Identification of potential key lipid metabolism-related genes involved in tubular injury in diabetic kidney disease by bioinformatics analysis.

AIMS: Accumulating evidences indicate that abnormalities in tubular lipid metabolism play a crucial role in the development of diabetic kidney disease (DKD). We aim to identify novel lipid metabolism-related genes associated with tubular injury in DKD by utilizing bioinformatics approaches. METHODS: Differentially expressed genes (DEGs) between control and DKD tubular tissue samples were screened from the Gene Expression Omnibus (GEO) database, and then were intersected with lipid metabolism-related genes. Hub genes were further determined by combined weighted gene correlation network analysis (WGCNA) and protein-protein interaction (PPI) network. We performed enrichment analysis, immune analysis, clustering analysis, and constructed networks between hub genes and miRNAs, transcription factors and small molecule drugs. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic efficacy of hub genes. We validated the relationships between hub genes and DKD with external datasets and our own clinical samples. RESULTS: There were 5 of 37 lipid metabolism-related DEGs identified as hub genes. Enrichment analysis demonstrated that lipid metabolism-related DEGs were enriched in pathways such as peroxisome proliferator-activated receptors (PPAR) signaling and pyruvate metabolism. Hub genes had potential regulatory relationships with a variety of miRNAs, transcription factors and small molecule drugs, and had high diagnostic efficacy. Immune infiltration analysis revealed that 13 immune cells were altered in DKD, and hub genes exhibited significant correlations with a variety of immune cells. Through clustering analysis, DKD patients could be classified into 3 immune subtypes and 2 lipid metabolism subtypes, respectively. The tubular expression of hub genes in DKD was further verified by other external datasets, and immunohistochemistry (IHC) staining showed that except ACACB, the other 4 hub genes (LPL, AHR, ME1 and ALOX5) exhibited the same results as the bioinformatics analysis. CONCLUSION: Our study identified several key lipid metabolism-related genes (LPL, AHR, ME1 and ALOX5) that might be involved in tubular injury in DKD, which provide new insights and perspectives for exploring the pathogenesis and potential therapeutic targets of DKD.

Association of circulating long-chain free fatty acids and incident diabetes risk among normoglycemic Chinese adults: a prospective nested case-control study.

BACKGROUND: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVES: Our study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS: This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS: The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18-26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS: These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

A cross-sectional study of the association between breastfeeding history and overweight/obesity in postmenopausal women.

OBJECTIVES: This study endeavors to augment comprehension of the association between breastfeeding and maternal weight within Asian populations. METHODS: Data were obtained from the comprehensive 2011 research titled "Risk Evaluation of Cancers in Chinese Diabetic Individuals (REACTION): a longitudinal analysis," focusing specifically on postmenopausal women residing in the metropolitan precincts of Guiyang. It presents a cross-sectional study involving 5,987 parous postmenopausal women, aged 60.1 ± 6.9 years, who underwent assessments of body mass index and waist-to-height ratio. The probability of excessive weight or obesity was evaluated in relation to the aggregate duration of breastfeeding, using single-factor and multivariate logistic regression analyses. RESULTS: Following multiple adjustments for different confounders, the odds ratios (ORs) demonstrated that women who had borne a single child and breastfed for more than 12 months exhibited an increased prevalence of excessive weight (body mass index ≥24 kg/m 2 ) in contrast to those who abstained from breastfeeding (model I: OR, 1.481; 95% confidence interval, 1.124-1.952; P = 0.005; model II: OR, 1.471; 95% confidence interval, 1.113-1.944; P = 0.007). Conversely, among the subset of women who had given birth to two or more children, no noteworthy associations emerged between breastfeeding duration and the propensity for excessive weight or obesity (all models). CONCLUSION: In the Asian population, the duration of breastfeeding does not appear to be necessarily linked to the prevalence of overweight or obesity in postmenopausal women.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

AIMS: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. MATERIALS AND METHODS: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. RESULTS: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

The Association between Educational Attainment and the Risk of Nonalcoholic Fatty Liver Disease among Chinese Adults: Findings from the REACTION Study.

Background/Aims: : Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: : A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: : Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions: : In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults.

