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Association between leisure sedentary behaviors and hypertension risk: A prospective cohort study and two-sample Mendelian randomization analysis in Europeans.
Li, Z, Zhong, W, Gao, J, Zhang, X, Lin, G, Qi, C, Mao, C, Zhou, H
Preventive medicine. 2024;:107915
Abstract
OBJECTIVE This study aimed to investigate the potential causal relationship between domain-specific sedentary behaviors (including television watching, computer use, and driving) and hypertension risk in European populations. METHODS Initially, we conducted a multivariable Cox regression analysis to evaluate the associations between domain-specific sedentary behaviors and the risk of developing hypertension using data from 261,829 hypertension-free participants in the UK Biobank. To validate the findings of observational analysis, we employed two-sample univariable mendelian randomization (UVMR) analysis utilizing summary statistics from genome-wide association study conducted on European populations. We then performed multivariable mendelian randomization (MVMR) analysis to account for the influence of the risk factors for hypertension. RESULTS In this prospective observational analysis, individuals who spent >3 h per day watching television had significantly higher risk of developing hypertension (HR = 1.24, 95% CI: 1.20-1.29, P < 0.001) compared to those who watched television for 0-1 h per day. The mendelian randomization analysis provided consistent evidence for a causal relationship between prolonged television watching time and hypertension risk (OR = 1.45, 95% CI: 1.25-1.69, P < 0.001; all PMVMR < 0.05) in both UVMR and MVMR results. No significant associations were found between computer use, driving behaviors and the risk of hypertension in either the observational or UVMR/MVMR analyses. CONCLUSIONS These findings provide evidence for a causal effect specifically linking higher television watching time to an increased risk of hypertension and indicate the potential effectiveness of reducing television viewing time as a preventive measure to mitigate the risk of hypertension.
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Toxins in Botanical Drugs and Plant-derived Food and Feed - from Science to Regulation: A Workshop Review.
Schrenk, D, Allemang, A, Fahrer, J, Harms, H, Li, X, Lin, G, Mahony, C, Mulder, P, Peijnenburg, A, Pfuhler, S, et al
Planta medica. 2024;(3):219-242
Abstract
In September 2022, the 3rd International Workshop on pyrrolizidine alkaloids (PAs) and related phytotoxins was held on-line, entitled 'Toxins in botanical drugs and plant-derived food and feed - from science to regulation'. The workshop focused on new findings about the occurrence, exposure, toxicity, and risk assessment of PAs. In addition, new scientific results related to the risk assessment of alkenylbenzenes, a distinct class of herbal constituents, were presented. The presence of PAs and alkenylbenzenes in plant-derived food, feed, and herbal medicines has raised health concerns with respect to their acute and chronic toxicity but mainly related to the genotoxic and carcinogenic properties of several congeners. The compounds are natural constituents of a variety of plant families and species widely used in medicinal, food, and feed products. Their individual occurrence, levels, and toxic properties, together with the broad range of congeners present in nature, represent a striking challenge to modern toxicology. This review tries to provide an overview of the current knowledge on these compounds and indicates needs and perspectives for future research.
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Safety of bempedoic acid in patients at high cardiovascular risk and with statin intolerance.
Bays, HE, Bloedon, LT, Lin, G, Powell, HA, Louie, MJ, Nicholls, SJ, Lincoff, AM, Nissen, SE
Journal of clinical lipidology. 2024;(1):e59-e69
Abstract
BACKGROUND Bempedoic acid is an oral adenosine triphosphate citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) blood levels. The Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes study demonstrated that bempedoic acid reduced cardiovascular (CV) risk in patients at high risk for CV events who were unwilling or unable to take guideline-recommended doses of statins. OBJECTIVE To describe detailed safety information from CLEAR Outcomes, including events in the United States (US) prescribing information based on previous phase 3 hyperlipidemia studies. METHODS CLEAR Outcomes was a double-blind trial conducted in 13,970 patients randomized to oral bempedoic acid 180 mg daily or placebo and followed for a median of 3.4 years. RESULTS In patients who received at least one dose (7,001 bempedoic acid, 6,964 placebo), treatment emergent adverse events (AE) occurred in 86.3 % and 85 % of patients, respectively. COVID-19 was the most frequently reported AE in both groups. Changes in serum creatinine, blood urea nitrogen, hemoglobin, aminotransaminases, and uric acid were consistent with the known safety profile of bempedoic acid. Gout or gouty arthritis occurred in 3.2 % of bempedoic acid and 2.2 % of placebo patients. AE associated with tendinopathies, including tendon rupture, occurred in 2 % of patients in both treatment groups. Cholelithiasis occurred in 2.2 % of bempedoic acid and 1.2 % of placebo patients; AE related to gallbladder disease were similar between treatment groups. CONCLUSIONS Bempedoic acid was well-tolerated compared with placebo. Safety data from the long-term CLEAR Outcomes study reinforce the positive benefit-risk profile of bempedoic acid.
