Artificial sweeteners and risk of incident cardiovascular disease and mortality: evidence from UK Biobank.

BACKGROUND: Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM). METHODS: This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed. RESULTS: In our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI < 30 kg/m2) also tended to be at greater risk of incident CVD from artificial sweetener, although the obesity interaction is not significant. Meanwhile, the CVD risk associated with artificial sweeteners is independent of genetic susceptibility, and no significant interaction exists between genetic susceptibility and artificial sweeteners in terms of either additive or multiplicative effects. Furthermore, our study revealed that the relationship between artificial sweetener intake and overall CVD is significantly mediated, in large part, by prior T2DM (proportion of indirect effect: 70.0%). In specific CVD subtypes (CAD, PAD, and HF), the proportion of indirect effects ranges from 68.2 to 79.9%. CONCLUSIONS: Our findings suggest significant or marginally significant associations between artificial sweeteners and CVD and its subtypes (CAD, PAD, and HF). The associations are independent of genetic predisposition and are mediated primarily by T2DM. Therefore, the large-scale application of artificial sweeteners should be prudent, and the responses of individuals with different characteristics to artificial sweeteners should be better characterized to guide consumers' artificial sweeteners consumption behavior.

Very virulent infectious bursal disease virus infection triggered microscopic changes, apoptosis, and inflammatory cytokines imbalance in chicken spleen and thymus.

AbstractInfectious bursal disease virus (IBDV) can cause a highly contagious disease, resulting in severe damage to the immune system that causes immunosuppression in young chickens. Both spleen and thymus are important immune organs, which play a key role in eliciting protective immune responses. However, the effects of very virulent IBDV (vvIBDV) strain LJ-5 infection on chicken spleen and thymus are still unknown. In the present study, three-week-old specific pathogen-free (SPF) chickens were infected with vvIBDV for one to five days. The vvIBDV infection significantly increased the spleen index and decreased the thymus index.Microscopic analysis indicated necrosis, depletion of the lymphoid cells and complete loss of structural integrity in spleen and thymus. Ultrastructural analysis displayed mitochondrial and nuclear damage, including mitochondrial cristae breaks, and deformation of nuclear membrane in vvIBDV-infected spleen and thymus tissues. Cytokine levels increased in the spleen and thymus after IBDV infection, promoting inflammation and causing an inflammatory imbalance. Moreover, the mRNA expression of apoptosis-related genes was significantly upregulated in the vvIBDV infection group compared to in the control group. Meanwhile, the mRNA expression of mitochondrial dynamics was altered in the spleen and thymus of vvIBDV-infected chickens. These results suggested that vvIBDV infection triggers an imbalance of inflammatory cytokines, and apoptosis in the spleen and thymus, resulting in immune injury in chickens. This study offered basic data for the further study of vvIBDV pathogenesis.

The Relationship Between Insulin Resistance Indicated by Triglyceride and Glucose Index and Left Ventricular Hypertrophy and Decreased Left Ventricular Diastolic Function with Preserved Ejection Fraction.

Aim: The evidence on the association between insulin resistance (IR) and the prevalence or incidence of cardiac dysfunction has been controversial, and the relationship between pre-diabetic IR and cardiac function is lacking. Large sample studies in the Chinese general population are urgently needed to explore the association between IR and the risk of left ventricular hypertrophy (LVH) and decreased left ventricular diastolic function with preserved ejection fraction (LVDFpEF). Methods: Based on a National Health Check-up database in China, we conducted a multicenter cross-sectional retrospective study in 344,420 individuals. Furthermore, at a single center, we performed two retrospective longitudinal studies encompassing 8270 and 5827 individuals to investigate the association between IR and the development of new-onset LVH and LVDFpEF, respectively. The median follow-up duration exceeded 2.5 years. The triglyceride and glucose (TyG) index, known for its high sensitivity in detecting IR, serves as a reliable alternative marker of IR. The logistic and cox proportional hazard regression models were used to determine the relationships. Results: In the cross-sectional study, IR showed a positive association with the prevalence of LVH and decreased LVDFpEF after adjusting for confounders. In the longitudinal cohort, IR was also correlated with the new onset of LVH and decreased LVDFpEF, with hazard ratios (HR) of 1.986 (95% CI: 1.307, 3.017) and 1.386 (95% CI: 1.167, 1.647) in the fourth quartile of TyG levels compared to the lowest quartile, respectively, after adjusting for confounders. The subgroup analysis in non-hypertensive or non-diabetic people and the sensitivity analysis in the population with homeostasis model assessment of insulin resistance (HOMA-IR) further verified the above-mentioned results. Conclusion: IR was associated with LVH and decreased LVDFpEF. Effective management of IR may prevent or delay the development of adverse LVH and decreased LVDFpEF.

