.

Titanium (Ti) and Ti alloys are widely used biomaterials, but they lack osteogenic capability for rapid bone integration. To improve osseointegration of Ti implants, TiO2 nanotubes were prepared using the anodizing oxidation technique, and strontium (Sr) combined with icariin (ICA) was loaded on TiO2 nanotube coatings. Cell adhesion and proliferation of MC3T3-E1 cells, alkaline phosphatase (ALP) activity, mineralization of extracellular matrix, and bone formation around titanium implants in ovariectomized rats, were examined separately. The results showed that compared with pure Ti, TiO2 and Sr-loaded TiO2 coatings, the coatings loaded with both Sr and ICA showed better effect on cell adhesion and proliferation, higher ALP activity and more red-stained mineralized nodules. Furthermore, more bone was formed around implants loaded with both Sr and ICA in osteoporotic rats. Therefore, coating with Sr and ICA is valuable for clinical application to strengthen the osseointegration of titanium implants, especially in osteoporotic patients.

OBJECTIVE Atrial fibrillation (AF) frequently occurs in patients with type 2 diabetes (T2D); however, the longitudinal associations of new-onset AF with risks of adverse health outcomes in patients with T2D remain unclear. In this study, we aimed to determine the associations of new-onset AF with subsequent risks of atherosclerotic cardiovascular disease (ASCVD), heart failure, chronic kidney disease (CKD), and mortality among patients with T2D. RESEARCH DESIGN AND METHODS We included 16,551 adults with T2D, who were free of cardiovascular disease (CVD) and CKD at recruitment from the UK Biobank study. Time-varying Cox regression models were used to assess the associations of incident AF with subsequent risks of incident ASCVD, heart failure, CKD, and mortality. RESULTS Among the patients with T2D, 1,394 developed AF and 15,157 remained free of AF during the follow-up. Over median follow-up of 10.7–11.0 years, we documented 2,872 cases of ASCVD, 852 heart failure, and 1,548 CKD and 1,776 total death (409 CVD deaths). Among patients with T2D, those with incident AF had higher risk of ASCVD (hazard ratio [HR] 1.85; 95% CI 1.59–2.16), heart failure (HR 4.40; 95% CI 3.67–5.28), CKD (HR 1.68; 95% CI 1.41–2.01), all-cause mortality (HR 2.91; 95% CI 2.53–3.34), and CVD mortality (HR 3.75; 95% CI 2.93–4.80) compared with those without incident AF. CONCLUSIONS Patients with T2D who developed AF had significantly increased risks of developing subsequent adverse cardiovascular events, CKD, and mortality. Our data underscore the importance of strategies of AF prevention to reduce macro- and microvascular complications in patients with T2D.

To prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes.Patients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health-AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non-current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020.A total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses.The international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes.

Accurate surveillance of diabetes is crucial for establishing relevant policies of diabetes prevention and control. Previous studies estimated the trends in diabetes among adults in the U.S.; however, many did not consider results of the oral glucose tolerance test (OGTT) (1), and those studies that included the OGTT results reported a higher prevalence of undiagnosed diabetes (2). Capitalizing on the OGTT data since 2005–2006 in the National Health and Nutrition Examination Survey (NHANES), we assessed the trends in diagnosed and undiagnosed diabetes among adults in the U.S. from 2005 to 2016. NHANES is a cross-sectional survey with a stratified, multistage probability design to assess the health status of the noninstitutionalized civilian population in the U.S. (3). A household interview was conducted to collect health-related information including demographic characteristics and medical history. A subset of participants was randomly selected to provide a fasting blood sample and take an OGTT at the mobile examination center. Sample weights were constructed to account for nonresponse and oversampling. The survey was approved by the research ethics review board of the National Center for Health Statistics. Written informed consent was obtained from each participant. This investigation included nonpregnant participants aged 20 years or older, recruited from 2005–2006 to 2015–2016 cycles, who had information on self-reported diagnosed diabetes or laboratory results of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and 2-h plasma glucose (2-h PG). We calibrated plasma glucose measurements to …

