Non-linear connection between the triglyceride-glucose index and prediabetes risk among Chinese adults: a secondary retrospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index has garnered recognition as a surrogate marker for insulin resistance, a pivotal factor in the pathogenesis of various metabolic disorders. Despite its emerging role, the empirical evidence delineating its association with prediabetes mellitus (Pre-DM) remains scant. This research aims to clarify the link between the TyG index and the likelihood of Pre-DM development within a Chinese demographic. METHODS: This investigation was structured as a retrospective cohort analysis, encompassing a sample of 179,177 Chinese adults. These individuals underwent medical examinations at the Rich Healthcare Group over a period spanning from 2010 to 2016. To ascertain the relationship between the TyG index and the incidence of Pre-DM, this study employed Cox regression analysis complemented by sensitivity and subgroup assessments. Furthermore, Cox proportional hazards regression with cubic spline functions and smooth curve fitting was incorporated to explore the existence of any non-linear connection within this association. RESULTS: Upon adjusting for a comprehensive array of confounding variables, a statistically significant positive correlation between the TyG index and the risk of Pre-DM was identified (HR: 1.60, 95%CI 1.56-1.65, P < 0.001). The analysis illuminated a non-linear relationship, with an inflection point at a TyG index value of 8.78. For TyG index values below and above this inflection point, the HR was calculated to be 1.94 (95%CI 1.86-2.03) and 1.26 (95%CI 1.20-1.33), respectively. Sensitivity analyses further fortified the reliability of these findings. CONCLUSIONS: This comprehensive examination delineated a significantly positive, non-linear correlation between the TyG index and the risk of Pre-DM within a Chinese population. Individuals with TyG index values below 8.78 have a significantly increased risk of developing prediabetes. These findings underscore the TyG index's potential efficacy as a predictive tool for assessing Pre-DM risk in clinical practice.

Non-linear relationship between relative fat mass and diabetes risk in Japanese adults: a retrospective cohort study.

BACKGROUND: Relative fat mass (RFM) represents a newly developed sex-specific anthropometric formula to estimate total body fat percentage. Nonetheless, research examining the correlation between RFM and the risk of diabetes remains scarce. This research assessed the link between RFM and DM risk within the Japanese demographic. METHODS: From 2004 to 2015, 15,462 Japanese individuals without diabetes underwent physical evaluations at Murakami Memorial Hospital. The relationship between RFM and the onset of diabetes was analyzed separately using Cox proportional-hazards regression models. This study employed Cox proportional hazards regression incorporating cubic spline functions and smooth curve fitting to detect non-linear associations between RFM and new cases of diabetes, categorized by sex. Sensitivity analyses were performed to confirm the robustness of the link between RFM and incident diabetes. RESULTS: After controlling for confounding factors, a significant positive correlation between RFM and diabetes risk was found in women (HR: 1.13, 95%CI: 1.04-1.24, P = 0.0061), while the association in men was not statistically significant (HR: 1.05, 95%CI: 0.98-1.13, P = 0.1511). Additionally, a non-linear relationship between RFM and the incidence of diabetes was detected in both genders. The RFM threshold was identified at 39.23 for women and 23.08 for men. For women, HR was 1.11 (95%CI: 1.01-1.21) below the threshold and 1.39 (95%CI: 1.17-1.65) above it. In men, an RFM above 23.08 was positively related to diabetes risk (HR: 1.16, 95%CI: 1.06-1.28, P = 0.0012), whereas an RFM below this point did not show a significant association (HR: 0.98, 95%CI: 0.91-1.06, P = 0.5899). CONCLUSION: Our findings suggest a non-linear relationship and threshold effect between RFM and the risk of diabetes. These findings imply that maintaining RFM at lower levels may be beneficial in mitigating the onset of DM.

Ulinastatin attenuates renal ischemia-reperfusion injury by inhibiting NLRP3 inflammasome-triggered pyroptosis.

Systemic inflammation is involved in developing acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB). Ulinastatin, a urinary trypsin inhibitor (UTI), has various anti-inflammatory effects. Our previous data displayed that UTI administration during CPB played a protective role in reducing the risk of AKI after cardiac surgery; however, its role in AKI pathogenesis remains unknown. In this study, UTI effectively decreased the expression levels of inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and interleukin (IL)-18, in patients with CPB. Moreover, the proportion of patients with postoperative AKI decreased significantly. Experimental AKI was induced by 35 min of ischemia, followed by 48 h of reperfusion.The results showed that the preoperative administration of UTI reduced inflammatory cell infiltration and decreased the levels of pro-inflammatory cytokines, including IL-6, IL-18, and TNFα. Meanwhile, UTI inhibited apoptosis, reduced mitochondrial reactive oxygen species production. We further revealed that UTI could inhibit NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation by increasing the expression of nuclear factor-κB (IκB) kinase-alpha (IKKα) interacting with apoptosis-associated speck-like protein containing CARD (ASC) to alleviate kidney damage. These findings provide evidence of the renoprotective role of UTI in cardiac surgery-associated (CSA)-AKI, which is associated with the inhibition of NLRP3 inflammasome activation by upregulating IKKα.