Role of microRNAs in host defense against porcine reproductive and respiratory syndrome virus infection: a hidden front line.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most globally devastating viruses threatening the swine industry worldwide. Substantial advancements have been achieved in recent years towards comprehending the pathogenesis of PRRSV infection and the host response, involving both innate and adaptive immune responses. Not only a multitude of host proteins actively participate in intricate interactions with viral proteins, but microRNAs (miRNAs) also play a pivotal role in the host response to PRRSV infection. If a PRRSV-host interaction at the protein level is conceptualized as the front line of the battle between pathogens and host cells, then their fight at the RNA level resembles the hidden front line. miRNAs are endogenous small non-coding RNAs of approximately 20-25 nucleotides (nt) that primarily regulate the degradation or translation inhibition of target genes by binding to the 3'-untranslated regions (UTRs). Insights into the roles played by viral proteins and miRNAs in the host response can enhance our comprehensive understanding of the pathogenesis of PRRSV infection. The intricate interplay between viral proteins and cellular targets during PRRSV infection has been extensively explored. This review predominantly centers on the contemporary understanding of the host response to PRRSV infection at the RNA level, in particular, focusing on the twenty-six miRNAs that affect viral replication and the innate immune response.

The long noncoding RNA loc107053557 acts as a gga-miR-3530-5p sponge to suppress the replication of vvIBDV through regulating STAT1 expression.

Infectious bursal disease virus (IBDV) causes immunosuppression and high mortality in young chickens. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are important regulators during viral infection. However, detailed the regulatory mechanisms of lncRNA-miRNA-mRNA have not yet been described in IBDV infection. Here, we analysed the role of lncRNA53557/gga-miR-3530-5p/STAT1 axis in very virulent IBDV (vvIBDV) infection. Evidently upregulated expression of lncRNA53557 was observed in bursa of Fabricius and DT40 cells. Meanwhile, overexpression of lncRNA53557 promoted STAT1 expression and inhibited vvIBDV replication and vice versa, indicating that the upregulation of lncRNA53557 was part of the host antiviral defence. The subcellular fractionation assay confirmed that lncRNA53557 can be localized in the cytoplasm. Further, dual-luciferase reporter, RNA pulldown, FISH and RT-qPCR assays revealed that lncRNA53557 were directly bound to gga-miR-3530-5p and had a negative regulatory relationship between them. Subsequent mechanistic analysis showed that lncRNA53557 acted as a competing endogenous RNA (ceRNA) of gga-miR-3530-5p to relieve the repressive effect of gga-miR-3530-5p on its target STAT1, as well as Mx1, OASL, and ISG15, thereby suppressing vvIBDV replication. The study reveals that a network of enriched lncRNAs and lncRNA-associated ceRNA is involved in the regulation of IBDV infection, offering new insight into the mechanisms underlying IBDV-host interaction.

Ill-fitting prosthesis is associated with an increased risk of elevated blood pressures.

