To explore the distribution characteristics of population with positive anti-gliadin antibody (AGA) and anti-Saccharomyces cerevisiae antibody (ASCA), reveal the important value of early detection of AGA and ASCA.

This is a retrospective comparative analysis. Comparative analysis of AGA and ASCA detected data in Baoding No.1 Central Hospital from February 2021 to February 2024. The rate between groups was compared by χ² test. P<0.01 was considered as statistically significant.

The ratio of male to female was 1:1.4. The number of male patients with AGA positive was significantly lower than that of females (χ²=88.76, P<0.01). Among the 1286 patients with ASCA positive, there were 726 males and 560 females. The ratio of male to female was 1:0.77. The number of male patients with AGA positive was significantly higher than that of females (χ²=42.86,P<0. 01). There are great differences in the distribution of AGA and ASCA between different genders. With the increase of age, the positive rate of AGA showed a downward trend and ASCA showed an upward trend. There are great differences in the distribution trend of AGA and ASCA with age.

Early detection of AGA and ASCA have definite guiding significance for early diagnosis and differential diagnosis of digestive diseases to reduce misdiagnosis and missed diagnosis.

Despite effective antiretroviral therapy (ART), serious non-AIDS events (SNAEs), including cardiovascular disease and death, remain prevalent among people with HIV (PWH). Imperfect ART adherence despite viral suppression may contribute to this risk, underscoring the need to clarify the relationship between adherence, viral load dynamics, and SNAE development.

We performed an analysis of deidentified data of participants in the prospective observational Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG) A5001 and A5322 studies. The baseline was defined as the time at the first viral suppression to <200 copies/mL after treatment initiation. Antiretroviral therapy adherence was assessed using the periodically administered ACTG self-report questionnaire and dichotomized as >90% versus ≤90% adherence. Data were primarily analyzed using inverse probability of censoring weights modeling.

Among 2940 participants followed for a median of 6.2 years, 237 SNAEs occurred, comprising 103 deaths and 134 cardiovascular events. Nearly all participants (95.9%) remained virally suppressed to <200 copies/mL over the full duration of follow-up. Adherence to ART >90% showed a protective effect on the development of all SNAEs: adjusted hazard ratio (aHR) 0.612 (95% confidence interval .390-.961). When only the development of the first SNAE was considered, the association remained substantially similar: aHR 0.641 (95% confidence interval .400-1.027).

Adherence to ART >90% compared to ≤90% reduces SNAE risk even in virally suppressed PWH, underscoring the need for continued adherence support to improve long-term health outcomes for PWH.

Cardiovascular diseases (CVDs) are the leading global cause of mortality, with potassium homeostasis playing a fundamental role in their pathophysiology. Tightly regulated potassium ions (K⁺) are essential for cardiac electrophysiological stability, and their dysregulation is a critical driver of disorders, particularly cardiac arrhythmias. Systemic potassium homeostasis is maintained by a complex network involving dietary intake, renal and intestinal handling, neuromodulatory control, skeletal muscle buffering and membrane ion channel activity, et al, which together determine extracellular and intracellular potassium homeostasis. This review summarizes the physiological mechanisms underlying potassium homeostasis and critically examines how potassium imbalance contributes to CVDs, with a primary focus on arrhythmia-related pathophysiology. By integrating experimental and clinical evidence, we highlight clinically relevant mechanisms and potential therapeutic strategies aimed at optimizing potassium homeostasis, thereby providing a conceptual framework to improve CVDs prevention and management.

Hypertension is often associated with elevated nighttime blood pressure and is a significant risk factor for cardiovascular and cerebrovascular diseases. This study explored the effects of renal denervation (RDN) on circadian blood pressure rhythms and clock gene expression in spontaneously hypertensive rats (SHRs).

Ten-week-old SHRs were randomized into RDN and sham surgery (Sham) groups, with Wistar-Kyoto (WKY) rats as controls. Blood pressure was measured at rest (14:00) and during activity (02:00) biweekly, and blood pressure variability was analyzed.