Nonlinear relationship between triglyceride-glucose index and the risk of prediabetes and diabetes: a secondary retrospective cohort study.

Background: The triglyceride-glucose (TyG) index, recognized for its cost-efficiency and simplicity, serves as an accessible indicator of insulin resistance. Yet, its correlation with the risk of prediabetes and diabetes (Pre-DM/DM) in the Chinese demographic remains uncertain. Consequently, our study explored the association between the TyG index and the development of Pre-DM/DM within the Chinese population. Methods: The retrospective cohort study was carried out utilizing data from a health screening initiative. The study included 179541 adults over 20 who underwent medical examinations at the Rich Healthcare Group over a period spanning from 2010 to 2016. The correlation between the TyG index and Pre-DM/DM risk was investigated using Cox regression analysis. Furthermore, Cox proportional hazards regression with cubic spline functions and smooth curve fitting was incorporated to explore their non-linear connection. Results: The mean age of study participants was 41.18 ± 12.20 years old, and 95255 (53.05%) were male. During a median follow-up of 3.01 years, 21281 (11.85%) participants were diagnosed with Pre-DM/DM. After adjusting the potential confounding factors, the results showed that the TyG index was positively correlated with incident Pre-DM/DM (HR: 1.67, 95%CI: 1.62-1.71, P< 0.001). Additionally, a non-linear association was observed between the TyG index and the onset of Pre-DM/DM, with an inflection point identified at 8.73. Hazard ratios (HR) to the left and right of this inflection point were 1.95 (95%CI: 1.86-2.04) and 1.34 (95%CI: 1.27-1.42), respectively. Furthermore, sensitivity analyses confirmed the stability of these findings. Conclusion: The TyG index exhibited a non-linear positive relationship with the risk of Pre-DM/DM. These findings imply that maintaining the TyG index at a lower, specified threshold may be beneficial in mitigating the onset of Pre-DM/DM.

The nonlinear connection between relative fat mass and non-alcoholic fatty liver disease in the Japanese population: an analysis based on data from a cross-sectional study.

BACKGROUND: Relative fat mass (RFM) is a newly developed, sex-specific anthropometric formula designed to estimate total body fat percentage. However, research investigating the correlation between RFM and the risk of non-alcoholic fatty liver disease (NAFLD) remains limited. This study evaluates the association between RFM and the risk of NAFLD within the Japanese population. METHODS: This study including 14,250 Japanese adults who underwent physical examinations at Murakami Memorial Hospital between 2004 and 2015. We employed binary logistic regression to elucidate the direct relationship between RFM levels and the incidence of NAFLD. Additionally, a generalized additive model (GAM) coupled with smooth curve fitting techniques was utilized to map the non-linear association. RESULTS: The cohort had an average age of 43.53 ± 8.89 years, with a male majority of 52.00%. NAFLD was identified in 17.59% of the participants. After adjusting for confounding factors, a significant positive correlation between RFM and NAFLD risk was observed (OR: 1.15, 95%CI: 1.10-1.21, P < 0.0001 for females; OR: 1.15, 95%CI: 1.10-1.19, P < 0.0001 for males). Additionally, a non-linear relationship between RFM and the incidence of NAFLD was detected in both genders. The RFM threshold was identified as 34.95 for women and 23.40 for men. RFM was positively associated with the risk of NAFLD when RFM was below the respective threshold (OR: 1.29, 95%CI: 1.19-1.40, P < 0.0001 for females; OR: 1.23, 95%CI: 1.17-1.29, P < 0.0001 for males), whereas no significant association was found when RFM was above the threshold (OR: 1.05, 95%CI: 0.98-1.12, P = 0.1829 for females; OR: 1.01, 95%CI: 0.95-1.08, P = 0.7392 for males). CONCLUSION: Our findings suggest a positive, nonlinear relationship between RFM and the risk of NAFLD, with a saturation effect. These results imply that maintaining RFM at a lower level may be advantageous in mitigating the risk of NAFLD.