OBJECTIVE: Previous studies focused on the benefits of adequate prosthodontic treatment, while few studies have investigated the prosthodontic-related risks to health. As a modifiable oral health indicator, the association of ill-fitting prosthesis (IFP) with hypertension has not been fully explored. METHODS: This cross-sectional study involved 158,659 adults in Beijing (2009-2017) receiving intra-oral examinations and blood pressure measurements. Logistic regression models were applied to assess the association of IFP with the prevalence of hypertension, systolic blood pressure (SBP) ≧ 140 mmHg and diastolic blood pressure (DBP) ≧ 90 mmHg, as well as subgroup analyses by different fixed IFP subgroups (according to involved teeth number) and removable IFP subgroup. We further investigated effect modifications among stratified populations. RESULTS: 158,659 individuals were included for analysis, 346 (26.86%) in IFP group and 27,380 (17.40%) in non-IFP group (p < 0.001) were hypertensive. After adjustment of sex, age, obesity, dyslipidaemia, diabetes, hsCRP, family history of CVD, self-reported smoking, self-reported drinking and WC, ORs of hypertension, SBP ≧ 140 mmHg and DBP ≧ 90 mmHg were 1.330 (95% CI: 1.162-1.522), 1.277 (95% CI: 1.098-1.486) and 1.376 (95% CI: 1.186-1.596), respectively (p < 0.05). Furthermore, after full adjustment, the number of involved teeth showed a significant incremental trend with hypertension risk in the population with and without IFP (p for trend <0.001). The IFP-blood pressure associations were more pronounced in females, 18-60 years, non-obese and diabetic participants. CONCLUSION: As a modifiable oral indicator, IFP was significantly associated with a higher risk of hypertension.

Structuring Cu Membrane Electrode for Maximizing Ethylene Yield from CO2 Electroreduction.

Electrocatalytic ethylene (C2H4) evolution from CO2 reduction is an intriguing route to mitigate both the energy and environmental crises; however, to acquire industrially relevant high productivity and selectivity at low energy cost remains to be challenging. Membrane assembly electrode has shown great prospect and tailoring its architecture for maximizing C2H4 yield at minimum voltage with long-term stability becomes critical. Here a freestanding Cu membrane cathode is designed and constructed by electrochemically depositing mesoporous Cu film on Cu foam to simultaneously manage CO2, electron, water, and product transport, which shows an extraordinary C2H4 Faradaic efficiency of 85.6% with a full cell power conversion efficiency of 33% at a current density of 368 mA cm-2, heading the techno-economic viability for electrocatalytic C2H4 production.

Major lipids and lipoprotein levels and risk of blood pressure elevation: a Mendelian Randomisation study.

BACKGROUND: Quantitative nuclear magnetic resonance (NMR) metabolomics techniques provide detailed measurements of lipoprotein particle concentration. Metabolic dysfunction often represents a cluster of conditions, including dyslipidaemia, hypertension, and diabetes, that increase the risk of cardiovascular diseases (CVDs). However, the causal relationship between lipid profiles and blood pressure (BP) remains unclear. We performed a Mendelian Randomisation (MR) study to disentangle and prioritize the potential causal effects of major lipids, lipoprotein particles, and circulating metabolites on BP and pulse pressure (PP). METHODS: We employed single-nucleotide polymorphisms (SNPs) associated with major lipids, lipoprotein particles, and other metabolites from the UK Biobank as instrumental variables. Summary-level data for BP and PP were obtained from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Two-sample MR and MR Bayesian model averaging approaches (MR-BMA) were conducted to analyse and rank causal associations. FINDINGS: Genetically predicted TG was the most likely causal exposure among the major lipids to increase systolic blood pressure (SBP) and diastolic blood pressure (DBP), with marginal inclusion probabilities (MIPs) of 0.993 and 0.847, respectively. Among the majority of lipoproteins and their containing lipids, including major lipids, genetically elevated TG in small high-density lipoproteins (S_HDL_TG) had the strongest association with the increase of SBP and DBP, with MIPs of 0.416 and 0.397, respectively. HDL cholesterol (HDL_C) and low-density lipoprotein cholesterol (LDL_C) were potential causal factors for PP elevation among the major lipids (MIP = 0.927 for HDL_C and MIP = 0.718 for LDL_C). Within the sub-lipoproteins, genetically predicted atherogenic lipoprotein particles (i.e., sub-very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and LDL particles) had the most likely causal impact on increasing PP. INTERPRETATION: This study provides genetic evidence for the causality of lipids on BP indicators. However, the effect size on SBP, DBP, and PP varies depending on the lipids' components and sizes. Understanding this potential relationship may inform the potential benefits of comprehensive management of lipid profiles for BP control. FUNDING: Key Research and Development Program of Hubei Province, Science and Technology Innovation Project of Huanggang Central Hospital of Yangtze University, the Hubei Industrial Technology Research Institute of Heart-Brain Diseases, and the Hubei Provincial Engineering Research Centre of Comprehensive Care for Heart-Brain Diseases.

