Copper is an essential trace element in the human body, extensively involved in key physiological and biochemical processes such as antioxidant defense, energy metabolism, neural signaling, and immune regulation. In recent years, increasing research has focused on the potential role of copper dyshomeostasis in the development of chronic diseases. Studies indicate that abnormal copper levels, particularly elevated free copper, may increase the risk of cardiovascular disease, neurodegenerative disorders, diabetes, and cancer by inducing oxidative stress, impairing mitochondrial function, and disrupting immune regulation. Concurrently, copper homeostasis abnormalities have been demonstrated to be closely associated with increased all-cause mortality and accelerated aging. This systematic review comprehensively examined physiological functions, metabolic pathways, and environmental exposure characteristics of copper. It emphasized the epidemiological and mechanistic links between copper metabolism disorders and multiple chronic diseases, while exploring the potential applications of copper ion transporters and chelating agents in disease intervention. This work provides scientific evidence for the prevention, control, and precision treatment of copper-related chronic diseases.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective To explore the role of resilience and stress in childhood maltreatment and adolescent depression and anxiety symptoms, and to provide a basis for adolescent psychological intervention. Methods From September to October 2022, a total of 11 217 students from four middle schools in Changsha were selected by multistage stratified sampling, and the Childhood Trauma Questionnaire, Depression–Anxiety–Stress Scales and the Resilience Scale for Chinese Adolescents were used to carry out online questionnaire survey. Results The detection rate of depressive symptoms and anxiety symptoms in adolescent was 19.43% (2 179) and 28.7% (3 224). The direct effect of childhood maltreatment on depressive symptoms was significant (β =0.09), Childhood maltreatment is a negative prediction of resilience (β = -0.57) and a positive prediction of pressure (β =0.06); Resilience can negatively predict stress (β = -0.61) and depressive symptoms (β = -0.25) (all P values <0.001); The direct effect of childhood maltreatment on anxiety symptoms was significant (β =0.03), resilience negatively predicts anxiety symptoms (β = -0.08) (all P values <0.01). Resilience and stress have a partially mediating role between childhood maltreatment and depressive symptoms, the mediation effect value was 0.39, accounting for 81.25% of the total effect. The effect values of the three pathways accounted for 29.17%, 8.33% and 43.75% of the total effect, respectively. Resilience and stress have a partial mediating effect between childhood abuse and anxiety symptoms, and the mediating effect was 0.36, accounting for 92.31% of the total effect, and the effect values of the three pathways accounted for 12.82%, 10.26% and 69.23% of the total effect, respectively. Conclusion Childhood maltreatment could affect adolescents’ depression and anxiety through the chain mediating effect of resilience and stress.

AIM:To clarify the expression characteristics and regulatory role of the long non-coding RNA(lncRNA)metastasis-associated lung adenocarcinoma transcript 1(MALAT1)in oxidative stress and apoptosis of H2O2-induced human lens epithelial cell line HLE-B3.METHODS: HLE-B3 cells were divided into Control group and H2O2 group(cultured with 200 μmol/L H2O2 for 24 h). Levels of reactive oxygen species(ROS)and cell apoptosis rates were detected by flow cytometry. Activities of superoxide dismutase(SOD)and catalase(CAT)were measured using kits, MALAT1 expression was quantified by real-time quantitative PCR, and its cellular localization was determined by fluorescence in situ hybridization. After selecting the Si-MALAT1 sequence with the highest silencing efficiency, the groups were established as Control, H2O2, H2O2+Si-NC, and H2O2+Si-MALAT1. Immunofluorescence staining was employed to detect the apoptosis marker TUNEL and Nrf2 nuclear translocation. RESULTS:Compared with the Control group, the H2O2group exhibited significantly elevated ROS levels, markedly decreased SOD and CAT activities(both P<0.001), and a significantly increased apoptosis rate(P<0.01). MALAT1 expression was upregulated(P<0.01)and localized in the nucleus. After silencing MALAT1, H2O2-induced cell apoptosis was significantly inhibited(P<0.01).CONCLUSION: H2O2-induced oxidative stress can increase the expression of MALAT1, and silencing MALAT1 reduces oxidative stress damage and apoptosis, providing a potential target for preventing and treating cataracts.