Various bone substitutes have been applied in sinus augmentation (SA) to overcome insufficient bone height at the posterior maxilla region caused by pneumatized sinus and severe alveolar bone resorption after teeth loss. However, their effectiveness in SA needs to be further elucidated. In this study, strontium-doped brushite (Sr-DCPD), a new bone substitute, together with bovine-derived hydroxyapatite (bHA) and synthetic hydroxyapatite (sHA) was used in rabbit maxillary SA with simultaneous implant installation. The sinus space-keeping capacity, resorption rate, osteoconductivity, and mechanical properties of regenerated bone, were evaluated by micro-computed tomography (CT), histological analysis, and mechanical testing. Sr-DCPD exhibited the best osteoconductivity and new bone formation (

Colorectal cancer (CRC) is the leading cause of cancer lethality worldwide, inflicting a heavy burden on society. Unfortunately, the complex nature of CRC pathogenesis renders current chemotherapies and targeted therapies unsatisfactory. Conventional medicine generally concentrates on the killing of tumor cells by inducing cell death or activation of the immune system, which often leads to adverse effects or relapsed chemoresistance. On the contrary, Chinese medicine theory pays attention to the patients’ whole inner system and helps to shrink the tumor with consideration of overall body condition. Since numerous Chinese herbal medicines (CHM) are used as food, the edible CHMs as diet resources therapy represent a promising alternative for the treatment of CRC. Recent research has made remarkable progress toward the therapeutic effects of edible CHM for CRC. In this review, experimental CRC models, the holistic characteristic of edible CHM, and recent research on the efficacy and mechanisms of edible CHM as anti-CRC agents are discussed, as well as the safety aspect of edible CHM.

Background and aims Cohort studies found blood lipid traits were associated with the risk of chronic kidney disease (CKD). We aimed to investigate whether blood lipid traits were causally associated with the risk of CKD in the Chinese. Methods 15,244 participants without kidney disease and cancer from the Dongfeng-Tongji cohort were recruited in 2008–2010 in Shiyan City, China. Blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglyceride (TG) levels were measured. 5251 participants had genotype data and were included in the Mendelian randomization analysis. Incident CKD was defined as estimated glomerular filtration rate Results Various blood lipid traits were associated with CKD risk, and the odds ratios (95% confidence intervals) for incident CKD comparing the extreme quartiles were 1.45 (1.24–1.70) for TG, 1.26 (1.08–1.46) for nonHDL-c, 2.21 (1.91–2.57) for TC:HDL-c ratio, 2.14 (1.83–2.51) for TG:HDL-c ratio, and 0.47 (0.40–0.55) for HDL-c. The Mendelian randomization analysis indicated that 1 mmol/l increase in the genetic predicted blood TG level was associated with a 5% (95% confidence interval, 0–10%) higher risk of CKD. Conclusions Although blood levels of HDL-c, TG, nonHDL-c, TC:HDL-c ratio, and TG:HDL-c ratio were observed to be associated with incident CKD, the Mendelian randomization analysis provided genetic evidence to support causal relation for blood TG level only.

A new aromatic glycoside (1) and a new natural product, neolignan (2), along with twenty-three known compounds (3-25), were isolated from the thorns of Gleditsia sinensis. According to the spectros...

BackgroundCancer poses a huge disease burden, which could be reduced by adopting healthy lifestyles mainly composed of healthy diet, body weight, physical activity, limited alcohol consumption, and avoidance of smoking. However, no systematic review has summarised the relations of combined lifestyle factors with cancer morbidity and mortality.MethodsEMBASE and PubMed were searched up to April 2019. Cohort studies investigating the association of combined lifestyle factors with risks of incident cancer and cancer mortality were selected. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity and publication bias tests were conducted.ResultsThe HRs (95% CIs) comparing individuals with the healthiest versus the least healthy lifestyles were 0.71 (0.66–0.76; 16 studies with 1.9 million participants) for incident cancer and 0.48 (0.42–0.54; 30 studies with 1.8 million participants) for cancer mortality. Adopting the healthiest lifestyles was also associated with 17 to 58% lower risks of bladder, breast, colon, endometrial, oesophageal, kidney, liver, lung, rectal, and gastric cancer. The relations were largely consistent and significant among participants with different characteristics in the subgroup analyses.ConclusionsAdopting healthy lifestyles is associated with substantial risk reduction in cancer morbidity and mortality, and thus should be given priority for cancer prevention.