Deficiency of geranylgeranyl biphosphate synthase in kidney tubules causes cystic kidney disease.

Polycystic kidney disease (PKD) is a common hereditary kidney disease. Although PKD occurrence is associated with certain gene mutations, its onset regulatory mechanisms are still not well understood. Here, we first report that the key enzyme geranylgeranyl diphosphate synthase (GGPPS) is specifically expressed in renal tubular epithelial cells of mouse kidneys. We aimed to explore the role of GGPPS in PKD. In this study, we established a Ggppsfl/fl:Cdh16cre mouse model and compared its phenotype with that of wild-type mice. A Ggpps-downregulation HK2 cell model was also used to further determine the role of GGPPS. We found that GGPPS was specifically expressed in renal tubular epithelial cells of mouse kidneys. Its expression also increased with age. Low GGPPS expression was observed in human ADPKD tissues. In the Ggppsfl/fl:Cdh16cre mouse model, Ggpps deletion in renal tubular epithelial cells induced the occurrence and development of renal tubule cystic dilation and caused the death of mice after birth due to abnormal renal function. Enhanced proliferation of cyst-lining epithelial cells was also observed after the knockout of Ggpps. These processes were related to the increased rate of Rheb on membrane/cytoplasm and hyperactivation of mTORC1 signaling. In conclusion, the deficiency of GGPPS in kidney tubules induced the formation of renal cysts. It may play a critical role in PKD pathophysiology. A novel therapeutic strategy could be designed according to this work.

Link between remnant cholesterol and the reversion to normoglycemia in Chinese adults with prediabetes: a 5-year cohort study.

Despite the clear association between remnant cholesterol (RC)and diabetes risk, no study to date has examined the relationship between RC and reversal of prediabetes to normoglycemia. This retrospective cohort study included a total of 15,023 patients with prediabetes who underwent a physical examination between 2010 and 2016. The link between initial RC levels and the reversion from prediabetes to normoglycemia was analyzed using the Cox proportional-hazards regression model. Additionally, the study explored the possible relationship between RC and the probability of returning normoglycemia by applying Cox proportional hazards regression models with cubic spline functions. To address competing risks, a multivariate Cox regression analysis was undertaken, treating the onset of diabetes as a competing risk event for reversing prediabetes to normoglycemia. Additionally, the study incorporated extensive subgroup analyses alongside multiple sensitivity analyses, enhancing the reliability and robustness of the results. After adjusting for covariates, the findings indicated that RC was inversely associated with the likelihood of reverting to normoglycemia (per 5 mg/dL increase, HR = 0.918, 95% CI 0.909-0.927). The analysis also revealed a nonlinear relationship between RC and normoglycemia reversion, with an inflection point at 51.08 mg/dL. For RC values below this inflection point (RC < 50.08 mg/dL), the HR for the probability of returning to normoglycemia was 0.907 (95% CI 0.897-0.917 per 5 mg/dL). Additionally, the competing risks model demonstrated a negative relationship between RC and the reversal of prediabetes to normoglycemia (SHR = 0.92, 95% CI 0.91-0.93). Sensitivity analyses confirmed the robustness and stability of these results. This study demonstrated a negative and non-linear association between RC and the probability of reversion to normoglycemia in Chinese adults with prediabetes. By actively intervening to reduce RC levels, at least to below 51.08 mg/dL, further reduction of RC may significantly increase the probability of returning to normoglycemia from prediabetes.

Inflammation-Derived and Clinical Indicator-Based Predictive Model for Ischemic Stroke Recovery.

BACKGROUND: Neuroinflammatory responses are closely associated with poststroke prognosis severity. This study aimed to develop a predictive model, combining inflammation-derived markers and clinical indicators, for distinguishing functional outcomes in patients with subacute ischemic stroke. METHODS AND RESULTS: Based on activities of daily living assessments, ischemic stroke participants were categorized into groups with little effective (LE) recovery and obvious effective (OE) recovery. Initial biocandidates were identified by overlapping differentially expressed proteins from proteomics of clinical serum samples (5 LE, 5 OE, and 6 healthy controls) and differentially expressed genes from an RNA sequence of the ischemic cortex in middle cerebral artery occlusion mice (n=3). Multidimensional validations were conducted in ischemia-reperfusion models and a clinical cohort (15 LE, 11 OE, and 18 healthy controls). Models of robust biocandidates combined with clinical indicators were developed with machine learning in the training data set and prediction in another test data set (15 LE and 11 OE). We identified 194 differentially expressed proteins (LE versus healthy controls) and 174 differentially expressed proteins (OE versus healthy controls) in human serum, and 5121 differentially expressed genes (day 3) and 5906 differentially expressed genes (day 7) in middle cerebral artery occlusion mice cortex. Inflammation-derived biomarkers TIMP1 (tissue inhibitor metalloproteinase-1) and galactosidase-binding protein LGLAS3 (galectin-3) exhibited robust increases under ischemic injury in mice and humans. TIMP1 and LGALS3 coupled with clinical indicators (hemoglobin, low-density lipoprotein cholesterol, and uric acid) were developed into a combined model for differentiating functional outcome with high accuracy (area under the curve, 0.8). CONCLUSIONS: The combined model is a valuable tool for evaluating prognostic outcomes, and the predictive factors can facilitate development of better treatment strategies.