Studies have found a U-shaped relationship between sleep duration and chronic kidney disease (CKD) risk, but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD. We included 104 538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study, with self-reported time of daily-life behavior. Using isotemporal substitution models, we found that substituting 1 h of sleeping with sitting, walking, or moderate-to-vigorous physical activity was associated with a lower CKD prevalence. Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population. In stratified analysis, a lower CKD prevalence related to substitution toward physical activity was found in long sleepers. More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes, and they benefited from other behavior substitutions toward a more active way. The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys, in which the pernicious link with oversleep could be reversed by time reallocation to physical activity. The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.

Early adulthood weight change, midlife "Life's essential 8" health status and risk of cardiometabolic diseases: a chinese nationwide cohort study.

BACKGROUND: The association between weight change during early adulthood and cardiometabolic diseases remains uncertain in Chinese population. Whether the association varies with comprehensive cardiovascular health (CVH) in midlife assessed by "Life's Essential 8" has not been characterized. We aim to examine the associations of early adulthood weight change and midlife "Life's Essential 8" CVH status with cardiometabolic outcomes in a Chinese cohort. METHODS: The study participants were from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study. This analysis included 72,610 middle-aged and older participants followed for a median of 3.6 years. At baseline, the participants recalled body weight at age 20 and 40 years, and we calculated change in weight and BMI between 20 and 40 years of age. Health behaviors information in "Life's Essential 8" was collected by questionnaire, and health factors were measured in the study center. During follow-up, we ascertained incident cardiovascular events based on medical records, and diagnosed incident diabetes according to the American Diabetes Association 2010 criteria. RESULTS: 72,610 study participants were included with a mean age of 56.0 ± 8.8 years and 29% of them were males. Weight gain of more than 10 kg between 20 and 40 years of age was associated with 22% increased risk of incident cardiovascular events (HR: 1.22; 95%CI: 1.04-1.43) and 38% increased risk of diabetes (HR: 1.38; 95%CI: 1.25-1.53) compared to stable weight. Besides, the association of weight gain more than 10 kg in early adulthood with cardiometabolic risk was even stronger in those with low CVH score in midlife (HR: 2.44; 95%CI: 2.01-2.97 for incident cardiovascular events; HR: 2.20; 95%CI: 1.90-2.55 for incident diabetes) or with few ideal cardiovascular health metrics in midlife. CONCLUSIONS: Our study indicated that weight gain in early adulthood was associated with significantly increased risk of cardiometabolic diseases. And the association could be stronger in those with poor CVH profiles in midlife. These findings confirmed the significance of weight management during early adulthood and suggested that individuals who experienced substantial weight gain in early life should be encouraged to maintain good CVH status in Chinese population.

The Incidence of Metabolic Syndrome in People Over 40 Years Old with Normal Fasting Plasma Glucose and the Predictive Cutoff Value of Effective Fasting Plasma Glucose for Metabolic Syndrome in Guiyang.

Purpose: This study aimed to investigate the incidence of metabolic syndrome (MS) in people over 40 years of age with normal blood glucose levels in Guiyang's urban areas and determine the effective glycemic cutoff value for predicting MS. Methods: The analysis was based on anthropometric and biochemical indicators of residents aged 40 years or older in urban areas of Guiyang City who participated in the "Epidemiological Study of Tumor Risk in Chinese Patients with Type 2 Diabetes" in 2011. This study included 3509 patients (2567 females and 942 males) with normal fasting plasma glucose (FPG) and no MS. Multivariate logistic regression was used to analyze the correlation between FPG and MS ROC was used to analyze the effective cutoff value of FPG for the incidence of MS. Results: After 3-year follow-up, 675 patients had MS (567 females and 108 males). MS incidence in the total population was 19.24%, 11.46% in males, and 22.09% in females, and it increased with FPG. After multivariate logistic regression analysis, the risk of MS corresponding to FPG in females and males was OR=4.607,95% CI (3.477-6.105) and OR=2.944, 95% CI (1.785-4.855), respectively. ROC results demonstrated that FPG could predict the onset of MS (AUC: 0.720 in males and 0.666 in females). Conclusion: Increased FPG correlated with the incidence of metabolic syndrome. Subjects with FPG in the normal range still had a high incidence of MS. The population cutoff value for predicting effective FPG for metabolic syndrome was 5.545 mmol/L in men and 5.605 mmol/L in women. Epidemiological investigations are needed to determine whether a lower FPG cutoff value is required to diagnose MS. FPG not only diagnoses diabetes but also serves as a cost-effective and convenient screening method for developing of MS in the general Chinese population.