This research was designed to detect the function of low-density lipoprotein receptor (LDLR)-related protein 8 (LRP8) in breast cancer (BC). Our results revealed that LRP8 was highly expressed in BC tissues and cell lines compared with human normal breast tissues. The poor prognosis of patients with BC was associated with the up-regulation of LRP8 while inversely connected with overexpression of miR-1262. Functionally, LRP8 depletion in BC cells impaired the proliferative, clonogenic, invasive, and migratory capabilities, which was consistent with the effects of upregulated miR-1262. Bioinformatics prediction and luciferase reporter assay confirmed that miR-1262 was an upstream factor for LRP8 and negatively regulated the expression of LRP8. Further experiments illustrated that the co-transfection of miR-1262 antamir and si-LRP8 could significantly suppress the promoting impacts caused by the transfection of miR-1262 antamir alone. These findings highlighted that LRP8 accelerated the BC development by contributing cellular aggressiveness, which was modulated by miR-1262.

Limited studies had investigated the potential benefits of workplace-based hypertension management programs on long-term blood pressure (BP) control and health outcomes. This study used the propensity score matching to examine the effectiveness of a workplace-based hypertension management program on BP control and risks of major adverse cardiovascular events and all-cause mortality. Within the Kailuan study, a workplace-based hypertension management program was initiated in 2009 among men with hypertension, which included regular BP measuring (twice a month), free antihypertensive medications, and individualized health consultation. Participants were followed until loss to follow-up, death, or December 31, 2019. Among 17 724 male hypertensives aged 18 to 60 years, 6400 participated in the program. The propensity score matching yielded 6120 participants in the management group and 6120 participants in the control group. Both systolic and diastolic BPs were significantly lower in the management group than in the control group over follow-up, and the mean between-group difference at the 10th year was −7.83 (95% CI, −9.06 to −6.62) mm Hg for systolic BP and −4.72 (95% CI, −5.46 to −3.97) mm Hg for diastolic BP. Participants in the program were more likely to achieve BP control (odds ratio, 1.70 [95% CI, 1.41–2.06]) and had significantly lower risks of major adverse cardiovascular events (hazard ratio, 0.83 [95% CI, 0.72–0.94]) and all-cause mortality (hazard ratio, 0.71 [95% CI, 0.58–0.86]), compared with those who were not in the program. A workplace-based hypertension management program was related to reduced BP levels and lower risks of major adverse cardiovascular events and mortality in Chinese men with hypertension.

Background To investigate the role of plasma metanephrines (MN) and normetanephrines (NMN), in predicting cardiovascular events in essential hypertensive patients. Methods This was a retrospective analysis of 688 hospitalized patients diagnosed with essential hypertension at the Beijing Anzhen hospital from October 2016 to August 2018, with a median (interquartile range) follow-up time of 24 (20–29) months. The primary endpoint was defined as all-cause death and/or readmission for cardiovascular or cerebrovascular events. Patients were divided into event (n = 57) and nonevent (n = 631) groups. High-performance liquid chromatography–tandem mass spectrometry was used to determine plasma MN and NMN levels. According to the cutoff value of plasma NMN from receiver operating characteristic analysis, patients were further divided into NMN ≤125.75 ng/l and NMN >125.75 ng/l groups. The effects of NMN on the prognosis of hypertensive patients were evaluated using Kaplan–Meier curves and multivariate Cox regression analysis. Results The plasma NMN levels of the event group were higher than those of the nonevent group [110.0 (74.0–135.0) vs. 88.5 (62.0–119.5) ng/l, P = 0.004]. The incidence of the primary endpoint event in NMN ≤125.75 ng/l and NMN >125.75 ng/l groups was 6.0% and 15.8%, respectively. Kaplan–Meier analysis showed that patients with higher baseline NMN levels were more likely to experience adverse events (P < 0.001). Cox regression analysis showed that patients in NMN >125.75 ng/l group had over twofold higher risk of the primary endpoint event than those in NMN ≤125.75 ng/l group (HR = 2.11, 95% CI 1.15–3.84, P = 0.015). Conclusions Elevated plasma NMN levels are associated with higher risk of cardiovascular and cerebrovascular events in patients with essential hypertension.

