Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

ObjectiveTo investigate the potential mechanism of Yiqi Yangyin Huoxue Formula （益气养阴活血方， YYHF） in the treatment of membranous nephropathy （MN） based on the NOX4-mediated stromal cell-derived factor-1α（SDF-1α）/CXC chemokine receptor 4 （CXCR4） signaling pathway. MethodsA total of 42 male SD rats were randomly divided into blank group （n=6） and modeling group （n=36）. The modeling rats were given a single injection of sheep antirat Fx1A （6 ml/kg） serum into the tail vein to establish MN model. Thirty-six rats with successful modeling were further divided into model group （normal saline， 10 ml/kg）， benazepril group （10 mg·kg^-1·d^-1）， the medium-dose YYHF group （11.0 g·kg^-1·d^-1） and high-dose YYHF group （22.0 g·kg^-1·d^-1）， with 9 rats in each group. All groups received daily intragastric administration for 6 consecutive weeks. During the experimental period， the general condition of rats in each group was observed. After gavage administration finished， a fully automated biochemical analyzer was used to measure the 24-hour urine total protein （24 h-UTP） and serum biochemical parameters， including albumin （ALB）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， serum creatinine （SCr）， total cholesterol （TC）， and triglyceride （TG）. Hematoxylin-eosin （HE） staining and periodic acid-silver metheramine （PASM） staining were used to observe the histopathological changes of renal tissues in each group of rats. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were detected by ELISA. The protein expression levels of NOX4， SDF-1α， CXCR4， Nrf2， nuclear factor kappa B subunit p65 （NF-κB p65） and podocyte slit diaphragm protein nephrin in rat renal tissues were detected by Western Blotting. The mRNA expressions of NOX4， SDF-1α， CXCR4， Nrf2， NF-κB p65 and Nephrin in renal tissues were detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultsCompared to the blank group， rats in the model group exhibited typical features of MN， including lethargy， reduced activity， dull and coarse fur， marked edema， and massive proteinuria. Compared to the model group， these abnormal conditions were improved to varying degrees in all treatment groups. The high-dose YYHF group showed a level of improvement comparable to that of the benazepril group， with overall recovery superior to that of the medium-dose YYHF group. Compared to the blank group， the model group showed increased levels of 24 h-UTP， BUN， SCr， TC and TG， decreased level of ALB， increased levels of MDA and protein and mRNA expressions of NOX4， SDF-1α， CXCR4 and NF-κB p65 in renal tissue， along with decreased levels of SOD and protein and mRNA expressions of Nrf2， Nephrin （P＜0.01）， accompanied by severe renal pathological damage. Compared to the model group， the benazepril and the medium- and high-dose YYHF groups showed significant improvements in the above indicators （P＜0.01）， along with alleviation of renal pathological injury. The 24 h-UTP level in the high-dose YYHF group was lower than that in the medium-dose group （P＜0.01）， while no statistically significant difference was observed among the other treatment groups （P＞0.01）. ConclusionYYHF may alleviate oxidative stress and inflammatory responses by down-regulating the expression of NOX4 and inhibiting the SDF-1α/CXCR4-Nrf2 signaling pathway， thereby improving podocyte damage and protecting renal function.

Armeniacae Semen Amarum， the dried mature seeds of plants such as Prunus armeniaca var. ansu （Rosaceae）， have a long history for medicinal use. Modern research indicates that the core active compounds of Armeniacae Semen Amarum， such as amygdalin， fatty acids， and volatile oils， exhibit multiple pharmacological effects including antitussive， bronchodilatory， anti-inflammatory， antioxidant， antitumor， antifibrotic， and immunomodulatory effects. Consequently， their potential applications in treating respiratory diseases， tumors， tissue injury， and metabolic disorders have garnered significant attention. However， a systematic integrated analysis of the relationship between the traditional efficacy， modern pharmacology， key material basis， and multi-pathway mechanisms of Armeniacae Semen Amarum remains lacking. Using bibliometric methods combined with CiteSpace visualization technology， this study systematically summarizes the research hotspots on Armeniacae Semen Amarum and its representative component amygdalin， including the key roles in inflammation regulation， apoptosis induction， cell cycle arrest， oxidative stress balance， and fibrosis modulation. This article reviews the research progress in Armeniacae Semen Amarum across from four major dimensions—traditional applications， visualization analysis， material basis， and modern pharmacological studies， providing a reference for the further basic and clinical studies of Armeniacae Semen Amarum in respiratory diseases， oncology， and immune-related disorders.

