ObjectiveTo investigate the relationship between solute carrier family 7 member 11 （SLC7A11） expression in esophageal squamous cell carcinoma （ESCC） and clinical prognosis， and to determine its effects on ESCC cell growth， migration， and other biological activities. MethodsSLC7A11 protein expression was measured in 310 ESCC tissues and 259 adjacent normal tissues using immunohistochemistry to statistically assess the association of SLC7A11 with clinicopathologic characteristics and prognosis in ESCC patients. The expression of SLC7A11 in ESCC cell lines was suppressed through siRNA-mediated knockdown. The specific effects of SLC7A11 knockdown on proliferation and migration were evaluated using CCK-8， clonogenic assay， and Transwell assays. Adenosine triphosphate （ATP）， lactic acid and pyruvate assays were used to measure ESCC metabolism. ResultsSLC7A11 protein expression was localized predominantly in the cytoplasm of ESCC tissues. Significantly higher SLC7A11 expression levels were observed in ESCC tissues compared to adjacent normal tissues （P<0.001）. High SLC7A11 expression was associated with poorer differentiation in patients （P<0.01）. Kaplan-Meier survival analysis demonstrated significantly shorter overall survival in patients with high SLC7A11 expression compared to those with low expression （P<0.05）. CCK-8 and colony formation assays demonstrated that the knockdown of SLC7A11 expression significantly suppressed the proliferative capacity of tumor cells （P<0.001）. Furthermore， Transwell assays revealed a marked decline in tumor cell migration capacity following SLC7A11 suppression （P<0.001）. Critically， SLC7A11 knockdown also reduced intracellular levels of ATP， lactate， and pyruvate， demonstrating that SLC7A11 modulated metabolic activity in ESCC cells（P<0.001）. ConclusionThe expression level of SLC7A11 is relatively high in ESCC and is strongly associated with poor prognosis. Silencing SLC7A11 significantly inhibits esophageal cancer cell growth and migration. SLC7A11 has the ability to regulate glucose， lactic acid and ATP metabolism levels in ESCC， thereby affecting the metabolic microenvironment of ESCC.

Objective To explore the potential targets and mechanism of Gufang Granules in treating osteoporosis through network pharmacology,molecular dynamics simulations,and in vitro experiment validation.Methods The active components of Gufang Granules were obtained from the TCMSP database and literature,and their related targets were predicted using SwissTargetPrediction database.Core drug targets were selected through protein-protein interaction(PPI)network analysis and machine learning models,and the predictive performance of the models was assessed by drawing receiver operating characteristic(ROC)curves on independent validation datasets.Gene Set Enrichment Analysis(GSEA)was used to analyze the expression and pathways of core targets.Molecular dynamics(MD)simulations were applied to evaluate the structural stability and interactions of the compound-target complexes.Non-cytotoxic concentrations of Gufang Granules containing serum were determined by the CCK-8 assay.RAW264.7 cells were treated with low,medium,and high concentrations of drug containing serum,respectively.The number of osteoclasts was quantified using TRAP staining.The expression levels of relevant genes and proteins were analyzed through qRT-PCR and Western blot methods.Results A total of 251 potential active components and 1 078 related targets of Gufang Granules were identified.The high expressions of core targets SRC and TNF were mainly associated with osteoclast differentiation,MAPK signaling pathway and PI3K/Akt signaling pathway.MD simulations showed that the core active component Glabridin exhibited strong stability and interaction with the SRC and TNF target proteins.The number of TRAP positive cells in all concentration groups of Gufang Granules was significantly reduced compared to the RANKL group(P<0.01,P<0.001).The serum containing Gufang Granules significantly reduced the mRNA expression of NFATc1,CTSK,SRC and TNF-α,and also downregulated the protein expression of NFATc1,CTSK,p-SRC and TNF-α(P<0.05,P<0.01,P<0.001).Conclusion Gufang Granules may inhibit osteoclast differentiation by downregulating the expression of NFATc1,CTSK,p-SRC and TNF-α,thereby slowing the pathological progression of osteoporosis.

