Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin,liquiritin apioside,verbascoside,narirutin,isoacteoside,apigetrin,hesperidin,isoliquiritin,ononin,liquiritigenin,glycyrrhizic acid,isoliquiritigenin,honokiol,obovatol,pogostone and magnolol in Jiawei Huoxiang Zhengqi Soft Capsules.METHODS The analysis was performed on a 40 ℃ thermostatic ZORBAX Eclipse Plus C18 column(2.1 mm×100 mm,1.8 μm),with the mobile phase comprising of 0.1％formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r＞0.990 0),whose average recoveries were 83.74％-105.12％with the RSDs of 1.10％-4.8％.CONCLUSION This accurate,sensitive,stable and reproducible method can provide a reference for the overall quality control of Jiawei Huoxiang Zhengqi Soft Capsules.

Objective:According to the"Technology-Organization-Environment"framework,it aims to analyze barriers of meaningful use of digital technologies in primary care facilities and propose corresponding optimization strategies.Methods:Nvivo 11.0 Software is used to conduct thematic framework analysis on interview data of primary healthcare and administrative staff in a district of Jiangsu Province.Results:The barriers are as follows:(1)technology level:infrastructure needs improvement,unified technology standards for data,low level of technology usability and usefulness,and limited economic benefits;(2)organizational level:insufficient digital literacy of medical staff,low organizational innovation ability,lack of training,inertia of healthcare staff,and limited size of primary care facilities;(3)environmental level:insufficient government support,high government requirements of performance evaluation,low digital literacy of residents,not covered by medical insurance schemes,constraints on interests among stakeholders,and mismatched digital scenarios.The main reason for insufficient effective use of digital technologies includes insufficient adaptability between digital technologies and the practical needs of grassroots health services,lack of organizational change and proactive personnel behavior,low level of external environment optimization and institutional support.Conclusion:Policy makers and implementers should be demand-oriented,continuously improve digital technologies maturity in primary healthcare system,integrate organizational resources,achieve changes in primary healthcare models,optimize the external environment,and enhance collaborative governance levels.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

The intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is currently the first-line therapy for retinopathy of prematurity (ROP) in clinical practice.This therapy has several advantages, including ease of operation, rapid onset of action, and minimal adverse reactions.However, the high reactivation rate observed in clinical applications limits its utility.Understanding reactivation characteristics is crucial for patient management and clinical trial design.The International Classification of Retinopathy of Prematurity (Third edition) updated the definition of reactivation and related concepts.This article summarizes the clinical manifestations and mechanisms of ROP reactivation after anti-VEGF therapy in recent studies and analyzes high-risk factors associated with reactivation, including those related to the infant, the disease, and the medication.The goal is to provide guidance for the early identification, prevention, and intervention in clinical practice.Nevertheless, significant clinical controversies remain regarding the prevention and retreatment of ROP reactivation.Future research should accumulate more evidence-based medical data and conduct large-scale prospective studies to further standardize diagnostic and treatment processes.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.

