Objective: To address the challenges of systematically identifying herb pairs in traditional Chinese medicine (TCM), we proposed HerbGL, a framework for predicting potential herb pairs that integrates network propagation and graph regularization. Methods: Based on the assumption that herbal actions induce subtle perturbations in biological systems, a framework named HerbGL was proposed. Random walk with restart (RWR) was first applied to the protein-protein interaction (PPI) network to reconstruct herb-specific perturbation effects and generate weighted subnetworks. Then, to quantify affinity between herb pairs, two network-proximity metrics, Closeness and PageRank, were computed from the weighted subnetworks to construct herb-pair affinity matrices. Finally, these matrices, together with known herb pairs (derived from co-occurrence analysis of TCM formulas with a threshold determined from the inflection point of the frequency distribution), were incorporated into a graph regularization model to predict potential herb pairs. Model performance was assessed through baseline comparison, ablation and robustness experiment under different ratios of positive and negative samples, using the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPRC), accuracy, and precision as evaluation metrics. Furthermore, the predicted herb pairs were validated through both literature evidence and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results: The weighted subnetworks constructed by RWR provided a refined simulation of herb-specific perturbation effects, which formed the basis for subsequent affinity modeling and prediction. Analysis of herb pair co-occurrence frequencies revealed a marked change around 150, which was selected as the threshold to distinguish herb pairs from non-herb pairs. HerbGL exhibited superior predictive performance compared with baseline models (AUROC = 0.970 5, AUPRC = 0.955 5, accuracy = 0.726 6, precision = 0.970 6). Ablation results showed that removing the Closeness and PageRank metrics substantially degraded performance (AUROC = 0.819 1, AUPRC = 0.876 8), confirming their necessity. Robustness evaluation under an imbalanced positive-to-negative sample ratio of 1 : 5 yielded AUROC = 0.969 6 and AUPRC = 0.840 4, indicating stable predictive ability. Moreover, multiple case studies further validated the rationality of the predicted herb pairs, such as Fangfeng (Saposhnikoviae Radix) and Qingpi (Citri Reticulatae Pericarpium Viride) which are recorded in Liangpeng Huiji (《良朋汇集》, Collection of Excellent Recipes) Vol. 3: Fangfeng Shengma Tang (防风升麻汤). Additionally, pathway enrichment analysis of the Renshen (Ginseng Radix et Rhizoma) and Lianqiao (Forsythiae Fructus) pair further supported the biological plausibility of their compatibility. Conclusion HerbGL offers an effective and biologically informed framework for identifying herb pairs in TCM. Beyond improving herb pair prediction, the framework also provides data support for research on herb compounds and mechanisms, thereby supporting data-driven exploration of TCM compatibility.

Objective To investigate the effect of Biejiajian Pill(BJJP)on malignant biological behavior of hepatocellular carcinoma Hep3B cells and its regulatory mechanism.Methods A total of 72 healthy SD rats were randomly divided into blank control(BC)group,low(0.55 g/kg),medium(1.10 g/kg)and high(2.20 g/kg)BJJP experimental group,and drug-containing serum was prepared.Hep3B cells were divided into BC group,normal rat serum treatment(NC)group,low dose BJJP(LBJJP)group,medium dose BJJP(MBJJP)group and high dose BJJP(HBJJP)group,empty plasmid(pcDNA3.1)group,and CKLF-like MARVEL transmembrane domain containing 6(CMTM6)overexpression(pcDNA3.1-CMTM6)group,and the NC+pcDNA3.1 group,MBJJP+pcDNA3.1 group,NC+pcDNA3.1-CMTM6 group and MBJJP+pcDNA3.1-CMTM6 group.The proliferation of hepatoma Hep3B cells was detected by CCK-8.The migration and invasion of hepatoma Hep3B cells were detected by Transwell assay.The expression levels of proliferation-related proteins proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)related proteins(E-cadherin,N-cadherin and Vimentin),and CMTM6 proteins in hepatoma Hep3B cells were detected by Western blotting experiments.Results Compared with those in BC group,there were no significant differences in the proliferation,migration and invasion abilities of Hep3B cells,or the expression levels of PCNA,EMT related proteins(E-cadherin,N-cadherin and Vimentin)and CMTM6 protein in NC group(P＞0.05).Compared with NC group,LBJJP,MBJJP and HBJJP drug-containing serum inhibited the proliferation,migration and invasion of Hep3B cells,downregulated the protein expression of PCNA;MBJJP and HBJJP upregulated the protein expression of E-cadherin.The protein expressions of N-cadherin,Vimentin and CMTM6 were downregulated,with significant differences(P＜0.05).Compared with pcDNA3.1 group,the protein expression of CMTM6,cell proliferation,migration,invasion,PCNA protein expression,N-cadherin protein expression,and Vimentin protein expression in Hep3B cells in pcDNA3.1-CMTM6 group were significantly upregulated,while the protein expression of E-cadherin was significantly downregulated(P＜0.05).Compared with NC+pcDNA3.1 group,the proliferation,migration and invasion abilities of Hep3B cells in MBJJP+pcDNA3.1 group were decreased,the expression levels of PCNA,Vimentin and N-cadherin protein were decreased,while the expression level of E-cadherin protein was increased.Compared with NC+pcDNA3.1-CMTM6 group,MBJJP+pcDNA3.1-CMTM6 group had the same results in the proliferation,migration and invasion abilities of Hep3B cells and the protein expression levels of PCNA,Vimentin,N-cadherin and E-cadherin.The differences were statistically significant(all P＜0.05).Conclusion BJJP may inhibit the proliferation,migration,invasion and EMT of hepatoma Hep3B cells by regulating the expression of CMTM6.

