Zhiming Yu

Background: Metabolic surrogate indices are increasingly used in atrial fibrillation (AF), but several algebraically incorporate body mass index (BMI). We examined whether their associations with left atrial diameter (LAD) provide information beyond a simple anthropometric benchmark. Methods: We analyzed 788 patients in a primary AF cohort and 813 in a replication cohort. Seven prespecified metabolic surrogate indices were compared with BMI using harmonized linear models. We evaluated adjusted associations and incremental R² (ΔR²), partitioned shared and unique ΔR² by commonality analysis, and quantified BMI-index ΔR² differences by paired bootstrap resampling. Sensitivity analyses addressed body-size indexing, additional height/BSA covariate adjustment, AF-phenotype stratification, and covariate specification. Results: Indices without BMI in their formulas—TyG, TG/HDL-C, TG/G, and CHG—added little ΔR² in either cohort (all <0.4 percentage points). SPISE, TyG-BMI, and METS-IR contributed 5.66, 4.79, and 4.45 percentage points in the primary cohort and 3.57, 3.51, and 3.35 percentage points in the replication cohort, versus 6.23 and 4.29 percentage points for BMI. Most ΔR² of the BMI-containing indices was shared with BMI, whereas index-unique components were small. Bootstrap comparisons supported numerically similar or greater ΔR² for BMI, although confidence intervals did not uniformly exclude zero. Height-adjusted raw-LAD models preserved the comparative pattern, whereas additional BSA adjustment substantially attenuated BMI-related associations, supporting a body-size/allometric component. Conclusions: Indices without BMI in their formulas added little ΔR² for contemporaneous LAD, whereas BMI-containing composites derived most of their ΔR² from variance shared with BMI. BMI provided numerically similar or greater ΔR², although paired bootstrap comparisons were not statistically distinguishable for all comparisons. Additional body-size covariate analyses indicated that a substantial component of these associations may reflect body-size/allometric structure. BMI should therefore be an explicit benchmark when evaluating metabolic surrogate indices for left atrial size.

Background: Cryoballoon ablation (CBA) for atrial fibrillation (AF) is associated with reduced procedural radiation exposure as operator experience accumulates, yet the mechanistic underpinning of this improvement remains incompletely characterized. We hypothesized that ablation temperature parameters, reflecting balloon-tissue contact quality, serve as a quantifiable mediator linking operator experience to radiation dose. Methods: We retrospectively analyzed 804 consecutive patients undergoing first-time CBA for symptomatic AF at a single tertiary center. Cumulative sum (CUSUM) analysis identified learning curve inflection points. Patients were stratified into early ( n = 385) and plateau ( n = 419) phases. Multivariable linear regression, restricted cubic spline (RCS) analysis, and formal causal mediation analysis (bootstrap 1,000 iterations) were performed to evaluate worst pulmonary vein (PV) minimum temperature as a mediator between learning curve phase and log-transformed radiation dose. Results: CUSUM analysis identified learning curve inflection points at case 385 (procedural time), 301 (radiation dose), and 329 (fluoroscopy time). Compared with the early phase, median radiation dose in the plateau phase decreased by 15.4% (506 vs. 428 mGy, p < 0.001), procedural time by 27.0% (89 vs. 65 min, p < 0.001), and fluoroscopy time by 26.3% (19 vs. 14 min, p < 0.001). In multivariable analysis (adjusted R ² = 0.509), worst PV minimum temperature was an independent predictor of radiation dose (exp[β] = 1.012 per °C, 95% CI 1.008–1.017, p < 0.001), as was plateau phase (exp[β] = 0.895, 95% CI 0.847–0.946, p < 0.001). BMI exhibited a significant nonlinear association with radiation dose ( p for nonlinearity < 0.001), with an inflection threshold near 25 kg/m ² . Mediation analysis demonstrated that worst PV minimum temperature mediated 14.5% (95% CI 5.5%–35.4%) of the total learning curve effect on radiation dose (average causal mediation effect [ACME] p < 0.001; performed on 734 patients with complete mediator data). Conclusions: Greater operator experience was associated with lower radiation exposure and more favorable cryoablation temperature profiles. Worst PV nadir temperature statistically mediated a modest proportion of the association between learning curve phase and radiation dose, although most of the association remained unexplained by this temperature metric. These findings support a potential role of balloon–tissue contact quality in experience-related procedural improvement but should be interpreted as hypothesis-generating rather than evidence of a causal mechanism or improved clinical outcomes.