OBJECTIVE To mine the risk signals associated with erectile dysfunction （ED） related to antihypertensive drugs based on real-world data， and to provide a reference for the safe clinical use and risk monitoring of these drugs.METHODS Reports of ED associated with 15 target antihypertensive drugs were extracted from the US FDA Adverse Event Reporting System （FAERS） database， covering the period from the first quarter of 2004 to the first quarter of 2026. Three proportional disproportionality measures （reporting odds ratio， proportional reporting ratio， and empirical Bayesian geometric mean） were used to mine the risk signals for ED associated with various antihypertensive drugs， and stratified analyses were performed based on patient age and body weight.RESULTS A total of 997 ED reports associated with 15 antihypertensive drugs were included. The majority were male patients （931 reports）， with age concentrated in the 18 to ＜65 years group （511 reports）， body weight in the 50 to ＜100 kg group （366 reports）， and reporters predominantly consumers/patients （497 reports）. The top three drugs by number of reports were amlodipine （413 reports）， metoprolol （133 reports）， and valsartan （82 reports）； the overall demographic distribution characteristics of reports associated with each drug were similar. Positive signals were detected for 8 drugs， including amlodipine and metoprolol. ED associated with atenolol， candesartan， metoprolol， hydrochlorothiazide， and losartan mostly occurred within 30 days after medication； ED associated with valsartan and perindopril mostly occurred over 360 days after medication； and the onset time of amlodipine-associated ED was evenly distributed across all time periods. There were a total of 835 serious reports， with calcium channel blockers （CCBs） accounting for the highest proportion （44.0%） and angiotensin-converting enzyme inhibitors for the lowest （3.7%）. The intensity of risk signals for amlodipine-associated ED increased with advancing age and higher body weight， while the signals for metoprolol were most pronounced in individuals aged 45 to ＜60 years and weighing≥100 kg； positive signals for valsartan were observed only in individuals aged≥60 years and those weighing 50 to ＜75 kg or ≥100 kg.CONCLUSIONS Reports of ED associated with antihypertensive drugs exhibit significant heterogeneity across drug types and differences in the distribution of onset times； CCBs have the highest proportion of serious reports； and the relationship between ED risk signals associated with amlodipine， metoprolol， and valsartan and age and body weight also shows marked heterogeneity.

Objective:To investigate the current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.

Objective To investigate the predictive value of serum uric acid(UA),homocysteine(Hcy)and the product index of UA and Hcy in patients with stable coronary artery disease(SCAD).Methods A total of 783 patients with suspected coronary heart disease were collected,all of whom underwent coronary angiography.Patients were divided into coronary heart disease(CHD)group and non-coronary heart disease(NCHD)group.The CHD group was further divided into low score group(≤35 points)and high score group(>35 points)according to Gensini scores.Baseline data,blood lipids,Hcy,UA,left ventricular function ultrasound indicators,and comorbidities were collected.Logistic regression analysis was used to evaluate the risk factors associated with the onset of SCAD and severe coronary artery disease,while the Receiver Operating Characteristic(ROC)curve was conducted to assess the predictive efficacy of the product index of UA and Hcy,and related risk factors,for SCAD onset and severe coronary artery disease.Results 1.In CHD group,UA,Hcy and the product index of UA and Hcy were all higher than in the NCHD group(P<0.001);the high-score group had higher UA,Hcy and the product index of UA and Hcy than the low Gensini score group(P<0.001).2.Multivariate logistic regression analysis showed that female age,sex,body mass index(BMI),product index of UA and Hcy,high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),type 2 diabetes mellitus(T2DM)and hypertension(HTN)were independent risk factors for SCAD(P<0.05).BMI,the product index of UA and Hcy,HDL-C,LDL-C and LVEF were independent risk factors for severe coronary artery disease(P<0.05).3.There was a positive correlation between UA and Hcy product index and Gensini scores(r=0.433,P<0.05).4.Receiver operating characteristic curve analysis showed that the product index of UA and Hcy and combined detection of coronary heart disease risk factors had predictive value for the occurrence of SCAD(P<0.05),and the predictive value of combined detection was higher(area under the curve 0.808);both the product index of UA and Hcy and the combined detection of coronary heart disease risk factors had predictive value for severe coronary artery lesions(P<0.05),with a higher predictive value for combined detection(area under the curve 0.771).Conclusion As an independent predictor of the risk of SCAD and severe coronary stenosis,the product index of UA and Hcy has a high predictive efficacy regarding disease risk and the severity of coronary artery in patients with SCAD.