Association of Spousal Diabetes Status and Ideal Cardiovascular Health Metrics With Risk of Incident Diabetes Among Chinese Adults.

Importance: Spouses share common socioeconomic, environmental, and lifestyle factors, and multiple studies have found that spousal diabetes status was associated with diabetes prevalence. But the association of spousal diabetes status and ideal cardiovascular health metrics (ICVHMs) assessed by the American Heart Association's Life's Essential 8 measures with incident diabetes has not been comprehensively characterized, especially in large-scale cohort studies. Objective: To explore the association of spousal diabetes status and cardiovascular health metrics with risk of incident diabetes in Chinese adults. Design, Setting, and Participants: This cohort study included individuals in the China Cardiovascular Disease and Cancer Cohort without diabetes who underwent baseline and follow-up glucose measurements and had spouses with baseline glucose measurements. The data were collected in January 2011 to December 2012 and March 2014 to December 2016. The spousal study had a mean (SD) follow-up of 3.6 (0.9) years (median [IQR], 3.2 [2.9-4.5] years). Statistical analysis was performed from July to November 2022. Exposure: Spousal diabetes status was diagnosed according to the 2010 American Diabetes Association (ADA) criteria. All participants provided detailed clinical, sociodemographic, and lifestyle information included in cardiovascular health metrics. Main Outcomes and Measures: Incident diabetes, diagnosed according to 2010 ADA criteria. Results: Overall, 34 821 individuals were included, with a mean (SD) age of 56.4 (8.3) years and 16 699 (48.0%) male participants. Spousal diabetes diagnosis was associated with an increased risk of incident diabetes (hazard ratio [HR], 1.15; 95% CI, 1.03-1.30). Furthermore, participants whose spouses had uncontrolled glycated hemoglobin (HbA1c) had a higher risk of diabetes (HR, 1.20; 95% CI, 1.04-1.39) but the risk of diabetes in participants whose spouses had controlled HbA1c did not increase significantly (HR, 1.10; 95% CI, 0.92-1.30). Moreover, this association varied with composite cardiovascular health status. Diabetes risk in individuals who had poor cardiovascular health status (<4 ICVHMs) was associated with spousal diabetes status (3 ICVHMs: HR, 1.50; 95% CI, 1.15-1.97), while diabetes risk in individuals who had intermediate to ideal cardiovascular health status (≥4 ICVHMs) was not associated with it (4 ICVHMs: HR, 1.01; 95% CI, 0.69-1.50). Conclusions and Relevance: In this study, spousal diabetes diagnosis with uncontrolled HbA1c level was associated with increased risk of incident diabetes, but strict management of spousal HbA1c level and improving ICVHM profiles may attenuate the association of spousal diabetes status with diabetes risk. These findings suggest the potential benefit of couple-based lifestyle or pharmaceutical interventions for diabetes.

Data-driven subgroups of prediabetes and the associations with outcomes in Chinese adults.

Prediabetes and its pathophysiology remain important issues. We aimed to examine the cluster characteristics of prediabetes and explore their associations with developing diabetes and its complications based on 12 variables representing body fat, glycemic measures, pancreatic ß cell function, insulin resistance, blood lipids, and liver enzymes. A total of 55,777 individuals with prediabetes from the China Cardiometabolic Disease and Cancer Cohort (4C) were classified at baseline into six clusters. During a median of 3.1 years of follow-up, significant differences in the risks of diabetes and its complications between clusters were observed. The odds ratios of diabetes stepwisely increase from cluster 1 to cluster 6. Clusters 1, 4, and 6 have increased chronic kidney diseases risks, while the prediabetes in cluster 4, characterized by obesity and insulin resistance, confers higher risks of cardiovascular diseases compared with others. This subcategorization has potential value in developing more precise strategies for targeted prediabetes prevention and treatment.

A case report and literature review of Carney complex with atrial adenomyxoma.