Background: Composite metabolic-oxidative scores have shown inconsistent associations with cognitive outcomes, yet whether their components move in the same direction remains unexamined. Objective: To test whether Metabolic Oxidative Risk Score (MORS) tracks cognitive change, and to decompose MORS to assess whether component effects on cognitive slope are concordant or opposing. Methods: We constructed a four-component MORS (uric acid, triglycerides, fasting glucose, reverse-scored HDL; range 4–20) and examined its association with cognitive change across four waves (2011–2018) in CHARLS (N = 7,300, age ≥ 45 years) using linear mixed models. Equivalence testing distinguished null findings from insufficient power. Components were decomposed individually and simultaneously. Cross-sectional triangulation used NHANES 2011–2014 (N = 1,340, age ≥ 60 years). Results: The adjusted MORS × time interaction was β = −0.00046 SD/year (95% CI −0.00185 to 0.00093; p = 0.516); equivalence testing rejected any clinically meaningful effect (p = 0.0002). Component decomposition revealed opposing effects: higher uric acid predicted steeper decline (β = −0.0055; p = 0.003) while higher triglycerides predicted attenuated decline (β = + 0.0042; p = 0.045), with near-perfect cancellation at the composite level. In NHANES, the MORS–cognition association reversed sign after socioeconomic adjustment and showed a significant non-linear association (p = 6 × 10 ⁻⁴ ); leave-one-out analysis identified uric acid as the dominant signal carrier. Conclusions: An equal-weight metabolic-oxidative composite does not track cognitive decline because its components exert opposing effects that cancel. Uric acid emerges as an independent, potentially modifiable risk factor with implications for Alzheimer's disease prevention research.

Oxidative stress and chronic inflammation share common upstream triggers and can mutually reinforce each other; however, few tools based on routine blood biomarkers are available to capture this interplay in Chinese adults. Using data from 6,044 participants in the 2009 China Health and Nutrition Survey (CHNS), a large multi-provincial population-based study, we developed a composite serum oxidative stress-related biomarker score (COSBS), hereafter referred to as a serum redox-metabolic biomarker score to reflect its overlap with metabolic phenotypes.The score was constructed by summing quintile-based points for six fasting biomarkers: uric acid, triglycerides, fasting glucose, and ferritin as pro-oxidant components, and HDL cholesterol and magnesium as antioxidant components, yielding a total score ranging from 6 to 30. Equal weighting was applied because no validated differential weights exist for this population and to avoid circularity with the outcome. Reliability and structural properties of COSBS were preliminarily evaluated using Cronbach's α (0.615) and principal component analysis (PC1 = 35.5% of variance), reflecting acceptable but moderate internal consistency for a heterogeneous biomarker panel. COSBS effectively discriminated established high-risk groups (all P < 0.001). Analyses did not apply post-stratification weights; a cluster-robust sensitivity analysis confirmed that community-level clustering did not alter conclusions. Each one-unit increase in COSBS was independently associated with higher log(hs-CRP) (β = 0.0255, 95% CI: 0.0213-0.0297, P = 1.73 × 10⁻³²), with a strictly linear dose-response relationship (P for non-linearity = 0.372). Results were consistent across all pre-specified subgroups and sensitivity analyses, including a clinical threshold count score (β = 0.081, P = 5.51 × 10⁻²⁸). These findings suggest that COSBS, derived entirely from routine blood tests, is independently and linearly associated with systemic inflammation as reflected by hs-CRP, providing a reproducible exposure index for population-based research on oxidative-inflammatory burden. Independent external validation in NHANES 2015-2018 (n = 2,752 U.S. adults) replicated the association directionally and quantitatively (β = 0.048, P = 2.33 × 10⁻¹³; 25.2% higher geometric mean hs-CRP per SD of COSBS-5), supporting cross-population generalizability. Prospective validation against hard endpoints is required before any clinical application can be considered.

Early repolarization syndrome (ERS) was initially thought to be a good prognostic manifestation detectable by electrocardiogram. In recent years, with the gradual deepening of research and understanding, ERS is considered to possess malignant tendency and related to ventricular fibrillation (VF) and sudden cardiac death (SCD). Implantable cardioverter defibrillator (ICD) is currently the first choice of treatment used to reduce the risk of potentially life-threatening arrhythmias and SCD in patients at high risk for ERS. The stress of living with an implanted device and receiving ICD shock has been noted to exert a psychological toll on patients, especially those who have previously experienced VF and syncope. The current case report describes symptoms and signs of a patient with ERS, and discusses the changes of psychological condition after ICD implantation. Moreover, we explored a targeted treatment approach for anxiety and depression in an individual with an ICD for ERS, which combined medication, cognitive behavioral therapy, and physical exercise. We believe that the psychological experience of ICD recipients, which is a critical component in designing the biopsychosocial therapeutic approach for this growing patient population, is worthy of more attention.