As a traditional Chinese medicine (TCM), borneol has shown superior ability for anti-inflammatory and analgesic activities when coupled with other active ingredients from ancient times. Furthermore, borneol is believed to improve blood concentration and bioavailability of drugs. Thus, it has been paired with various TCM formulas since ancient time. The physiological barriers in human can cause significant limitations in drug efficiency as the drug is primarily restricted from entering into blood and brain. Borneol has been proven to enhance the permeability of biological barriers such as the blood-brain, transdermal, corneal, and intestinal barriers. Moreover, growing interest has been shown in the drug delivery system design for trans-barrier transport involving borneol. Nano-drug delivery system with increased surface area and improved active sites, has been applied to increase the bioactivity of water insoluble drugs. Nano-drug delivery system has been used to enhance drug efficacy by reducing the time of action as compared to conventional administration approach of TCM formulas. Given its ability to enhance cross-barrier permeation and drug efficacy, borneol has been integrated into TCM formulas of drug delivery system for precise and prolonged targeting at tumor sites. However, the design and preparation of a drug delivery system consisting of borneol still face great challenges. Current research fails to unravel the difference in mechanism of action between nano-drug delivery systems comprised of borneol and conventional drug systems coupled with borneol. Enhanced penetration of borneol in drug delivery system is rarely verified compared to conventional administration with identical drug formulation consisting of borneol regarding dosage and medical indications. This study outlines the current state of research on the properties, formulation and pharmacological effects of borneol, allowing cross-comparison of borneol coupled with single compound and classical TCM formulas for various medical indications. This study aims to provide insights into the design of borneol-based enhanced cross-barrier delivery drug formulation, and the potential development of nano-drug system for TCM formulas with borneol for enhanced bioavailability.

Spinal cord injury(SCI)can result in varying degrees of spinal motor dysfunction,partial sensory loss and sphincter dysfunction.SCI is divided into two stages:primary injury and secondary injury.The spinal cord cell necrosis during the primary injury period and apoptosis,oxidative stress and autophagy during the secondary injury period lead a large number of cell injury and permanant neurodysfunction.The histone deacetylase(HDAC)plays a key role in regulating the cellular viability and gene transcription.Neuro-dysfunction induced by SCI is associated with transcriptional dysfunction associated with unbalanced levels of protein acetylation.Valproic acid(VPA)is a inhibitor of HDAC and is usually used as an antiepileptic drug in clinic.Studies show that VPA may have the potential to treat the central nervous system diseases.VPA inhib-its HDAC,and then regulates oxidative stress,cellular autophagy,ion imbalance,microglia differentiation and inflammatory response,and plays the neuroprotective effect.This paper reviewed the related molecular mecha-nism of VPA in treating SCI.