RDN significantly reduced BP and enhanced circadian BP variation, particularly during the resting phase. The Sham group displayed minimal circadian variations in plasma and renal norepinephrine levels, whereas the RDN group exhibited an overall reduction in norepinephrine levels, with lower levels at rest than during activity. Furthermore, the Sham group showed no significant circadian variation in the renin-angiotensin-aldosterone system (RAS), whereas RDN restored circadian rhythms in ACE1, Ang II, ACE2, and Ang1-7. Additionally, the Sham group demonstrated consistently high renal BMAL1 protein expression throughout the day, whereas RDN reduced BMAL1 expression during the resting phase, indicating restored circadian variation.

These findings suggest that RDN not only lowers blood pressure but also improves circadian rhythm, likely through the modulation of sympathetic nervous activity, the RAS system, and the circadian clock gene BMAL1.

Rationale: Given the crucial role of the Nrf2 pathway in cellular adaptability to stress, targeting small-molecule activation of Nrf2 represents a promising therapeutic strategy for acute ischemic stroke (AIS). However, the clinical translation of existing Nrf2 activators is hindered by adverse effects, such as liver damage, and none are currently approved for AIS. Therefore, we aimed to develop a novel Nrf2 activator that specifically activates neuronal Nrf2 while mitigating adverse effects, with the goal of providing a lead compound for AIS. Methods: We validated the anti-AIS effects and mitochondrial protective functions of the novel Nrf2 activator Cpd.51 through multiple in vivo and in vitro experiments. Mechanistic studies involving surface plasmon resonance, cellular thermal shift assay, co-immunoprecipitation, chromatin immunoprecipitation, GST pull-down, and RNA sequencing were used to determine how Cpd.51 activates Nrf2. A comparative toxicological evaluation was conducted to demonstrate its superior safety profile over parent compound (Omaveloxolone). Results: Cpd.51 exhibited favorable blood-brain barrier permeability, improved safety profile, enhanced mitochondrial function protection and significant neuroprotective effect through the specific activation of neuronal Nrf2. Mechanistically, Cpd.51 interacted with Cys151 and Gly148 in the BTB domain of Keap1, inhibiting Nrf2 degradation, consequently suppressing the transcription of its downstream target DHRS3, a member of the short-chain dehydrogenase/reductase family. Furthermore, Cpd.51 exerted additional Nrf2-activating activity by disrupting protein-protein interactions between Nrf2 and DHRS3. Conclusions: Our work identified Cpd.51 as a novel and safe Nrf2 activator and unveils a unique feedback mechanism involving Nrf2-DHRS3 interaction, providing a new therapeutic avenue for AIS.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation, posing a high risk of death, particularly from cardiovascular events. Finding simple and cost-effective prognostic biomarkers is crucial for risk stratification and improved patient management. The neutrophil-to-lymphocyte ratio (NLR), as a systemic inflammatory marker, has shown prognostic value in various diseases, but its comprehensive evidence in RA remains unclear.

Following the PRISMA 2020 guidelines, relevant literature up to October 2025 was systematically searched in PubMed, Embase, Web of Science, and Cochrane databases. Observational studies were included. Random-effects models were used to pool odds ratios (OR) and 95% confidence intervals (CI). Robustness and publication bias were assessed using heterogeneity tests (I²), sensitivity analyses, and Egger's tests. Evidence quality was graded using the GRADE system.

Overall, seven studies were analyzed, and the meta-analytic findings indicated that elevated NLR was significantly correlated with all-cause mortality (OR = 1.70, 95%CI: 1.39-2.09, P<0.00001) and cardiovascular mortality (OR = 2.60, 95%CI: 1.61-4.21, P = 0.0001) in RA patients, and also with reduced disease remission rate (OR = 0.81, 95%CI: 0.68-0.96, P = 0.02). Heterogeneity for all outcomes was low (I²=0-16%), sensitivity analysis confirmed robustness, and publication bias was not statistically significant. GRADE assessment indicated low quality of evidence for all-cause mortality, moderate for cardiovascular mortality, and very low quality for remission rate.