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The cost-effectiveness of school-based interventions for chronic diseases: a systematic review.
Lin, G, Werner, K, Alqunaiebet, A, Hamza, MM, Alkanhal, N, Alsukait, RF, Alruwaily, A, Rakic, S, Cetinkaya, V, Herbst, CH, et al
Cost effectiveness and resource allocation : C/E. 2024;(1):26
Abstract
BACKGROUND Chronic diseases, or non-communicable diseases (NCD), are conditions of long duration and often influenced and contributed by complex interactions of several variables, including genetic, physiological, environmental, and behavioral factors. These conditions contribute to death, disability, and subsequent health care costs. Primary and secondary school settings provide an opportunity to deliver relatively low cost and effective interventions to improve public health outcomes. However, there lacks systematic evidence on the cost-effectiveness of these interventions. METHODS We systematically searched four databases (PubMed/Medline, Cochrane, Embase, and Web of Science) for published studies on the cost-effectiveness of chronic-disease interventions in school settings. Studies were eligible for inclusion if they assessed interventions of any chronic or non-communicable disease, were conducted in a school setting, undertook a full cost-effectiveness analysis and were available in English, Spanish, or French. RESULTS Our review identified 1029 articles during our initial search of the databases, and after screening, 33 studies were included in our final analysis. The most used effectiveness outcome measures were summary effectiveness units such as quality-adjusted life years (QALYs) (22 articles; 67%) or disability-adjusted life years (DALYs) (4 articles; 12%). The most common health condition for which an intervention targets is overweight and obesity. Almost all school-based interventions were found to be cost-effective (30 articles; 81%). CONCLUSION Our review found evidence to support a number of cost-effective school-based interventions targeting NCDs focused on vaccination, routine physical activity, and supplement delivery interventions. Conversely, many classroom-based cognitive behavioral therapy for mental health and certain multi-component interventions for obesity were not found to be cost-effective.
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Risk factors for and outcomes of heatstroke-related intracerebral hemorrhage.
Lin, G, Xu, C, Wu, J, Peng, H, Liu, A, He, X, Chen, W, Hou, X, Wen, Q, Pan, Z
Medicine. 2024;(16):e37739
Abstract
Some patients with heatstroke also experience intracerebral hemorrhage (ICH). However, clinical case reports of heatstroke-induced ICH are rare. The risk factors for cerebral hemorrhage after heatstroke remain unknown. The present study evaluated the clinical characteristics and risk factors of patients with heatstroke-related ICH. In this retrospective observational study, we collected data on all ICHs after heatstroke occurred between 2012 and 2022. The characteristics of patients with heatstroke-induced ICH were described. The risk factors for cerebral hemorrhage after heatstroke were examined using logistic regression analysis. In total, 177 patients were included in this study, and 11 patients with ICH secondary to heatstroke were identified. Variables with P values of <.05 in univariate models, comparing the cerebral hemorrhage and control groups, included heatstroke cause, temperature, heart rate, respiratory rate, vasopressor use, mechanical ventilation use, Acute Physiology and Chronic Health Evaluation II, total bilirubin, creatinine, platelet count, prothrombin time, procalcitonin, creatine kinase, disseminated intravascular coagulation (DIC) occurrence, and DIC score. Multivariate logistic regression showed that heatstroke patients with higher DIC scores (odds ratio, 18.402, 95% confidence interval, 1.384-244.763, P = .027) and higher creatine kinase levels (odds ratio, 1.021, 95% confidence interval, 1.002-1.041, P = .033) were at a higher risk of developing ICH. The death rate was higher in the cerebral hemorrhage group than in the control group (P = .042). Heatstroke-related cerebral hemorrhage may be associated with elevated creatinine levels and DIC severity (International Society on Thrombosis and Hemostasis score) after heatstroke, and heatstroke with cerebral hemorrhage may accelerate death.
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Differential outcomes of high-fat diet on age-related rescaling of cochlear frequency place coding.
