Background/Aims: Hepatitis E virus (HEV)–associated acute liver failure (ALF) lacks reliable biomarkers for risk stratification at hospital admission. This study evaluated the diagnostic utility of serum glypican-3 (GPC3) and aldo-keto reductase family 1 member B10 (AKR1B10). Materials and Methods: Between May 2023 and May 2025, 231 adults with acute HEV infection were classified as HEV-ALF (n = 43) or HEV without ALF (n = 188). Serum GPC3 and AKR1B10 concentrations were measured using enzyme linked immunosorbent assay. Associations were evaluated using Pearson correlation coefficient r; diagnostic performance was assessed by receiver operating characteristic curves, and independent predictors of ALF were identified using multivariable logistic regression. Results: Patients with HEV-ALF had lower albumin, triglyceride, and cholesterol levels and higher total bilirubin, prothrombin time, and international normalized ratio values than patients without ALF (all P < .05). GPC3 and AKR1B10 concentrations were markedly elevated in the HEV-ALF group (both P < .001) and were strongly correlated (r = 0.610, P < .001). The combination of GPC3 and AKR1B10 demonstrated superior diagnostic performance for identifying ALF, with an area under the curve (AUC) of 0.931, outperforming either GPC3 alone (AUC, 0.832) or AKR1B10 alone (AUC, 0.792). In multivariable logistic regression analysis, elevated GPC3 (odds ratio [OR], 2.138; 95% CI, 1.213-3.771) and AKR1B10 (OR, 2.304; 95% CI, 1.215-4.368) remained independent risk factors for ALF. Conclusion: Serum GPC3 and AKR1B10 were independent predictors of HEV-ALF and may facilitate risk stratification at hospital admission. Cite this article as: Zhang G, Liu X, Wang Y, Lu K, Wang Y. Serum GPC3 and AKR1B10 as diagnostic biomarkers for hepatitis E virus–associated acute liver failure. Turk J Gastroenterol. Published online July 21, 2026. doi: 10.5152/tjg.2026.26017.

Purpose: Airway remodeling is a key pathological feature of asthma. The CD30ligand (CD30L), a member of the tumor necrosis factor (TNF) superfamily encoded by the Tnfsf8 gene, has been linked to immune-inflammatory pathologies. Nevertheless, the role of CD30L in airway remodeling has not been elucidated. Methods: We investigated CD30L expression and localization in lung specimens from asthma patients and ovalbumin (OVA)-induced asthmatic mice. Subsequently, we established asthmatic mice with macrophage-specific Tnfsf8 knockout or intranasal administration of recombinant CD30L protein, and analyzed airway pathology using multiple techniques. In vitro, an indirect co-culture system of macrophages and bronchial epithelial cells was employed to investigate the impact of CD30L on airway epithelial remodeling. The mechanisms of CD30L in human bronchial epithelial (HBE) cells were explored using small interfering RNA targeting CD30 (the receptor for CD30L), c-Jun N-terminal kinase (JNK) inhibitor, and p38 inhibitor. Results: CD30L expression was upregulated in asthmatic lung tissues (human/mice) and colocalized with macrophage markers. In vivo, macrophage-specific Tnfsf8 knockout attenuated extracellular matrix (ECM) deposition and epithelial-mesenchymal transition (EMT) during OVA-induced airway remodeling, whereas intranasal CD30L exacerbated these pathologies. Transcriptomic analysis of lung tissues revealed that CD30L regulated ECM deposition, cell adhesion, and epithelial cell migration. In vitro co-culture of macrophages with bronchial epithelial cells demonstrated that macrophage-specific CD30L silencing reversed remodeling-related proteins and EMT in bronchial epithelial cells. Furthermore, we found that CD30L significantly upregulated the JNK/p38 mitogenactivated protein kinase (MAPK) pathway in HBE cells. Silencing CD30 in HBE cells alleviated CD30L-induced remodeling and EMT, accompanied by downregulation of the JNK/p38 MAPK pathway. Treatment with JNK inhibitor (SP600125) or p38 inhibitor (SB203580) reversed the CD30L-induced pathological effects. Conclusions: Collectively, these findings demonstrate that CD30L critically regulates asthma airway remodeling via the JNK/p38 MAPK pathway, strongly suggesting its therapeutic potential as a target for airway remodeling in asthma.

