BACKGROUND:Acute hypoxemic respiratory failure (AHRF) is a critical syndrome frequently encountered in intensive care, characterized by substantial pathophysiological heterogeneity and poor clinical outcomes. Traditional static risk assessments based on a single time point struggle to capture the dynamic physiological responses to early interventions, thereby limiting precise risk stratification. This study aimed to identify distinct clinical phenotypes in patients with AHRF using dynamic arterial blood gas (ABG) trajectories during early intensive care unit (ICU) stay and evaluate their association with 28-day mortality. METHODS:This was a single-center retrospective cohort study including patients with AHRF admitted to the ICU of Sichuan Provincial People's Hospital between January 2020 and June 2025. Multiple ABG parameters within the first 24 h of ICU admission-including PaO2/FiO2, PaCO2, pH, HCO₃-, and lactate-were extracted to construct longitudinal trajectory features. Unsupervised K-means clustering was performed to identify dynamic clinical phenotypes. Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression models (adjusted for iatrogenic confounding variables such as the 24-h ABG sampling frequency) were utilized to assess the association between phenotypes and 28-day survival outcomes. The incremental predictive value of the phenotypes relative to the APACHE II score was evaluated using the concordance index (C-index). RESULTS:A total of 2793 patients with AHRF were included and classified into three distinct clinical phenotypes with unique physiological evolution patterns: Phenotype 1 (Respiratory, n = 882), Phenotype 2 (Metabolic, n = 683), and Phenotype 3 (Stable, n = 1228). Phenotype 2 was characterized by persistent hyperlactatemia and profound oxygenation impairment, exhibiting the highest ICU mortality (18%), 28-day mortality (24%), and hospital mortality (18%) among the three groups. Kaplan-Meier analysis indicated that the 28-day overall survival for Phenotype 2 was significantly worse than that of the other two groups (log-rank P < 0.001). Multivariable Cox regression demonstrated that after adjusting for age, gender, APACHE II score, mechanical ventilation, 24-h ABG sampling frequency, and routine laboratory biomarkers (WBC, creatinine, AST, ALT), Phenotype 2 (Metabolic)remained independently associated with an increased 28-day mortality risk compared with Phenotype 1 (Respiratory, HR = 1.38, 95% CI: 1.12-1.70, P = 0.003). The ABG sampling frequency itself showed no independent association with mortality (HR = 1.01, 95% CI: 0.94-1.10, P = 0.773). Phenotype 3 (Stable) showed a trend toward reduced mortality risk (HR = 0.83, 95% CI: 0.67-1.00, P = 0.104). Integrating dynamic phenotypes into the baseline prediction model significantly improved the C-index for predicting 28-day mortality from 0.657 to 0.671 (P < 0.001). CONCLUSIONS:Unsupervised clustering based on early dynamic ABG trajectories effectively identifies three distinct clinical phenotypes with divergent prognostic features in patients with AHRF. Phenotype 2 (Metabolic) denotes a substantially higher 28-day mortality risk, whereas Phenotype 3 (Stable) confers a relatively favorable outcome. This dynamic subphenotyping framework provides valuable incremental prognostic information beyond traditional static scoring systems.

It is still unclear how the risk of cardiovascular disease (CVD) changes across life course and the specific influence of body mass index (BMI) on risk trajectory. We included 106,962 participants aged 35–74 from a Chinese longitudinal cohort during 1992 to 2021 with 4 repeated measurements. China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) equation was applied to calculate 10-year CVD risk. General additional mixed model and Joinpoint model were used to elaborate CVD risk trajectory and the potential benefits of normal BMI. The 10-year CVD risk for Chinese adults increased from 1.11