Background: The purpose of this systematic review and meta-analysis was to determine the effects of SGLT2 inhibitors on major heart failure outcomes (such as HHF and CVD) in patients with heart failure and preserved ejection fraction Methods: We searched four English databases from inception to February 14, 2023. The primary efficacy outcome was a composite of hospitalization for HF (HHF) or cardiovascular death (CVD). Two reviewers independently screened literature and extracted data. Fixed-effects models were used to estimate pooled Hazard risks (HRs) for binary outcomes, and weighted mean differences for continuous outcomes with 95% confidence intervals. Results: We included data from five randomized controlled trials (RCTs) comprising data for 15733 patients. The composite outcome of hospitalization for HF (HHF) or cardiovascular death (CVD) was reduced with SGLT2 inhibitor therapy compared with placebo (HR 0.80, 95%CI 0.74–0.87,P0.05). Conclusions: SGLT2 inhibitors can significantly reduce the hospitalization rate for heart failure and the composite endpoint of cardiovascular mortality or hospitalization for heart failure in patients with heart failure and preserved ejection fraction. Further RCTs with sufficient representation of patients in this population are warranted to corroborate our analysis.

A connection exists between hypertension (HTN) and cognitive impairment (CI) or gut microbiota (GM) and neuropsychiatric disease. However, the link between GM and HTNCI has not been illustrated. This study endeavoured to profile the landscape of GM in HTNCI patients and evaluate the value of GM as HTNCI biomarkers. We recruited 128 patients with hypertension and assigned them to two groups of different MoCA scores. Clinical and biological data were recorded. GM composition was illustrated with 16S ribosomal RNA sequencing, and the dominant species were identified by linear discriminant analysis Effect Size (LEfSe). It showed higher abundance of TM7 and lower abundances of Veillonella and Peptoniphilus in the HTNCI group than in the HTN without cognitive impairment (HTNnCI) group. We next clarified the link between GM and MoCA scores or HTNCI factors. KEGG analysis revealed the involvement of decreased bile secretion. An evident correlation showed up between HTNCI and Veillonella abundance ( ). We concluded that some representative GM species, especially Veillonella, could predict cognitive impairment in hypertension patients, making them potential benchmarks of HTNCI.

Background Diabetes is associated with a high risk of developing cognitive impairment, but the underlying mechanism remains unclear. Recent studies have found that gut microbiota may be involved in the progression of diabetes-associated cognitive impairment. Aims To analyze the diversity of gut microbiota in type 2 diabetes with or without cognitive impairment Methods 16S rRNA sequencing was used to detect the gut microbiota composition in 154 type 2 diabetes (T2DM) subjects Results Among 154 elderly T2DM participants included in our study, 73 with normal and 81 with impaired cognition. Lower levels of hemoglobin and HDL were observed in subjects with cognitive impairment. Patients with cognitive impairment had a lower abundance of Tenericutes. Comparison at the genus level revealed that T2DM patients with cognitive impairment had a decreased abundance of Bifidobacterium and unranked-RF39 and an increased abundance of Peptococcus and unranked-Leuconostocaceae. Additionally, the relative abundance of Veillonella and Pediococcus were decreased in subjects with cognitive impairment. Furthermore, the relative abundance of 7 sub-functions was significantly changed in the group with cognitive impairment. Calcium signaling pathways and the Renin-angiotensin system were upregulated in the cognitive impairment group while GnRH signaling, Fc gamma R-mediated phagocytosis, endocytosis, isoflavonoid biosynthesis, and cytochrome P450 were deregulated. Conclusion Bifidobacterium may be associated with cognition in T2DM. Calcium signaling and renin-angiotensin system were shown to be associated with diabetes-associated cognitive impairment through gut microbiota.

Background: Mesenchymal stem cells (MSCs) have been widely applied to treat various inflammatory diseases. Inflammatory cytokines can induce both apoptosis and autophagy in MSCs. However, whether autophagy plays a pro- or con-apoptosis effect on MSCs in an inflammatory microenvironment has not been clarified. Methods: We inhibited autophagy by constructing MSCs with lentivirus containing small hairpin RNA to knockdown Beclin-1 and applied these MSCs to a model of sepsis to evaluate therapeutic effect of MSCs. Results: Here we show that inhibition of autophagy in MSCs increases the survival rate of septic mice more than control MSCs, and autophagy promotes apoptosis of MSCs during application to septic mice. Further study demonstrated that autophagy aggravated tumor necrosis factor alpha plus interferon gamma-induced apoptosis of MSCs. Mechanically, autophagy inhibits the expression of the pro-survival gene Bcl-2 via suppressing reactive oxygen species/mitogen-activated protein kinase 1/3 pathway. Conclusions: Our findings indicate that an inflammatory microenvironment-induced autophagy promotes apoptosis of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel approach to improve MSC survival during immunotherapy.