Background and ObjectivesAdequate sedation with preserved spontaneous breathing and stable hemodynamics is critical for the success and safety of fiberoptic bronchoscopy (FOB). Remimazolam, a novel ultra-short-acting benzodiazepine with rapid metabolism and favorable sedative profiles, has shown promising sedative effects for procedural sedation. However, comparative data on its application in FOB with preserved spontaneous breathing remain limited. This retrospective study aimed to compare the safety and efficacy of remimazolam and propofol for sedation in patients undergoing FOB with preserved spontaneous breathing.Materials and MethodsA retrospective chart review was conducted from October 2024 to October 2025. All patients undergoing FOB with preserved spontaneous breathing were enrolled. Patients were divided into two groups based on the sedative used: remimazolam (Group R) and propofol (Group P). The primary outcome was the sedation success rate. Secondary outcomes included hemodynamic parameters, incidence of adverse events, anesthesia-related times, satisfaction scores of endoscopists and patients.ResultsThirty-six patients in group R and Forty in group P were collected in this retrospective study. Sedation success rate was 100% in both groups. Oxygen saturation (SpO2) levels were higher in group R at beginning of the bronchoscopy, 5, 10, and 15 min after the start of bronchoscopy (P = 0.012, 0.001, 0.017, and 0.006, respectively). Group R had a lower incidence of hypoxemia (16.67% vs. 35.0%, P = 0.034), injection pain (0% vs. 17.5%, P = 0.008), and hypotension (5.56% vs. 22.5%, P = 0.036). Recovery time was shorter in group R (P = 0.017). Onset time, and satisfaction scores were comparable in the two groups.ConclusionOur study uncovered remimazolam demonstrates a comparable success rate to propofol and exhibits favorable safety profiles, including reduced hypoxemia, injection pain, and hypotension during FOB with preserved spontaneous breathing. However, the shorter recovery time in Group R was confounded by the routine use of flumazenil, and the findings are limited by the retrospective design, small sample size and exclusive enrollment of ASA I–II patients, requiring validation in larger, prospective studies.

This paper introduced the classification, sources, and human exposure status of synthetic antioxidants as emerging environmental pollutants, highlighting their widespread presence in human biological matrices, including urine, blood, adipose tissue, and follicular fluid. It summarized the physicochemical properties and exposure characteristics of four major classes of synthetic antioxidants—synthetic phenolic antioxidants, amine antioxidants, organophosphite antioxidants, and sulfur-containing antioxidants—and systematically outlined their effects on reproductive function at multiple levels, including testicular development and sperm quality, ovarian reserve, endocrine homeostasis, pregnancy establishment and maintenance, and fetal development. Additionally, this paper analyzed the adverse impacts of synthetic antioxidant exposure on the pregnancy outcomes of assisted reproductive technology. Based on current evidence, this paper contends that synthetic antioxidants exhibit multi-target and multi-mechanism reproductive toxicity, potentially impairing reproductive function through pathways such as the induction of oxidative stress, disruption of calcium homeostasis, and activation of autophagy and apoptosis. However, current epidemiological evidence remains insufficient, particularly with respect to exposure data derived from reproductive-related biological samples, such as follicular fluid and semen. Future research should prioritize the reproductive toxicity of synthetic antioxidants, explore interactions among underlying mechanisms, and promote the identification of relevant biomarkers. These efforts will provide a scientific basis for understanding reproductive toxicity, improved population risk assessment, developing targeted intervention strategies, and optimizing clinical practices in assisted reproductive technology.