Association between excessive alcohol consumption and incident diabetes mellitus among Japanese based on propensity score matching.

The available evidence on the connection between excessive alcohol consumption and diabetes is controversial. Therefore, the primary objective of this investigation was to examine the connection between excessive alcohol consumption and incident diabetes in a Japanese population through the utilization of propensity score matching (PSM) analysis. Our retrospective cohort study encompassed a sample of 15,464 Japanese individuals who were initially free of diabetes between the years 2004 and 2015. The study utilized comprehensive medical records of individuals who underwent a physical examination. Employing a one:one PSM analysis, the current research included 2298 individuals with and without excessive alcohol consumption. Furthermore, a doubly robust estimation method was employed to ascertain the connection between excessive alcohol consumption and diabetes. The findings revealed that individuals with excessive alcohol consumption exhibited a 73% higher likelihood of developing diabetes (HR = 1.73, 95% CI 1.08-2.77). Furthermore, upon adjusting for variables, the PSM cohort demonstrated that individuals with excessive alcohol consumption had a 78% increased risk of developing diabetes in comparison to those with non-excessive alcohol consumption (HR = 1.78, 95% CI 1.08-2.93). Individuals with excessive alcohol consumption were found to have a 73% higher risk of developing diabetes compared to those with non-excessive alcohol consumption, even after controlling for propensity score (HR = 1.73, 95% CI 1.08-2.78). Participants in the PSM cohort with excessive alcohol consumption had a 73% higher risk of developing diabetes than those with non-excessive alcohol consumption after controlling for confounding factors. These findings underscore the importance of alcohol consumption guidelines aimed at reducing excessive drinking. Clinicians should be vigilant in screening for alcohol use in patients, particularly those at risk for diabetes, and provide appropriate counseling and resources to support alcohol reduction.

Protection of blood-brain barrier by endothelial DAPK1 deletion after stroke.

Death-associated protein kinase (DAPK) 1 is a critical mediator for neuronal cell death in cerebral ischemia, but its role in blood-brain barrier (BBB) disruption is incompletely understood. Here, we found that endothelial-specific deletion of Dapk1 using Tie2 Cre protected the brain of Dapk1fl/fl mice against middle cerebral artery occlusion (MCAO), characterized by mitigated Evans blue dye (EBD) extravasation, reduced infarct size and improved behavior. In vitro experiments also indicated that DAPK1 deletion inhibited oxygen-glucose deprivation (OGD)-induced tight junction alteration between cerebral endothelial cells (CECs). Mechanistically, we revealed that DAPK1-DAPK3 interaction activated cytosolic phospholipase A2 (cPLA2) in OGD-stimulated CECs. Our results thus suggest that inhibition of endothelial DAPK1 specifically prevents BBB damage after stroke.

Fluorescent identification of immunomagnetically captured CTCs using triplex-aptamer-targeted dendritic SiO2@Fe3O4 nanocomposite.

The enumeration of circulating tumor cells (CTCs) in peripheral blood plays a crucial role in the early diagnosis, recurrence monitoring, and prognosis assessment of cancer patients. There is a compelling need to develop an efficient technique for the capture and identification of these rare CTCs. However, the exclusive reliance on a single criterion, such as the epithelial cell adhesion molecule (EpCAM) antibody or aptamer, for the specific recognition of epithelial CTCs is not universally suitable for clinical applications, as it usually falls short in identifying EpCAM-negative CTCs. To address this limitation, we propose a straightforward and cost-effective method involving triplex fluorescently labelled aptamers (FAM-EpCAM, Cy5-PTK7, and Texas Red-CSV) to modify Fe3O4-loaded dendritic SiO2 nanocomposite (dmSiO2@Fe3O4/Apt). This multi-recognition-based strategy not only enhanced the efficiency in capturing heterogeneous CTCs, but also facilitated the rapid and accurate identification of CTCs. The capture efficiency of heterogenous CTCs reached up to 93.33%, with a detection limit as low as 5 cells/mL. Notably, the developed dmSiO2@Fe3O4/Apt nanoprobe enabled the swift identification of captured cells in just 30 min, relying solely on the fluorescently modified aptamers, which reduced the identification time by approximately 90% compared with the conventional immunocytochemistry (ICC) technique. Finally, these nanoprobe characteristics were validated using blood samples from patients with various types of cancers.

