It is proposed that cold qi-induced accumulation encapsulates the core pathogenesis of the inflammation-cancer transformation in inflammatory bowel disease （IBD）. Cold pathogens may serve as the initiating factor. When first invading the intestines， cold pathogens obstruct the flow of qi； over time， the lingering cold impairs the middle jiao （焦）， eventually leading to the accumulation of cold-phlegm and blood stasis. Based on the progressive nature of this transformation， the process can be divided into three stages， active stage， remission stage， and carcinogenic stage. In the active stage， the main pathogenesis involves stagnation of cold qi and accumulation of damp-heat in the intestines； in the remission stage， cold qi impairs the spleen， disrupting its transport and transformation functions； and in the carcinogenic stage， the mechanisms include cold-induced accumulation， phlegm accumulation from cold， and stagnation of cold and blood stasis. Accordingly， the treatment strategies are proposed.In the active stage， regulating qi， relieving stagnation， and harmonizing cold and heat； in the remission stage， warming yang， dispersing cold， tonifying qi， and strengthening the spleen； and in the carcinogenic stage， promoting qi circulation， dispersing cold， resolving phlegm， activating yang， and eliminating stasis to remove accumulation. These approaches aim to interrupt the transformation of IBD into colorectal cancer.

In recent years， diabetic nephropathy （DN） has become an increasingly serious health challenge worldwide， and its morbidity and mortality rates are rapidly increasing. The patients suffering from the disease tend to be younger. DN is not only accompanied by a wide range of renal pathological changes， such as renal hypertrophy， inflammatory cell infiltration， expansion of the tethered membrane stroma， and thickening of the basement membrane but is also the main cause of end-stage renal disease and death in patients with diabetes mellitus. Therefore， it is particularly urgent to explore new strategies for the prevention and treatment of DN. The pathogenesis of DN is intricate and complex， with current research focusing on multifactorial interactions between metabolic and hemodynamic factors， such as hypoxia， inflammatory responses， and fibrotic processes. Notably， hypoxia plays a pivotal role in the initiation and progression of DN. Hypoxia-inducible factor （HIF-1α）， as a key regulatory protein commonly found in hypoxic cells， has a profound impact on various physiological and pathological processes， such as cell metabolism， vascular neogenesis， oxidative stress， and apoptosis. With its unique theoretical system and therapeutic approach， traditional Chinese medicine has demonstrated significant advantages in coping with hypoxic diseases and can slow down the progression of DN by regulating the expression level of HIF-1α and its downstream signaling molecules and exerting anti-inflammatory， antioxidant， and antifibrotic effects， which has positive clinical significance for drug development and early prevention and treatment of DN.

ObjectiveTo improve the therapeutic effect of Buyang Huanwutang（BYHW） on diabetic kidney disease （DKD） and explore new methods for developing new Chinese medicine decoctions，we utilized 5-hydroxymethylcytosine （5hmC）-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus （DM） patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA （cfDNA） in the patients’ plasma was sequenced. After data processing and screening， we performed temporal clustering analysis to select a DKD 5hmC gene set， which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）， and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction （PPI） network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed on non-common DKD genes， and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes， and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass， random blood glucose， urinary microalbumin （mALB）， serum creatinine （Scr）， and blood urea nitrogen （BUN） and by hematoxylin-eosin staining， periodic acid-Schiff staining， Masson staining， immunofluorescence assay， and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes， of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 （IL-6）， Toll-like receptor 4 （TLR4）， lactotransferrin （LTF）， lipoprotein lipase （LPL）， and sterol regulatory element-binding transcription factor 1 （SREBF1）. Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes， among which TBC1 domain family member 5 （TBC1D5）， RAD51 paralog B （RAD51B）， and proteasome 20S subunit alpha 6 （PSMA6） had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine， glycine， myristicin， serine， and tyrosine， corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus， Ginseng Radix et Rhizoma， Dioscoreae Rhizoma， Rehmanniae Radix Praeparata， Isatidis Radix， Glehniae Radix， Ophiopogonis Radix， Allii Sativi Bulbus， Isatidis Folium， and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory， the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice， with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions， potentially offering new perspectives for the exploration of these prescriptions