Background and Objectives:Asthma represents a heterogeneous chronic respiratory condition. Type 2 (T2) inflammation is the most crucial pathological event in asthma. In terms of whether T2 inflammation is dominant or not, asthma can be classified into T2-high and T2-low asthma. Currently, there exists a significant gap in our understanding of the heterogeneity of treatment-naive T2-high asthma patients. Moreover, no studies have examined the impacts of inhaled corticosteroids (ICS) on the airway microenvironment and metabolism of T2-high asthma during the early stage of treatment. This study, by employing multi-omic techniques, investigated the pathophysiological features and heterogeneity of untreated T2-high asthma, as well as the effects of ICS treatment. This study provided more in-depth insights into the pathophysiological mechanisms underlying T2-high asthma heterogeneity. Methods:Thirty-one treatment-naive T2-high asthma patients and fourteen healthy individuals were enrolled in this study. On the basis of hierarchical clustering analysis of T2 inflammation markers, fractional exhaled nitric oxide (FeNO) level and blood eosinophil count (BEC), the T2-high asthma patients were divided into three subgroups in terms of FeNO levels (≤ 25 ppb, 26-50 ppb, and > 50 ppb). All asthma patients underwent asthma control scoring, pulmonary function tests, and FeNO measurement at baseline and during a regular 3-month follow-up. Induced sputum and plasma were collected. Other tests included 16S rRNA microbiome profiling of the induced sputum, Luminex xMAP immunoassays of cytokines, and plasma metabolomic analysis using Q-Exactive liquid chromatography-mass spectrometry (LC-MS/MS). Meanwhile, data from the healthy population were also harvested. Results:T2-high asthma patients differed significantly from healthy controls in terms of airway inflammatory cytokines, airway microbial community structure, and plasma metabolic profiles. At baseline, T2-high asthma patients with different FeNO levels exhibited remarkable similarities in clinical symptoms, pulmonary function indices, airway cytokines, airway microbial diversity, and metabolites. After treatment with ICS, symptoms improved in T2-high asthma patients. The levels of FeNO, blood eosinophils, and total immunoglobulin E (tIgE) decreased significantly, while pulmonary function did not show substantial improvement. Some indices of airway cytokines underwent changes. No differences were found in airway microbial diversity; however, the abundance of Actinomyces increased. Moreover, the levels of glycerophospholipids and arachidonic acid metabolites decreased. Differentially expressed metabolites were enriched in arachidonic acid metabolism. The effect of ICS treatment varied among different T2-high asthma subgroups. Conclusions:The airway local microenvironment and systemic metabolic profiles of treatment-naive T2-high asthma patients were distinctly different from those of healthy individuals. Limited heterogeneity was observed among patients stratified in terms of T2-inflammatory burden. ICS altered the airway microenvironment and rectified the lipid/arachidonic acid metabolic dysregulation. However, ICS effects varied across various T2-high subgroups.

The tumor microenvironment (TME) is crucial for tumor formation and progression, but its specific impact on NF2-related tumors has not been well described. The aim of this study was to analyze the differences in the TME among NF2-related schwannomatosis (NF2-SWN) patients with different clinical phenotypes, explore the reasons for these differences, and identify targets for treatment while gaining a deeper understanding of the pathogenesis of the disease. 20 vestibular schwannomas (VSs) from 20 clinically diagnosed NF2-SWN patients, including 11 milder patients (Gardner) and 9 severe patients (Wishart), were analyzed. Single-cell sequencing, TCR sequencing, spatial transcriptomics analysis, multiplex immunofluorescence, immunohistochemistry, and cell experiments were performed to compare the TME of Gardner and Wishart and to elucidate the mechanisms underlying these differences. Our results revealed that NF2-VS consist of 12 significant cell subpopulations, with Gardner and Wishart presenting distinct TME. Wishart exhibited more pronounced immune suppression. Conversely, CD8+ T cells from Gardner demonstrated potential for clonal proliferation. In macrophages, a subtype exhibited higher capacity of angiogenesis and high inflammatory cytokine activity was identified in Wishart, suggested its role in promoting tumor progression. Moreover, we found fibroblasts in Wishart showed excessive stromal deposition, potentially indicated the existence of immunologic barrier. Receptor‒ligand pair analysis revealed that Schwann cells in Wishart regulate immune cell activity via pleiotrophin (PTN), PTN positivity promotes anti-inflammatory cytokine activity, contributing to the formation of an immunosuppressive microenvironment to promote tumor progression. In summary, our study provides an in-depth analysis of the TME of NF2-VS, revealing the differences between Wishart and Gardner. Our study explains how Schwann cells influence the immune landscape to promote tumor development and clarifies the role of the TME in NF2-SWN progression, establishing a theoretical and experimental foundation for future immunotherapeutic strategies for NF2-SWN.

