Objective:To observe the clinical efficacy of repetitive transcranial magnetic stimulation(rTMS)combined with mindfulness-based cognitive therapy(MBCT)in patients with alcohol withdrawal syndrome(AWS).Methods:The 120 patients with AWS who were observed in this study were all male patients admitted to our hospital from June 2021 to June 2024,the patients were divided into group A(conventional treatment,40 cases),group B(group A combined with rTMS,40 cases),and group C(group B combined with MBCT,40 cases)according to random number table method.The clinical efficacy,self-control ability[Modified Clinical Institution Alcohol Dependence Withdrawal Assessment Scale(CIWA-Ar)score,Visual Analog Scale of Psychological Craving for Alcohol(VAS)score and Pennsylvania Alcohol Craving Scale(PACS)score],anxiety and depression degree assessment[Hamilton Depression Scale(HAMD)score,Hamilton Anxiety Scale(HAMA)score]and quality of life[36 Short Form Health Survey(SF-36)Score],relapse rate and readmission rate were compared among the three groups.Results:The total effective rate of group A,group B and group C increased successively(P＜0.05).The CIWA-Ar,PACS and VAS scores in group B and group C after treatment were lower than those in group A,and group C was lower than that in group B(P＜0.05).The HAMD and HAMA scores of group B and group C after treatment were lower than those in group A,and group C was lower than that in group B(P＜0.05).The SF-36 score of group B and group C after treatment was higher than those in group A,and group C was higher than that in group B(P＜0.05).Relapse rate and readmission rate in groups B and C were lower than those in group A,and group C was lower than that in group B(P＜0.05).Conclusion:The application of rTMS combined with MBCT in patients with AWS can improve clinical efficacy and quality of life,alleviate anxiety and depression,improve patients' self-control ability,reduce relapse rate and readmission rate,with definite effects.

Objective:To investigate the effects of combination therapy with aqueous extract of corn silk(CS)and training on exercise capacity and glycolipid metabolism in mice with metabolic syndrome(MS).Methods:In this study,db/db mice were used as the animal model of MS.The mice were administered aqueous extract of CS via gavage and subjected to different intensities of training for 12 weeks(3 months).The specific experimental design was as follows:24 db/db mice were randomly divided into four groups on average:negative control group(NC),aqueous extract of CS group(CS),aqueous extract of CS+moderate-intensity training group(CS+MT),and CS aqueous extract of CS+high-intensity training group(CS+HT).The maximum running speed,forelimb grip strength,body weight and fasting blood glucose of mice were measured before and after treatment.After the intervention,oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were conducted to assess glucose metabolism,while serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)levels were measured to evaluate lipid metabolism.Results:After 3 months of intervention,there were significant differences in the maximum running speed and forelimb grip strength among the four groups(P＜0.05).The maximum running speed and forelimb grip strength of CS group,CS+MT group and CS+HT group were higher than those of NC group(P＜0.05).The CS+MT group exhibited higher forelimb grip strength,and the CS+HT group showed higher maximum running speed and forelimb grip strength compared to the CS group(P＜0.05),while no significant difference was found between the CS+MT and CS+HT groups(P＞0.05).Significant differences in body weight were observed among the four groups after 3 months of intervention(P＜0.05).Specifically,the CS+MT and CS+HT groups exhibited significantly lower body weight compared to both the NC and CS groups(P＜0.05),with the CS+MT group having the lowest body weight(P＜0.05).Fasting blood glucose levels also differed significantly among the groups after 2 and 3 months of intervention(P＜0.05).The CS,CS+MT,and CS+HT groups had lower fasting blood glucose levels compared to the NC group(P＜0.05),with the CS+MT and CS+HT groups showing the lowest levels(P＜0.05).No significant difference was found between the CS+MT and CS+HT groups(P＞0.05).After 3 months of intervention,significant differences in the area under the curve(AUC)of OGTT and ITT were observed among the four groups(P＜0.05).The AUC of OGTT and ITT were significantly lower in the CS,CS+MT,and CS+HT groups compared to the NC group(P＜0.05).The CS+MT and CS+HT groups exhibited the lowest AUC values for both OGTT and ITT(P＜0.05),with the CS+MT group showing the lowest AUC for OGTT(P＜0.05).Significant differences in serum lipid levels were observed among the four groups after 3 months of intervention(P＜0.05).TG,TC,and LDL-C levels were significantly lower,while HDL-C levels were higher in the CS,CS+MT,and CS+HT groups compared to the NC group(P＜0.05).The CS+MT group had the lowest TG levels and the highest HDL-C levels compared to the CS+HT group(P＜0.05),with no significant differences in TC and LDL-C levels between these two groups(P＞0.05).Conclusion:Aqueous extract of CS combined with different intensity training can significantly improve the exercise capacity and glycolipid metabolism of MS mice and reduce body weight,especially CS combined with MT treatment is more effective in improving lipid metabolism.In addition,when combined with HT,aqueous extract of CS can also play an auxiliary role in reducing the side effects of high-intensity exercise and improving the therapeutic effect.