Objective To investigate the protective effects of ferroptosis inhibitor ferrostatin-1(Fer-1)on high-altitude hypoxic lung injury and explore novel preventive strategies for high-altitude hypoxia-induced lung injury.Methods ①Eighteen SPF male Wistar rats(5～6 weeks old,210～230 g)were randomly divided into 3 groups(n=6):normoxic control,hypoxic lung injury,and Fer-1 pretreatment groups.A hypobaric chamber was used to establish a rat model of high-altitude hypoxic lung injury.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was employed to compare pulmonary protein profiles between normoxic and hypoxic groups,followed by bioinformatics analysis of pathways enriched with differentially expressed proteins(DEPs).Histopathological changes and lung injury scores were assessed with HE staining.ELISA was used to quantify the inflammatory cytokines,flow cytometry and immunofluorescence assay were employed to measure the production of reactive oxygen species(ROS),and spectrophotometry was utilized to determine the contents of Fe2?,glutathione(GSH),malondialdehyde(MDA),and superoxide dismutase(SOD)to evaluate oxidative stress and detect ferroptosis-related markers.② Human bronchial epithelial cells(bronchial epithelium transformed with Ad12-SV40,BEAS-2B)and macrophages induced by tumor human peripheral blood monocytes-1(THP-1)cells were placed in a low oxygen conditions for 48 h to establish a cellular model of hypoxic lung injury,on which Fer-1 was administered as a preventive group.Ferroptosis markers in BEAS-2B cells and inflammatory cytokine secretion in macrophages were analyzed.Results ①Proteomics identified 2 962 proteins,with 357 DEPs(199 up-regulated,158 down-regulated).Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed ferroptosis as the most enriched pathway.Hypoxic lung injury resulted in elevated ROS,MDA,Fe2?,and inflammatory cytokines(P<0.05),reduced SOD,GSH,solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and ferritin heavy chain 1(FTH1),and increased acyl-coa synthetase long chain family member 4(ACSL4)(P<0.05).Fer-1 pretreatment significantly mitigated oxidative stress(ROS,MDA,SOD,GSH;P<0.05),up-regulated SLC7A11 and FTH1,down-regulated ACSL4(P<0.05),and reduced inflammation(P<0.05).②In cellular models,Fer-1 increased SLC7A11,GPX4,FTH1,GSH,and SOD(P<0.05),declined ROS(P<0.05),and suppressed macrophage inflammatory cytokines(P<0.05).Conclusion Fer-1 alleviates high-altitude hypoxic lung injury by inhibiting ferroptosis in pulmonary epithelial cells and attenuating macrophage-driven inflammation,providing experimental evidence for novel therapeutic strategies.

Objective To explore the potential clinical value of the ratio of glycated albumin to albumin(GA/ALB)in the occurrence of heart failure(HF)among patients with coronary atherosclerotic heart disease(CHD).Methods A total of 337 CHD patients admitted to the Department of Cardiology in Shanxi Provincial People's Hospital from July 2023 to June 2024 were selected in this study.CHD patients were divided into HF group and non-HF group based on whether they progressed to HF.The clinical data and laboratory parame-ters of the two groups were compared.Restricted cubic spline curve was used to analyze the relationship be-tween GA/ALB levels and the risk of HF in CHD patients.Receiver operating characteristic curve was applied to evaluate the diagnostic efficacy of GA/ALB,GA,platelet to lymphocyte ratio(PLR),and monocyte to lym-phocyte ratio(MLR)in CHD patients with the occurrence of HF.Logistic regression was used to explore the relationship between serum GA/ALB levels and the risk of CHD patients occurrence of HF,and to analyze the degree of influence and stability of subgroup variables on results.Results There were statistically significant differences in GA/ALB,GA,PLR,MLR,and other indicators between the HF group and the non-HF group in CHD patients(P＜0.05).A non-linear relationship was observed between GA/ALB levels and the risk of HF in CHD patients.When the value of GA/ALB multiplied by 10 was less than 5.751,the risk of HF in CHD pa-tients increased with the increase of GA/ALB levels(P＜0.001).GA/ALB was an effective predictor for HF occurrence in CHD patients.Multivariable Logistic regression model showed that GA/ALB was an independ-ent risk factor for CHD patients with occurrence of HF.Subgroup analysis also confirmed the stability of GA/ALB in predicting the occurrence of HF in CHD patients.Conclusion GA/ALB is an independent risk factor for the occurrence of HF in CHD patients,and monitoring GA/ALB levels provides predictive value for the oc-currence of HF in these patients.