Al2 O3 -coated BiVO4 Photoanodes for Photoelectrocatalytic Regioselective C-H Activation of Aromatic Amines.

Photoelectrochemistry is becoming an innovative approach to organic synthesis. Generally, the current photoelectrocatalytic organic transformations suffer from limited reaction type, low conversion efficiency and poor stability. Herein, we develop efficient and stable photoelectrode materials using metal oxide protective layer, with a focus on achieving regioselective activation of amine compounds. Notably, our photoelectrochemistry process is implemented under mild reaction conditions and does not involve any directing groups, transition metals or oxidants. The results demonstrate that beyond photocatalysis and electrocatalysis, photoelectrocatalysis exhibits high efficiency, remarkable repeatability and good functional group tolerance, highlighting its great potential for applications.

Association between questionnaire-based and accelerometer-based physical activity and the incidence of chronic kidney disease using data from UK Biobank: a prospective cohort study.

Background: Prior studies on the relationship between chronic kidney disease (CKD) and physical activity (PA) mainly relied on subjective PA data and rarely considered the genetic risk. This study aims to thoroughly investigate this relationship by utilizing both accelerometer-measured and questionnaire-measured PA data. Methods: This prospective cohort study encompasses two cohorts from the UK Biobank. The questionnaire-based cohort involves 448,444 CKD-free participants who completed an International Physical Activity Questionnaire between 2006 and 2010 and had genetic data. PA was categorized into distinct activities: leisure, housework, job-related, and transportation. The accelerometer-based cohort involves 89,296 CKD-free participants who provided a full week of accelerometer-based physical activity data between 2013 and 2015 and had genetic data. PA was classified as light-intensity, moderate-intensity, vigorous-intensity, moderate to vigorous-intensity PA (LPA, MPA, VPA, MVPA), and total PA. Incident CKD was ascertained from linked hospital inpatient and death records. Genetic risk was assessed using polygenic risk scores. Cox proportional hazard models with restricted cubic splines were used for the analysis. Findings: In the questionnaire-based cohort, 18,184 (4.05%) participants developed CKD during 13.6 years of follow-up. Engaging in strenuous sports, other exercises, walking for pleasure, stair climbing, and heavy DIY were associated with a reduced risk of CKD. In the accelerometer-based cohort, 2297 (2.57%) participants developed CKD during 7.9 years of follow-up. Higher levels [highest quartile vs lowest quartile] of MPA (HR 0.639, 95% CI 0.554-0.737), VPA (HR 0.639, 95% CI 0.549-0.745), MVPA (HR 0.630, 95% CI 0.545-0.729), and total PA (HR 0.649, 95% CI 0.563-0.750) were associated with a lower CKD risk. There were significant interactions between MPA and genetic risk on the risk of CKD incidence (P for interaction = 0.025). A linear dose-response relationship was observed between MPA, total PA, and the risk of CKD incidence with no minimal or maximal threshold. These associations are robust in different subgroups and a series of sensitivity analyses. Interpretation: Engaging in multiple types of PA and higher levels of total PA, MPA, VPA, and MVPA may be associated with a lower risk of developing CKD, regardless of genetic risk. This finding holds substantial implications for clinical approaches to CKD prevention and provides evidence to inform future PA guideline development. Funding: Medical Science Advancement Program of Wuhan University, and the National Science Foundation of China.

The association of apolipoprotein B with chronic kidney disease in the Chinese population.