BACKGROUND: Carney complex (CNC) is a rare multiple endocrine neoplasia syndrome characterized by mucocutaneous lentigines/ blue nevi, cardiac myxoma and endocrine overactivity. Here, we report a CNC case with PRKAR1A gene mutation characterized by left atrial adenomyxoma to explore the diagnosis and treatment of CNC. CASE PRESENTATION: A 42-year-old woman with a history of cardiac tumour surgery presented with typical features of Cushing syndrome, including central obesity, buffalo hump, mild facial plethora, purple striae on the lower abdomen, and spotty skin pigmentation. Left atrial adenomyxoma and thyroid papillary carcinoma were identified by postoperative histologic assays. Genetic screening revealed a pathogenic germline heterozygous mutation of c.682C > T (p.R228X) in exon 7 of the PRKAR1A gene. The clinical features and normal ACTH levels suggest this patient suffered the ACTH-independent primary pigmented nodular adrenocortical disease (PPNAD) with cyclic hypercortisolism or ACTH-dependent Cushing syndrome. CONCLUSION: CNC is uncommon, however, if a patient develops clinical features involving multiple endocrine and non-endocrine tumors, especially Cushing syndrome and cardiac myxoma, CNC should be considered. Genetic analysis is recommended in patients with suspected CNC.

Clinical expert consensus on the assessment and protection of pancreatic islet ß-cell function in type 2 diabetes mellitus.

Islet ß-cell dysfunction is a basic pathophysiological characteristic of type 2 diabetes mellitus (T2DM). Appropriate assessment of islet ß-cell function is beneficial to better management of T2DM. Protecting islet ß-cell function is vital to delay the progress of type 2 diabetes mellitus. Therefore, the Pancreatic Islet ß-cell Expert Panel of the Chinese Diabetes Society and Endocrinology Society of Jiangsu Medical Association organized experts to draft the "Clinical expert consensus on the assessment and protection of pancreatic islet ß-cell function in type 2 diabetes mellitus." This consensus suggests that ß-cell function can be clinically assessed using blood glucose-based methods or methods that combine blood glucose and endogenous insulin or C-peptide levels. Some measures, including weight loss and early and sustained euglycemia control, could effectively protect islet ß-cell function, and some newly developed drugs, such as Sodium-glucose cotransporter-2 inhibitor and Glucagon-like peptide-1 receptor agonists, could improve islet ß-cell function, independent of glycemic control.

Effects of artificial light with different spectral composition on eye axial growth in juvenile guinea pigs.

The purpose of the study was to investigate the effect of artificial light with different spectral composition and distribution on axial growth in guinea pigs. Three-week-old guinea pigs were randomly assigned to groups exposed to natural light, low color temperature light-emitting diode (LED) light, two full spectrum artificial lights (E light and Julia light) and blue light filtered light with the same intensity. Axial lengths of guinea pigs' eyes were measured by A-scan ultrasonography prior to the experiment and every 2 weeks during the experiment. After light exposure for 12 weeks, retinal dopamine (DA), dihydroxy-phenylacetic acid (DOPAC) levels and DOPAC/DA ratio were analyzed by high-pressure liquid chromatography electrochemical detection and retinal histological structure was observed. Retinal melanopsin expression was detected using Western blot and immunohistochemistry. After exposed to different kinds of light with different spectrum for 4 weeks, the axial lengths of guinea pigs' eyes in LED group and Julia light group were significantly longer than those of natural light group. After 6 weeks, the axial lengths in LED light group were significantly longer than those of E light group and blue light filtered group. The difference between axial lengths in E light group and Julia light group showed statistical significance after 8 weeks (p<0.05). After 12 weeks of light exposure, the comparison of retinal DOPAC/DA ratio and melanopsin expression in each group was consistent with that of axial length. In guinea pigs, continuous full spectrum artificial light with no peak or valley can inhibit axial elongation via retinal dopaminergic and melanopsin system.

Risk of cardiovascular disease, death, and renal progression in diabetes according to albuminuria and estimated glomerular filtration rate.

