BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

Objective To investigate the efficacy of Fumai Zhuyu Decoction combined with radial shock wave therapy(RSWT)in treating convalescent stroke patients with lower limb spasm,and to observe its effect on serum neuron-specific enolase(NSE)and transforming growth factor-β1(TGF-β1).Methods From January 2022 to January 2024,a total of 111 convalescent stroke patients with lower limb spasm of qi deficiency and blood stasis syndrome were selected from the First Affiliated Hospital of Hebei North University.According to the treatment method,the patients were divided into two groups.The 55 patients in the western medicine(WM)group were treated with RSWT,and 56 patients in the traditional Chinese medicine(TCM)group were treated with Fumai Zhuyu Decoction orally and RSWT.The course of treatment for the two groups covered 6 months.Before and after treatment,the two groups were observed in the changes of modified Ashworth Scale(MAS)score for the evaluation of muscle tone of hemiplegic limbs,Clinical Spasticity Index(CSI)score,Barthel Index(BI)score for the evaluation of activities of daily living,three-dimensional gait parameters(velocity,cadence,step length),serum levels of NSE and TGF-β1,and hemorheological indicators of plasma viscosity(PV),low-shear blood viscosity(LBV),high-shear blood viscosity(HBV)and platelet aggregation rate(PAR).After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 6 months of treatment,the total effective rate of the TCM group was 94.64%(53/56),and that of the WM group was 76.36%(42/55).The intergroup comparison(tested by chi-square test)showed that the efficacy of the TCM group was significantly superior to that of the WM group(P＜0.01).(2)After treatment,the MAS and CSI scores of the two groups were lowered(P＜0.05)and the BI scores were increased compared with those before treatment(P＜0.05).The decrease of MAS and CSI scores and the increase of BI scores in the TCM group were significantly superior to those in the WM group(P＜0.01).(3)After treatment,the three-dimensional gait parameters of velocity,cadence,and step length in the two groups were increased compared with those before treatment(P＜0.05),and the increase of gait parameters in the TCM group was significantly superior to that in the WM group(P＜0.01).(4)After treatment,the serum NSE level of the two groups was significantly decreased that before treatment(P＜0.05),and the serum TGF-β1 level was significantly increased compared with that before treatment(P＜0.05).The decrease of serum NSE level and the increase of serum TGF-β1 level in the TCM group were significantly superior to those in the WM group(P＜0.01).(5)After treatment,the hemorheological indexes such as PV,LBV,HBV and PAR in the two groups were significantly lowered compared with those before treatment(P＜0.05),and the decrease in the TCM group was significantly superior to that in the WM group(P＜0.01).Conclusion Fumai Zhuyu Decoction combined with RSWT can effectively improve the limb spasm degree and walking function,reduce serum NSE level,increase serum TGF-β1 level,and correct the abnormal blood hemorheology in convalescent stroke patients with lower limb spasm of qi deficiency and blood stasis syndrome.The curative effect of the combined treatment is significantly superior to that of RSWT alone.

Objective To evaluate the effects of Qitan Decoction(QTD)combined with radial shockwave therapy(RSWT)on walking ability,balance function,and neural injury markers in stroke patients with lower limb spasticity during convalescence.Methods A retrospective study was conducted on 100 stroke patients with lower limb spasticity of qi deficiency and blood stasis type treated at the First Affiliated Hospital of Hebei North University from December 2021 to December 2023.Patients were divided into a conventional group(n=49,receiving RSWT alone)and an trial group(n=51,receiving RSWT plus QTD)based on treatment protocols.Both groups received standard stroke care(including cerebral metabolism improvement,neurotrophic support,and antiplatelet therapy).The intervention lasted 6 months.The changes in Modified Ashworth Scale(MAS)scores,Functional Gait Assessment(FGA)scores,Berg Balance Scale(BBS)scores,Stroke-Specific Quality of Life(SS-QOL)scores,serum neural injury markers[gama-aminobutyric acid(GABA),brain-derived neurotrophic factor(BDNF)],and kinematic parameters(peak knee flexion,peak hip flexion)were observed,and the clinical efficacy was compared between groups.Results(1)After 6 months of treatment,the total effective rate of the trial group was 94.12％(48/51),and that of the conventional group was 75.51％(37/49),and the intergroup(by chi-square test)comparison showed that the efficacy of the trial group was significantly superior to that of the conventional group(P＜0.01).(2)After treatment,the MAS scores of patients in the two groups were lower than before treatment(P＜0.05),and the FGA,BBS,and SS-QOL scores were higher than before treatment(P＜0.05),and the reduction of the MAS scores and the increase of the FGA,BBS,and SS-QOL scores of the trial group were significantly superior to those of the conventional group(P＜0.01).(3)After treatment,the serum GABA and BDNF levels of patients in the two groups were higher than those before treatment(P＜0.05),and the increase in serum GABA and BDNF levels in the trial group was significantly superior to that in the conventional group(P＜0.01).(4)After treatment,the peak knee flexion and peak hip flexion of patients in the two groups were elevated compared with those before treatment(P＜0.05),and the trial group's elevation of peak knee flexion and peak hip flexion was significantly superior to that of the conventional group(P＜0.01).Conclusion QTD combined with RSWT effectively alleviates spasticity,enhances walking/balance function,mitigates neural injury,and improves quality of life in stroke patients with lower limb spasticity of qi deficiency and blood stasis syndrome during convalescence.