Background: Whether serum apolipoprotein B (ApoB) is a risk factor for the development of Chronic kidney disease (CKD) has not been fully established in the general population. Therefore, our study evaluated the correlation between serum ApoB level and CKD to look for an alternative approach for CKD prevention and treatment in the general population. Methods: There were 146,533 participants in this cross-sectional study. 3,325 participants with more than 2 measurements were enrolled in the retrospective longitudinal study with at least a 3-year follow-up. ApoB was measured by the immunoturbidimetric method in 6 centers. Our study defined CKD as an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2. The Spearman rank correlation analysis and the Random Forest algorithm were applied to rank the importance of variables determining the levels of eGFR. We used the logistic regression model to explain the correlation between serum ApoB and CKD. We used the Cox model to detect the correlation between baseline serum ApoB and the subsequent occurrence of CKD. Results: Based on a cross-sectional study, 66.5% of the participants were males, with a median age of 49 (interquartile range [IQR] 43-55). Compared to the non-CKD group, the CKD group has higher levels of lipid profile and fasting glucose as well as the proportion of hypertension and hyperuricemia. The Spearman rank correlation analysis and the Random Forest algorithm revealed that ApoB has the highest correlation with eGFR decline among lipid profiles. The logistic regression analysis revealed that ApoB had a positive correlation with the prevalence of CKD after fully controlling confounders (odds ratio [OR], 1.07; 95% confidence interval [CI]: 1.02-1.11). Moreover, baseline ApoB level was correlated with a new-onset CKD in the longitudinal cohort after full adjustment for confounding factors (hazard ratio [HR], 1.61; 95% CI: 1.02-2.54). The correlation between ApoB level and the new-onset CKD was consistently observed in all sensitivity analyses. Conclusion: Serum ApoB had the strongest correlation with CKD among all lipid variables. Moreover, high serum ApoB levels might precede the occurrence of CKD, suggesting that monitoring and reducing serum ApoB levels may provide an alternative method to prevent and treat CKD.

The regulatory role of metabolic organ-secreted factors in the nonalcoholic fatty liver disease and cardiovascular disease.

Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disease characterized by an excessive accumulation of fat in the liver, which is becoming a major global health problem, affecting about a quarter of the population. In the past decade, mounting studies have found that 25%-40% of NAFLD patients have cardiovascular disease (CVD), and CVD is one of the leading causes of death in these subjects. However, it has not attracted enough awareness and emphasis from clinicians, and the underlying mechanisms of CVD in NAFLD patients remain unclear. Available research reveals that inflammation, insulin resistance, oxidative stress, and glucose and lipid metabolism disorders play indispensable roles in the pathogenesis of CVD in NAFLD. Notably, emerging evidence indicates that metabolic organ-secreted factors, including hepatokines, adipokines, cytokines, extracellular vesicles, and gut-derived factors, are also involved in the occurrence and development of metabolic disease and CVD. Nevertheless, few studies have focused on the role of metabolic organ-secreted factors in NAFLD and CVD. Therefore, in this review, we summarize the relationship between metabolic organ-secreted factors and NAFLD as well as CVD, which is beneficial for clinicians to comprehensive and detailed understanding of the association between both diseases and strengthen management to improve adverse cardiovascular prognosis and survival.

Long-Term Exposure to Fine Particulate Constituents and Vascular Damage in a Population with Metabolic Abnormality in China.

AIM: To date, PM2.5-associated vascular damage in metabolic abnormalities has remained controversial. We knew little about the vascular damage of PM2.5 constituents. Thus, this study aimed to investigate the relationship between long-term exposure to PM2.5 and its constituents and vascular damage in metabolic abnormalities. METHODS: A total of 124,387 participants with metabolic abnormalities (defined as at least one metabolic disorder, such as obesity, elevated blood pressure, elevated triglyceride level, elevated fasting glucose level, or low HDL cholesterol level) were recruited in this study from 11 representative centers in China between January 2011 and December 2017. PM2.5 and its constituents (black carbon [BC], organic matter [OM], sulfate [SO42-], nitrate [NO3-], and ammonium salts [NH4＋]) were extracted. Elevated brachial-ankle pulse wave velocity (baPWV) (≥ 1,400 cm/s) and declined ankle-brachial index (ABI) (＜0.9) indicated vascular damage. Multivariable logistic regression and Quantile g-Computation models were utilized to explore the impact on outcomes. RESULTS: Of the 124,387 participants (median age, 49 years), 87,870 (70.64%) were men. One-year lag exposure to PM2.5 and its constituents was significantly associated with vascular damage in single pollutant models. The adjusted odds ratios (OR) for each 1-µg/m3 increase in PM2.5 was 1.013 (95% CI, 1.012-1.015) and 1.031 (95% CI, 1.025-1.037) for elevated baPWV and decreased ABI, respectively. PM2.5 constituents were also associated with vascular damage in multi-pollutant models. Among the PM2.5 constituents, BC (47.17%), SO42- (33.59%), and NH4＋ (19.23%) have the highest contribution to elevated baPWV and NO3- (47.89%) and BC (23.50%) to declined ABI. CONCLUSION: Chronic exposure to PM2.5 and PM2.5 constituents was related to vascular damage in the abnormal metabolic population in China. The heterogeneous contribution of different PM2.5 constituents to vessel bed damage is worthy of attention when developing targeted strategies.

