Taiyuan Central Hospital

Hepatocellular carcinoma (HCC) develops from chronic inflammatory conditions to malignancy, with the immune microenvironment playing a significant role in this progression. However, the changes in the dynamic immune microenvironment during the transition from hepatitis to HCC remain poorly understood. Systematic analysis of stage-specific immune microenvironment alterations is essential for identifying therapeutic targets and creating precision strategies for HCC. Using single-cell RNA sequencing (scRNA-seq), we created dynamic transcriptome maps of the immune microenvironment across healthy liver, hepatitis, cirrhosis, and HCC stages. Cell-cell communication, trajectory, and enrichment analyses were utilized to characterize relationships between clusters. TCGA-LIHC data were used to validate gene expression and its prognosis. The spatial distribution of ligand-receptor complexes in HCC was confirmed by spatial transcriptomics and multiplexed immunofluorescence. The effects of the tumor microenvironment on cancer cell behavior were examined using co-immunoprecipitation and cell co-culture assays. Finally, the impact of the immune microenvironment on in vivo tumor progression was evaluated using a mouse transplantation model. We identified specific immune cell clusters across HCC progression and revealed significant correlations between the abundance of immune cells (macrophages, B cells)and fibroblasts with disease severity. Crosstalk between SPP1+ macrophages and ITGA5+ fibroblasts was observed explicitly in HCC. In vitro and in vivo data demonstrated that the SPP1-ITGA5 interaction triggered the secretion of MMP2 by fibroblasts, thereby promoting malignant progression in HCC. We present a dynamic transcriptional profile of immune microenvironment evolution during HCC development, aiding in the refinement of diagnostics and the optimization of therapy strategies.

Older adults with severe dysphagia who require percutaneous endoscopic gastrostomy (PEG) feeding and/or total parenteral nutrition (TPN) have substantial mortality risk, yet practical tools for prognostic stratification are limited. Whether age- and sex-adjusted adiposity estimation formulas (CUN-BAE, ECORE-BF, and the Deurenberg formula) can improve risk prediction for all-cause and pneumonia-related mortality in this setting remains unclear. This study is a secondary analysis of a previously established single-center Japanese retrospective cohort of 247 patients aged ≥50 years with severe dysphagia receiving percutaneous endoscopic gastrostomy (PEG) and/or total parenteral nutrition (TPN). Associations of adiposity estimators with all-cause and pneumonia-related mortality were evaluated using Kaplan-Meier analysis, Cox regression, restricted cubic splines (RCS), time-dependent ROC analysis, and the C-index. Incremental predictive value beyond the baseline model was assessed using net reclassification improvement (NRI) and integrated discrimination improvement (IDI), with sensitivity analyses including multiple imputation, exclusion of deaths within 30 days, and additional adjustment for the Clinical Frailty Scale. Across tertiles, Kaplan-Meier curves separated significantly for both all-cause and pneumonia-related mortality. In fully adjusted Cox models, the highest tertile was associated with higher all-cause mortality (HR 2.02-2.33) and markedly higher pneumonia-related mortality (HR 3.78-5.09) compared with the lowest tertile, with evidence of monotonic trends. Restricted cubic spline analyses supported largely linear dose-response relationships. Predictive discrimination improved over time; at 3 years, CUN-BAE and Deurenberg showed higher AUCs than ECORE-BF for both endpoints. Incremental analyses indicated added value for all-cause mortality with CUN-BAE and Deurenberg. Adiposity estimation formulas, particularly CUN-BAE and Deurenberg, provide clinically useful mortality risk stratification in severe dysphagia receiving PEG/TPN.

Myocardial ischemia-reperfusion injury (MIRI) is a secondary injury that occurs upon the restoration of blood flow to ischemic myocardium, significantly diminishing the clinical benefits of reperfusion therapy. Excessive production of reactive oxygen species (ROS) and subsequent oxidative stress are recognized as central pathological mechanisms underlying MIRI. In recent years, significant progress has been made in the development of therapeutic agents targeting ROS scavenging and the modulation of oxidative stress. This review systematically summarizes recent advancements in MIRI interventions based on antioxidant mechanisms, including strategies for direct ROS elimination and the activation of endogenous antioxidant pathways. Through integrated target prediction and network analysis, the molecular basis and interactions of various antioxidant strategies are elucidated, highlighting compounds such as Honokiol as critical nodes within the intervention network. Additionally, utilizing the National Center for Biotechnology Information (NCBI) database, this work compiles and discusses the clinical progress of related antioxidant drugs in myocardial protection, offering a comprehensive overview and future perspectives. Ultimately, this review provides valuable insights for the future development of effective and low-toxicity anti-MIRI pharmaceutical agents. Keywords: Myocardial ischemia-reperfusion injury; ROS; Oxidative stress; Antioxidants