Objective:To evaluate the relationship between postoperative changes in femoral head coverage (FHC) after S 2-Alar-Iliac (S 2AI) screw fixation and the development of sagittal imbalance during follow-up in patients with adult spinal deformity (ASD), providing insights for clinical assessment and treatment strategies. Methods:A consecutive cohort of 98 ASD patients who underwent S2AI fixation between September 2019 and September 2021 was retrospectively analyzed. Patients were divided into two groups based on changes in femoral head coverage (ΔFHC): the FHC-C group (upper quartile ΔFHC, 25 cases) and the FHC-NC group (lower quartile ΔFHC, 24 cases). Additionally, patients were classified into proximal junctional kyphosis (PJK) and non-PJK groups based on their clinical outcomes at the last follow-up. Standing full-spine anteroposterior and lateral X-rays were taken preoperatively, postoperatively, and at the two-year follow-up to measure and document the following spinal parameters: Cobb angle, proximal lumbar lordosis (PLL), distal lumbar lordosis (DLL), lumbar lordosis (LL), lordosis distribution index (LDI), sagittal vertical axis (SVA), coronal balance distance (CBD), thoracic kyphosis (TK), T 1 pelvic angle (T 1PA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), PI-LL, and proximal junctional angle (PJA). Parameters related to hip joint coverage included: femoral head coverage (FHC), lateral center-edge angle (LCE angle), acetabular index (AI), Sharp angle, and extrusion index (EI). Comparisons of radiographic indicators between the two groups were performed at preoperative, postoperative, and final follow-up assessments. The visual analogue scale (VAS) was used to evaluate the hip pain and back pain. Results:At final follow-up, the incidence of PJK was significantly higher in the FHC-NC group [37.5% (9/24)] compared to the FHC-C group [16.0% (4/25)] (χ 2=3.952, P=0.042). Moreover, the increase in sagittal vertical axis (ΔSVA) was significantly greater in the FHC-NC group (35.9±44.7 mm vs. 14.6±31.8 mm, t=2.216, P=0.031). Patients with PJK had significantly higher preoperative T 1PA (36.8°±10.8° vs. 31.9°±18.4°, t=2.150, P=0.034) and lower immediate postoperative ΔFHC (1.7%±1.5% vs. 3.3%±2.5%, t=2.987, P=0.004), as well as lower changes in lateral center-edge angle during follow-up (0.3°±3.0° vs. 1.1°±8.9°, t=2.334, P=0.022). Pearson correlation analysis revealed significant negative correlations between postoperative ΔFHC and both ΔSVA ( r=-0.374, P=0.008) and proximal junctional angle changes (ΔPJA, r=-0.429, P=0.006). Additionally, increases in VAS leg pain scores correlated negatively with immediate postoperative FHC ( r=-0.314, P=0.025) and ΔFHC ( r=-0.298, P=0.031). Logistic regression indicated that immediate postoperative ΔFHC was a protective factor against PJK [ OR=0.722, 95% CI (0.541, 0.963), P=0.009), with a ROC-determined optimal ΔFHC cut-off of 3.90% (AUC=0.723, Youden index=0.847). Conclusions:Postoperative evaluation of femoral head coverage is clinically important for ASD patients undergoing S2AI screw fixation. A pre-to-post ΔFHC below 3.90% may indicate reduced hip compensation capacity, increasing risks for hip pain, sagittal imbalance progression, and PJK postoperatively.

Objective:To predict mechanical complications (MC) following spinal deformity surgery for adult spine deformity (ASD) using machine learning models, identify key risk factors, and develop a visualizable tool for individualized risk assessment.Methods:Clinical and radiological data from 525 patients with ASD who underwent surgery in our hospital between January 2017 and December 2021 were collected. Patients were randomly assigned to a training set (70%) and a test set (30%) for model development. The cohort included 88 males and 437 females, with a mean age of 42.2±18.1 years. Variables included demographic data, comorbidities, local and systemic radiological parameters, paraspinal muscle fat infiltration (FI), and vertebral bone quality (VBQ) scores. Multiple machine learning algorithms: Random Forest (RF), Gaussian Naive Bayes (GNB), Light GBM, Support Vector Machine (SVM), XGBoost (XGB), and Logistic Regression (LR) were trained and evaluated. Model performance was compared using the receiver operating characteristic curve (ROC) and precision-recall curve (PRC). SHAP (Shapley Additive Explanations) was used to rank risk factors, while LIME (Local Interpretable Model-Agnostic Explanations) was applied to visualize MC risk in individual cases.Results:Of the 525 patients, 135 (25.7%) developed postoperative MC. Among these, 80 (59.3%) experienced proximal junction kyphosis or failure (PJK/PJF), 7 (5.2%) had distal junction kyphosis or failure (DJK/DJF), 28 (20.7%) sustained rod fractures, and 29 (21.5%) showed significant loss of correction. In the validation cohort, the RF model achieved the highest area under the curve (AUC=0.80), followed by GNB (0.77), XGB (0.76), LR (0.74), LightGBM (0.73), and SVM (0.66). The RF model also demonstrated the best PRC value (0.58), highest sensitivity (0.65), and lowest Brier score (0.20). GNB, Light GBM, and LR models achieved the highest accuracy (0.78 each), while LightGBM exhibited the highest specificity (0.93). SHAP analysis identified higher preoperative VBQ scores, larger T 1 pelvic angle (TPA), and higher paraspinal muscle FI as the main risk factors for MC. Based on the RF model, a LIME-based tool was successfully constructed for individualized MC risk estimation. Conclusion:The RF model demonstrated the best overall predictive performance for MC. A machine learning-based prediction model has the potential to provide valuable guidance for surgical decision-making in ASD patients.