Lipoprotein(a) distribution and its association with carotid arteriopathy in the Chinese population.

BACKGROUND AND AIMS: The distribution of lipoprotein(a) [Lp(a)] has not been well-studied in a large population in China. The relationship between Lp(a) and carotid atherosclerosis remains undefined. In this study, we aimed to investigate the distribution of Lp(a) levels and to assess their association with carotid arteriopathy in China. METHODS: In this cross-sectional study, 411,634 adults with Lp(a) measurements from 22 health check-up centers were used to investigate Lp(a) distribution in China. Among participants with Lp(a) data, carotid ultrasound was performed routinely at seven health check-up centers covering 75,305 subjects. Carotid intima-media thickness (cIMT) and carotid plaque were used as surrogate biomarkers of carotid arteriopathy. The multivariate logistic regression model was applied to evaluate the association of increased Lp(a) levels with carotid arteriopathy. RESULTS: The distribution of Lp(a) concentrations was right-skewed, with a median concentration of 10.60 mg/dL. The proportions of Lp(a) levels ≥30 mg/dL and ≥50 mg/dL were 16.75% and 7.10%, respectively. The median Lp(a) level was higher in females individuals in northern China, and increased with age. Spearman's analysis revealed weak correlations between the Lp(a) concentration as a continuous variable and other lipid profiles. The multiple logistic regression analysis showed that participants with Lp(a) levels ≥50 mg/dL had an increased risk of cIMT ≥1.0 mm (OR = 1.138, 95% CI, 1.071-1.208) and carotid plaque (OR = 1.296, 95% CI, 1.219-1.377) compared with those with Lp(a) levels <50 mg/dL. CONCLUSIONS: This is the first study of the Lp(a) distribution in a large population in China. Our findings revealed a positive association between elevated Lp(a) levels (≥50 mg/dL) and increased prevalence of carotid atherosclerosis, which implies an increased risk of cardiovascular disease in the future.

Metabolic dysfunction-associated fatty liver disease increased the risk of subclinical carotid atherosclerosis in China.

Background and aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to substitute NAFLD in 2020. This new term highlights the systematic metabolic disturbances that accompany fatty liver. We evaluated the correlations between MAFLD and subclinical carotid atherosclerosis (SCA) based on a nationwide health examination population in China. Methods: We performed a nationwide cross-sectional population and a Beijing retrospective cohort from 2009 to 2017. SCA was defined as elevated carotid intima-media thickness. The multivariable logistic and Cox models were used to analyze the association between MAFLD and SCA. Results: 153,482 participants were included in the cross-sectional study. MAFLD was significantly associated with SCA in fully adjusted models, with an odds ratio of 1.66; 95% confidence interval (CI): 1.62-1.70. This association was consistent in the cohort, with a hazard ratio (HR) of 1.31. The association between baseline MAFLD and incident SCA increased with hepatic steatosis severity. Subgroup analysis showed an interaction between age and MAFLD, with a higher risk in younger groups (HR:1.67, 95% CI: 1.17-2.40). Conclusion: In this large cross-section and cohort study, MAFLD was significantly associated with the presence and development of SCA. Further, the risk was higher among MAFLD individuals with high hepatic steatosis index and young adults.

Association of the components of ambient fine particulate matter (PM2.5) and chronic kidney disease prevalence in China.