ABSTRACTBackgroundPD‐1 inhibitors have revolutionized cancer immunotherapy but present significant neurological safety concerns. While clinical trials have documented neurological adverse events (nAEs), a comprehensive understanding of their patterns and risk factors remains limited. This study systematically analyzed a decade of FAERS data to investigate PD‐1 inhibitor–associated neurotoxicities.MethodsUsing FAERS data (2014–2024), we conducted disproportionality analyses (ROR, IC, PRR) to assess PD‐1 inhibitor–nAE associations. Risk factors were evaluated using logistic regression; timing analyses used log‐rank and Mann–Whitney U tests, while group comparisons used Chi‐square tests.ResultsAmong 115,000 PD‐1 inhibitor–associated adverse events, 7968 (6.93%) involved nAEs, showing an increasing trend from 4.96% (Q4 2014) to 7.67% (Q1‐Q2 2024). PD‐1 inhibitors showed significant nAE signals (ROR: 1.21, 95% CI: 1.18–1.23), with cemiplimab showing the strongest association (ROR: 1.38, 95% CI: 1.18–1.62). The most common nAEs were dizziness (N = 942, 10.3%), encephalitis (N = 435, 4.8%), and cerebrovascular accident (N = 451, 4.9%). Risk factors included age > 65 years (OR: 1.10), female sex (OR: 1.04), skin cancer (OR: 1.36), and nervous system cancers (OR: 1.44). The median onset time was 34 days (IQR: 12–104), with 63.8% occurring within 2 months and 59% resulting in severe outcomes.ConclusionThis study reveals a spectrum of PD‐1 inhibitor–related neurological toxicities, mainly involving central nervous system dysfunction, providing important insights into risk patterns and timing characteristics. These findings support improved clinical monitoring practices and inform the development of personalized patient care strategies.

Despite BRI being a novel measure for chronic disease risk, the relationship between BRI and stroke risk under varying circadian syndrome (CircS) conditions is still unclear. The analysis utilized data from 7535 participants involved in the China Health and Retirement Longitudinal Study (CHARLS). CircS was defined by at least four concurrent metabolic disturbances due to circadian rhythm disruption. To ensure robustness, the BRI-stroke association was assessed using Cox models, restricted cubic splines, Kaplan-Meier curves, and mediation analyses, along with subgroup and sensitivity analyses. The receiver operating characteristic (ROC) analysis was used to compare the stroke risk prediction performance of BRI with conventional metabolic indices. Following full adjustment, higher log (BRI) values were significantly associated with an increased risk of stroke (HR = 2.50, 95% CI: 1.81-3.44, p < 0.001), with Q4 showing a greater risk than Q1 (HR = 2.23, 95% CI: 1.63-3.04, p < 0.001). In CircS patients, no significant association was observed (log (BRI) HR = 1.23, 95% CI: 0.55-2.76; Q4 vs. Q1 HR = 0.61, 95% CI: 0.21-1.77; all p > 0.05). However, the association remained significant in non-CircS individuals (log (BRI) HR = 2.36, 95% CI: 1.61-3.47; Q4 vs. Q1 HR = 2.08, 95% CI: 1.46-2.98; all p < 0.001). Subgroup and sensitivity analyses bolstered the robustness of our findings. CircS mediated 21.0% of the association between BRI and stroke risk (95% CI: 18%-91%, p < 0.001). With an area under the curve (AUC) of 0.656, BRI demonstrated moderate predictive capability for stroke, outperforming other anthropometric indices. An increased BRI is associated with a higher stroke risk, partially mediated by CircS, highlighting the potential role of circadian health in stroke prevention.

Plasma fibrinogen is essential in thrombosis and fibrinolysis, yet its dynamic changes pre- and post-intravenous thrombolysis (IVT) for predicting brain injury severity and prognosis in acute ischemic stroke (AIS) patients remain unclear. This study examined how fibrinogen trends before and after IVT correlate with brain injury severity and clinical outcomes in IVT-treated patients. This multicenter study prospectively enrolled AIS patients treated with IVT at 16 hospitals and recorded their fibrinogen trends before and after thrombolysis. Levels of brain injury markers were measured to represent the extent of brain injury, including glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), S100β, and neuron-specific enolase (NSE). Prognostic indicators included early neurological deterioration (END), hemorrhagic transformation, infarct volume, National Institutes of Health Stroke Scale (NIHSS) score at 7 days, 3-month poor outcome (modified Rankin Scale [mRS] score > 1), and mortality. A total of 827 patients were enrolled, with 207 exhibiting elevated fibrinogen levels 24 h after IVT. Patients with elevated fibrinogen levels exhibited significantly higher levels of brain injury markers (GFAP, UCH-L1, S100β), larger infarct volumes, higher NIHSS scores at 7 days, and a higher incidence of END and poor outcomes compared to those with non-elevated fibrinogen levels. Both univariate and multivariate analyses identified elevated fibrinogen levels after IVT as an independent predictor of severe brain injury, larger infarct volume, higher NIHSS score, occurrence of END, and poor outcomes. Elevated fibrinogen levels 24 h after IVT are independently associated with more severe brain injury and worse clinical outcomes in AIS patients.