China has the largest number of adults with diabetes. Although multiple metabolic risk factors (MRFs) are implicated in the development of diabetes, it remains unclear how they progress during the development of diabetes among Chinese. We examined trajectories of multiple MRFs among Chinese and identified the critical period when drastic changes occurred during the development of diabetes.This prospective cohort study included participants since 2006-2007 in the Kailuan study. People attended biennial examinations until 2017 with additions of new participants at each examination cycle. The time when a participant first completed the examination was served as the baseline. A total of 122,659 participants without prevalent diabetes at baseline and with complete follow-up data were included. MRFs were collected via biennial physical examinations and laboratory measures. Incident diabetes cases were identified via biennial fasting glucose tests and self-reported physician-diagnosis.During up to 12 years of follow-up, 14,922 incident diabetes cases were identified. Compared with participants who did not develop diabetes, those who developed diabetes had more adverse levels of most MRFs at baseline and during follow-up. Abrupt increases in multiple MRFs (including fasting glucose, surrogate insulin resistance indicators, lipids, systolic blood pressure, pulse pressure, heart rate, alanine aminotransferase, and C-reactive protein) were observed 3 years before the diagnosis of diabetes.We identified 3 years before diabetes diagnosis as a critical period when multiple MRFs experienced drastic changes. This would have implications for early monitoring and timely prevention for individuals who experience sudden adverse progression of multiple MRFs.

A healthy lifestyle has been widely recommended for the prevention and management of type 2 diabetes. However, no systematic review has summarised the relationship between combined lifestyle factors (including, but not limited to, smoking, alcohol drinking, physical activity, diet and being overweight or obese) and incident type 2 diabetes and risk of health outcomes among diabetic individuals. EMBASE and PubMed were searched up to April 2019 without language restrictions. References included in articles in relevant publications were also screened. Cohort studies investigating the combined associations of at least three lifestyle factors with incident type 2 diabetes and health outcomes among diabetic individuals were included. Reviewers were paired and independently screened studies, extracted data and evaluated study quality. Random-effects models were used to calculate summary HRs. Heterogeneity and publication bias tests were also conducted. Compared with participants considered to have the least-healthy lifestyle, those with the healthiest lifestyle had a 75% lower risk of incident diabetes (HR 0.25 [95% CI 0.18, 0.35]; 14 studies with approximately 1 million participants). The associations were largely consistent and significant among individuals from different socioeconomic backgrounds and baseline characteristics. Among individuals with type 2 diabetes (10 studies with 34,385 participants), the HRs (95% CIs) were 0.44 (0.33, 0.60) for all-cause death, 0.51 (0.30, 0.86) for cardiovascular death, 0.69 (0.47, 1.00) for cancer death and 0.48 (0.37, 0.63) for incident cardiovascular disease when comparing the healthiest lifestyle with the least-healthy lifestyle. Adoption of a healthy lifestyle is associated with substantial risk reduction in type 2 diabetes and long-term adverse outcomes among diabetic individuals. Tackling multiple risk factors, instead of concentrating on one certain lifestyle factor, should be the cornerstone for reducing the global burden of type 2 diabetes.