ObjectiveTo improve the therapeutic effect of Buyang Huanwutang（BYHW） on diabetic kidney disease （DKD） and explore new methods for developing new Chinese medicine decoctions，we utilized 5-hydroxymethylcytosine （5hmC）-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus （DM） patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA （cfDNA） in the patients’ plasma was sequenced. After data processing and screening， we performed temporal clustering analysis to select a DKD 5hmC gene set， which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）， and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction （PPI） network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed on non-common DKD genes， and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes， and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass， random blood glucose， urinary microalbumin （mALB）， serum creatinine （Scr）， and blood urea nitrogen （BUN） and by hematoxylin-eosin staining， periodic acid-Schiff staining， Masson staining， immunofluorescence assay， and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes， of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 （IL-6）， Toll-like receptor 4 （TLR4）， lactotransferrin （LTF）， lipoprotein lipase （LPL）， and sterol regulatory element-binding transcription factor 1 （SREBF1）. Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes， among which TBC1 domain family member 5 （TBC1D5）， RAD51 paralog B （RAD51B）， and proteasome 20S subunit alpha 6 （PSMA6） had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine， glycine， myristicin， serine， and tyrosine， corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus， Ginseng Radix et Rhizoma， Dioscoreae Rhizoma， Rehmanniae Radix Praeparata， Isatidis Radix， Glehniae Radix， Ophiopogonis Radix， Allii Sativi Bulbus， Isatidis Folium， and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory， the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice， with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions， potentially offering new perspectives for the exploration of these prescriptions

Objective Excavate the prescriptions containing the drug pair of Aurantii Fructus Immaturus-Magnoliae Officinalis Cortex(AFI-MOC),and statistically analyze the rules of prescription medication,and explore its potential mechanism of action in the treatment of food retention disorder.Methods The prescriptions containing the pair of AFI-MOC in the Great Dictionary of Traditional Chinese Medicine Prescriptions were retrieved and typed into Excel to establish a database.The source,dosage form,frequency of compatibility of traditional Chinese medicine,nature,taste and meridian attribution and indications were analyzed.Using R language(4.3.3)software with OriginPro to analysis co-occurrence frequency,association rule,correlation clustering analysis,and visualization.Then,the network construction,Protein-Protein Interaction Network(PPI)analysis,Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genome(KEGG)pathway enrichment analysis of the"AFI-MOC-active ingredient-food retention disorder target"network were performed for the AFI-MOC drug pair and its indications food retention disorder.The binding between the core active ingredients and key target proteins was evaluated by molecular docking.Results A total of 349 prescriptions containing the pair of AFI-MOC were included,involving 267 Chinese herbs.Among them,the high-frequency compatibility drugs included Citri Reticulatae Pericarpium,Glycyrrhizae Radix et Rhizoma,Atractylodis Macrocephalae Rhizoma,Rhei Radix et Rhizoma and Aucklandiae Radix.They are mainly warm in nature,spicy,bitter and sweet in taste,spleen,liver and stomach in meridian.There were 141 kinds of indications,most of which were diseases of the spleen and stomach system such as food retention disorder,dysentery and fullness.Correlation cluster analysis shows that the AFI-MOC drug pair is frequently combined with drugs that have the efficacy of promoting qi circulation,strengthening the spleen,clearing heat,and eliminating dampness.Found through the analysis of network pharmacology AFI-MOC drug pair on the core of the active ingredient of Luteolin,BU3,Naringenin,Honokiol and Nobiletin.Key targets for food retention disorder are BDNF,AKT1,ESR1,TNF and IL-6.Molecular docking results show Luteolin,combined with AKT1 is most closely.Conclusion AFI-MOC drug pair often compatible with Citri Reticulatae Pericarpium,Atractylodis Macrocephalae Rhizoma,Aucklandiae Radix.The advantages of the prescription containing AFI-MOC drug pair is food retention disorder.Its key active components can exert therapeutic effects through multiple targets such as AKT1 and TNF.This study reveals the AFI-MOC drug pair on compatibility laws,preliminary interpretation of the mechanism for the treatment of food retention disorder.It can provide references and a basis for studying the compatibility mechanism of AFI-MOC and guiding rational clinical medication.

Objective:To develop and validate the Online Fraud Susceptibility Scale(OFSS).Methods:The construct of online fraud susceptibility was defined through qualitative interviews(n=14)and expert evaluations(n=6).Based on prior literature,an initial item pool was generated.A sample of 805 adults completed the preliminary scale for item analysis and exploratory factor analysis(EFA).Another sample of 491 adults completed the formal scale for confirmatory factor analysis(CFA),criterion validity,and internal consistency analysis.Of these,233 par-ticipants were retested after four months.The Vulnerability to Fraud Questionnaire(VFQ)and the Susceptibility to Persuasion-Ⅱ Scale(StP-Ⅱ)were used as criterion measures.Results:The 25-item OFSS consisted of 5 factors,na-rely monetary motivation,heuristic processing,financial risk-seeking,anti-fraud knowledge,and susceptibility to so-cial influence,explaining 51.94％of the total variance.The factor loadings ranged from 0.52 to 0.80.The 5-factor model showed an acceptable structural fit(x2/df=2.39,CFI=0.86,TLI=0.84,CFI=0.86,RMSEA=0.05).The OFSS scores were positively correlated with the scores of VFQ and StP-Ⅱ(r=0.51,0.47,Ps＜0.001).The inter-nal consistency reliabilities of the total score and 5 factors ranged from 0.64 to 0.80,and the retest reliabilities(ICC)of the total score and 5 factors ranged from 0.53 to 0.78.Conclusion:The Online Fraud Susceptibility Scale demonstrates satisfactory psychometric properties providing a practical tool to assess the vulnerability to online fraud.