Objective:To discuss the expression of Rh family C glycoprotein(RHCG)in the esophageal squamous cell carcinoma(ESCC)tissue and its effect on the malignant biological behavior of ESCC cells,and to clarify the value of RHCG as a diagnostic and prognostic marker for the ESCC patients.Methods:A total of 143 ESCC tissue samples and 105 adjacent normal tissue samples were collected.Using immunohistochemical staining method,141 ESCC samples were divided into two groups:RHCG low expression group(immunohistochemistry score≤6)and RHCG high expression group(immunohistochemistry score>6).Immunohistochemical method was used to detect the RHCG protein expression in 143 ESCC tissues and 105 normal tissues,and the relationship between the clinicopathological characteristics of the ESCC patients was analyzed.Receiver operating characteristic(ROC)curve and Kaplan-Meier survival analysis were used to evaluate the value of RHCG in diagnosis and prognosis of the ESCC patients;univariate and multivariate COX regression analysis were used to determine the independent risk factors affecting the prognosis of the ESCC patients.Gene Expression Profiling Interactive Analysis(GEPIA2)database was used to analyze the expression of RHCG mRNA in various tumor tissues.The ESCC TE-1 cells were cultured and transfected in to 6-well cell culture plates with different Lipofectamine2000∶RHCG ratios;the cells in RHCG transfection group were transfected with weights of 2.0,2.5,and 3.0 μg for 24 and 48 h,respectively,and the cells in NC group transfected with empty vector as control.Western blotting method was used to detect the RHCG protein expression level in the TE-1 cells in various groups after transfection at different concentrations and verify the optimal transfection conditions;cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of the TE-1 cells;plate clone formation assay was used to detect the colony formation numbers of the TE-1 cells;Transwell chamber assay was used to detect the numbers of migrating TE-1 cells.Results:Compared with adjacent normal tissue,the RHCG gene expression level in various cancer tissues including ESCC,glioblastoma multiforme,and head and neck squamous cell carcinoma was significantly decreased(P<0.05).RHCG protein was mainly located on the cell membrane of normal esophageal squamous epithelial cells;the RHCG protein expression intensity in ESCC tissues was lower than that in adjacent normal esophageal tissue(χ2=109.373,P<0.001),and the patients in RHCG low expression group had poorer differentiation than those in RHCG high expression group(P=0.041).The area under the curve(AUC)value of RHCG for diagnosing ESCC was 0.86,with sensitivity and specificity of 95.1%and 75.0%,respectively;the Kaplan-Meier survival analysis results showed that compared with high RHCG expression group,the patients in low RHCG expression group had shorter survival time and poorer prognosis[harard ratio(HR)=0.269,95%confidence interval(CI):0.113-0.639,P=0.020];the COX regression analysis results showed that low RHCG expression could serve as an independent risk factor affecting the prognosis of ESCC[HR=4.569,95%CI=1.315-15.877,P=0.017)].The Western blotting results verified that the optimal transfection condition was 3.0 μg RHCG plasmid for 48 h,at which time RHCG overexpression was optimal and RHCG protein expression level was highest.The CCK-8 assay results showed that compared with control group,the proliferation activity in RHCG overexpression group was decreased on the 4th day after cell seeding(P<0.001).In the TE-1 cells,the colony formation number of the TE-1 cells in RHCG over-expression group was lower than that in control group(t=17.70,P<0.001).The Transwell chamber assay results showed that compared with control group,the number of migrating cells in RHCG over-expression group was decreased(t=23.74,P<0.001).Conclusion:RHCG expression is decreased in ESCC tissues and associated with poor prognosis in ESCC patients;overexpression of RHCG can inhibit the proliferation and migration of the TE-1 cells,providing a theoretical basis for RHCG as a novel diagnostic and prognostic marker and therapeutic target for ESCC.