AIMS:Adipose tissue insulin resistance, reflecting impaired insulin-mediated suppression of lipolysis in adipose tissue, is recognized as an early metabolic abnormality. However, its associations with fasting blood glucose (FBG) and haemoglobin A1c (HbA1c) have not been well characterized in adults without diabetes. The study aims to evaluate these associations under conditions of normoglycaemia and prediabetes. MATERIALS AND METHODS:The study enrolled 9011 adults without diabetes. Adipose tissue insulin resistance index (Adipo-IR) was calculated by the product of fasting insulin and free fatty acid levels. We categorized FBGand HbA1c separately into three groups. We conducted logistic regression after adjustment for potential confounders. RESULTS:Adipo-IR gradually increased with the increase of FBG categories and HbA1c categories. The positive association between Adipo-IR and FBG levels varied by body mass index (BMI) (p for interaction <0.001), with a strengthened relationship in the condition of BMI <24 kg/m2. One unit increase in log-Adipo-IR was associated with 2.74 (95% CI: 2.02, 3.73, p < 0.001) times odds of having high FBG levels (denoted as FBG ≥5.6 mmol/L) after adjustment for other risk factors in participants with BMI <24 kg/m2. However, the ORs turned out to be 1.67 (95% CI: 1.36, 2.07, p < 0.001) and 1.30 (95% CI: 0.98, 1.74, p = 0.07) in participants with BMI 24 to <28 and ≥28 kg/m2, respectively. The positive associations between Adipo-IR and HbA1c levels were also observed among participants with body mass index <24, 24 to <28, and ≥28 kg/m2, and among females and males, respectively. CONCLUSIONS:Adipose tissue insulin resistance demonstrated a significant dose-response relationship with both FBG and HbA1c levels in individuals without diabetes, which may reflect early glycaemic alterations. The association between Adipo-IR and FBG was more pronounced under conditions of normal or low body weight.

Immune dysregulation and scar tissue formation following traumatic spinal cord injury (SCI) result in the generation of a microenvironment that significantly inhibits nerve regeneration and functional recovery. Continuous drug delivery across the dura, with minimal damage, and modulation of this inhibitory microenvironment pose substantial challenges in SCI treatment. This study fabricated a pH-responsive immunomodulatory microneedle (MN) patch by incorporating zeolitic imidazolate framework-8 (Zif-8) nanoparticles loaded with chondroitinase ABC (ChABC) into a gelatin methacrylate (GelMA) hydrogel (Z@C-MN). As the patch progressively degraded, this system continuously released Zn2+ and ChABC in a pH-responsive manner to facilitate in situ SCI repair. In vitro, Z@C-MN can down-regulate macrophage inflammatory responses, promote axon extension, and differentiate neural stem cells into neurons. In vivo, Z@C-MN reduced the inflammatory microenvironment in an injury model and promoted angiogenesis in a rat SCI model. In addition, it promoted axonal regeneration and neurogenesis by inhibiting nerve scar formation and regulating CD4+ T cell transformation. These effects contributed to the recovery of motor and neurological functions. Thus, this drug delivery system offers a highly efficient, transdural, and continuous-release multifunctional platform for patients with SCI.

There is limited information on the uncontrolled status and burden of asthma among patients using inhaled corticosteroids (ICS) combined or not with long-acting β2-agonists (LABA) in China. This study aims to characterize the disease burden among these patients and identify risk factors for unfavorable outcomes. This retrospective observational study utilized data from a regional Electronic Medical Record (EMR) database in China. Patients (≥ 12 years) with asthma having at least two prescriptions for medium-to-high dose ICS or ICS/LABA within any 6 months were identified from the Shanghai Medical Database between 2016 and 2020. Data on characteristics and treatment patterns 1-year pre-index (baseline) and disease burden 1-year post-index (follow-up) were obtained from the database. Uncontrolled asthma was defined based on exacerbations and specific treatment. A multivariate logistic regression model was used to identify risk factors associated with the follow-up adverse outcomes. A total of 35,900 patients with asthma receiving medium-to-high dose ICS or ICS/LABA were included. Of these, 10,842 (30.2