Objective To analyze the symptomatic improvement effects of vitamin D in children with autism spectrum disorder(ASD)based on the microbiota-gut-brain axis.Methods Seventy-two children with ASD were randomly divided into an observation group and a control group,with 36 cases in each group.Three cases dropped out in the control group.The observation group received 1200 IU/day of vitamin D supplementation in addition to conventional rehabilitation training,while the control group received only conventional rehabilitation training.The intervention lasted for 12 weeks.Assessments were conducted before and after the intervention using the childhood autism rating scale(CARS),autism behavior checklist(ABC),and repetitive behavior scale-revised(RBS-R).Resting-state functional connectivity of the brain was measured using near-infrared functional imaging,and serum levels of 25(OH)D3,inflammatory cytokines,and gut microbiota were analyzed.The differences in these indicators before and after the intervention were compared between the two groups to evaluate clinical efficacy.Results The between-group differences in pre-and post-intervention changes showed that the observation group had significantly greater improvements than the control group in the following measures:CARS scores(-5.92±1.40 vs.-2.55±1.43),RBS-R scores(-5.99±1.01 vs.-3.10±1.47),resting-state brain functional connectivity(0.19±0.15 vs.0.10±0.18),serum 25(OH)D3 levels[(34.89±8.18)ng/mL vs.(0.68±6.73)ng/mL],serum interleukin-6(IL-6)levels[(-6.60±6.07)pg/mL vs.(-0.74±9.45)pg/mL],IL-1β levels[(-2.56±1.33)pg/mL vs.(-0.04±2.13)pg/mL],and tumor necrosis factor-α(TNF-α)levels[(-4.09±3.85)pg/mL vs.(0.21±4.05)pg/mL](P<0.05).Post-intervention,significant differences in gut microbial β-diversity were observed between the two groups(R2=0.030,P=0.040,Adonis).LEfSe analysis revealed that the observation group exhibited enrichment in Clostridia(LDA=4.747,P=0.003),Clostridiales(LDA=4.747,P=0.003),Clostridiaceae(LDA=3.476,P=0.001),Lachnospiraceae(LDA=4.709,P=0.004),Odoribacteraceae(LDA=3.458,P=0.027),Odoribacter(LDA=3.458,P=0.027),Burkholderiales(LDA=3.339,P=0.038),Firmicutes(LDA=4.764,P=0.003),and Betaproteobacteria(LDA=3.338,P=0.037).Conclusion Vitamin D supplementation can modulate gut microbial diversity in children with ASD,significantly influence the abundance of specific gut microbiota,reduce systemic inflammatory cytokines,enhance brain functional connectivity,and alleviate clinical symptoms of ASD.

Objective To provide a reference for the clinical individualized medication of hypertension,the antihypertensive efficacy of Gouteng Xuanshen prescription in the treatment of hypertension was verified,and its improvement on the discomfort symptoms of patients was explored.Methods This study adopted a retrospective cohort study design.The data were derived from the electronic medical records of 6770 hypertensive patients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1,2013 to January 1,2023.The exposure factor was the treatment of Uncaria rhynchophylla,Scrophularia ningpoensis,and Radish Seed.After the propensity score was used to deal with the confounding factors,the changes in blood pressure of the patients after treatment were observed.At the same time,in order to analyze the improvement of patients'symptoms,the Apriori algorithm to mine the core symptoms of patients was explored,and the patient symptom network was constructed.The BGLL algorithm was used to divide the symptoms into communities to form a symptom map.Finally,survival analysis and Cox regression were used to find the sensitive symptom community of Gouteng Xuanshen prescription,and the related factors were analyzed.Results 468 people were included in the exposure group and the control group.After treatment,more patients in the exposure group reached the target blood pressure(P<0.01),and the effect was better in lowering systolic blood pressure(P<0.05),and no obvious abnormalities in safety indicators were found.In terms of symptom improvement,the 134 symptoms recorded in the medical records were divided into 6 groups.As the medication time increased,the patient's head discomfort was easier to relieve.The effect was best at 8 weeks of treatment,and it was more sensitive to patients with extremely high cardiovascular risk or grade 3 hypertension.Conclusion This study verified the clinical efficacy of the Gouteng Xuanshen prescription in the treatment of hypertension through electronic medical record data,which preliminarily revealed the potential role and law of the Gouteng Xuanshen prescription in the treatment of hypertension.