Spinal infections, particularly those caused by Aspergillus terreus, represent complex and rare clinical challenges. They are even less common in patients with a normal immune system. This case report details the complex diagnosis and treatment process of a 52-year-old female with A. terreus-induced spinal infection. Diagnosis was initially delayed due to non-specific clinical manifestations and ambiguous imaging findings. After treatment with voriconazole (a targeted antifungal agent), the patient’s clinical symptoms and imaging indicators improved significantly—this fully demonstrates the effectiveness of voriconazole in treating such specific fungal spinal infections. This case highlights that fungal infection should be considered in immunocompetent patients with suspected spinal infection, and emphasizes the importance of timely diagnosis and individualized targeted antifungal therapy.

Prior studies have validated a novel index, designated as the cholesterol-HDL-glucose (CHG) index, which has emerged as a promising biological marker for abnormalities in lipid metabolism and insulin resistance. At present, however, there is an absence of data demonstrating its capacity to predict the risk of CMD. The objective of this study is to evaluate the comparative efficacy of the CHG index and the triglyceride-glucose (TyG) index in predicting cardiovascular metabolic disease (CMD) risk. This study was conducted on a cohort of 6471 participants from CHARLS. A binary logistic regression analysis was performed using R software, utilizing restricted cubic spline techniques to evaluate the dose–response relationship. The evaluation of predictive performance was carried out through the use of receiver operating characteristic curves. To quantify the improvements in predictive capability, two important indices were calculated: Net Reclassification Improvement and Integrated Discrimination Improvement were used to assess the enhancements in our predictive models. Finally, a sensitivity analysis was conducted. An increase in each unit of CHG and TyG was associated with a 83% and 46% rise in the risk of CMD, respectively. The occurrence of CMD in the highest quartile for the CHG index (OR = 1.69, 95% CI 1.42–2.00) increased by 69%, while the TyG index (OR = 1.61, 95% CI 1.36–1.92) exhibited an increase of 61%. A linear correlation was identified between the two indices and the risk of CMD. The predictive capabilities and incremental predictive value of both indices were found to be analogous. The CHG index exhibited a substantial linear positive correlation with CMD, demonstrating assessment capabilities for CMD risk that were analogous to those of the TyG index.

Although combined modality therapy is frequently recommended for early-stage natural killer/T-cell lymphoma (NKTCL), the additional benefit of chemotherapy over radiation therapy (RT) alone in stage I disease remains unclear. We retrospectively analyzed 294 stage I NKTCL patients treated with RT with or without asparaginase-based chemotherapy across three centers in China and validated the findings in 242 patients from the SEER database. In the Chinese cohort, local invasion (defined as bone involvement, skin infiltration, perforation, or extension into the paranasal sinuses) and treatment modality were independent prognostic factors for progression-free survival (PFS) and overall survival (OS) (all P < 0.05). Chemotherapy plus RT significantly improved 5-year PFS (85.3% vs. 65.2%, P = 0.007) and OS (91.4% vs. 82.0%, P = 0.027) compared to RT alone. In subgroup analyses, patients without local invasion did not benefit from chemotherapy (5-year PFS: 91.9% vs. 87.6%, P = 0.19; 5-year OS: 96.4% vs. 96.3%, P = 0.55), whereas those with local invasion experienced substantial improvements (5-year PFS: 78.4% vs. 45.4%, P = 0.008; 5-year OS: 86.3% vs. 65.4%, P = 0.018). These findings were consistent after propensity score matching. In an exploratory analysis of the SEER cohort, chemotherapy improved OS among patients with primary involvement of non-nasal/nasopharyngeal sites (P = 0.044), but not in those with nasal/nasopharyngeal disease (P = 0.23). RT alone appears to provide excellent outcomes for stage I NKTCL without local invasion, while chemotherapy remains necessary for those with local invasion.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10238-025-01930-6.