Objective To investigate the relationship between morphometric parameters of the cerebral cortex and the efficacy of repetitive transcranial magnetic stimulation(rTMS)in the treatment of tardive dyskinesia(TD).Methods A total of 105 schizophrenic patients with TD undergoing basic treatment were enrolled,and randomly divided into group A(n=35),group B(n=35)and group C(n=35).Group A received rTMS at 1 Hz,group B received rTMS at 10 Hz,and group C received sham stimulation.All groups were treated for 12 weeks.The severity of TD was assessed using the Ab-normal Involuntary Movement Scale(AIMS)before and after treatment.The Repeatable Battery for the Assessment of Neuropsychological Status(RBANS)and the Positive and Negative Syndrome Scale(PANSS)in Chinese were used to evaluate patients'neuropsychological status and symptom severity.magnetic resonance imaging(MRI)was employed to scan the left prefrontal cortex of patients to obtain parameters of cortical thickness,surface area and volume.Pearson correlation analysis was used to an-alyze the relationship between cortical morphological parameters and the efficacy of rTMS for TD in pa-tients.Results After treatment,AIMS scores in the three groups were significantly lower than before treatment,and the group A was significantly lower than the group B and group C(P＜0.05).After treatment,RBANS scores were significantly higher and PANSS scores were significantly lower in three groups than before treatment(P＜0.05).After treatment,the RBANS score of the group A was significantly higher than that of the group B and group C,and the group B was significantly higher than the group C(P＜0.05);the PANSS score of the group A was significantly lower than that of the group B and group C,and the group B was significantly lower than the group C(P＜0.05).Af-ter treatment,cortical morphological parameters(cortical thickness,surface area and volume)in the group A and group B were significantly higher than before treatment,and the group A was signif-icantly higher than the group B(P＜0.05).The therapeutic effect of the group A was positively correlated with cortical thickness,surface area and volume(P＜0.05).Conclusion The morpho-metric parameters of the left prefrontal cortex are associated with the efficacy of rTMS in treating TD.The rTMS at 1 Hz can facilitate structural remodeling of the motor cortex,thereby improving treat-ment outcomes for TD patients.

BACKGROUND:The controlling nutritional status score and systemic immune-inflammation index,as tools to assess individual nutritional and inflammatory states,have been proven to be related to the risk and prognosis of various chronic diseases.However,their value in predicting postmenopausal osteoporosis has not yet been fully explored.OBJECTIVE:To explore the applicative value of the controlling nutritional status score and systemic immune-inflammation index in predicting postmenopausal osteoporosis.METHODS:A retrospective analysis was conducted on the clinical data of 420 postmenopausal patients treated from January 2022 to April 2024 at the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine and its Kangping branch.There were 205 cases in osteoporosis group and 215 in normal bone mass group.Age,years of menopause,body mass index,history of fracture,smoking history and alcohol consumption were selected as covariates.Patients were matched at a 1∶1 ratio using the nearest neighbor method of propensity score matching to balance covariates between the two groups.Therefore,there were 142 patients in each of the two groups after matching.Serum levels of type Ⅰ precollagen amino-terminal prepeptide,β-collagen degradation products,parathyroid hormone,and 25-hydroxyvitamin D were measured in both groups.The controlling nutritional status score and systemic immune-inflammation index were assessed by serum albumin,total cholesterol levels,neutrophil counts,lymphocyte counts,and platelet counts.The receiver operating characteristic curve was employed to analyze the optimal cutoff values and predictive effectiveness of the controlling nutritional status score and systemic immune-inflammation index.Pearson or Spearman correlations were used to analyze the relationships among the controlling nutritional status score,systemic immune-inflammation index,and bone mineral density.A multivariable logistic regression model was utilized to identify factors influencing postmenopausal osteoporosis.RESULTS AND CONCLUSION:(1)After matching,compared with the normal bone mass group,the osteoporosis group had higher serum pre-collagen type I amino-terminal prepeptide,β-collagen degradation products,and parathyroid hormone levels(P＜0.001),lower 25-hydroxyvitamin D levels(P＜0.001),and higher malnutrition rates and immunoinflammatory indices(P＜0.001).(2)Correlation analysis showed a positive correlation between the controlling nutritional status score and systemic immune-inflammation index(r=0.462,P＜0.001),and both were negatively correlated with femoral neck bone density and lumbar spine L1-L4 bone mineral density(r=-0.322,P＜0.001;r=-0.362,P＜0.001;r=-0.322,P＜0.001;r=-0.340,P＜0.001).(3)Multivariable logistic regression analyses,before and after propensity score matching,indicated that both the controlling nutritional status score and systemic immune-inflammation index were risk factors for osteoporosis in postmenopausal patients.(4)The receiver operating characteristic curves post-matching showed that the areas under the curve for the controlling nutritional status score and systemic immune-inflammation index were 0.758 and 0.754,respectively,and the two best cutoff values were 2.50 and 694.62,respectively,suggesting that both tools perform well in predicting postmenopausal osteoporosis.To conclude,the controlling nutritional status score and systemic immune-inflammation index are effective tools for predicting postmenopausal osteoporosis,suitable for clinical use in prevention and early identification of high-risk individuals.These findings also suggest that nutritional status and inflammatory markers may be part of the pathogenesis of postmenopausal osteoporosis.