Objective To evaluate the predictive value of changes in serum homocysteine(Hcy),high-density lipoprotein cholesterol(HDL-C),and the homocysteine-to-HDL-C ratio(HHR)for the incidence and short-term prognosis of patients with premature coronary heart disease(PCHD).Methods Between January 2022 and December 2023,301 patients with the suspected coronary heart disease(males≤55 years,females≤65 years)were retrospectively selected from the Department of Cardiology at the Third People's Hospital of Yunnan Province.All patients who underwent coronary angiography(CAG)were divided into the premature coronary heart disease(PCHD)group(n=98)and the non-coronary heart disease(NCHD)group(n=203).Patients with PCHD were followed up six months after the discharge and were further classified into the good prognosis group(n=55)and the poor prognosis group(n=43)based on the presence of worsening clinical symptoms such as chest tightness,chest pain,arrhythmias,heart failure,or death.Data collected included general patient information,blood lipid levels,Hcy levels,left ventricular function ultrasound indicators,and the presence of hypertension and type 2 diabetes.Results Hcy and HHR levels were significantly higher in the PCHD group compared to the NCHD group,while HDL-C levels were lower(P<0.001).In the poor prognosis group,Hcy and HHR levels were elevated,and HDL-C levels were reduced compared to the good prognosis group(P<0.001).The Hcy and HHR levels in the severe coronary artery stenosis group were markedly higher than those in the normal coronary artery group and the mild to the moderate stenosis group,with HDL-C levels being lower(P<0.001).Multivariate logistic regression analysis identified that male sex,HHR,Hcy,low-density lipoprotein cholesterol(LDL-C),and left ventricular ejection fraction(LVEF)were independent factors influencing premature coronary heart disease(P<0.05).HHR was found to be an independent risk factor for the poor short-term prognosis in PCHD.The analysis of the operating characteristic curve of the subjects showed that serum Hcy and HHR had the predictive value for the occurrence of PCHD(P<0.05),with HHR showing higher predictive value(area under the curve[AUC]=0.713).HHR also had the substantial predictive value for the short-term prognosis of PCHD(AUC=0.715).Conclusion Elevated HHR levels are associated with the severe coronary artery disease in patients with PCHD.HHR serves as a significant predictor for both the occurrence and short-term prognosis of PCHD.