Background and objectiveTo investigate the relationship between inflammation and hypertension by comparing epigenetic and serum biomarkers of inflammation and their association with target organ damage (TOD).MethodsThe epigenome-wide methylation profiles of peripheral leukocyte DNA from 176 patients with hypertension were analyzed using Illumina Infinium Methylation EPIC BeadChips. The commercially available Olink® Target 96 Inflammation panels were utilized to evaluate markers associated with inflammation. We identified CpG-protein association protein quantitative trait methylation loci (pQTMs) using mixed linear regression, adjusting for potential confounders. The possible roles of the discovered pQTMs were ascertained by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analyses. The association between pQTMs and TOD was also analyzed.ResultsIn our analysis, we found 771 significant associations across 11 biomarkers, with a false discovery rate (FDR) of less than 0.05. Lambda estimates ranged from 0.847 to 1.202. Among these, 39 pQTMs showed an association with urine albumin-creatinine ratio, while 82 pQTMs showed an association with carotid intima-media thickness.ConclusionOur findings contribute to the understanding of inflammatory biomarkers associated with alterations in DNA methylation in hypertension. However, these results will need to be validated in future studies.

The distal-to-proximal pressure ratio (dpPR) has emerged as a superior indicator compared to the diameter stenosis rate (DSR) for assessing the functional severity of carotid artery stenosis (CAS). However, unlike DSR, dpPR cannot be directly determined by vascular imaging. In this study, we developed a hemodynamic modeling method to predict dpPR based on medical images available in clinical settings. A multiscale modeling method was employed to integrate a three-dimensional (3D) hemodynamic model of CAS into a lumped-parameter model of systemic hemodynamics, while incorporating patient-specific geometric information of large cerebral arteries derived from computed tomography angiography (CTA) images. The 3D modeling method was validated through in vitro fluid dynamics experiments, while the accuracy of the resulting multiscale model in predicting dpPR was evaluated by comparing model predictions with invasive pressure wire measurements. The model-predicted dpPR values for 27 carotid artery stenoses demonstrated strong agreement with invasive measurements, with a mean relative error of − 0.8

Trans-stenotic pressure ratio (herein denoted by dpPR) has been proposed as a complementary index to stenosis rate (SR) for assessing the functional severity of carotid artery stenosis (CAS); however, it remains unclear how well dpPR can indicate cerebral ischemia. In this study, a physiology-based computational model of the cerebral circulation was developed to yield a tool for generating large-scale in silico data to characterize the changes of the dpPR of the left internal CAS in response to variations in SR and various anatomical/pathophysiological factors that represent inter-patient differences. In addition, a cerebral ischemia index (CII) was defined to evaluate the predictive value of dpPR for cerebral ischemia. Results showed that dpPR was affected by many factors unrelated to the severity of stenosis, such as the anatomical structure and geometrical size of cerebral arteries, mean systemic arterial blood pressure (MAP), flow autoregulation function of cerebral microcirculation (quantified by CFAI), and coexisting contralateral CAS. In comparison with SR, dpPR exhibited a stronger correlation with CII. In particular, the relationship between dpPR and CII was found to be describable by a mathematical function if MAP and CFAI were fixed. The findings not only deepen our understanding of the physiological implications of dpPR but also provide valuable theoretical insights to guide the application of dpPR in clinical practice.

This study aimed to evaluate the clinical efficacy of indocyanine green angiography (ICGA) in optimising anterolateral thigh (ALT) flap reconstruction for oral and maxillofacial defects. Fifteen consecutive patients (10 males, mean (SD) age 53.8 (14.5) years) undergoing ALT flap reconstruction following tumour resection were prospectively enrolled. Intravenous indocyanine green (ICG) (2.5 mg/ml) administration combined with hand-held Doppler ultrasound (DUS) enabled preoperative mapping of the descending branch of the lateral circumflex femoral artery and localisation of the perforator. Intraoperative real-time ICGA guidance facilitated precise flap trimming, while postoperative monitoring incorporated both DUS and ICGA assessments. Preoperative imaging revealed comparable perforator detection rates between modalities (DUS: 35/42 confirmed vs ICGA: 33/39 confirmed; accuracy 83.3% vs 84.6%, Z = 0.096, p = 0.081, kappa = 0.82, p = 0.026). ICGA-guided intraoperative modifications proved critical in seven cases, all achieving marginal flap viability. Four high-risk patients avoided reoperation through ICGA-guided perfusion monitoring. Notably, ICGA detected salvageable perfusion in two cases with absent DUS signals, and confirmed arterial patency following re-anastomosis in one case. ICGA enhances surgical precision in ALT flap reconstruction through perfusion mapping, enabling real-time intraoperative decision-making and improved postoperative monitoring sensitivity.