Objective To evaluate the effects of argatroban combined with Shuxuening injection on homocysteine(Hcy),vascular endothelial growth factor(VEGF),and soluble CD40 ligand(sCD40L)levels,as well as its clinical efficacy in patients with acute cerebral infarction.Methods From June 2023 to March 2024,98 patients with acute cerebral infarction were randomly assigned to experimental group(n=49)or control group(n=49)using stratified random sampling method.The control group received standard symptomatic treatment along with argatroban injection,and the experimental group additionally received intravenous Shuxuening injection.The neurological function[(National Institute of Health stroke scale,NIHSS)and(modified Rankin scale,mRS)scores],motor function[(Fugl-Meyer assessment scale,FMA)score],coagulation function[(activated partial thromboplastin time,APTT),(prothrombin time,PT),(fibrinogen,FIB),D-dimer],hemorheology parameters[(plasma viscosity,PV),(erythrocyte aggregation index,EAI),(hematocrit,HCT),(erythrocyte sedimentation rate,ESR)],serum cytokines[(homocysteine,Hcy),(vascular endothelial growth factor,VEGF),(soluble CD40 ligand,sCD40L)],and adverse reactions(dizziness,nausea,vomiting,rash,loss of appetite,abdominal distension,thrombocytopenia,and intracranial hemorrhage)were compare between the two groups.Results There were no significant differences in the NIHSS score,FMA score,mRS score,APTT,PT,FIB,D-dimer,PV,EAI,HCT,ESR,Hcy,VEGF,or sCD40L between the two groups before treatment(P>0.05).After 2 weeks of treatment,the experimental group showed lower NIHSS score,mRS score,FIB,D-dimer,PV,EAI,HCT,ESR,Hcy,and sCD40L,and higher total effective rate,FMA score,APTT,PT and VEGF than the control group(P<0.05).The incidence of adverse reactions in the experimental group was lower than that in the control group,but the difference was not statistically significant(P>0.05).Conclusion Argatroban combined with Shuxuening injection can enhance motor function,reduce neurological damage,improve coagulation function and hemorheological parameters,regulate serum cytokine levels,offer good safety,and provide a new option for the treatment of acute cerebral infarction.

Objective To investigate the clinical efficacy and safety of sintilimab combined with gemcitabine hydrochloride plus cisplatin in treating patients with advanced lung squamous cell carcinoma(LSCC).Methods A total of 102 patients with advanced LSCC who were admitted to our hospital between November 2020 and January 2024 were enrolled and randomly assigned to control group(n=51,treated with gemcitabine hydrochloride plus cisplatin)or sintilimab group(n=51,treated with sintilimab,gemcitabine hydrochloride and cisplatin).Clinical efficacy,tumor markers,immune function,quality of life,survival outcomes,and safety were compared between the two groups.Results The objective response rate(ORR)in the sintilimab group was significantly higher than that in the control group(60.78%vs.39.22%,P<0.05).Serum levels of squamous cell carcinoma antigen(SCCAg),carcinoembryonic antigen(CEA),and cytokeratin 19 fragment(CYFRA 21-1)in the sintilimab group were significantly lower than those in the control group after treatment(P<0.05).The sintilimab group had higher CD4+T-cell levels and CD4+/CD8+ratio and lower CD8+T-cell levels than the control group after treatment(P<0.05).The Karnofsky Performance Status(KPS)score was significantly improved in the sintilimab group compared to the control group(P<0.05).Median progression-free survival(PFS)and overall survival(OS)in the sintilimab group were significantly higher than those in the control group(both P<0.05).No significant difference in adverse event rates was observed between the two groups(P>0.05).Conclusion Sintilimab combined with gemcitabine hydrochloride and cisplatin can significantly increase tumor control rates and immune function,prolong survival,improve quality of life,and demonstrate favorable safety in advanced LSCC patients.