Aim To study the effect of anti-PD-L1 monoclonal antibody on high-fat diet-induced athero-sclerosis in ApoE-/-mice.Methods Twenty-four ApoE-/-mice were randomly divided into the normal group,high-fat group,and high-fat+anti-PD-L1 mAb group.After 70 days,the blood samples were harves-ted.Blood vessels(aortic root to abdominal aorta)and liver from each groups were stained with Oil Red O.Hematoxylin-eosin staining(HE)was employed to vis-ualize structural changes in liver.Enzyme-linked im-munosorbent assay(ELISA)was applied to detect the serum levels of total cholesterol(CHO),triglyceride(TG),high-density lipoprotein(HDL-c),low-density lipoprotein(LDL-c)and inflammatory factors(IFN-γ,TNF-α,IL-1 β).Flow cytometry was used to detect the proportion of lymphocytes(CD4 and CD8).RT-PCR was utilized to assess the expressions of IFN-γ,TNF-α,IL-1 β,CD4 and CD8 in liver.Results Compared with the high-fat group,the treatment with anti-PD-L1 monoclonal antibody promoted vascular wall and liver lipid accumulation,and also up-regulated serum and liver content of cholesterol(CHO),triglyceride(TG)and high-density lipoprotein(HDL-c).Treatment with anti-PD-L1 monoclonal antibody up-regulated the con-tent of alanine aminotransferase(GPT)and aspartate aminotransferase(GOT)in serum and liver,but not al-kaline phosphatase(AKP).ELISA test indicated that treatment with anti-PD-L1 monoclonal antibody stimu-lated the serum level of IFN-γ,TNF-α and IL-1 β.Fur-thermore,the mRNA level of IFN-γ,TNF-α and IL-1 βin liver was also up-regulated after treatment with anti-PD-L1 monoclonal antibody.With flow cytometry,we observed that treatment with anti-PD-L1 monoclonal antibody promoted hepatic CD8+T and CD8+IFN-γ+T cell activation,but had no effect on CD4+IFN-γ+T cell activation under high-fat feeding conditions.Con-clusions Anti-PD-L1 monoclonal antibody adminis-tered under high-fat feeding conditions can damage liv-er function and aggravate atherosclerosis by activating liver CD8+IFN-γ+T cells.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Objective:To observe the clinical efficacy of repetitive transcranial magnetic stimulation(rTMS)combined with mindfulness-based cognitive therapy(MBCT)in patients with alcohol withdrawal syndrome(AWS).Methods:The 120 patients with AWS who were observed in this study were all male patients admitted to our hospital from June 2021 to June 2024,the patients were divided into group A(conventional treatment,40 cases),group B(group A combined with rTMS,40 cases),and group C(group B combined with MBCT,40 cases)according to random number table method.The clinical efficacy,self-control ability[Modified Clinical Institution Alcohol Dependence Withdrawal Assessment Scale(CIWA-Ar)score,Visual Analog Scale of Psychological Craving for Alcohol(VAS)score and Pennsylvania Alcohol Craving Scale(PACS)score],anxiety and depression degree assessment[Hamilton Depression Scale(HAMD)score,Hamilton Anxiety Scale(HAMA)score]and quality of life[36 Short Form Health Survey(SF-36)Score],relapse rate and readmission rate were compared among the three groups.Results:The total effective rate of group A,group B and group C increased successively(P＜0.05).The CIWA-Ar,PACS and VAS scores in group B and group C after treatment were lower than those in group A,and group C was lower than that in group B(P＜0.05).The HAMD and HAMA scores of group B and group C after treatment were lower than those in group A,and group C was lower than that in group B(P＜0.05).The SF-36 score of group B and group C after treatment was higher than those in group A,and group C was higher than that in group B(P＜0.05).Relapse rate and readmission rate in groups B and C were lower than those in group A,and group C was lower than that in group B(P＜0.05).Conclusion:The application of rTMS combined with MBCT in patients with AWS can improve clinical efficacy and quality of life,alleviate anxiety and depression,improve patients' self-control ability,reduce relapse rate and readmission rate,with definite effects.