Counteracting TGM2 by a Fibroin peptide ameliorated Adriamycin-induced nephropathy via regulation of lipid metabolism through PANX1-PPAR α/PANK1 pathway.

Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence 'YEVEDYR') from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing. Further analysis showed that YR-7 alleviated the accumulation of lipid droplets via regulation of the lipid metabolism-related proteins PPAR α and PANK1. Using chemical proteomics, fluorescence polarization, microscale thermophoresis, surface plasmon resonance, and molecular docking, YR-7 was proven to directly bind to ß-barrel domains of TGM2 protein to inhibit lipid accumulation. TGM2 knockdown in vivo increased the protein levels of PPAR α and PANK1 while decreased the levels of fibrotic-related proteins to alleviate nephropathy. In vitro, overexpression TGM2 reversed the protective effects of YR-7. Co-immunoprecipitation indicated that TGM2 interacted with PANX1 to promote lipid deposition, and pharmacological inhibition or knockdown of PANX1 decreased the levels of PPAR α and PANK1 induced by ADR. Taken together, our findings revealed that TGM2-PANX1 interaction in promoting lipid deposition may be a new signaling in promoting ADR-induced nephropathy. And a novel natural peptide could ameliorate renal fibrosis through TGM2-PANX1-PPAR α/PANK1 pathway, which highlight the potential of it in the treatment of CKD.

A nonlinear relationship between the triglycerides to high-density lipoprotein cholesterol ratio and stroke risk: an analysis based on data from the China Health and Retirement Longitudinal Study.

OBJECTIVE: The connection between triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio and stroke risk is controversial. Our goal was to explore this relationship in individuals aged 45 and older enrolled in the China Health and Retirement Longitudinal Study (CHARLS). METHODS: Our analysis encompassed 10,164 participants from the CHARLS cohorts. We applied the Cox proportional-hazards regression model to evaluate the potential correlation between the TG/HDL-C ratio and stroke incidence. Using a cubic spline function and smooth curve fitting within the Cox model allowed us to unearth a possible non-linear pattern in this relationship. We also conducted thorough sensitivity and subgroup analyses to deepen our understanding of the TG/HDL-C ratio's impact on stroke risk. RESULTS: Adjusting for various risk factors, we observed a significant link between the TG/HDL-C ratio and increased stroke risk in individuals aged 45 and above (HR: 1.03, 95% CI 1.00-1.05, P = 0.0426). The relationship appeared non-linear, with an inflection at a TG/HDL-C ratio of 1.85. Ratios below this threshold indicated a heightened stroke risk (HR: 1.28, 95% CI 1.06-1.54, P = 0.0089), while ratios above it did not show a significant risk increase (HR: 1.01, 95% CI 0.98-1.04, P = 0.6738). Sensitivity analysis confirmed the robustness of these findings. Notably, non-smokers exhibited a stronger correlation between the TG/HDL-C ratio and stroke risk compared to past and current smokers. CONCLUSION: Our investigation revealed a significant, yet non-linear, association between the TG/HDL-C ratio and the incidence of stroke among individuals aged 45 and above. Specifically, we found that stroke risk increased in correlation with TG/HDL-C ratio below the threshold of 1.85. These insights may guide healthcare providers in advising and developing more effective strategies for stroke prevention in this demographic.

Association between alanine aminotransferase to high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease: a retrospective cohort study in lean Chinese individuals.