Objective:To investigate the effects of repetitive transcranial magnetic stimulation(rTMS) on the core symptoms, brain functional connectivity and activation in children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS).Methods:From September 2022 to March 2024, a total of 35 children with ADHD were selected as research subjects and they were randomly divided into observation group ( n=17) and control group ( n=18). The control group received conventional rehabilitation therapy, while the observation group received rTMS therapy in addition to the conventional therapy. Both groups were treated every other day, with each course of treatment lasting four weeks, and a total of three courses of treatment were administered consecutively. The clinical symptoms of the children with ADHD were assessed using Swanson, Nolan, and Pelham-Ⅳ(SNAP-Ⅳ) before and after treatment. fNIRS was used to detect the relative concentration changes of oxyhemoglobin (HbO 2) and deoxyhemoglobin (HbR) in the prefrontal cortex under resting-state and Go/Nogo task conditions before and after treatment. Statistical analysis was performed using SPSS 26.0 software. Paired sample t-test were used for within-group comparisons, and independent sample t-test were used for between-group comparisons. Results:(1) After treatment, the scores for inattention, hyperactivity/impulsivity and oppositional defiant behavior in the two groups were significantly lower than before treatment ( t=3.51-18.86, all P<0.05). The scores for inattention, hyperactivity/impulsivity and oppositional defiant behavior in the observation group were significantly lower than those in the control group ( t=2.21, 2.03, 2.39, all P<0.05). (2) After treatment, the functional connectivity strength between all regions of interest in both groups was significantly higher than before treatment ( t=3.53-37.90, all P<0.05). The functional connectivity strength of the left dorsolateral prefrontal cortex (0.25±0.03, 0.21±0.03), right dorsolateral prefrontal cortex (0.12±0.02, 0.09±0.02), left medial prefrontal cortex (0.13±0.02, 0.10±0.01) and right medial prefrontal cortex (0.31±0.04, 0.24±0.06) in the observation group was significantly higher than those in the control group (all P<0.05). (3) In the Go/Nogo task, after treatment, the average HbO 2 concentrations in the left dorsolateral prefrontal cortex, right dorsolateral prefrontal cortex, left medial prefrontal cortex, right medial prefrontal cortex, left temporal lobe, and right temporal lobe in both groups were all higher than before treatment (all P<0.05). After treatment, the average HbO 2 concentrations in the left dorsolateral prefrontal cortex, right dorsolateral prefrontal cortex, left medial prefrontal cortex and right medial prefrontal cortex of the observation group were significantly higher than those of the control group (all P<0.05). Conclusion:rTMS therapy can improve the core symptoms of children with ADHD, which may be related to the strength of brain functional connectivity and activation of ADHD brain function by rTMS.

Objective To investigate the comparative efficacy of different frequencies of pelvic floor electrical stimulation(PFES)on stress urinary incontinence(SUI)in rats.Methods Twenty female Sprague-Dawley rats were randomly divided into 6,15,30 and 50 Hz group by random number table method.All rats underwent vaginal dilatation(VD)to simulate postpartum SUI.One week after VD,the sneeze test was conducted to determine whether the modeling was successful.If the sneeze test was positive,the modeling was successful.The miniature and wireless electric pelvic floor stimulator were implanted into the pelvic floor muscle of the modeled rats,and PFES were treated for 2 weeks in each group at the rates of 6,15,30 and 50 Hz,respectively.The Leak point pressure(LPP)of all rats before VD,1 week after VD and 2 weeks after stimulation were measured by cystometrograms(CMGs)for comparison.Results LPP was significantly reduced in all groups of rats after VD 1 week(P<0.001).Compared with after VD 1 week,after two consecutive weeks of PFES at four different frequencies of 6,15,30 and 50 Hz,LPP was again significantly increased(P<0.001)and reached the baseline level(P>0.05)in all groups of rats.In the between-group comparison of the rats in each group,there was no significant difference in their LPP at baseline value,after VD 1 week and after stimulation 2 weeks(P>0.05).Conclusion The present study suggests that of the several stimulation frequencies explored so far,6 Hz may be a more appropriate choice for PFES.Further studies are still needed to evaluate more frequencies and the long-term efficacy of PFES.