Background: The specific effects of different exercises on cardiovascular health remain unclear. This study aimed to compare the effects of acute anaerobic threshold intensity continuous exercise (ATE), high-intensity interval training (HIIT), and stepwise incremental exercise (SIE) on heart rate variability (HRV) and vascular endothelial function in sedentary college students. Methods: Thirty-five sedentary students were randomized to the ATE group (20.6 ± 2.4 years), the HIIT group (21.7 ± 4.2 years), or the SIE group (21.2 ± 2.8 years). Brachial artery flow-mediated dilation was measured at 10 and 30 minutes after exercise. HRV was measured within 35 minutes postexercise. Results: It showed that the normalized low frequency postexercise was lower than baseline in the ATE group ( P < .05). Flow-mediated dilation was decreased ( P = .006) 30 minutes after exercise (6.4 ± 2.2%) compared to baseline (8.1 ± 1.4%) in the HIIT group and increased (+1.4%) in the ATE group with no statistical difference ( P > .05). Significant correlations were detected between HRV frequency domain indices and brachial artery baseline diameter ( P < .05). Conclusion: Acute HIIT impairs vascular function 30 minutes after exercise, whereas acute ATE improves vascular function 10 minutes after exercise. Changes in vascular function may be related to changes in autonomic nervous system activity induced by acute exercise.

Uric acid (UA) is essential in the physiological and pathophysiological processes of various diseases. The linkage between serum uric acid (SUA) levels and epilepsy has been investigated by observational studies. However, these findings are susceptible to confounding factors, making the causal relationship unelucidated. This project aimed to apply Mendelian randomization (MR) to clarify the causal linkage between SUA and epilepsy. We utilized data from GWAS and the UK Biobank to analyze the causal link between SUA and epilepsy by utilizing the two-sample bidirectional MR method. Additionally, SUA data from the Global Urate Genetics Consortium and epilepsy data from the International League Against Epilepsy were included as validation sets. The two-sample bidirectional MR analysis yielded no evidence of a causal relationship between SUA and epilepsy. Similar results were generated by analyzing the validation set data. Sensitivity analysis and heterogeneity test confirmed that there was no pleiotropy or heterogeneity in instrumental variables. The MR results of this project were robust. Our project does not give compelling evidence of a significant causal link between SUA and epilepsy.

Background: Whereas a potential connection between epilepsy and frailty has been proposed in past research, the causal nature of this relationship requires additional study. Objective: This research was designed to evaluate the bidirectional causality between epilepsy and frailty index (FI) through 2-sample Mendelian randomization (MR). Methods: In this study, we applied genome-wide association studies to perform forward and reverse MR within a 2-sample context to explore the potential bidirectional causality between FI and epilepsy. The main analysis approach was the inverse variance weighted (IVW) used to assess the potential influence of causal relationships and to carry out sensitivity checks. Results: MR analysis revealed a positive correlation between FI and the heightened risk of epilepsy [ORIVW = 1.2126, 95% confidence interval (CI): 1.0143-1.4497, P = 0.0343]. This correlation persists in MR analysis that excluded aberrant single nucleotide polymorphisms (ORIVW = 1.1862, 95% CI: 1.0236-1.3746, P = 0.0232). Reverse MR analysis corroborated a significant positive relationship between epilepsy and FI (ORIVW=1.0896, 95% CI: 1.0242-1.1592, P = 0.0066), which was confirmed in subsequent replication analysis (ORIVW = 1.0975, 95% CI: 1.0532-1.1436, P = 9.69e-06). Sensitivity analysis further supported the hypothesis of a causal link between FI and epilepsy. Conclusion: There is an evident bidirectional causal relationship between FI and epilepsy.