Analysis based on a multivariate adjusted model showed that high NLR is an important predictor of poor prognosis in RA patients. As an economical and readily available inflammatory marker, it holds promise for use in RA risk stratification and personalized treatment decision support, but further prospective studies are required to clarify the causal relationship and optimize the clinical cutoff value.

https://www.crd.york.ac.uk/prospero/, identifier CRD420251234933.

Ischemia-reperfusion injury (IRI) can activate multiple cell death pathways, leading to dysfunction of multiple organs. PANoptosis is a new inflammatory cell death form recently discovered and it is also an integrated cell death mode, which includes the features of pyroptosis, apoptosis, necroptosis. Rather than a simple addition of these routes, PANoptosis is a special type of biology process with its own regulatory mechanism and plays an important regulatory role in the occurrence of IRI. The review focuses on the concept of PANoptosis, elaborating on its molecular mechanisms and detection methods, with a particular emphasis on exploring the regulatory networks of PANoptosis in various IRI. In addition, various potential treatment strategies targeting PANoptosis analyzed in depth, including small molecule inhibitors, natural products, gene intervention, and stem cell therapy. The overall goal is to clarify the importance of PANoptosis in the pathological mechanism of IRI and to explore the possibility of using it as a focus for clinical treatment.

Myocardial ischemia-reperfusion (I/R) injury presents a significant clinical challenge characterized by a complex pathological mechanism. The role of protein ubiquitination in I/R injury has not been systematically investigated. Global ubiquitinome profiling was conducted to identify the potential key players in myocardial I/R injury.

The ubiquitination levels of proteins in mouse hearts subjected to either sham surgery or I/R injury were analyzed using ubiquitinome. A combined analysis of ubiquitinome, single-cell RNA sequencing (RNA-seq), and proteomics data was employed to predict potential E3 ubiquitin ligases associated with myocardial I/R injury. Global heterozygous 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase degradation 1 (Hrd1) knockout, endothelial cell (EC)-specific Hrd1 deficiency (Hrd1^f/f; Cdh5^Cre), and EC-specific Hrd1 overexpression (AAV-EC-Hrd1) mice were used to assess the role of Hrd1 in myocardial I/R injury. Mass spectrometry and immunoprecipitation were used to elucidate the interaction between Hrd1 and aldehyde dehydrogenase 2 (ALDH2). Additionally, we assessed ubiquitination and vasomotor reactivity to clarify the mechanisms by which Hrd1 regulates ALDH2 activity and EC dysfunction during I/R injury.

Ubiquitinome analysis revealed that protein ubiquitination exacerbates endothelial dysfunction after myocardial I/R injury. Integrative analysis of the ubiquitinome, proteomics, and single-cell RNA-seq revealed a significant upregulation of the E3 ubiquitin-protein ligase Hrd1 in CD45⁺ ECs. In both humans and mice, the level of endothelial Hrd1 protein was found to increase in response to I/R in vivo. Genetic ablation of Hrd1 significantly alleviated myocardial infarction, endothelial dysfunction, and infiltration of inflammatory cells after I/R injury. Mechanistically, Hrd1 promoted the K33-linked polyubiquitination of ALDH2 and then inhibited the formation of its active tetramers, which reduced the apoptosis of CD45⁺ ECs and exacerbated endothelial dysfunction through the NO/cGMP/PKG (nitric oxide-cyclic guanosine monophosphate-protein kinase G) signaling pathway. Furthermore, our findings demonstrated that pharmacological inhibition of Hrd1 robustly ameliorated myocardial I/R injury and endothelial dysfunction.

Our findings demonstrated a previously unidentified crucial role of cardiac EC Hrd1 in myocardial I/R injury. Hrd1 may serve as a therapeutic target for preventing myocardial I/R injury.

Massive left ventricular hypertrophy (LVH) is a risk factor for sudden cardiac death in children with hypertrophic cardiomyopathy (HCM), but little is understood about its natural history.