There is limited research on the association between the alanine aminotransferase to high-density lipoprotein cholesterol ratio (ALT/HDL-C) ratio and nonalcoholic fatty liver disease (NAFLD). The purpose of the current research was to look into the connection between the ALT/HDL-C ratio and the risk of NAFLD in lean Chinese individuals. Between January 2010 and December 2014, 11,975 non-obese people participated in this prospective cohort research. The relationship between the ALT/HDL-C ratio and the risk of developing NAFLD was assessed using the Cox proportional-hazards regression model, Cox proportional hazards regression with cubic spline functions and smooth curve fitting, sensitivity analysis, and subgroup analyses. The ALT/HDL-C ratio's potential value as a NAFLD prognostic marker was to be evaluated using the receiver operating characteristic curve analysis. A total of 5419 (45.253%) women comprised the research's participant population, and the research participants' average age was 43.278 ± 14.941 years. The ALT/HDL-C ratio was 11.607 (7.973-17.422) at the median (interquartile ranges). 2087 (17.428%) patients had NAFLD diagnoses throughout a median follow-up of 24.967 months. The study's findings demonstrated a positive connection between the ALT/AHDL-C ratio and the incident NAFLD (HR = 1.037, 95% CI: 1.031-1.042) when adjusting for relevant factors. The ALT/HDL-C ratio and NAFLD risk had a nonlinear connection, with 12.963 as the ratio's inflection point. Effect sizes (HR) were 1.023 (95% CI: 1.017-1.029) and 1.204 (95% CI: 1.171-1.237), respectively, on the right and left sides of the inflection point. The sensitivity analysis also showed how reliable our findings were. According to subgroup analysis, those with BMI < 24 kg/m2 and DBP < 90 mmHg had a stronger correlation between the ALT/HDL-C ratio and NAFLD risk. The current study shows a positive and non-linear connection between the ALT/HDL-C ratio and NAFLD risk in lean Chinese individuals. When the ALT/HDL-C ratio is less than 12.963, it is significantly linked to NAFLD. Therefore, from a therapy standpoint, it is advised to keep the ALT/HDL-C ratio less than the inflection point.

A non-linear connection between the total cholesterol to high-density lipoprotein cholesterol ratio and stroke risk: a retrospective cohort study from the China Health and Retirement Longitudinal Study.

OBJECTIVE: The connection between total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio and stroke risk is controversial. This study aims to examine the connection between the TC/HDL-C ratio and stroke in middle-aged and older individuals who are part of the China Health and Retirement Longitudinal Study (CHARLS). METHODS: This study conducted a retrospective cohort analysis, enrolling a total of 10,184 participants who met the designated criteria from CHARLS between 2011 and 2012. We then used the Cox proportional-hazards regression model to analyze the relationship between the TC/HDL-C ratio and stroke risk. Using a Cox proportional hazards regression model with cubic spline functions and smooth curve fitting, we were able to identify the non-linear relationship between the TC/HDL-C ratio and stroke occurrence. The sensitivity and subgroup analyses were also performed to investigate the connection between TC/HDL-C ratio and stroke. RESULTS: This study revealed a statistically significant association between the TC/HDL-C ratio and stroke risk in subjects aged 45 years or older after adjusting for risk factors (HR: 1.05, 95%CI 1.00-1.10, P = 0.0410). Furthermore, a non-linear connection between the TC/HDL-C ratio and stroke risk was detected, with a TC/HDL-C ratio inflection point of 3.71. We identified a significant positive connection between the TC/HDL-C ratio and stroke risk, when the TC/HDL-C ratio was less than 3.71 (HR: 1.25, 95%CI 1.07-1.45, P = 0.0039). However, their connection was not significant when the TC/HDL-C ratio exceeded 3.71 (HR: 1.00, 95%CI 0.94-1.06, P = 0.9232). The sensitivity analysis and subgroup analyses revealed that our findings were well-robust. CONCLUSION: Our study demonstrated a positive, non-linear connection between the TC/HDL-C ratio and stroke risk in middle-aged and older individuals. There was a significant positive connection between the TC/HDL-C ratio and stroke risk, when the TC/HDL-C ratio was less than 3.71. The current research can be used as a guideline to support clinician consultation and optimize stroke prevention measures for middle-aged and older adults.

Non-linear relationship between pulse pressure and the risk of pre-diabetes: a secondary retrospective Chinese cohort study.