8047 Background: While neoadjuvant immunotherapy (nIO) is the standard of care for resectable NSCLC, its efficacy in "potentially resectable" (PR) stage III lung squamous cell carcinoma (LUSC)—specifically patients with T4 invasion or multi-station N2 disease—remains underrepresented in clinical trials. We evaluated whether nIO could facilitate surgical conversion in PR patients comparable to initially resectable (IR) candidates and constructed a multidimensional risk stratification system to optimize decision-making. Methods: We retrospectively analyzed patients with stage III LUSC treated with neoadjuvant PD-1/PD-L1 inhibitors plus chemotherapy (January 2019–December 2024). The cohort was stratified into IR and PR groups, with PR defined by complex anatomy (T4 invasion or multi-station N2). Endpoints included surgical conversion, major pathological response (MPR), disease-free survival (DFS), and overall survival (OS). Baseline predictors were identified via logistic regression. A pathological risk score (pRS) was developed using Cox regression based on independent risk factors for DFS in the R0 resection cohort. Results: Of 210 evaluable patients, 170 (81.0%) underwent surgery with a 96.5% R0 resection rate. The PR cohort (n = 128) achieved surgical conversion rates comparable to the IR cohort (n = 82) (82.9% vs. 90.7%; P = .19). Notably, PR patients demonstrated superior nodal downstaging (74.5% vs. 58.8%; P = .047) compared with IR patients. Long-term survival outcomes showed no statistically significant difference between PR and IR groups (DFS: HR, 1.25; 95% CI, 0.77-2.04; OS: HR, 1.41; 95% CI, 0.76-2.62). Multivariable analysis identified baseline NLR ≥ 2.75 and CYFRA 21-1 ≥ 6.0 ng/mL as independent predictors of poor therapeutic benefit. The constructed pRS system (integrating non-MPR status, vascular, and pleural invasion) effectively stratified postoperative recurrence risk (P < .0001; 1-year AUC, 0.73). Analysis of treatment failure (n = 40) revealed that baseline fibrinogen > 3.5 g/L was associated with disease progression, while grade 3–5 pneumonitis was a primary cause of surgical dropout in patients with high PD-L1 expression. Conclusions: In this real-world cohort, nIO facilitated high R0 resection rates in complex stage III LUSC, allowing potentially resectable patients to achieve survival outcomes equivalent to initially resectable candidates. Nodal clearance appears to be a key driver of benefit in the PR subgroup. The novel pRS system and biomarkers (NLR, CYFRA 21-1, fibrinogen) provide a robust framework for patient selection and postoperative management.

Cardiovascular disease(CVD) remains a leading cause of mortality worldwide. Among CVDs, coronary heart disease (CHD) is the most prevalent and represents the primary contributor to chronic disease-related deaths globally. The triglyceride-glucose (TyG) index has been shown to correlate significantly with both mortality and cardiovascular events, indicating its potential as an independent prognostic marker for cardiovascular outcomes. This study aimed to investigate variations in the TyG index among patients stratified by disease severity using Gensini scores and to evaluate the association between the TyG index and disease severity, as well as its diagnostic efficacy in combination with serum biomarkers. A total of 861 patients diagnosed with CHD who underwent coronary angiography were included. All participants were admitted to the Fifth Ward, Department of Cardiovascular Medicine, at the Fourth Affiliated Hospital of Harbin Medical University between June 2022 and June 2024. Comprehensive data, including demographics, laboratory findings, and medical history, were collected from medical records. Based on the Gensini scores derived from coronary angiography, patients were categorized into three groups-low, moderate, and high stenosis-representing the severity of coronary artery occlusion. Multivariate logistic regression analysis was performed to assess the relationship between the TyG index and coronary artery disease severity. TyG levels differed significantly between the mild and severe stenosis groups (p = 0.0021), and between the moderate and severe groups (p = 0.0173). The TyG index, treated as a continuous variable, was significantly associated with coronary stenosis (odds ratio [OR] = 1.591; 95% confidence interval [CI]: 1.237-1.866). After adjusting for confounding factors including age, sex, diabetes, and hypertension, individuals in the second, third, and fourth TyG quartiles exhibited higher odds ratios for severe coronary stenosis compared to the reference group (OR = 0.932; 95% CI: 0.642-1.351; OR = 1.045; 95% CI: 0.691-1.581; OR = 1.101; 95% CI: 0.605-2.004). These findings indicate that the TyG index is positively associated with the extent of coronary artery stenosis and may serve as an indicator of atherosclerosis severity.