AIM:To investigate whether melatonin can ameliorate acute myocardial infarction(AMI)by in-hibiting ferroptosis.METHODS:H9C2 cells were cultured in AnaeroPack system with low sugar and serum-free medium for 10 h to construct a cell model of AMI.Then cells were treated with melatonin and ferroptosis inducer erastin.The cell activity,reactive oxygen species(ROS),lipid peroxidation,mitochondrial membrane potential(MMP),and ferroptosis related protein expression were detected.A rat model of AMI induced by isoprenaline(ISO)injection was established to evaluate the effects of melatonin,in which the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,iron ion and ferroptosis related protein expression were examined.RESULTS:Melatonin decreased the oxidative stress,lipid peroxidation and expression of ferroptosis protein in cardiomyocytes induced by hypoxia,but these effects could be impeded by the ferroptosis inducer erastin.Furthermore,in vivo experiments,we also found that melatonin im-proved the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,and alleviated iron ion accu-mulation and ferroptosis.CONCLUSION:The cardioprotective effects of melatonin in AMI are associated with the inhi-bition of ferroptosis.

AIM:To investigate whether melatonin can ameliorate acute myocardial infarction(AMI)by in-hibiting ferroptosis.METHODS:H9C2 cells were cultured in AnaeroPack system with low sugar and serum-free medium for 10 h to construct a cell model of AMI.Then cells were treated with melatonin and ferroptosis inducer erastin.The cell activity,reactive oxygen species(ROS),lipid peroxidation,mitochondrial membrane potential(MMP),and ferroptosis related protein expression were detected.A rat model of AMI induced by isoprenaline(ISO)injection was established to evaluate the effects of melatonin,in which the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,iron ion and ferroptosis related protein expression were examined.RESULTS:Melatonin decreased the oxidative stress,lipid peroxidation and expression of ferroptosis protein in cardiomyocytes induced by hypoxia,but these effects could be impeded by the ferroptosis inducer erastin.Furthermore,in vivo experiments,we also found that melatonin im-proved the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,and alleviated iron ion accu-mulation and ferroptosis.CONCLUSION:The cardioprotective effects of melatonin in AMI are associated with the inhi-bition of ferroptosis.

Objective To explore the potential targets and mechanism of Gufang Granules in treating osteoporosis through network pharmacology,molecular dynamics simulations,and in vitro experiment validation.Methods The active components of Gufang Granules were obtained from the TCMSP database and literature,and their related targets were predicted using SwissTargetPrediction database.Core drug targets were selected through protein-protein interaction(PPI)network analysis and machine learning models,and the predictive performance of the models was assessed by drawing receiver operating characteristic(ROC)curves on independent validation datasets.Gene Set Enrichment Analysis(GSEA)was used to analyze the expression and pathways of core targets.Molecular dynamics(MD)simulations were applied to evaluate the structural stability and interactions of the compound-target complexes.Non-cytotoxic concentrations of Gufang Granules containing serum were determined by the CCK-8 assay.RAW264.7 cells were treated with low,medium,and high concentrations of drug containing serum,respectively.The number of osteoclasts was quantified using TRAP staining.The expression levels of relevant genes and proteins were analyzed through qRT-PCR and Western blot methods.Results A total of 251 potential active components and 1 078 related targets of Gufang Granules were identified.The high expressions of core targets SRC and TNF were mainly associated with osteoclast differentiation,MAPK signaling pathway and PI3K/Akt signaling pathway.MD simulations showed that the core active component Glabridin exhibited strong stability and interaction with the SRC and TNF target proteins.The number of TRAP positive cells in all concentration groups of Gufang Granules was significantly reduced compared to the RANKL group(P<0.01,P<0.001).The serum containing Gufang Granules significantly reduced the mRNA expression of NFATc1,CTSK,SRC and TNF-α,and also downregulated the protein expression of NFATc1,CTSK,p-SRC and TNF-α(P<0.05,P<0.01,P<0.001).Conclusion Gufang Granules may inhibit osteoclast differentiation by downregulating the expression of NFATc1,CTSK,p-SRC and TNF-α,thereby slowing the pathological progression of osteoporosis.