Purpose: We conducted a meta-analysis to systematically assess the prospective association between vitamin K and cardiovascular disease (CVD) events and all-cause mortality.Methods: We searched Pubmed and EMBASE through January 2019 for prospective studies that reported the association of vitamin K (assessed by dietary intake or circulating concentration) with CVD events (including total CVD, CVD mortality, total coronary heart disease [CHD], fatal CHD, nonfatal myocardial infarction [MI] and stroke) and all-cause mortality. Multivariable-adjusted hazard ratios (HRs) comparing top versus bottom tertiles of vitamin K were combined using random-effects meta-analysis.Results: Twenty-one articles were included with 222,592 participants. A significant association was found between dietary phylloquinone and total CHD (pooled HR: 0.92; 95% CI: 0.84, 0.99; I2 = 0%; 4 studies), as well as menaquinone and total CHD (0.70; 95% CI: 0.53, 0.93; I2 = 32.1%; 2 studies). No significant association was observed between dietary vitamin K and all-cause mortality, CVD mortality or stroke. Elevated plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K deficiency, was associated with an increased risk of all-cause mortality (1.84; 95% CI: 1.48, 2.28; I2 = 16.8%; 5 studies) and CVD mortality (1.96; 95% CI: 1.47, 2.61; I2 = 0%; 2 studies). No significant association was observed between circulating total osteocalcin and all-cause mortality or total CVD.Conclusions:Our findings showed that higher dietary vitamin K consumption was associated with a moderately lower risk of CHD, and higher plasma dp-ucMGP concentration, but not total circulating osteocalcin, was associated with increased risks of all-cause and CVD mortality. However, causal relations cannot be established because of limited number of available studies, and larger prospective studies and randomized clinical trials are needed to validate the findings.

Limited studies have investigated the association between statin use and progression of arterial stiffness, a key player in the pathophysiology of cardiovascular disease.To examine the association between statin use and progression of arterial stiffness in Chinese adults with high atherosclerotic risk measured by brachial-ankle pulse wave velocity (baPWV).This retrospective cohort study enrolled 5105 adults with high atherosclerotic risk from the Kailuan General Hospital from 2010 to 2020. Data were analyzed from February 2021 to April 2022.Statin use information was retrieved from electronic medical records from 2010 to 2020, and statin users were those who have been prescribed any statin medications at least 6 months before baPWV measurements. Statin users were 1:1 matched with non-statin users by propensity score method.Progression of baPWV was assessed using the absolute difference between baseline and follow-up baPWV, divided by the follow-up time in years. Multivariable linear regression models were used to estimate the association between statin use and arterial stiffness.Among 5105 adults with assessment of baPWV (mean [SD] age: 60.8 [9.7] years; 3842 [75.3%] men and 1263 [24.7%] women), 1310 statin users were matched with 1310 non-statin users (mean [SD] age, 63.2 [9.3] years). Compared with non-statin users, statin users were associated with significantly lower baPWV at baseline (difference: -33.6 cm/s; 95% CI, -62.1 to -5.1 cm/s). Among 1502 adults with repeated assessment of baPWV, 410 statin users were matched with 410 non-statin users (mean [SD] age, 62.9 [9.2] years). Compared with non-statin users, statin users had significantly slower progression of baPWV (difference, -23.3 cm/s per year; 95% CI, -40.6 to -6.0 cm/s per year) during a mean (SD) follow-up of 4.8 (2.7) years. A significantly slower progression of baPWV was observed in continuous statin users (difference, -24.2 cm/s per year; 95% CI, -42.2 to -6.3 cm/s per year) and high adherent users (difference, -39.7 cm/s per year; 95% CI, -66.9 to -12.4 cm/s per year), but not in discontinued users (difference, -17.3 cm/s per year; 95% CI, -52.4 to 17.8 cm/s per year) and low adherent users (difference, -17.9 cm/s per year; 95% CI, -36.5 to 0.7 cm/s per year), compared with non-statin users.In this cohort study, statin use was associated with slower progression of arterial stiffness in Chinese adults with high atherosclerotic risk.