AIM: We aimed to examine risks of major cardiovascular events (MACEs), renal outcomes, and all-cause mortality in type 2 diabetes mellitus (T2DM) patients with different diabetic kidney disease (DKD) subtypes. METHODS: A total of 36,509 participants with T2DM recruited from 20 community sites across mainland China were followed up during 2011-2016. DKD subtypes were categorized based on albuminuria (urinary albumin-to-creatinine ratio, UACR ≥ 30 mg/g) and reduced estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) as Alb-/eGFR-, Alb+/eGFR-, Alb-/eGFR+, and Alb+/eGFR+. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of developing clinical outcomes in DKD subtypes. RESULTS: More than half (53.5%) of participants with diabetes and reduced eGFR had normal UACR levels (Alb-/eGFR+), termed as non-albuminuria DKD. These patients had a modest increase in the risks of MACEs (hazard ratio, HR 1.42 [95% CI 1.08;1.88]) and mortality (HR 1.42 [1.04;1.92]) compared with patients without DKD, whereas CKD progression was not significantly increased (HR 0.97 [0.60;1.57]). Participants with albuminuria (Alb+/eGFR- or Alb+/eGFR+) had higher risks of clinical outcomes. Subgroup analysis revealed that the associations between non-albuminuria DKD and risks of MACEs and mortality were more evident in those aged <65 years. CONCLUSION: Non-albuminuria DKD accounts for more than half of DKD cases with low eGFR in Chinese diabetes patients. Diabetes patients with albuminuria are at higher risks of developing clinical outcomes and warrant early intervention, as well as patients with non-albuminuria DKD with age < 65 years.

Blood Pressure Levels, Cardiovascular Events, and Renal Outcomes in Chronic Kidney Disease Without Antihypertensive Therapy: A Nationwide Population-Based Cohort Study.

BACKGROUND: High blood pressure (BP) is highly prevalent in patients with chronic kidney disease. However, the thresholds to initiate BP-lowering treatment in this population are unclear. We aimed to examine the associations between BP levels and clinical outcomes and provide evidence on potential thresholds to initiate BP-lowering therapy in people with chronic kidney disease. METHODS: This nationwide, multicenter, prospective cohort study included 12 523 chronic kidney disease participants without antihypertensive therapy in mainland China. Participants were followed up during 2011 to 2016 for cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, hospitalized or treated heart failure, and cardiovascular death) and renal events (≥20% decline in the estimated glomerular filtration rate, end-stage kidney disease, and renal death). RESULTS: Overall, 652 cardiovascular events and 1268 renal events occurred during 43 970 person-years of follow-up. We observed a positive and linear relationship between systolic BP and risks of cardiovascular and renal events down to 90 mm Hg, as well as between diastolic BP and risks of renal events down to 50 mm Hg. A J-shaped trend was noted between diastolic BP and risks of cardiovascular events, but a linear relationship was revealed in participants <60 years (P for interaction <0.001). A significant increase in the risk of cardiovascular and renal outcomes was observed at systolic BP ≥130 mm Hg (versus 90-119 mm Hg) and at diastolic BP ≥90 mm Hg (versus 50-69 mm Hg). CONCLUSIONS: In people with chronic kidney disease, a higher systolic BP/diastolic BP level (≥130/90 mm Hg) is significantly associated with a greater risk of cardiovascular and renal events, indicating potential thresholds to initiate BP-lowering treatment.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Bioactive steroids from seed germination supporting fungus (Ceratobasidium GS2) of the terrestrial orchid Gymnadenia conopsea.

Almost all orchids rely on mycorrhizal fungus to support their seed germination. To date, the effect of active components in mycorrhizal fungus on orchid seed germination largely remains unknown. In this study, we aimed to investigate the impact of active components found in mycorrhizal fungus on orchid seed germination. Specifically, we focused on a terrestrial orchid Gymnadenia conopsea and its host-specific seed germination supporting fungus Ceratobasidium GS2. In total, several steroids (1-7) were isolated from this fungus. Notably, compounds 1, 2, 4, and 5 exhibited significant enhancements in protocorm volume. Moreover, compounds 1-6 demonstrated strong promotion of protocorm differentiation. These findings suggest that steroids may play a crucial role in the symbiotic germination of G. conopsea seeds. Future studies should continue to explore the specific mechanisms through which these steroids exert their effects, contributing to our understanding of orchid biology and mycorrhizal interaction.