Background:The association between relative changes in fractional exhaled nitric oxide (FeNO) in chronic obstructive pulmonary disease (COPD) with patient-reported symptoms improvements remains uncertain. Objective:To assess the association of the rate of FeNO decline with the achievement of the minimum clinically important difference (MCID) in COPD Assessment Test (CAT) score. Methods:We conducted a single-center, retrospective real-world study involving 111 adults with COPD. Patients were classified into two groups: those with symptom improvement (CAT decline ≥2 points) and those with no improvement (CAT decline <2 points). Logistic regression evaluated associations between FeNO decline rate and CAT MCID, adjusting for clinically relevant covariates. Receiver operating characteristic (ROC) curve analysis estimated the discriminatory performances of it. Results:Of 111 patients, 53 (47.7%) achieved the CAT MCID. Multivariate logistic regression found that the rate of FeNO decline was independently associated with symptom improvement (adjusted OR 2.08, 95% CI 1.01-4.29, P=0.047). Baseline CAT also showed association with symptom improvement (adjusted OR 1.06, 95% CI 1.00-1.12, P=0.034). BMI showed a positive trend but without statistical significance (adjusted OR 1.13, 95% CI 1.00-1.29, P=0.056). AUC of FeNO decline rate, baseline CAT, combined with BMI in discriminating CAT MCID were 0.713 (95% CI 0.617, 0.809). Conclusion:The rate of FeNO decline was significantly associated with clinically meaningful CAT improvement in this study, which indicated dynamic measures of type-2 inflammation can complement blood eosinophil counts to refine phenotyping and inform precision management in COPD.

Objectives:C1QBP is a multi-compartmental protein implicated in diverse cellular processes. However, its clinical predictive value, particularly its association with immune cell infiltration, in lung adenocarcinoma (LUAD) remains unelucidated. Thus, the present study aimed to comprehensively evaluate C1QBP expression patterns, prognostic significance, and its correlation with the tumor immune microenvironment (TIME) in LUAD. Methods:We first assessed C1QBP expression levels and prognostic relevance in LUAD using multiple bioinformatics platforms. Subsequently, we analyzed the associations of C1QBP expression with immune cell infiltration and immunotherapeutic response, and identified signaling pathways linked to C1QBP expression via Gene Set Enrichment Analysis (GSEA). Finally, enzyme-linked immunosorbent assay (ELISA) was employed to validate the correlation between serum C1QBP concentration and prognosis in non-small cell lung cancer (NSCLC) patients receiving immunotherapy. Results:C1QBP was highly expressed in LUAD tissues, and this high expression was significantly associated with advanced tumor stage. Moreover, high C1QBP expression emerged as an independent risk factor for overall survival (OS) in LUAD patients. Bioinformatics analyses revealed that C1QBP expression was negatively correlated with the infiltration levels of multiple immune cell subsets (including T cells, B cells, and dendritic cells) in LUAD, while patients with low C1QBP expression exhibited higher Immunophenoscore (IPS). GSEA further demonstrated that high C1QBP expression was positively correlated with pathways regulating the tumor cell cycle, but negatively correlated with immune-related signaling pathways. Finally, in NSCLC patients treated with immune checkpoint inhibitors (ICIs), those with higher serum C1QBP concentrations had significantly shorter OS and progression-free survival (PFS). Conclusions:Our study identifies C1QBP as a potential oncogene that is closely associated with the TIME in LUAD. Collectively, these findings suggest that C1QBP holds promise as a novel indicator of poor prognosis in LUAD patients.

BACKGROUND:Intensive blood pressure (BP) lowering increased acute kidney injury risk, despite cardiovascular benefits. We investigated the association between treatment-induced BP changes and kidney function decline, while accounting for arterial stiffness. METHODS:This post‑hoc analysis included 266 patients with hypertension from a 20‑week double‑blind trial treated with calcium-channel blockers. Kidney dysfunction was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min·1.73 m2 or a decrease ≥30% from baseline. Arterial stiffness was measured as brachial-ankle pulse wave velocity (baPWV). RESULTS:At baseline, systolic/diastolic BP (mean±SD, 153.2±9.3/91.8±9.5 mmHg) was associated positively (r = 0.20 [95% CI, 0.09 to 0.32]/0.23 [95% CI, 0.11 to 0.34]) with serum creatinine (72.1±16.2 μmol/l), and inversely (r=-0.25 [95% CI, -0.36 to -0.14]/-0.16 [95% CI, -0.28 to -0.04]) with eGFR (91.6±13.8 ml/min·1.73 m2). The associations with clinic systolic BP were weakened with higher baPWV, being observed in tertiles 1 and 2 (r ≥ 0.30 or ≤-0.27), but not tertile 3. After 20 weeks treatment, the incidence of kidney dysfunction was 0%, 4.8%, and 6.4%, respectively, in tertiles 1, 2 and 3 of baPWV (odds ratio for tertile 3 versus tertile 1, 2.23 [95% CI, 0.84-5.95]). In longitudinal analysis, the least square mean change from baseline in eGFR was -3.7 ml/min·1.73 m2 (95% CI, -4.3 to 1.1) in patients within tertile 3 of both baseline baPWV and treatment-induced clinic systolic BP changes. CONCLUSIONS:In patients with stiffer arteries, kidney function at baseline was not associated with higher BP, and its decline during follow-up was greater when clinic BP was intensively reduced.