IMPORTANCE: Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed. OBJECTIVE: To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines. DESIGN, SETTING, AND PARTICIPANTS: Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively. INTERVENTIONS: Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)–only control (n = 13 458); they received 2 intramuscular injections 21 days apart. MAIN OUTCOMES AND MEASURES: The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose. RESULTS: Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase–polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P

Background We aimed to assess the safety and immunogenicity of an inactivated vaccine against COVID-19 in Chinese adults aged ≥18 years. Methods This is an ongoing randomized, double-blind, placebo-controlled, phase 1/2 clinical trial among healthy adults aged ≥18 years in Henan Province, China. Participants (n = 336 in 18–59 age group and n = 336 in ≥60 age group) were enrolled between April 12 and May 17 2020, and were equally randomized to receive vaccine or placebo (aluminum hydroxide adjuvant) in a three-dose schedule of 2·5, 5, or 10 µg on days 0, 28, and 56. Another 448 adults aged 18–59 years were equally allocated to four groups (a one-dose schedule of 10 µg, and two-dose schedules of 5 µg on days 0 and 14/21/28) and received vaccine or placebo (ratio 3:1 within each group). The primary outcomes were 7-day post-injection adverse reactions and neutralizing antibody titres on days 28 and 90 after the whole-course vaccination. Trial registration: www.chictr.org.cn #ChiCTR2000031809. Findings The 7-day adverse reactions occurred in 4·8% to 32·1% of the participants in various groups, and most adverse reactions were mild, transient, and self-limiting. Twenty participants reported 68 serious adverse events which were judged to be unrelated to the vaccine. The 90-day post-injection geometric mean titres of neutralizing antibody ranged between 87 (95% CI: 61–125) and 129 (99–169) for three-dose schedule among younger and older adults; 20 (14–27), 53 (38–75), and 44 (32–61) in 5 µg days 0 and 14/21/28 groups, respectively, and 7 (6–9) in one-dose 10 µg group. There were no detectable antibody responses in all placebo groups. Interpretation The inactivated vaccine against COVID-19 was well tolerated and immunogenic in both younger and older adults. The two-dose schedule of 5 µg on days 0 and 21/28 and three-dose schedules on days 0, 28, and 56 could be further evaluated for long-term safety and efficacy in the phase 3 trials. Funding The study was funded by the National Program on Key Research Project of China (2020YFC0842100) and Major Science and Technology Project of the National New Drug Development of China (2018ZX09734-004).

Background Modular prosthesis fracture, especially distal femoral fracture, is a rare complication of total hip arthroplasty (THA). However, it is catastrophic, and may have a serious impact on the patients. A distal femoral prosthesis fracture in a patient with developmental dysplasia of the hip (DDH) with nonunion at the subtrochanteric osteotomy site has not yet been reported in any literature. This report presents the first such case, with a purpose of analyzing the causes of modular prosthesis fractures and nonunion of the osteotomy area, so as to provide orthopedic surgeons with experience and lessons. Case presentation We report the case of a 52-year-old woman with the distal femoral prosthesis fracture after THA and subtrochanteric osteotomy for Crowe type IV DDH. The patient had severe pain in the left thigh and her activities were limited. Plain radiographs revealed fracture of the left distal femoral prosthesis and nonunion in the subtrochanteric osteotomy region of the left femur. After a revision of the THA, the patient’s symptoms were resolved. Conclusions A prosthesis fracture combined with nonunion at the subtrochanteric osteotomy site is a rare complication. Modular THA combined with a subtrochanteric osteotomy in the treatment of Crowe type IV DDH should reduce the damage to blood supply and avoid further nonunion of the osteotomy area, which may otherwise lead to modular prosthesis fractures. A detailed preoperative plan and suitable rehabilitation program may help minimize the occurrence of subtrochanteric osteotomy nonunion and reduce complications, including femoral prosthesis fractures, in patients with DDH.