Objective To investigate the effects of curcumin on the proliferation,migration,invasion,and apoptosis of pheochromocytomacell line PC12.Methods PC12 cells were incubated with different concentrations of curcumin.Cell proliferation was assessed using the CCK-8 assay to determine the IC50.The scratch assay was used to evaluate cell migration and Transwell chambers were employed to assess cell invasiveness.Flow cytometry was used to analyze apoptosis.qPCR was conducted to measure the mRNA expression of pro-apoptotic(Bax)and anti-apoptotic(Bcl-2)genes,and Western blot was performed to detect Bax and Bcl-2 protein expressions.Results Curcumin(10-80 μmol/L)inhibited PC12 cell proliferation in a concentration-dependent manner,with an IC50 as 29 μmol/L.Curcumin also suppressed PC12 cell migration in a concentration-dependent mode;the migration rate decreased from 66％in the control group down to 51％,5％,and 0.5％in the 10,20,and 30 μmol/L curcumin groups,respectively.Curcumin at concentrations of 20-30 μmol/L significantly reduced PC12 cell invasiveness(P<0.000 1).Moreover,curcumin significantly promoted PC12 cell apoptosis;the percentage of apoptotic cells increased by 2.25％,18.53％,and 26.89％in the 10,20,and 30 μmol/L curcumin groups as compared to those of control group,respectively.Curcumin treatment resulted in a significant up-regulation of Bax mRNA and protein expression,and a significant down-regulation of Bcl-2 mRNA and protein expression(P<0.05).Conclusions Curcumin may significantly inhibit the proliferation,migration,and invasion of PC12 cells and arouse cell apopto-sis.Its pro-apoptotic effect may be associated with alterations in the expression of Bax and Bcl-2 genes.

Objective To investigate the clinical value of serum mast cell carboxypeptidase(MC-CP),C-C motif chemokine 26(CCL26),and decoy receptor 3(DcR3)in the diagnosis of obstructive sleep apnea syndrome(OSAS)in chronic obstructive pulmonary disease(COPD).Methods Ninety COPD patients who visited the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were collected.Among them,48 patients with simple COPD were included in the COPD group,and 42 patients with COPD combined with OSAS were included in the COPD-OSAS group.During the same period,48 healthy volunteers who underwent physical examination in that Hospital of Hebei North collected as the control group.Enzyme linked immunosorbent assay(ELISA)was applied to detect serum level of MC-CP,CCL26,and DcR3.Receiver operating characteristic(ROC)curve was applied to analyze the clinical value of serum level of MC-CP,CCL26,and DcR3 in the diag-nosis of COPD complicated with OSAS.Multivariate Logistic regression was applied to analyze the influencing fac-tors of COPD complicated with OSAS.Results Compared with the control group,the smoking index,C-reactive protein(CRP)and white blood cell count(WBC)in the COPD and COPD-OSAS groups increased obviously in sequence,the ratio of forced expiratory volume in first second to forced vital capacity(FEV1/FVC)decreased obviously in sequence(P<0.05);Compared with the control group,the level of MC-CP,CCL26,and DcR3 in patients with COPD and COPD-OSAS increased significantly in sequence(P<0.05);The combination of serum MC-CP,CCL26 and DcR3 had a higher area under the curve(AUC)for the diagnosis of COPD complicated with OSAS compared to the individual diagnosis(Z=4.066,P<0.001;Z=2.391,P<0.05;Z=2.353,P<0.05).Multivariate Logistic regression analysis showed that smoking index,serum level of MC-CP,CCL26 and DcR3 were influencing factors for COPD complicated with OSAS(P<0.05).Conclusions The simultane-ously increased expression of MC-CP,CCL26 and DcR3 in the serum of COPD may support clinical diagnostic of COPD patients with OSAS.