OBJECTIVE: Previous research has shown that pulse pressure (PP) has a significant role in the start and development of type 2 diabetes mellitus. However, there is little proof that PP and pre-diabetes mellitus (Pre-DM) are related. Our study aimed to investigate the relationship between PP and incident pre-DM in a substantial cohort of Chinese participants. DESIGN: The 'DATADRYAD' database (www.Datadryad.org) was used to retrieve the data for this secondary retrospective cohort analysis. PARTICIPANTS: Data from 182 672 Chinese individuals who participated in the medical examination programme were recorded in this retrospective cohort study between 2010 and 2016 across 32 sites and 11 cities in China. SETTING: PP assessed at baseline and incident pre-DM during follow-up were the target-independent and dependent variables. The association between PP and pre-DM was investigated using Cox proportional hazards regression. PRIMARY OUTCOME MEASURES: The outcome was incident pre-DM. Impaired fasting glucose levels (fasting blood glucose between 5.6 and 6.9 mmol/L) were used to define pre-DM. RESULTS: After controlling for confounding variables, PP was positively correlated with incident pre-DM among Chinese adults (HR 1.009, 95% CI 1.007 to 1.010). Additionally, at a PP inflection point of 29 mm Hg, a non-linear connection between the PP and incident pre-DM was discovered. Increased PP was an independent risk factor for developing pre-DM when PP was greater than 29 mm Hg. However, their association was not significant when PP was less than 29 mm Hg. According to subgroup analyses, females, never-smokers and non-obesity correlated more significantly with PP and pre-DM. CONCLUSION: We discovered that higher PP independently correlated with pre-DM risk in this study of Chinese participants. The connection between PP and incident pre-DM was also non-linear. High PP levels were related to a higher risk of pre-DM when PP was above 29 mm Hg. ARTICLE FOCUS: Our study investigated the relationship between PP and incident pre-DM in a secondary retrospective cohort of Chinese participants.

Nrf2 activation by neferine mitigates microglial neuroinflammation after subarachnoid hemorrhage through inhibiting TAK1-NF-κB signaling.

Oxidative stress and neuroinflammation are two major causes leading to early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor E2-related factor 2 (Nrf2) is a critical transcription factor that contributes to antioxidant responses. Additionally, Nrf2 could inhibit transforming growth factor beta-activated kinase 1 (TAK1), which plays a vital role in microglial activation-mediated neuroinflammation. Neferine (NE) exhibits considerable protective effects in diverse disease models. However, the detailed effect and mechanism of NE on SAH remain unknown. Our data showed that NE treatment significantly reduced behavior and cognitive impairment, and brain edema in the early period after SAH. In addition, NE mitigated SAH-induced oxidative damage, neuroinflammation, and neural death. Moreover, NE inhibited M1 microglial polarization and enhanced M2 phenotype microglia both in vivo and in vitro. Further investigations revealed that NE enhanced the Nrf2-antioxidant response element (ARE) signaling pathway and suppressed TAK1-NF-κB signaling. In contrast, depletion of Nrf2 by ML385 suppressed Nrf2-ARE signaling, induced TAK1-NF-κB activation, and further promoted M1 microglial polarization. Additionally, ML385 abated the neuroprotective effects of NE against SAH. Notably, LPS also aggravated TAK1-NF-κB activation and reversed the beneficial effects of NE after SAH. In summary, NE provides protection after SAH by inhibiting oxidative stress and modulating microglial polarization through Nrf2 activation and TAK1-NF-κB suppression.

Relationship between glycated hemoglobin levels and three-month outcomes in acute ischemic stroke patients with or without diabetes: a prospective Korean cohort study.

OBJECTIVE: In patients experiencing acute ischemic stroke, there is ongoing debate surrounding the connection between chronic hyperglycemic status and their initial clinical outcomes. Our objective was to examine the connection between glycated hemoglobin (HbA1c) levels and adverse clinical outcomes at both 3-months adverse clinical outcomes in individuals with acute ischemic stroke (AIS) with and without diabetes. METHODS: The present prospective cohort study involved 896 AIS patients without diabetes and 628 with diabetes treated at a South Korean hospital from January 2010 to December 2016. The target independent variable is HbA1c. The outcome variable is a modified Rankin scale score ≥ 3. A binary logistic regression model was applied to assess the connection between HbA1c levels and 3-month poor clinical outcomes in AIS patients with and without diabetes. Additionally, a generalized additive model and smoothed curve fitting were utilized to explore potential nonlinear associations between HbA1c levels and 3-month adverse clinical outcomes in AIS patients with and without diabetes. RESULTS: The binary logistic regression model could not identify any statistically significant connection between HbA1c and 3-month adverse clinical outcomes in AIS patients, both those with and without diabetes, after correcting for various factors. However, a nonlinear relationship emerged between HbA1c and 3-month adverse clinical outcomes in AIS patients with diabetes. The inflection point for HbA1c was determined to be 6.1%. For HbA1c values ≤ 6.1%, an inverse association was observed between HbA1c and 3-month adverse clinical outcomes in diabetic AIS patients, and each 1% increase in HbA1c in AIS patients with DM was associated with an 87% reduction in 3-month adverse clinical outcomes (OR = 0.13, 95% CI: 0.02-0.81). Conversely, when HbA1c exceeded 6.1%, a positive association between HbA1c and 3-month adverse clinical outcomes became apparent in diabetic AIS patients, and each 1% increase in HbA1c in AIS patients with DM was associated with a 23% increase in 3-month adverse clinical outcomes (OR = 1.23, 95%CI: 1.03-1.47). However, it's important to note that no significant linear or nonlinear relationships were observed between HbA1c levels and 3-month adverse clinical outcomes in AIS patients without diabetes. CONCLUSION: Our findings suggest a nonlinear connection and threshold effect between HbA1c and 3-month adverse clinical outcomes in AIS patients with diabetes. AIS patients with diabetes had a lower risk of 3-month adverse clinical outcomes when their HbA1c control was close to 6.1%. Our findings may aid treatment decision-making and potentially guide interventions to optimize glycemic control in AIS patients.