Zhang, Y, Lin, G, Xue, N, Wang, Y, Du, T, Liu, H, Xiong, W, Shang, W, Wu, H, Song, L
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2023;(10):e23167
Abstract
Auditory frequency coding is place-specific, which depends on the mechanical coupling of the basilar membrane-outer hair cell (OHC)-tectorial membrane network. Prestin-based OHC electromotility improves cochlear frequency selectivity and sensitivity. Cochlear amplification determines the frequency coding wherein discrete sound frequencies find a 'best' place along the cochlear length. Loss of OHC is the leading cause of age-related hearing loss (ARHL) and is the most common cause of sensorineural hearing loss and compromised speech perception. Lipid interaction with Prestin impacts OHC function. It has been established that high-fat diet (HFD) is associated with ARHL. To determine whether genetic background and metabolism preserve cochlear frequency place coding, we examined the effect of HFD in C57BL/6J (B6) and CBA/CaJ (CBA) on ARHL.We found a significant rescuing effect on ARHL in aged B6 HFD cohort. Prestin levels and cell sizes were better maintained in the experimental B6-HFD group. We also found that distortion product otoacoustic emission (DPOAE) group delay measurement was preserved, which suggested stable frequency place coding. In contrast, the response to HFD in the CBA cohort was modest with no appreciable benefit to hearing threshold. Notably, group delay was shortened with age along with the control. In addition, the frequency dependent OHC nonlinear capacitance gradient was most pronounced at young age but decreased with age. Cochlear RNA-seq analysis revealed differential TRPV1 expression and lipid homeostasis. Activation of TRPV1 and downregulation of arachidonic acid led to downregulation of inflammatory response in B6 HFD, which protects the cochlea from ARHL. The genetic background and metabolic state-derived changes in OHC morphology and function collectively contribute to a redefined cochlear frequency place coding and improved age-related pitch perception.
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Effects of a two meals-a-day ketogenic diet on newly diagnosed obese patients with type 2 diabetes mellitus: A retrospective observational study.
Li, S, Yuan, S, Lin, G, Zhang, J
Medicine. 2023;(43):e35753
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Abstract
To investigate the effects of a two-meals-a-day energy-restricted ketogenic diet (KD) on newly diagnosed obese patients with type 2 diabetes mellitus. In total, 60 obese patients with newly diagnosed type 2 diabetes mellitus were divided into 2 groups: 1 group followed a 2-meals-a-day KD and the other group followed a conventional diabetic diet. Changes in weight, blood glucose, blood lipids, insulin resistance, and uric acid levels were observed before and after 2 months of adhering to the respective diets under energy restriction. Both groups showed significant reductions in weight, waist circumference, body mass index, total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, fasting blood glucose, fasting insulin, and glycated hemoglobin (P < .05). The twice-daily KD group showed more significant improvements in these parameters compared to the conventional diabetic diet group. In addition, the 2-meals-a-day KD group showed a slight increase in uric acid levels compared to the conventional diabetic diet control group (P < .05). The 2-meals-a-day KD can significantly improve weight, blood glucose, and lipid control in newly diagnosed obese patients with type 2 diabetes mellitus.
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Transcriptomic profiles reveal the characteristics of oocytes and cumulus cells at GV, MI, and MII in follicles before ovulation.
Hu, Y, Zhang, R, Zhang, S, Ji, Y, Zhou, Q, Leng, L, Meng, F, Gong, F, Lu, G, Lin, G, et al
Journal of ovarian research. 2023;(1):225
Abstract
BACKGROUND The oocyte and its surrounding cumulus cells (CCs) exist as an inseparable entity. The maturation of the oocyte relies on communication between the oocyte and the surrounding CCs. However, oocyte evaluation is primarily based on morphological parameters currently, which offer limited insight into the quality and competence of the oocyte. Here, we conducted transcriptomic profiling of oocytes and their CCs from 47 patients undergoing preimplantation genetic testing for aneuploidy (PGT-A). We aimed to investigate the molecular events occurring between oocytes and CCs at different stages of oocyte maturation (germinal vesicle [GV], metaphase I [MI], and metaphase II [MII]). Our goal is to provide new insights into in vitro oocyte maturation (IVM). RESULTS Our findings indicate that oocyte maturation is a complex and dynamic process and that MI oocytes can be further classified into two distinct subtypes: GV-like-MI oocytes and MII-like-MI oocytes. Human oocytes and cumulus cells at three different stages of maturation were analyzed using RNA-seq, which revealed unique transcriptional machinery, stage-specific genes and pathways, and transcription factor networks that displayed developmental stage-specific expression patterns. We have also identified that both lipid and cholesterol metabolism in cumulus cells is active during the late stage of oocyte maturation. Lipids may serve as a more efficient energy source for oocytes and even embryogenesis. CONCLUSIONS Overall, our study provides a relatively comprehensive overview of the transcriptional characteristics and potential interactions between human oocytes and cumulus cells at various stages of maturation before ovulation. This study may offer novel perspectives on IVM and provide a reliable reference data set for understanding the transcriptional regulation of follicular maturation.
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The effect of periodic ketogenic diet on newly diagnosed overweight or obese patients with type 2 diabetes.