Objective To examine whether overall lifestyles mediate associations of socioeconomic status (SES) with mortality and incident cardiovascular disease (CVD) and the extent of interaction or joint relations of lifestyles and SES with health outcomes. Design Population based cohort study. Setting US National Health and Nutrition Examination Survey (US NHANES, 1988-94 and 1999-2014) and UK Biobank. Participants 44 462 US adults aged 20 years or older and 399 537 UK adults aged 37-73 years. Exposures SES was derived by latent class analysis using family income, occupation or employment status, education level, and health insurance (US NHANES only), and three levels (low, medium, and high) were defined according to item response probabilities. A healthy lifestyle score was constructed using information on never smoking, no heavy alcohol consumption (women ≤1 drink/day; men ≤2 drinks/day; one drink contains 14 g of ethanol in the US and 8 g in the UK), top third of physical activity, and higher dietary quality. Main outcome measures All cause mortality was the primary outcome in both studies, and CVD mortality and morbidity in UK Biobank, which were obtained through linkage to registries. Results US NHANES documented 8906 deaths over a mean follow-up of 11.2 years, and UK Biobank documented 22 309 deaths and 6903 incident CVD cases over a mean follow-up of 8.8-11.0 years. Among adults of low SES, age adjusted risk of death was 22.5 (95% confidence interval 21.7 to 23.3) and 7.4 (7.3 to 7.6) per 1000 person years in US NHANES and UK Biobank, respectively, and age adjusted risk of CVD was 2.5 (2.4 to 2.6) per 1000 person years in UK Biobank. The corresponding risks among adults of high SES were 11.4 (10.6 to 12.1), 3.3 (3.1 to 3.5), and 1.4 (1.3 to 1.5) per 1000 person years. Compared with adults of high SES, those of low SES had higher risks of all cause mortality (hazard ratio 2.13, 95% confidence interval 1.90 to 2.38 in US NHANES; 1.96, 1.87 to 2.06 in UK Biobank), CVD mortality (2.25, 2.00 to 2.53), and incident CVD (1.65, 1.52 to 1.79) in UK Biobank, and the proportions mediated by lifestyle were 12.3% (10.7% to 13.9%), 4.0% (3.5% to 4.4%), 3.0% (2.5% to 3.6%), and 3.7% (3.1% to 4.5%), respectively. No significant interaction was observed between lifestyle and SES in US NHANES, whereas associations between lifestyle and outcomes were stronger among those of low SES in UK Biobank. Compared with adults of high SES and three or four healthy lifestyle factors, those with low SES and no or one healthy lifestyle factor had higher risks of all cause mortality (3.53, 3.01 to 4.14 in US NHANES; 2.65, 2.39 to 2.94 in UK Biobank), CVD mortality (2.65, 2.09 to 3.38), and incident CVD (2.09, 1.78 to 2.46) in UK Biobank. Conclusions Unhealthy lifestyles mediated a small proportion of the socioeconomic inequity in health in both US and UK adults; therefore, healthy lifestyle promotion alone might not substantially reduce the socioeconomic inequity in health, and other measures tackling social determinants of health are warranted. Nevertheless, healthy lifestyles were associated with lower mortality and CVD risk in different SES subgroups, supporting an important role of healthy lifestyles in reducing disease burden.

Titanium (Ti) and Ti alloys are widely used biomaterials, but they lack osteogenic capability for rapid bone integration. To improve osseointegration of Ti implants, TiO

Background In order to reveal the mechanism of fruit color changes in plum, two common plum cultivars Changli84 (Ch84, red fruit) and Dahuangganhe (D, yellow fruit) in Northeast China were selected as plant materials. Transcriptome sequencing and metabonomic analyzing were performed at three different developmental stages: young fruit stage, colour-change stage, and maturation stage. Results “Flavonoid biosynthesis” was significantly enriched in the KEGG analysis. Some DEGs in “Flavonoid biosynthesis” pathway had an opposite trend between the two cultivars, such as CHS , DFR and FLS . Also, transcriptional control of MBW (MYB–bHLH–WD) protein complexes showed a close relationship with plum fruit color, especially the expression of MYBs and bHLHs . In the current study, procyanidin B1 and B2 had the highest level at young fruit stage in Ch84 and the content of procyanidin B2 decreased sharply at the color change stage. Conversely, the content of cyanidin increased with the growth of fruit and reached the peak at the maturation stage. Conclusion The content of procyanidin B1 and B2 in plums at young fruit stage might be the leading factors of the matured fruit color. At the maturation stage, the cyanidin produced by procyanidins keeps the color of the fruit red. Correspondingly, genes in “flavonoid biosynthesis” pathway play critical roles in regulating the accumulation of anthocyanin in plum.