AbstractBackgroundWe aim to analyze the effect of home blood pressure (HBP) level and variability on both asymptomatic intracranial (aICAS) and extracranial arterial stenosis (aECAS).MethodsA total of 534 patients completed HBP measurements (HBP) on at least 3 days. The stenoses of ICAS and ECAS were evaluated by CTA. HBP variability (HBPV) was quantified using the standard deviation and maximum--minimum difference between measures. The association of HBP level and variability with both aICAS and aECAS was evaluated using multivariate logistic regression.ResultsMorning HBPV was significantly associated with isolated aICAS, isolated aECAS, and concurrent aICAS and aECAS, respectively, even after being adjusted for HBP level. Besides, HBP were independently related to concurrent aICAS and aECAS (P<0.05). Instead, neither morning nor evening HBP associated with isolated aICAS or aECAS.ConclusionThe findings of this study confirmed the strong correlation of aICAS/aECAS with HBP in the hypertensive population, particularly morning HBPV.

BACKGROUND:Despite advances in understanding hypertension's genetic structure, how noncoding genetic variants influence it remains unclear. Studying their interaction with DNA methylation is crucial to deciphering this complex disease's genetic mechanisms. METHODS:We investigated the genetic and epigenetic interplay in hypertension using whole-genome bisulfite sequencing. Methylation profiling in 918 males revealed allele-specific methylation and methylation quantitative trait loci. We engineered rs1275988T/C mutant mice using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9), bred them for homozygosity, and subjected them to a high-salt diet. Telemetry captured their cardiovascular metrics. Protein-DNA interactions were elucidated using DNA pull-downs, mass spectrometry, and Western blots. A wire myograph assessed vascular function, and analysis of the Kcnk3 gene methylation highlighted the mutation's role in hypertension. RESULTS:We discovered that DNA methylation-associated genetic effects, especially in non-cytosine-phosphate-guanine (non-CpG) island and noncoding distal regulatory regions, significantly contribute to hypertension predisposition. We identified distinct methylation quantitative trait locus patterns in the hypertensive population and observed that the onset of hypertension is influenced by the transmission of genetic effects through the demethylation process. By evidence-driven prioritization and in vivo experiments, we unearthed rs1275988 in a cell type-specific enhancer as a notable hypertension causal variant, intensifying hypertension through the modulation of local DNA methylation and consequential alterations in Kcnk3 gene expression and vascular remodeling. When exposed to a high-salt diet, mice with the rs1275988C/C genotype exhibited exacerbated hypertension and significant vascular remodeling, underscored by increased aortic wall thickness. The C allele of rs1275988 was associated with elevated DNA methylation levels, driving down the expression of the Kcnk3 gene by attenuating Nr2f2 (nuclear receptor subfamily 2 group F member 2) binding at the enhancer locus. CONCLUSIONS:Our research reveals new insights into the complex interplay between genetic variations and DNA methylation in hypertension. We underscore hypomethylation's potential in hypertension onset and identify rs1275988 as a causal variant in vascular remodeling. This work advances our understanding of hypertension's molecular mechanisms and encourages personalized health care strategies.

OBJECTIVES:Intracerebral hemorrhage (ICH) is a severe neurological disorder with substantial societal implications. Cellular senescence plays a critical role in ICH pathogenesis. This study aims to identify senescence-related biomarkers in ICH for diagnostic and therapeutic purposes. METHODS:Raw data from GSE24265 in Gene Expression Omnibus was downloaded. Senescence-related genes were acquired from CellAge. Differential gene analysis was done between patients with ICH and controls. The intersection of ICH differentially expressed genes and senescence-related genes for senescence-related ICH genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. Protein-protein interaction network was constructed through the Search Tool for the Retrieval of Interacting Genes. Single sample gene set enrichment analysis was done for immune cell infiltration and function evaluation in control and ICH groups. miRWalk2.0 database was used for microRNA predictions targeting ICH biomarkers. Transcriptional regulatory relationships unraveled by sentence-based text mining database was employed to predict transcription factors regulating identified biomarkers. RESULTS:Thirteen senescence-related ICH genes were identified. They were primarily enriched in the positive regulation of angiogenesis and the Advanced Glycation End Product -Receptor for AGE signaling pathway in diabetic complications. Validation in the GSE149317 data set and receiver operating characteristic analysis highlighted Caveolin 1, C-X-C Motif Chemokine Ligand 1, ETS proto-oncogene 1, transcription factor, and Serpin Family E Member 1 as potential ICH biomarkers. Single sample gene set enrichment analysis revealed increased Type 2 T helper cell 2_cells, Treg cells, and immune functions like Antigen-presenting cells_co_stimulation in patients with ICH. Fourteen microRNA, including has-miR-6728-3p, were predicted to regulate these biomarkers. transcription factors such as PPARG, RARA, HMGA1, and NFKB1 were identified as potential regulators of the ICH biomarkers. CONCLUSION:Caveolin 1, C-X-C Motif Chemokine Ligand 1, ETS proto-oncogene 1, transcription factor, and Serpin Family E Member 1 may serve as valuable biomarkers in ICH. Targeting these genes could contribute to ICH prevention and treatment.