BACKGROUND:The controlling nutritional status score and systemic immune-inflammation index,as tools to assess individual nutritional and inflammatory states,have been proven to be related to the risk and prognosis of various chronic diseases.However,their value in predicting postmenopausal osteoporosis has not yet been fully explored.OBJECTIVE:To explore the applicative value of the controlling nutritional status score and systemic immune-inflammation index in predicting postmenopausal osteoporosis.METHODS:A retrospective analysis was conducted on the clinical data of 420 postmenopausal patients treated from January 2022 to April 2024 at the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine and its Kangping branch.There were 205 cases in osteoporosis group and 215 in normal bone mass group.Age,years of menopause,body mass index,history of fracture,smoking history and alcohol consumption were selected as covariates.Patients were matched at a 1∶1 ratio using the nearest neighbor method of propensity score matching to balance covariates between the two groups.Therefore,there were 142 patients in each of the two groups after matching.Serum levels of type Ⅰ precollagen amino-terminal prepeptide,β-collagen degradation products,parathyroid hormone,and 25-hydroxyvitamin D were measured in both groups.The controlling nutritional status score and systemic immune-inflammation index were assessed by serum albumin,total cholesterol levels,neutrophil counts,lymphocyte counts,and platelet counts.The receiver operating characteristic curve was employed to analyze the optimal cutoff values and predictive effectiveness of the controlling nutritional status score and systemic immune-inflammation index.Pearson or Spearman correlations were used to analyze the relationships among the controlling nutritional status score,systemic immune-inflammation index,and bone mineral density.A multivariable logistic regression model was utilized to identify factors influencing postmenopausal osteoporosis.RESULTS AND CONCLUSION:(1)After matching,compared with the normal bone mass group,the osteoporosis group had higher serum pre-collagen type I amino-terminal prepeptide,β-collagen degradation products,and parathyroid hormone levels(P＜0.001),lower 25-hydroxyvitamin D levels(P＜0.001),and higher malnutrition rates and immunoinflammatory indices(P＜0.001).(2)Correlation analysis showed a positive correlation between the controlling nutritional status score and systemic immune-inflammation index(r=0.462,P＜0.001),and both were negatively correlated with femoral neck bone density and lumbar spine L1-L4 bone mineral density(r=-0.322,P＜0.001;r=-0.362,P＜0.001;r=-0.322,P＜0.001;r=-0.340,P＜0.001).(3)Multivariable logistic regression analyses,before and after propensity score matching,indicated that both the controlling nutritional status score and systemic immune-inflammation index were risk factors for osteoporosis in postmenopausal patients.(4)The receiver operating characteristic curves post-matching showed that the areas under the curve for the controlling nutritional status score and systemic immune-inflammation index were 0.758 and 0.754,respectively,and the two best cutoff values were 2.50 and 694.62,respectively,suggesting that both tools perform well in predicting postmenopausal osteoporosis.To conclude,the controlling nutritional status score and systemic immune-inflammation index are effective tools for predicting postmenopausal osteoporosis,suitable for clinical use in prevention and early identification of high-risk individuals.These findings also suggest that nutritional status and inflammatory markers may be part of the pathogenesis of postmenopausal osteoporosis.

Objective To explore the interventional effect of repetitive transcranial magnetic stimulation (rTMS) on tardive dyskinesia (TD) in schizophrenic patients. Methods A total of 105 schizophrenic patients were selected as subjects and randomly divided into 1 Hz treatment group, 10 Hz treatment group and control group, with 35 patients in each group. All three groups received rTMS treatment for 12 weeks. The Abnormal Involuntary Movement Scale (AIMS), Scale for the Assessment of Negative Symptoms (SANS), Positive and Negative Syndrome Scale (PANSS) and Treatment Emergent Symptom Scale (TESS) scores were compared among the three groups. Physiological indicators such as electrocardiogram, blood routine, blood biochemistry and hormone levels were monitored. Results After treatment, the total AIMS scores in the 1 Hz and 10 Hz treatment groups were significantly lower than before treatment, and those in the 1 Hz and 10 Hz treatment groups were significantly lower than those in the control group (P < 0.05). The reduction rates of AIMS scores in the 1 Hz and 10 Hz treatment groups were 68.6% and 65.7%, respectively, which were significantly higher than the 22.9% in the control group (P < 0.05). After treatment, the total SANS and PANSS scores in the 1 Hz and 10 Hz treatment groups were significantly lower than before treatment, and those in the 1 Hz and 10 Hz treatment groups were significantly lower than those in the control group (P < 0.05). There was no statistically significant difference in the total AIMS score, efficacy and total PANSS score between the 1 Hz and 10 Hz treatment groups (P>0.05). There were no significant differences in the total TESS scores and physiological indicators among the three groups before and after treatment (P>0.05). Conclusion Both 1 Hz and 10 Hz rTMS can effectively improve TD in schizophrenic patients with good safety and have no significant side effects or physiological damage.