Link between triglyceride-glucose-body mass index and future stroke risk in middle-aged and elderly chinese: a nationwide prospective cohort study.

OBJECTIVE: Current literature is deficient in robust evidence delineating the correlation between the triglyceride glucose-body mass index (TyG-BMI) and the incidence of stroke. Consequently, this investigation seeks to elucidate the potential link between TyG-BMI and stroke risk in a cohort of middle-aged and senior Chinese individuals. METHODS: This study employs longitudinal data from four waves of the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2011, 2013, 2015, and 2018, encompassing 8,698 participants. The CHARLS cohort was assembled using a multistage probability sampling technique. Participants underwent comprehensive evaluations through standardized questionnaires administered via face-to-face interviews. Our analytic strategy involved the application of Cox proportional hazards regression models to investigate the association between TyG-BMI and the risk of stroke. To discern potential non-linear relationships, we incorporated Cox proportional hazards regression with smooth curve fitting. Additionally, we executed a battery of sensitivity and subgroup analyses to validate the robustness of our findings. RESULTS: Our study utilized a multivariate Cox proportional hazards regression model and found a significant correlation between the TyG-BMI and the risk of stroke. Specifically, a 10-unit increase in TyG-BMI corresponded to a 4.9% heightened risk of stroke (HR = 1.049, 95% CI 1.029-1.069). The analysis also uncovered a non-linear pattern in this relationship, pinpointed by an inflection point at a TyG-BMI value of 174.63. To the left of this inflection point-meaning at lower TyG-BMI values-a 10-unit hike in TyG-BMI was linked to a more substantial 14.4% rise in stroke risk (HR 1.144; 95% CI 1.044-1.253). Conversely, to the right of the inflection point-at higher TyG-BMI values-each 10-unit increment was associated with a smaller, 3.8% increase in the risk of stroke (HR 1.038; 95% CI 1.016-1.061). CONCLUSIONS: In the middle-aged and elderly Chinese population, elevated TyG-BMI was significantly and positively associated with stroke risk. In addition, there was also a specific non-linear association between TyG-BMI and stroke (inflection point 174.63). Further reduction of TyG-BMI below 174.63 through lifestyle changes and dietary control can significantly reduce the risk of stroke.

Relationships between triglyceride-glucose index and incident gestational diabetes mellitus: a prospective cohort study of a Korean population using publicly available data.

Background: The connection between the triglyceride-glucose index (TyG index) and gestational diabetes mellitus (GDM) is currently debated. Our study aimed to investigate the connection between the TyG index and GDM within the Korean population. Methods: Using publically accessible data in Korea, we performed a secondary study on a sample of 589 pregnant women who were carrying a single fetus. The analysis employed a binary logistic regression model, some sensitivity analyses, and subgroup analysis to investigate the association between the TyG index and the occurrence of GDM. To assess the TyG index's potential to predict GDM, a receiver operating characteristic (ROC) study was also carried out. Results: The mean age of the pregnant women was 32.065 ± 3.798 years old, while the mean TyG index was 8.352 ± 0.400. The prevalence rate of GDM was found to be 6.112%. Upon adjusting for potential confounding variables, a positive association was detected between the TyG index and incident GDM (OR = 12.923, 95%CI: 3.581-46.632, p = 0.00009). The validity of this connection was further confirmed by subgroup analysis and sensitivity analyses. With an area under the ROC curve of 0.807 (95%CI: 0.734-0.879), the TyG index showed strong predictive power for GDM. The TyG index's ideal cutoff value for detecting GDM was found to be 8.632, with a sensitivity of 78.7% and a specificity of 72.2%. Conclusion: The findings of our study provide evidence that an increased TyG index is significantly associated with the occurrence of GDM. Utilizing the TyG index during the 10-14 week gestational period may be a valuable tool in identifying pregnant individuals at a heightened risk for developing GDM. Early detection enables timely and efficacious interventions, thereby enhancing the prognosis of affected individuals.