Objective:To investigate the differences in prognosis between different surgical approaches in elderly patients with advanced ovarian cancer.Methods:Based on the Surveillance, Epidemiology and End Results (SEER) database, a cohort of elderly patients with advanced ovarian cancer from 2000 to 2020 was established. Through propensity score matching, 2 094 patients were selected from those who underwent two different surgical approaches to form a matched cohort (SEER database cohort), including 1 039 patients who received cytoreductive surgery and 1 055 patients who underwent local resection. Meanwhile, 148 elderly patients with advanced ovarian cancer who were treated at the First Affiliated Hospital of Shandong First Medical University from January 2012 to January 2024 were selected (hospital cohort), among whom 85 underwent cytoreductive surgery and 63 underwent local resection. The prognostic differences among patients who underwent cytoreductive surgery and local resection in two cohorts and stratified by the International Federation of Gynecology and Obstetrics (FIGO) staging were evaluated, respectively. The relationship between the causes of death and surgical approaches in elderly patients with advanced ovarian cancer was analyzed.Results:In the SEER database cohort, the median overall survival (OS) for patients who underwent cytoreductive surgery and local resection was 37 and 40 months, respectively, with 5-year OS rates of 31.47% and 33.74%, with no statistically significant difference ( χ2=0.78, P=0.378). After stratification by FIGO staging, the median OS for patients with stage ⅢB-ⅢC who underwent cytoreductive surgery ( n=998) and local resection ( n=962) was 38 and 40 months, respectively, with no statistically significant difference ( χ2=0.20, P=0.659). For patients with stage Ⅳ, the median OS for those who underwent cytoreductive surgery ( n=41) and local resection ( n=93) was 17 and 36 months, respectively, with a statistically significant difference ( χ2=9.37, P=0.002). Among 2 094 elderly patients with advanced ovarian cancer, 1 581 had clearly identified causes of death. In patients who underwent cytoreductive surgery, the proportions of deaths due to ovarian cancer and non-ovarian cancer were 94.52% (742/785) and 5.48% (43/785), respectively. In patients who underwent local resection, the proportions of deaths due to ovarian cancer and non-ovarian cancer were 91.46% (728/796) and 8.54% (68/796), respectively. There was a statistically significant difference in the distribution of causes of death between the two surgical approaches ( χ2=5.69, P=0.017). In the hospital cohort, the median OS for patients undergoing cytoreductive surgery and local resection was 39 and 51 months, respectively, with 5-year OS rates of 22.85% and 23.81%, with a statistically significant difference ( χ2=6.71, P=0.010). After stratification by FIGO staging, the median OS for patients with stage ⅢB-ⅢC undergoing cytoreductive surgery ( n=29) and local resection ( n=26) was 50 and 51 months, respectively, with no statistically significant difference ( χ2=0.15, P=0.699) ; for patients with stage Ⅳ undergoing cytoreductive surgery ( n=56) and local resection ( n=37), the median OS was 35 and 47 months, respectively, with a statistically significant difference ( χ2=6.55, P=0.011) . Conclusions:The survival outcomes of local resection in elderly patients with advanced ovarian cancer are not inferior to those of cytoreductive surgery. For FIGO stage Ⅳ patients, the survival period following local resection is superior to that of cytoreductive surgery.

Mitophagy is a selective degradation process of damaged mitochondria in response to mitochondrial toxicity,which plays a crucial role in regulating mitochondrial quality and quantity.Abnormal mitophagy can cause or exacerbate mitochondrial dysfunction,which is closely associated with the pathogenesis of numerous diseases.Given that cochlear hair cells are highly sensitive to energy metabolism,proper regulation of mitophagy is essential for maintaining auditory function.Mitochondrial damage resulting from mitophagy dysfunction involves diverse pathophysiological mechanisms underlying sensorineural hearing loss.This review summarizes the latest progress on mitophagy and its role in the pathogenesis of sensorineural hearing loss,aiming to enhance our understanding of the involvement of mitophagy in auditory function and provide a theoretical basis for future research on targeted therapy for mitochondria.