BACKGRUOUND:Our previous studies have investigated the role of hepatic insulin resistance (hepatic IR) and islet β-cell function in the pathogenesis of diabetes. This study aimed to explore the contributions of hepatic IR and islet β-cell dysfunction to the blood glucose spectrum in patients with newly diagnosed type 2 diabetes mellitus. METHODS:Hepatic IR was assessed by the hepatic insulin resistance index (HIRI). Islet β-cell function was assessed by insulin secretion- sensitivity index-2 (ISSI2). The associations between blood glucose spectrum and hepatic IR and ISSI2 were analyzed. RESULTS:A total of 707 patients with new-onset diabetes were included. The fasting blood glucose (FBG) and 30 minutes postload blood glucose elevated with rising HIRI (both P for trend <0.001). The FBG, 30 minutes, 2 hours, and 3 hours post-load blood glucose elevated with decreasing ISSI2 quartiles (all P for trend <0.001). There was a negative correlation between ISSI2 and HIRI after adjusting blood glucose levels (r=-0.199, P<0.001). CONCLUSION:Hepatic IR mainly contributed to FBG and early-phase postprandial plasma glucose, whereas β-cell dysfunction contributed to fasting and postprandial plasma glucose at each phase.

BackgroundThe management of bone metastases requires careful balancing of therapeutic efficacy against distinct safety profiles. Current understanding of differential adverse event patterns between zoledronic acid and denosumab warrants more sophisticated analytical approaches to identify clinically relevant risk biomarkers and underlying molecular mechanisms.MethodsWe conducted an advanced pharmacovigilance study utilizing the FDA Adverse Event Reporting System (FAERS) database (2004-2024). Our multidimensional analytical framework integrated five established signal detection algorithms (ROR, PRR, BCPNN, MGPS, and MHRA) with comprehensive temporal and demographic stratification to identify clinically relevant safety patterns. Additionally, a network pharmacology approach was employed to explore the molecular mechanisms of zoledronic acid-associated osteonecrosis, involving target prediction, protein-protein interaction (PPI) network construction, and functional enrichment analysis.ResultsAnalysis of 8849 reports revealed distinct toxicity profiles: Denosumab demonstrated significant associations with metabolic complications including hypocalcemia (ROR: 4.32; 95% CI: 3.87-4.82) and osteonecrosis of the jaw, whereas zoledronic acid showed stronger signals for nonjaw osteonecrosis and renal impairment. Temporal analysis revealed significantly earlier onset of adverse events with denosumab (median: 178 days) compared to zoledronic acid (median: 378 days). Network pharmacology identified 271 common targets shared by bone metastasis, zoledronic acid, and osteonecrosis. Subsequent PPI network and module analysis prioritized 76 key genes, with hub genes (e.g., TP53, TNF, IL-6, AKT1, and STAT3) enriched in inflammatory signaling, apoptosis regulation, and pathways such as PI3K-Akt and TNF signaling.ConclusionThis comprehensive safety analysis demonstrates distinct risk architectures for these bone-targeting therapies. The integration of real-world pharmacovigilance with network pharmacology provides data-driven insights for personalized treatment selection and reveals potential molecular mechanisms underlying zoledronic acid-associated osteonecrosis. The identification of key risk-modifying factors, temporal patterns, and candidate molecular pathways enables the development of biomarker-informed monitoring strategies, representing a significant advancement in pharmacovigilance methodology for optimizing safety in cancer patients with bone metastases.