ObjectiveThis study aimed to explore the relationship between total burden of cerebral small vessel disease (CSVD) and daytime and nighttime heart rate variability (HRV) parameters.MethodConsecutive patients with nondisabling ischemic cerebrovascular events were recruited from the cerebrovascular disease clinic of Changzhou Second People's Hospital between January 2022 and June 2023. A total of 144 enrolled participants were divided into a mild CSVD group (74 patients) and a moderate-to-severe CSVD group (70 patients) based on total burden of CSVD. Various HRV parameters measured during 24-h, 4-h daytime, and 4-h nighttime periods (including natural log–transformed [ln] root mean square of successive RR interval differences [RMSSD], ln absolute power of the high-frequency band [0.15–0.4 Hz] [HF], ln absolute power of the low-frequency band [0.04–0.15 Hz][LF], and LF-to-HF ratio [LF/HF]) were then assessed in the 2 groups. Spearman correlation analysis was used to assess the correlation between total burden of CSVD and HRV parameters. HRV parameters with P-value < 0.05 in correlation analysis were included in the multivariable logistic regression analysis, and restricted cubic spline analysis was performed to assess dose-response relationships.ResultsDaytime 4-h lnRMSSD (r = –0.221; P = 0.008) and 4-h lnHF (r = –0.232; P = 0.005) were negatively correlated with total burden of CSVD, and daytime 4-h lnLF/HF (r = 0.187; P = 0.025) was positively correlated with total burden of CSVD. There was no correlation between nighttime HRV parameters and total burden of CSVD. After adjustments were made for potential confounders, daytime 4-h lnRMSSD (OR = 0.34; 95% CI: 0.16–0.76), 4-h lnHF (OR = 0.57; 95% CI: 0.39–0.84), and 4-h lnLF/HF (OR = 2.12; 95% CI: 1.18–3.82) were independent predictors of total burden of CSVD (all P < 0.05). S-shaped linear associations with moderate-to-severe total burden of CSVD were seen for daytime 4h-lnRMSSD (P for nonlinearity = 0.543), 4-h lnHF (P for nonlinearity = 0.31), and 4-h lnLF/HF (P for nonlinearity = 0.502).ConclusionDaytime parasympathetic HRV parameters are independent influencing factors of total burden of CSVD and may serve as potential therapeutic observation indicators for CSVD.

Cardiometabolic index (CMI) is a comprehensive clinical parameter which integrates overweight and abnormal lipid metabolism. However, its relationship with all-cause, cardiovascular disease (CVD), and cancer mortality is still obscure. Thus, a large-scale cohort study was conducted to illustrate the causal relation between CMI and CVD, cancer, and all-cause mortality among the common American population. Our research was performed on the basis of National Health and Nutrition Examination Survey (NHANES) database, involving 40,275 participants ranging from 1999 to 2018. The formula of CMI is [waist circumference (cm) / height (cm)] × [triglyceride (mg/dL) / high-density lipoprotein cholesterol (mg/dL)]. Outcome variables consisted of CVD, cancer, and all-cause mortality, which were identified by the International Classification of Diseases (ICD)-10. The correlation between CMI and mortality outcomes was analyzed utilizing the Kaplan–Meier survival modeling, univariate/multivariate Cox regression analysis, smooth curve fitting analysis, threshold effect analysis, and subgroup analysis. Stratification factors for subgroups included age, race/ethnicity, sex, smoking behavior, drinking behavior, BMI, hypertension, and diabetes. The baseline characteristics table includes 4,569 all-cause-induced death cases, 1,113 CVD-induced death cases, and 1,066 cancer-induced death cases. Without adjustment for potential covariates, significantly positive causal correlation existed between CMI and all-cause mortality (HR = 1.03, 95

