ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

Purpose To investigate the clinicopathological significance of peritumoral retraction clefts(PRC)in esophageal squamous cell cancer(ESCC)and its correlation with prognosis.Methods 266 cases of esophageal squa-mous cell carcinoma were collected.Excluding the cases due to incomplete clinical data,cracks caused by the produc-tion process,and receiving preoperative adjuvant treatment,248 cases were finally counted.PRC was determined by the proportion of retraction clefts in the tumor volume of 10％.A retrospective analysis was conducted to explore the re-lationship between PRC and the clinicopathological features as well as prognosis of ESCC.Results Among 248 ESCC patients,114 cases had PRC,while 134 cases did not.Correlation analysis showed that PRC was closely related to his-tological grade,lymphatic invasion,lymph node metastasis,depth of tumor invasion and TNM stage of ESCC,and ES-CC patients with PRC were more likely to have lymphatic invasion and lymph node metastasis(P＜0.05).In patients without lymphatic invasion,the probability of nodal metastasis in patients with PRC was higher than those without PRC,and the difference was statistically significant(P＜0.001).Kaplan-Meier survival analysis showed that 5-year overall survival(P=0.001)and progression-free survival(P=0.002)in ESCC patients with PRC were significantly lower than those without PRC.Conclusion ESCC patients with PRC are more likely to have local invasiveness,lymphatic invasion and nodal metastasis,may predict the poor prognosis of ESCC patients.Patients with nodal metastasis are more common with PRC.

Objective To investigate the correlation between plasma vitamin D levels and a novel inflam-matory marker,the systemic immune-inflammatory index(SII),in patients with type 2 diabetes.Methods This study adopted a cross-sectional design,in which patients diagnosed with type 2 diabetes who were admitted to the First Affiliated Hospital of Guangxi Medical University were enrolled as study participants.Data on demographic characteristics,medical history,physical examination findings,and laboratory test results were systematically collected.Participants were categorized into three groups based on their serum vitamin D levels:deficient,insuffi-cient,and sufficient.The relationship between vitamin D levels and the SII was evaluated using a multivariate linear regression model.Additionally,a restricted cubic spline model was employed to assess the nonlinear dose-response association between vitamin D levels and SII.Results This study enrolled a total of 5,716 patients with type 2 diabetes.A statistically significant difference in the SII was observed across groups with varying vitamin D levels(P<0.05),with the highest SII value found in the vitamin D-deficient group.Multivariate linear regression analysis revealed that,after adjusting for potential confounding factors including gender,age,season of blood collection,body mass index,hypertension,dyslipidemia,and chronic kidney disease,vitamin D levels were negatively associ-ated with SII(β=-2.68,95%CI:-3.56 to-1.81,P<0.001).Compared with the vitamin D-deficient group,the vitamin D-sufficient group exhibited significantly lower SII levels(β=-78.42,95%CI:-137.90 to-18.93,P=0.01).Furthermore,the restricted cubic spline model indicated a nonlinear dose-response relationship between vita-min D levels and SII(P<0.001).Conclusion There is a significant inverse correlation between plasma vitamin D levels and the SII in patients with type 2 diabetes.

Lung cancer represents as one of the most prevalent malignant tumors globally,necessitating the urgent identification of additional biomarkers to facilitate precise stratified treatment and elevate its survival rates.Previous studies have focused on the correlation between the histopathological characteristics,driver gene mutations,and progno-sis of non-small cell lung cancer(NSCLC),with the aim of predicting the potential molecular background,treatment efficacy,and possible clinical outcomes of patients from the morphological perspective.This article aims to briefly sum-marize the advancements in emerging histopathological indicators of NSCLC,and discuss their implications for guiding the prognosis of this disease.

Male reproductive aging is characterized by degenerative changes in the structure and function of the testes. Testicular aging involves alterations in various types of cells, among which lysosomal dysfunction in Sertoli cells is particularly critical. Recent studies have shown that abnormal lysosomal acidification leads to impaired phagosome degradation, which fails to maintain normal nutrient cycling and thereby exacerbates damage to the testicular microenvironment. In addition, endoplasmic reticulum stress, mitochondrial dysfunction, and epigenetic changes are also important factors contributing to reproductive aging. Therefore, molecular intervention strategies targeting lysosomal dysfunction, mitochondrial oxidative stress, and endoplasmic reticulum stress, such as the use of lysosomal activators like ML-SA1 and antioxidants, may offer new therapeutic directions for alleviating male reproductive aging. Future research should further explore the interactions between these mechanisms and potential intervention targets to improve reproductive health and quality of life in middle-aged and older men.