Previous research has implicated PM2.5 as a potential environmental risk factor for CKD, but little is known about the associations between its components and CKD. We conducted a nationwide cross-sectional study using the updated air pollution data in the nationwide population (N = 2,938,653). Using generalized additive models, we assessed the association between long-term exposure to PM2.5 and its components (i.e., black carbon [BC], organic matter [OM], nitrate [NO3-], ammonium [NH4+], sulfate [SO42-]), and CKD prevalence. The air pollution data was estimated using high-resolution and high-quality spatiotemporal datasets of ground-level air pollutants in China. Besides, we adopted a novel quantile-based g-computation approach to assess the effect of a mixture of PM2.5 constituents on CKD prevalence. The average concentration of PM2.5 was 78.67 ± 22.5 µg/m3, which far exceeded WHO AQG. In the fully adjusted generalized additive model, at a 10 km × 10 km spatial resolution, the ORs per IQR increase in previous 1-year average PM2.5 exposures was 1.380 (95%CI: 1.345-1.415), for NH4+ was 1.094 (95%CI: 1.062-1.126), for BC was 1.604 (95%CI: 1.563-1.646), for NO3- was 1.094 (95%CI: 1.060-1.130), for SO42- was 1.239 (95%CI: 1.208-1.272), and for the OM was 1.387 (95%CI: 1.354-1.421), respectively. Subgroup analysis showed females, younger, and healthier were more vulnerable to this effect. In the further exploration of the joint effect of PM2.5 compositions (OR 1.234 [95%CI 1.222-1.246]) per quartile increase in all 5 PM2.5 components, we found that PM2.5SO42- contributed the most. These findings provide important evidence for the positive relationship between long-term exposure to PM2.5 and its chemical constituents and CKD prevalence in a Chinese health check-up population, and identified PM2.5SO42- has the highest contribution to this relationship. This study provides clinical and public health guidance for reducing specific air particle exposure for those at risk of CKD.

The nonlinear relationship between thyroid function parameters and metabolic dysfunction-associated fatty liver disease.

Background: The relationship between thyroid function parameters and metabolic dysfunction-associated fatty liver disease (MAFLD) remains controversial. Additionally, little is known about the relationship between thyroid function parameters and MAFLD in the Chinese population. Methods: We conducted a retrospective cross-sectional study involving 177,540 individuals with thyroid function tests and MAFLD diagnosis from 2010-2018. The association between thyroid function parameters and MAFLD was evaluated on a continuous scale with restricted cubic spline (RCS) models and by the prior-defined centile categories with multivariable-adjusted logistic regression models. Thyroid function parameters included free triiodothyronine (FT3), free tetra-iodothyronine (FT4), and thyroid stimulating hormone (TSH). Additionally, fully adjusted RCS models stratified by sex, age, and location were studied. Results: In the RCS models, the risk of MAFLD increased with higher levels of FT3 when FT3 <5.58pmol/L, while the risk of MAFLD decreased with higher levels of FT3 when FT3 ≥5.58pmol/L (P nonlinearity <0.05). While RCS analysis suggested that the FT4 levels had a negative association with MAFLD (P nonlinearity <0.05), indicating an increase in FT4 levels was associated with a decreased risk of MAFLD. RCS analysis suggested an overall positive association between the concentration of TSH and MAFLD risk (P nonlinearity <0.05). The rising slope was sharper when the TSH concentration was less than 1.79uIU/mL, which indicated the association between TSH and MAFLD risk was tightly interrelated within this range. The multivariable logistic regression showed that populations in the 81st-95th centile had the highest risk of MAFLD among all centiles of FT3/TSH, with the 1st-5th centile as the reference category. Conclusions: Our study suggested nonlinear relationships between thyroid function parameters and MAFLD. Thyroid function parameters could be additional modifiable risk factors apart from the proven risk factors to steer new avenues regarding MAFLD prevention and treatment.

An epulis-like camrelizumab related reactive cutaneous capillary endothelial proliferation (RCCEP) in the oral cavity: A case report.