Patients with pediatric-onset HCM identified from 2 registries (SHaRe [Sarcomeric Human Cardiomyopathy Registry] and IPHCC [International Paediatric Hypertrophic Cardiomyopathy Consortium]) with or without massive LVH were compared. Massive LVH was defined as absolute maximal left ventricular wall thickness (MLVWT) ≥30 mm or MLVWT z score ≥+20 at <18 years of age. Data from SHaRe and IPHCC include encounters from January 1960 through March 2024 and January 1970 through March 2024, respectively. Demographic, clinical, and serial MLVWT data were collected. Composite outcomes included major ventricular arrhythmia event (sudden cardiac death, aborted sudden cardiac death, or appropriate implantable cardioverter defibrillator therapy); heart failure (HF) event (left ventricular ejection fraction <50%, New York Heart Association class III or IV, transplant, or HF-related death); major adverse cardiac event (stroke or any major ventricular arrhythmia or HF outcome aside from left ventricular ejection fraction <50%); and HCM-related mortality (sudden cardiac death or HF-related death). Time-to-event analyses were performed using Cox proportional hazards models.

We identified 587 patients (54 female [30%]). In 186 children with massive LVH, age at diagnosis was younger (median, 9.2 years [interquartile range, 2.1-13.1 years]) versus 13.6 years (9.7-15.5 years; P<0.001) and sarcomeric genetic variants more prevalent (72% versus 61%; P=0.034), as was HCM-related mortality (unadjusted hazard ratio, 3.3 [95% CI,1.2-9.7]; P=0.026), major adverse cardiac events (hazard ratio, 2.6 [1.7-3.9]; P<0.001), major ventricular arrhythmia (hazard ratio, 3.1 [1.8-5.2]; P<0.001), and HF (hazard ratio, 1.9 [1.1-3.1]; P=0.013). These associations remained significant when adjusted for sex and age at HCM diagnosis. In 115 patients with massive LVH with serial MLVWT data (62%), MLVWT increased significantly from first to last measurements (median, 26 mm [interquartile range, 18-32 mm] versus 31 mm [26-35 mm]; P<0.001), but there was no difference between z scores (median, +22 [interquartile range, +18 to +26] versus +23 [+20 to +28]; P=0.25). The last absolute MLVWT recorded was >5 mm less than the largest recorded MLVWT in 25 patients (22%).

In pediatric HCM, massive LVH disproportionately affects those diagnosed in early childhood with sarcomeric disease, with increased risk for adverse events. Significant MLVWT regression is seen in nearly a quarter of patients.

The aim of this study was to investigate whether allopurinol and oxypurinol treatment could mitigate oxidative stress and germ cell apoptosis in testicular ischemia-reperfusion (IR) injury.

Thirty-two male rats were divided into four groups: Group 1 (Sham-Operated, n=8), in which the testicle was exposed but torsion was not performed; Group 2 (IR + Saline, n=8), in which torsion/detorsion was applied to the left testicle and 1 mL of normal saline was administered; Group 3 (IR + Allopurinol, n=8), in which torsion/detorsion was applied to the left testicle and 50 mg/kg allopurinol was administered; and Group 4 (IR + Oxypurinol, n=8), in which torsion/detorsion was applied to the left testicle and 50 mg/kg oxypurinol was administered. On postoperative day 28, left testicular tissue samples were collected, and total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were measured. Additionally, the gene expression levels of Bax, B-cell lymphoma 2 (Bcl-2), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor A (VEGF-A) were analyzed.

Allopurinol and oxypurinol significantly decreased OSI levels (p<0.001). Oxypurinol was found to be significantly more effective in reducing oxidative stress (p<0.001). Both allopurinol and oxypurinol significantly reduced Bax gene expression levels (p<0.001). Treatment with allopurinol (p=0.009) and oxypurinol (p=0.001) significantly increased Bcl-2 levels. Additionally, both agents significantly reduced the apoptosis index (p<0.001). Allopurinol (p1=0.007, p2<0.001) and oxypurinol (p1,2<0.001) treatments significantly increased eNOS and VEGF-A gene expression levels.

Allopurinol and oxypurinol reduce oxidative stress in the testis following IR injury, with oxypurinol demonstrating a greater antioxidant effect. Both treatments also reduce apoptosis by contributing positively to the eNOS and VEGF-A-mediated repair processes. Therefore, allopurinol and oxypurinol may serve as potential therapeutic agents for clinical application in testicular torsion.