On 18 December 2023, a 6.2-magnitude earthquake struck Jishishan, affecting multiple counties and cities in Gansu and Qinghai Provinces. The seismic intensity of the meizoseismal area was VIII, resulting in extensive structural damage and building collapses. A damage assessment was conducted of the epicenter and surrounding high-intensity zones. To understand the typical structures and characteristics of the buildings that were damaged in these high-intensity zones, this study summarizes the characteristics of the damage to typical rural houses, compares the damage of the rural houses across different sites, and analyzes the causes behind these variations. The findings of the study indicate the following: (1) Timber and some brick–timber structures, due to their age, insufficient material strength, and lack of adequate connections between parts of the building, primarily experienced severe damage or total collapse, characterized by through-wall cracks, partial collapses, or complete collapses. (2) Brick–concrete structures predominantly suffered moderate to severe damage due to factors such as improper layout, uneven façades, and inadequate or incomplete seismic measures. The observed damage included significant wall cracks and extensive damage to two-story buildings. (3) Frame structures, mainly used for public facilities like schools, hospitals, and health centers, exhibited strong integrity and excellent seismic performance, resulting in minimal to no damage, with damage largely confined to non-load-bearing components. (4) The amplification effects of seismic waves in thick loess basin areas, slope sites, and the hanging wall effect of faults exacerbated structural damage to rural houses located in certain villages within the high-intensity areas. The results of this study can serve as a reference for post-disaster reconstruction and seismic retrofitting of buildings and contribute positively to enhancing the disaster resilience of rural housing.

Objectives To determine the independent effect of high-sensitivity C-reactive protein (hs-CRP) and the combined effects of hs-CRP and other traditional risk factors on microalbuminuria in hypertensive patients during the 3-year follow-up period. Methods and results Baseline hs-CRP levels and other risk factors were measured in 280 adults in 2007. In the third year of examination, 199 patients (mean age 62.5 ± 9.5, men 59.3%) were approached for the measurement of microalbuminuria. The subjects were classified into two groups by the median of baseline hs-CRP. Compared to the patients with baseline hs-CRP below the median group ( n = 99, 50%), the group with baseline hs-CRP above the median ( n = 100, 50%) had higher urinary albumin-to-creatinine ratio (ACR) ( P = 0.007) at the end of follow-up period. ACR at the end of follow-up period was significantly correlated with baseline diabetes ( β = 0.342; P < 0.001), baseline SBP ( β = 0.148; P = 0.02), and baseline log-transformed hs-CRP ( β = 0.169; P = 0.01), while adversely correlated with baseline estimated glomerular filtration rate (eGFR) ( β = −0.163; P = 0.02) in multivariate stepwise linear analysis. In addition, ACR change during follow-up period was significantly correlated with baseline diabetes ( β = 0.359; P < 0.001) and baseline log-transformed hs-CRP ( β = 0.190; P = 0.004) in multivariate stepwise linear analysis. The combined effects of baseline hs-CRP and conventional risk factors, such as male sex, diabetes, smoking status, hyperlipidemia, hyperuricemia, and mildly reduced eGFR had a greater risk for microalbuminuria progression. There was no difference in eGFR changes during the follow-up period between two groups. Conclusion Our findings offer a new piece of evidence on the predictive value of baseline hs-CRP for microalbuminuria progression in essential hypertensive patients, and highlight those who combined with traditional cardiovascular risk factors had a greater risk for developing microalbuminuria.