Furanoids from the Gymnadenia conopsea (Orchidaceae) seed germination supporting fungus Ceratobasidium sp. (GS2).

Five furanoids including a new analog (S)-1,4-di(furan-2-yl)-2-hydroxybutane-1,4-dione (1) together with four known ones, rhizosolaniol (2), 5-hydroxymethylfurfural (3), 2-furoic acid (4) and (2-furyl) oxoacetamide (5), were isolated from the fungal strain Ceratobasidium sp. (GS2) inducing seed germination of the endangered medicinal plant Gymnadenia conopsea of Orchidaceae. The structure of new furanoid 1 was determined mainly based on HR-ESI-MS and NMR spectral data. Modified Mosher's reactions were used to establish the stereochemistry of the hydroxyl group in 1, which was not stable in Mosher's reagents and transformed into four analogs 6-9. These degraded products (6-9) were elucidated based on UPLC-Q-TOF-MS/MS analysis, and compound 8 was further isolated from the degraded mixture and its structure was characterized through NMR experiments. Therefore, the absolute configuration of compound 1 was determined by electronic circular dichroism combined with quantum-chemical calculations adopting time-dependent density functional theory. Compounds (1-5), and 8 showed weak antioxidant activities, and compounds (2-4) displayed phytotoxicity on punctured detached green foxtail leaves. In addition, compounds 3 and 4 strongly showed inhibition activities on the seed germination of G. conopsea. This was the first chemical investigation of the symbiotic fungus of G. conopsea.

Identification of biomarkers in nonalcoholic fatty liver disease: A machine learning method and experimental study.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease. However, the early diagnosis of NAFLD is challenging. Thus, the purpose of this study was to identify diagnostic biomarkers of NAFLD using machine learning algorithms. Differentially expressed genes between NAFLD and normal samples were identified separately from the GEO database. The key DEGs were selected through a protein‒protein interaction network, and their biological functions were analysed. Next, three machine learning algorithms were selected to construct models of NAFLD separately, and the model with the smallest sample residual was determined to be the best model. Then, logistic regression analysis was used to judge the accuracy of the five genes in predicting the risk of NAFLD. A single-sample gene set enrichment analysis algorithm was used to evaluate the immune cell infiltration of NAFLD, and the correlation between diagnostic biomarkers and immune cell infiltration was analysed. Finally, 10 pairs of peripheral blood samples from NAFLD patients and normal controls were collected for RNA isolation and quantitative real-time polymerase chain reaction for validation. Taken together, CEBPD, H4C11, CEBPB, GATA3, and KLF4 were identified as diagnostic biomarkers of NAFLD by machine learning algorithms and were related to immune cell infiltration in NAFLD. These key genes provide novel insights into the mechanisms and treatment of patients with NAFLD.

Amiodarone-drove XBP1s aggravates endoplasmic reticulum stress and apoptosis in Hashimoto's thyroiditis through regulating LINC00842/miR-214/FASL axis.

Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease, that eventually lead to hypothyroidism. XBP1s is an endoplasmic reticulum stress related protein and participates in the pathogenesis of several diseases. Nevertheless, the potential role of XBP1s in amiodarone (AMIO)-treated HT patients remains unknown. In this study, AMIO aggravated the endoplasmic reticulum stress responses in HT patients and thyroid epithelial follicular cells. Moreover, MTT assay and flow cytometry analysis revealed that knockdown of XBP1s suppressed AMIO-induced thyroid epithelial follicular cells apoptosis. Mechanically, the Chromatin Immunoprecipitation (ChIP) and luciferase activity assay proved that XBP1s enhanced LINC00842 expression in HT patients and thyroid epithelial follicular cells via binding to LINC00842 promoter. LINC00842 functioned as a miR-214 sponge in HT patients and thyroid epithelial follicular cells. Besides, LINC00842 up-regulated Fas ligand (FASL) expression via inhibition of miR-214. In rescue experiments, overexpression of FASL reversed shXBP1s-induced suppression of cell apoptosis in AMIO-treated thyroid epithelial follicular cells. These findings concluded that AMIO-drove XBP1s aggravated endoplasmic reticulum stress and apoptosis in HT via modulating LINC00842/miR-214/FASL axis, providing a new sight for the therapeutic strategy of AMIO-induced HT.