BACKGROUND: Immunotherapy, especially anti-PD-1 and anti-PD-L1 antibodies, have observably improved the overall survival of patients with advanced solid tumors following the unavoidable immune-related adverse events (irAEs). Camrelizumab is a novel anti-PD-1 agent with the reported most common irAEs of reactive cutaneous capillary endothelial proliferation (RCCEP). Despite it is widely occurred in the skin, oral RCCEP is rarely reported. CASE SUMMARY: A 59-year-old man complained about a painless nodule on left mandibular gingiva for two weeks. He started to inject Camrelizumab because of the recurrence of esophageal squamous cell carcinoma two month ago. An 8 mm lesion was observed on his mucosa. Several disseminated bright purple red papules were then found on his skins. The oral lesion and one lesion on his face was removed by surgery. After the final diagnosis of reactive cutaneous capillary endothelial proliferation was confirmed by histological examination. Other operable lesions on his face were removed by ligation. All the removed lesions had a good prognosis without recurrence within the follow-up visit. CONCLUSION: With the widespread use of Camrelizumab in other solid tumors, the occurrence of oral RCCEP will increase. Surgery and ligation are both effective treatment for RCCEP with a good prognosis.

The rising death burden of atrial fibrillation and flutter in low-income regions and younger populations.

Objective: The aim of the study was to depict the global death burden of atrial fibrillation and/or flutter (AFF) between 1990 and 2019 and predict this burden in the next decade. Methods: We retrieved annual death data on cases and rates of AFF between 1990 and 2019 from the Global Burden of Disease (GBD) Study 2019 and projected the trends for 2020-2029 by developing the Bayesian age-period-cohort model. Results: The global number of deaths from AFF increased from 117,038.00 in 1990 to 315,336.80 in 2019. This number is projected to reach 404,593.40 by 2029. The age-standardized mortality rates (ASMRs) of AFF have increased significantly in low- to middle-sociodemographic index (SDI) regions, which will surpass that in high SDI regions and reach above 4.60 per 100,000 by 2029. Globally, women have a higher ASMR than men, which is largely attributed to disproportionately higher mortality in women than men in lower SDI regions. Notably, AFF-related premature mortality continues to worsen worldwide. A pandemic of high systolic blood pressure and high body mass index (BMI) largely contributes to AFF-associated death. In particular, low- to middle-SDI regions and younger populations are increasingly affected by the rapidly growing current and future risk of high BMI. Conclusion: The global death burden of AFF in low-income countries and younger generations have not been sufficiently controlled in the past and will continue growing in the future, which is largely attributed to metabolic risks, particularly for high BMI. There is an urgent need to implement effective measures to control AFF-related mortality.

The increasing incidence and high body mass index-related burden of gallbladder and biliary diseases-A results from global burden of disease study 2019.

Background: Gallbladder and biliary diseases are common gastrointestinal conditions associated with huge socioeconomic costs and are considered risk factors for cardiovascular diseases and digestive system cancers. The prevalence and incidence of gallbladder and biliary diseases have not received enough attention from 1990 to 2019. Several non-communicable diseases were associated with the incidence of gallbladder and biliary diseases. It is necessary to clarify the change in the incidence and disability burden of gallbladder and biliary diseases worldwide. Methods: Data on high body mass index (BMI)-related disease burden and incidence, years of life lost prematurely, and years lived with disability (YLDs) due to gallbladder and biliary diseases were obtained from the Global Burden of Disease 2019. The estimated annual percentage change was calculated to qualify the gallbladder and biliary disease burden change. Results: The global age-standardized incidence rate has increased from 585.35 per 100,000 (95% UI: 506.05-679.86) in 1990 to 634.32 per 100,000 (95% UI: 540.21-742.93) in 2019. And the increase in incidence was positively correlated with rising high BMI-related summary exposure value. The high BMI-related YLDs of gallbladder and biliary diseases have increased worldwide over time. Globally, the 25-49 age group suffered a rapid rise in incidence and high BMI attributable to the YLDs rate of gallbladder and biliary diseases. Conclusion: The global incidence and high BMI-related YLDs of gallbladder and biliary diseases remain prominent to increase over the past 30 years. Notably, the incidence and high BMI-related YLDs among people aged 25-49 years have rapidly increased over time. Therefore, high BMI should be emphasized in strategic priorities for controlling gallbladder and biliary diseases.