This phase II trial investigated perioperative camrelizumab plus neoadjuvant chemotherapy for patients with stage IIB-IIIB lung squamous cell carcinoma (LUSC) and explored predictive biomarkers of treatment response. Patients received neoadjuvant camrelizumab (200 mg, Day 1) in combination with nab-paclitaxel (130 mg/m2, Days 1 and 8) and carboplatin (area under the curve = 5, Day 1) every 3 weeks for two cycles, followed by surgery and adjuvant camrelizumab for 1 year. The primary endpoint was major pathological response (MPR) rate. Forty-five patients were treated, of whom 41 underwent surgery. Twenty-seven of 45 patients (60.0%) achieved MPR and 20 (44.4%) achieved pathological complete response (pCR). With a median follow-up of 37.5 months, the 3-year disease-free survival and overall survival rates were 65.9% and 68.7%, respectively. Among eight patients with stage IIIB disease, three (37.5%) achieved pCR. Baseline neutrophil percentage and smoking history were associated with MPR. T-cell receptor (TCR) sequencing revealed that three V-J gene pairs in TCR beta clones differed between the pCR and non-pCR groups. This study supports the application of perioperative immunotherapy combined with neoadjuvant chemotherapy in patients with resectable locally advanced LUSC. The identification of blood biomarkers for precise patient selection warrants further in-depth investigation.

Background and objectivesLacosamide (LCM) is a third-generation concomitant antiseizure medication (ASM) that is widely used in epilepsy treatment. Reported data on the predictors of efficacy of LCM in children with epilepsy are scarce. This study aimed to explore the predictors of LCM efficacy in pediatric patients with epilepsy.MethodsThis single-center retrospective cohort study was conducted in China, consecutively enrolled pediatric epilepsy patients receiving lacosamide treatment; the study period for data collection was September 2021 to April 2025. Demographic data, LCM daily dose, serum concentration, concentration-to-dose ratio (CDR), ASMs, and seizure frequency before and after treatment were collected. Patients were categorized into effective (≥50% seizure reduction) and ineffective groups. Univariate analysis and ridge regression were used to assess the impact of the factors on the efficacy of LCM. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the ridge regression model.ResultsA total of 71 children with epilepsy were enrolled in this study (boys: 35, 49.3%; girls: 36, 50.7%). The overall effectiveness rate was 81.69%. Univariate analysis showed a significantly higher CDR in the effective group compared to the ineffective group (0.768 vs. 0.58, P = 0.031). In this exploratory pilot analysis, ridge regression implied that CDR has a positive effect on the efficacy of LCM. The AUC of the predictive performance of the ridge regression model was 0.767 (95% CI: 0.651–0.875).DiscussionCDR, reflecting weight- and dose-adjusted LCM exposure, is a predictor of LCM efficacy in pediatric epilepsy. These findings support the use of CDR for guiding individualized LCM therapy. Further multicenter studies with larger samples are warranted to validate these results and establish an optimal CDR range.

BackgroundThe relationship between plasma remnant cholesterol (RC) level and cognitive function in middle-aged and older Chinese adults with type 2 diabetes (T2DM) was unclear.MethodsOne thousand eight hundred seventeen participants aged 55 to 75 were recruited from communities in Beijing. Demographic information and daily dietary intakes were collected by self-designed questionnaire. Fasting venous blood was obtained for quantitative analysis of plasma lipid parameters. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. To explore the association between plasma RC and the risk of mild cognitive impairment (MCI), we performed logistic regression analysis and restricted cubic spline (RCS). Additionally, subgroup analyses were conducted to assess the influence of potential co-founders on the association.ResultsPlasma RC level was negatively correlated with daily intakes of vegetable, legume and fish intakes in patients with T2DM, and with daily intakes of cereals, vegetables, and legumes in non-T2DM subjects. Participants with plasma RC levels in the second (Q2), third (Q3), and fourth (Q4) quartiles had a higher risk for MCI compared to those in the first quartile (Q1) level of plasma RC, both in T2DM and non-T2DM participants. RCS results indicated a nonlinear relationship between plasma RC levels and the risk of MCI. Subgroup analysis showed that the association between plasma RC levels and the risk of MCI was pronounced in females and subjects aged 60 and above.ConclusionAn increase in plasma RC level is a potential risk factor for MCI. A plasma RC concentration below 0.578 mmol/L can decrease the risk of MCI in middle-aged and older individuals with T2DM. Similarly, a plasma RC concentration below 0.581 mmol/L may lower the risk of MCI in non-T2DM subjects. Consuming vegetables and legumes daily could help reduce the concentration of RC.