Objective:To elucidate the regulatory role of matrix metallopeptidase 14 (MMP14) in the migration of chondrogenic precursor cells, thereby providing data support for investigating the pathogenesis of microtia.Methods:An in vitro differentiation model was established using human induced pluripotent stem cells (iPSCs) sequentially induced into neural crest cells (iNCCs) and subsequently into chondrogenic precursor cells (iCPCs), combined with lentivirus-mediated knockdown of MMP14, to investigate the effects of MMP14 on the biological characteristics of iCPCs, including proliferation, differentiation, and migration. Collective cell migration was assessed using scratch wound healing and Transwell migration assays; directional migration was characterized via high-content live-cell imaging; single-cell adhesion force was measured using a micromanipulation system. Collagen degradation was evaluated through hydroxyproline digestion assays. Cell proliferation was analyzed using the CCK-8 assay, and the expression of osteogenic/chondrogenic-related genes (SOX5/6/9, COL1A1, COL2A1, RUNX2, TWIST1) were quantified by real-time quantitative PCR. Immunofluorescence staining was used to assess the expression of F-actin and CD44 proteins. Additionally, transcriptomic sequencing was performed on iCPCs before and after MMP14 knockdown. Results:iPSC→iNCC→iCPC differentiation model was established in vitro. The resulting iCPCs expressed osteo/chondrogenic marker genes, including SOX5, SOX6, SOX9, COL1A1, COL2A1, RUNX2, and TWIST1, and exhibited positive expression of mesenchymal stem cell markers CD90, CD105, and CD73. Upon further induction, functional cartilage spheroids were formed. Compared with normal auricular chondrocytes, auricular chondrocytes from microtia patients showed reduced expression of MMP14 at both mRNA and protein levels. Lentivirus-mediated shRNA knockdown of MMP14 in iCPCs resulted in a marked decrease in its mRNA and protein expression. MMP14 knockdown significantly impaired collective migration of iCPCs, as evidenced by reduced wound closure rates in scratch assays and decreased numbers of migrated cells in Transwell assays. High-content live-cell imaging revealed that MMP14-deficient iCPCs displayed more erratic migration trajectories and a lower straight-line migration ratio. Single-cell adhesion assays showed extracellular matrix (ECM)-dependent alterations: cell adhesion was enhanced on matrigel-coated surfaces but weakened under uncoated conditions. MMP14 knockdown also led to reduced proliferation, decreased collagen degradation, diminished F-actin expression, fewer peripheral adhesion sites, and downregulation of CD44 protein expression, without significantly affecting the expression of chondrogenic genes such as SOX6, SOX9, COL1A1, COL2A1, RUNX2, and TWIST1. Transcriptomic analysis further revealed that MMP14 knockdown significantly downregulated genes involved in extracellular matrix organization, cell adhesion, migration, and tissue development, with enrichment in pathways including ECM-receptor interaction, focal adhesion, and MAPK signaling. Conclusion:MMP14 plays a critical role in the directional migration of chondrogenic precursor cells by regulating ECM remodeling, adhesion signaling, and cytoskeletal proteins.

Non-small cell lung cancer(NSCLC)is the leading cause of cancer-related morbidity and mortality worldwide and is the most pre-valent thoracic malignancy in China.With regards to the diagnosis and treatment of NSCLC,advances in radiomics have enabled the high-throughput extraction and quantification of intratumoral spatial heterogeneity.18F-fluorodeoxyglucose positron emission tomography/com-puted tomography(18F-FDG PET/CT),which integrates high-resolution anatomical details with functional metabolic data,has been widely used in oncologic imaging.By synergistically combining 18F-FDG PET/CT with radiomics to construct machine learning models,the clinical util-ity of this modality has markedly expanded,and it has been rapidly integrated into the comprehensive management of lung cancer.In the diagnostic setting,these integrated models can differentiate benign from malignant pulmonary nodules with high reliability,thereby enhan-cing the accuracy of early stage NSCLC detection and enabling a non-invasive prediction of histopathologic subtypes.Radiomics signatures can also provide robust support for precision oncology by facilitating accurate TNM staging,predicting actionable genomic alterations,and estimating immune checkpoint expression levels.Moreover,machine learning-based radiomic analyses are valuable in treatment response monitoring and prognostication,effectively forecasting therapeutic efficacy and patient survival outcomes.In this review,we summarize re-cent advances in the application of 18F-FDG PET/CT radiomics across the entire continuum of NSCLC care.