IntroductionDiabetic kidney disease (DKD) is a prevalent and costly complication of diabetes with limited therapeutic options, being the leading cause of end-stage kidney disease in most developed regions. Recent big data studies showed that add-on Chinese medicine (CM) led to a reduced risk of end-stage kidney disease and mortality among patients with chronic kidney disease (CKD) and diabetes. Astragalus, commonly known as huang-qi, is the most prescribed CM or used dietary herb in China for diabetes and DKD. In vivo and in vitro studies showed that astragalus ameliorated podocyte apoptosis, foot process effacement, mesangial expansion, glomerulosclerosis and interstitial fibrosis. Nevertheless, the clinical effect of astragalus remains uncharacterised. This pragmatic clinical trial aims to evaluate the effectiveness of add-on astragalus in patients with type 2 diabetes, stage 2–3 CKD and macroalbuminuria, and to identify related response predictors.Methods and analysisThis is an add-on, assessor-blind, parallel, pragmatic randomised controlled clinical trial. 118 patients diagnosed with DKD will be recruited and randomised 1:1 to receive 48 weeks of add-on astragalus or standard medical care. Primary endpoints are the changes in estimated glomerular filtration rate and urine albumin-to-creatinine ratio between baseline and treatment endpoint. Secondary endpoints include adverse events, fasting blood glucose, glycated haemoglobin, lipids and other biomarkers. Adverse events are monitored through self-complete questionnaire and clinical visits. Outcomes will be analysed by regression models. Subgroup and sensitivity analyses will be conducted for different epidemiological subgroups and statistical analyses. Enrolment started in July 2018.Ethics and disseminationThis study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West/East/Kowloon Central clusters (UW 16-553/HKEC-2019-026/REC (KC/KE)-19-0049/ER-4). We will report the findings in medical journals and conferences. The dataset will be available on reasonable request.Trial registration numberNCT03535935

Colorectal cancer ranks among the most common cancers. 5-Fluorouracil (5-FU) based first-line chemotherapy for colorectal cancer treatment often leads to chemoresistance and gastrointestinal mucositis.This study aimed to find potential therapeutic agents from herbal medicine with anti-colorectal cancer and anti-mucositis activities.Chinese medicine theory, network pharmacology analyses, and antioxidant activity coupled with liquid chromatography tandem mass spectrometry analyses were used to identify potential bioactive compounds. HT-29 human colorectal cancer cell culture and xenograft tumor models were employed to study anti-colorectal cancer efficacy. Lipopolysaccharide-induced RAW 264.7 and 5-FU treated Dark Agouti rats were used to evaluate anti-inflammatory and anti-mucositis activities. Histological staining, immunofluorescence imaging, western blots, and flow cytometric analyses were employed to explore the underlying mechanisms.Both Chinese medicine theory and network pharmacology analyses indicated pomegranate peels as a potential anti-colorectal cancer and anti-mucositis agent. Antioxidant activity coupled with liquid chromatography tandem mass spectrometry analyses revealed granatin B and punicalagin as the most potent antioxidant compounds in pomegranate peels. Granatin B and punicalagin demonstrated superior anti-colorectal cancer activities in both cell culture and xenograft tumor models. Granatin B and punicalagin also exhibited strong anti-inflammatory activities in lipopolysaccharide-induced RAW264.7 cells and anti-mucositis activities in 5-FU-treated rats. Mechanistic studies revealed that granatin B and punicalagin induced reactive oxygen species-mediated S-phase cell cycle arrest and apoptosis in HT-29 cells. Moreover, these compounds sensitized HT-29 cells to 5-FU-induced cell death and S-phase cell cycle arrest.We report that granatin B and punicalagin exhibit superior anti-colorectal cancer and anti-mucositis activities. To the best of our knowledge, these results are novel and suggest that utilizing phenols from herbal medicine, such as granatin B and punicalagin, to target reactive oxygen species may be an innovative therapy to treat colorectal cancer and intestinal mucositis.