Li, S, Lin, G, Chen, J, Chen, Z, Xu, F, Zhu, F, Zhang, J, Yuan, S
BMC endocrine disorders. 2022;22(1):34
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Plain language summary
Currently, the ketogenic diet is gaining popularity in managing Type 2 diabetes (T2D). Ketogenic diets replace carbohydrates with fat and include limited carbohydrates and adequate protein. This randomised controlled trial evaluated the effects of the 12-week ketogenic diet on sixty overweight or obese T2D patients. Both the ketogenic and control diabetes diet groups achieved significant reductions in weight, body mass index, waist circumference, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, fasting blood glucose, fasting insulin, and HbA1c. However, the ketogenic group showed significantly greater reductions in body mass, blood lipids, and blood glucose than the control group. In the ketogenic diet group, serum uric acid levels were higher than those in the control diet group. It was found that the control diet group adhered to the diet for a longer period than the ketogenic diet group, whose willingness to adhere to the diet long-term was weaker. More robust long-term studies are needed to evaluate the long-term effects of a ketogenic diet. In this study, more patients who followed the ketogenic diet experienced hypoglycaemic events during the first four weeks. Healthcare providers should exercise caution when recommending a short term therapeutic ketogenic diet.
Abstract
BACKGROUND The ketogenic diet (KD) is characterized by fat as a substitute of carbohydrates for the primary energy source. There is a large number of overweight or obese people with type 2 diabetes mellitus (T2DM), while this study aims to observe periodic ketogenic diet for effect on overweight or obese patients newly diagnosed as T2DM. METHODS A total of 60 overweight or obese patients newly diagnosed as T2DM were randomized into two groups: KD group, which was given ketogenic diet, and control group, which was given routine diet for diabetes, 30 cases in each group. Both dietary patterns lasted 12 weeks, and during the period, the blood glucose, blood lipid, body weight, insulin, and uric acid before and after intervention, as well as the significance for relevant changes, were observed. RESULTS For both groups, the weight, BMI(body mass index), Waist, TG (triglyceride), TC(cholesterol), LDL (low-density lipoprotein cholesterol), HDL (high-density lipoprotein cholesterol), FBG (fasting glucose), FINS (fasting insulin), HbA1c (glycosylated hemoglobin) were decreased after intervention (P < 0.05), while the decrease rates in the KD group was more significant than the control group. However, UA(serum uric acid) in the KD group showed an upward trend, while in the control group was not changed significantly (P > 0.05).The willingness to adhere to the ketogenic diet over the long term was weaker than to the routine diet for diabetes. CONCLUSION Among the overweight or obese patients newly diagnosed as type 2 diabetes mellitus, periodic ketogenic diet can not only control the body weight, but also control blood glucose and lipid, but long-term persistence is difficult.
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Lipid-Lowering Efficacy of the Capsaicin in Patients With Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Jiang, Z, Qu, H, Lin, G, Shi, D, Chen, K, Gao, Z
Frontiers in nutrition. 2022;:812294
Abstract
BACKGROUND Patients with metabolic syndrome (MetS) have increased cardiovascular risk. Capsaicin (CAP) has been shown to reduce lipids, but efficacy for patients with MetS is unknown. METHODS A systematic review was performed according to PRISMA guidelines, to compare the effects of CAP against a placebo. Differences in the weight mean difference (WMD) with 95% confidence intervals (95% CI) were then pooled using a random effects model. RESULTS Nine randomized controlled trials including 461 patients were identified in the overall analysis. CAP significantly decreased total cholesterol (TC) (WMD = -0.48, 95% CI: -0.63 to -0.34, I 2= 0.00%) and low-density lipoprotein cholesterol (LDL-C) (WMD = -0.23, 95% CI: -0.45 to -0.02, I 2 = 68.27%) among patients with MetS. No significant effects of CAP were found on triglycerides (TG) or high-density lipoprotein cholesterol (HDL-C) (WMD = -0.40, 95% CI: -1.50 to 0.71, I 2 = 98.32%; WMD = -0.08, 95% CI: -0.21 to 0.04, I 2 = 86.06%). Subgroup analyses indicated that sex and intervention period were sources of heterogeneity. The results revealed that CAP decreased TG levels in women (WMD = -0.59, 95% CI: -1.07 to -0.10) and intervention period <12 weeks (WMD = -0.65; 95% CI: -1.10 to -0.20). And there was no potential publication bias according to funnel plot, Begg' test and Egger regression test. CONCLUSIONS CAP supplementation is a promising approach to decreasing TC and LCL-C levels in patients with MetS. However, short-term (<12 weeks) use of CAP in women may also reduce TG levels. SYSTEMATIC REVIEW REGISTRATION Identifier: CRD42021228032.