Purpose To investigate the clinicopathological significance of peritumoral retraction clefts(PRC)in esophageal squamous cell cancer(ESCC)and its correlation with prognosis.Methods 266 cases of esophageal squa-mous cell carcinoma were collected.Excluding the cases due to incomplete clinical data,cracks caused by the produc-tion process,and receiving preoperative adjuvant treatment,248 cases were finally counted.PRC was determined by the proportion of retraction clefts in the tumor volume of 10％.A retrospective analysis was conducted to explore the re-lationship between PRC and the clinicopathological features as well as prognosis of ESCC.Results Among 248 ESCC patients,114 cases had PRC,while 134 cases did not.Correlation analysis showed that PRC was closely related to his-tological grade,lymphatic invasion,lymph node metastasis,depth of tumor invasion and TNM stage of ESCC,and ES-CC patients with PRC were more likely to have lymphatic invasion and lymph node metastasis(P＜0.05).In patients without lymphatic invasion,the probability of nodal metastasis in patients with PRC was higher than those without PRC,and the difference was statistically significant(P＜0.001).Kaplan-Meier survival analysis showed that 5-year overall survival(P=0.001)and progression-free survival(P=0.002)in ESCC patients with PRC were significantly lower than those without PRC.Conclusion ESCC patients with PRC are more likely to have local invasiveness,lymphatic invasion and nodal metastasis,may predict the poor prognosis of ESCC patients.Patients with nodal metastasis are more common with PRC.

Objective To investigate the correlation between plasma vitamin D levels and a novel inflam-matory marker,the systemic immune-inflammatory index(SII),in patients with type 2 diabetes.Methods This study adopted a cross-sectional design,in which patients diagnosed with type 2 diabetes who were admitted to the First Affiliated Hospital of Guangxi Medical University were enrolled as study participants.Data on demographic characteristics,medical history,physical examination findings,and laboratory test results were systematically collected.Participants were categorized into three groups based on their serum vitamin D levels:deficient,insuffi-cient,and sufficient.The relationship between vitamin D levels and the SII was evaluated using a multivariate linear regression model.Additionally,a restricted cubic spline model was employed to assess the nonlinear dose-response association between vitamin D levels and SII.Results This study enrolled a total of 5,716 patients with type 2 diabetes.A statistically significant difference in the SII was observed across groups with varying vitamin D levels(P<0.05),with the highest SII value found in the vitamin D-deficient group.Multivariate linear regression analysis revealed that,after adjusting for potential confounding factors including gender,age,season of blood collection,body mass index,hypertension,dyslipidemia,and chronic kidney disease,vitamin D levels were negatively associ-ated with SII(β=-2.68,95%CI:-3.56 to-1.81,P<0.001).Compared with the vitamin D-deficient group,the vitamin D-sufficient group exhibited significantly lower SII levels(β=-78.42,95%CI:-137.90 to-18.93,P=0.01).Furthermore,the restricted cubic spline model indicated a nonlinear dose-response relationship between vita-min D levels and SII(P<0.001).Conclusion There is a significant inverse correlation between plasma vitamin D levels and the SII in patients with type 2 diabetes.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective To establish a high-throughput non-targeted screening and prioritization method for emerging pollutants(EPs)in sewage using direct injection high-resolution mass spectrometry(HRMS).Methods The sewage samples were filtered by membrane filter and directly subjected to the liquid chromatography-time-of-flight mass spectrometer based on a method modified from our previous study.A C18 chromatographic column was applied for a gradient elution separation,and accurate mass and mass spectral fragment information were obtained through the MS full scan mode and MS/MS DIA data collection mode.After peak detection and alignment,the features from the raw data through open source software MZmine 3,and then high-throughput screening strategies such as MassBank and PubChem databases were used for compound annotation.Finally,the candidate features were confirmed with chemical standards by compared their retention time and mass spectrum fragmentation ion peaks.Results 13 EPs were identified,including 7 industrial chemicals,4 pharmaceuticals,1 pesticide and 1 metabolite.High detection rates were observed for metformin(86.2％),2-hydroxybenzothiazole(79.3％),1,2-benzisothiazole-3-one(72.4％),and 1,2-benzisothiazole-3-one(72.4％).The quantitative concentration range of EPs was 1.37～19.05 ng/mL,with the high concentrations observed for melamine(19.05 ng/mL)and furosemide(18.49 ng/mL).Ecological risk assessment identified 1,2-benzisothiazol-3-one,4-aminoacetophenone,creatinine,2-hydroxybenzothiazole,and furosemide as key pollutants.Conclusion This direct injection coupled with HRMS workflow enables efficient non-targeted screening and prioritization of emerging EPs in sewage samples,highlighting five ecotoxicologically critical EPs.The methodology enhances environmental monitoring capabilities and provide critical technical support for interdisciplinary research such as environmental forensics and health risk assessment.