Objective To report two cases of type A insulin resistance syndrome with new insulin receptor gene mu-tations.Methods Clinical data,laboratory examination,imaging examination and mutation scanning of insulin re-ceptor gene were collected,and type A insulin resistance syndrome reported by domestic and foreign scholars were analyzed retrospectively.Results One case had dry mouth,polydipsia and hyperandrogenemia,and another case had primary amenorrhea,both of them had insulin resistance.Two cases had heterozygous missense mutation in in-sulin receptor gene C.3449T＞c(p.L1150P).The mothers of the two probands all carried this mutation,while the fathers did not.This mutation has not been reported previously.Literature review shows that the onset age of this disease is young,and it is more common in women.BMI 20.37±5.47 kg/m2,fasting blood-glucose 4.50 mmol/L(4.10,13.00),the proportion of insulin resistance is 100％,92.0％has acanthoid nigricans,and the proportion of Testosterone above normal is 81.3％,diabetes complications appear earlier.Conclusions Genetic analysis is helpfulfor the etiological diagnosis in children with severe insulin resistance.

Objective To investigate the effect of Echinacoside(Ech)on liver injury in hepatitis B rats.Methods SD rats were divided into control group,Hepatitis B(HBV,5 mL/kg HBV virus was injected into the tail vein twice a week for 3 consecutive weeks),low(Ech-L)and high(Ech-H)doses of Ech were injected into the stom-ach for HBV(8.33 and 33.32 mg/kg,respectively),HBV group was treated with positive drugs(lamivudine,10 mg/kg)and Ech-H+BKM120(40 mg/kg BKM120),with 12 animals in each group.The drug was administered once a day for 8 weeks.The activity of ALT and AST in serum of were detected.Serum level of gam-ma-interferon(IFN-γ)and interleukin(IL-4)was detected by ELISA;Flow cytometry was applied to detect Th1/Th2 in peripheral blood;Chromatin immunoprecipitation was applied to detect HBV DNA expression in liver tissue;HE staining was used to detect the pathological changes of liver tissue and score the damage;Western blot was ap-plied to detect phosphorylated phosphatidylinositol 3 kinase(p-PI3K),phosphorylated protein kinase B(p-AKT)proteins in liver tissue.Results Compared with the control group,hepatocytes in the hepatitis B group were swollen,nuclear staining was excessive,hepatic lobular structure was disorganized,pathological injury score,serum AST,ALT activity,IL-4 level,peripheral blood Th2,HBV DNA expression in liver tissue were all increased.Serum IFN-γ level,Th1,Th1/Th2 in peripheral blood,p-PI3K and p-AKT protein in liver tissue were all decreased(P＜0.05);Treatment with Ech-L,Ech-H and lamivudine reduced the swelling of HBV rat hepatocytes,cleared the structure of some liver cords,reduced pathological injury score,the activity of AST,ALT and IL-4 levels in serum,Th2 in peripheral blood and HBV DNA in liver tissue;The level of serum IFN-γ,Th1,Th1/Th2 in peripheral blood,and protein expression p-PI3K and p-AKT protein in liver tissue were increased(P＜0.05).BKM120 attenuated the ameliorative effect of high-dose Ech on hepatitis B-induced liver injury in rats.Conclusions Ech ameliorates liver in-jury in rats with hepatitis B,and the mechanism may be related to the activation of the PI3K/AKT pathway.

This review systematically summarizes the unique metabolic mechanisms of breast cancer,their interac-tions with the tumor microenvironment(TME),and the latest advances in targeted therapies.The interplay between metabolic reprogramming and the TME underpins malignant progression and therapeutic resistance.Breast cancer cells reshape energy supply through the Warburg effect,aberrant fatty acid synthesis,and amino acid metabolism,while immune cells,fibroblasts,and the acidic milieu within the TME promote immune evasion and drug resistance via metabolic coupling.Although traditional strategies targeting key metabolic enzymes remain valuable,they are often insufficient to overcome metabolic adaptability.In recent years,combined metabolic and immunotherapeutic approaches have emerged as promising strategies:by reducing lactate accumulation,restoring T-cell function,and reprogramming tumor-associated macrophages and cancer-associated fibroblasts,these therapies can remodel the immunosuppressive microenvironment and enhance immunotherapy efficacy.The application of metabolomics and single-cell sequencing further elucidates breast cancer heterogeneity,providing a basis for individualized precision treatment.Future challenges include deciphering resistance mechanisms,developing highly selective metabolic in-hibitors,and designing integrated multi-omics-based therapeutic regimens.