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Menstrual migraine is a specific subtype of migraine unique to women,closely related to the menstrual cycle,characterized by periodic and intractable headaches,often accompanied by nausea,vomiting or photophobia and phonophobia,which seriously affects life and has a high degree of disability.Its pathogenesis is complex,involving multi-dimensional regulation such as estrogen fluctuations,neurovascular responses and genetic and environmental factors,but the specific mechanism has not been fully clarified.In recent years,with the increasing social attention to women's health,the clinical research demand for menstrual migraine has become increasingly urgent.Currently,modern medicine can alleviate symptoms through acute drug intervention(such as non-steroidal anti-inflammatory drugs,triptans)and preventive treatment(such as beta-blockers,CGRP antagonists),but there are problems such as drug dependence and insufficient individualization.Traditional Chinese medicine,based on the"holistic concept"and"syndrome differentiation and treatment"theory,regulates the balance of qi,blood,yin and yang through therapies such as traditional Chinese medicine and acupuncture,showing unique advantages in improving symptoms and preventing recurrence.The combination of traditional Chinese and Western medicine can optimize the therapeutic effect and reduce side effects through synergistic effects,but the full-cycle prevention and treatment strategy still needs further exploration.This article systematically reviews the pathogenesis and research progress of treatment of menstrual migraine in traditional Chinese and Western medicine,emphasizes the interaction between hormone fluctuations and neurovascular responses,and proposes an individualized intervention plan based on the menstrual cycle,providing new ideas for clinical practice and reference directions for future research.

Menstrual migraine is a specific subtype of migraine unique to women,closely related to the menstrual cycle,characterized by periodic and intractable headaches,often accompanied by nausea,vomiting or photophobia and phonophobia,which seriously affects life and has a high degree of disability.Its pathogenesis is complex,involving multi-dimensional regulation such as estrogen fluctuations,neurovascular responses and genetic and environmental factors,but the specific mechanism has not been fully clarified.In recent years,with the increasing social attention to women's health,the clinical research demand for menstrual migraine has become increasingly urgent.Currently,modern medicine can alleviate symptoms through acute drug intervention(such as non-steroidal anti-inflammatory drugs,triptans)and preventive treatment(such as beta-blockers,CGRP antagonists),but there are problems such as drug dependence and insufficient individualization.Traditional Chinese medicine,based on the"holistic concept"and"syndrome differentiation and treatment"theory,regulates the balance of qi,blood,yin and yang through therapies such as traditional Chinese medicine and acupuncture,showing unique advantages in improving symptoms and preventing recurrence.The combination of traditional Chinese and Western medicine can optimize the therapeutic effect and reduce side effects through synergistic effects,but the full-cycle prevention and treatment strategy still needs further exploration.This article systematically reviews the pathogenesis and research progress of treatment of menstrual migraine in traditional Chinese and Western medicine,emphasizes the interaction between hormone fluctuations and neurovascular responses,and proposes an individualized intervention plan based on the menstrual cycle,providing new ideas for clinical practice and reference directions for future research.