Objective To elucidate the effects and mechanisms of Biejiajian pill(BJJP)-containing serum on the malignant biological behaviors of hepatocellular carcinoma Huh7 cells.Methods This research knocked down CKLF-like MARVEL transmembrane domain containing 6(CMTM6)expression using a CMTM6-specific small interfering RNA(siRNA).Healthy Sprague-Dawley rats were used to prepare normal rat serum and low-(0.55 g/kg),medium-(1.1 g/kg),and high-(2.2 g/kg)BJJP-containing.Huh7 cells were cultured with normal fetal bovine serum(BC),normal rat serum(NC),and low-,medium-,and high-dose BJJP serum(LBJJP,MBJJP,and HBJJP,respectively).BJJP-containing serum and si-CMTM6 were applied to Huh7 cancer cells,and the proliferation,migration,and invasion abilities were evaluated by CCK-8 and Transwell assays,respectively.Protein expression levels of proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)markers,and CMTM6 were detected by Western blot.Results CMTM6 knockdown significantly reduced the mRNA and protein expression level of CMTM6 in Huh7 cells(P＜0.05).There were no significant differences between the BC and NC groups in terms of cell proliferation,migration,invasion,expression levels of PCNA,EMT markers,and CMTM6(all P＞0.05).BJJP-containing serum markedly inhibited Huh7 cell proliferation,migration,and invasion(P＜0.05),downregulated PCNA,CMTM6,N-cadherin,and Vimentin expression,and upregulated E-cadherin compared with the NC group(all P＜0.05).CMTM6 knockdown suppressed malignant behaviors,with reduced PCNA,Vimentin,and N-cadherin and elevated E-cadherin expression(all P＜0.05).Conclusions BJJP-containing serum can significantly inhibit Huh7 cell growth,invasion,migration,and EMT progression,potentially mediated via CMTM6 suppression.

Objective To investigate the effect of Biejiajian Pill(BJJP)on malignant biological behavior of hepatocellular carcinoma Hep3B cells and its regulatory mechanism.Methods A total of 72 healthy SD rats were randomly divided into blank control(BC)group,low(0.55 g/kg),medium(1.10 g/kg)and high(2.20 g/kg)BJJP experimental group,and drug-containing serum was prepared.Hep3B cells were divided into BC group,normal rat serum treatment(NC)group,low dose BJJP(LBJJP)group,medium dose BJJP(MBJJP)group and high dose BJJP(HBJJP)group,empty plasmid(pcDNA3.1)group,and CKLF-like MARVEL transmembrane domain containing 6(CMTM6)overexpression(pcDNA3.1-CMTM6)group,and the NC+pcDNA3.1 group,MBJJP+pcDNA3.1 group,NC+pcDNA3.1-CMTM6 group and MBJJP+pcDNA3.1-CMTM6 group.The proliferation of hepatoma Hep3B cells was detected by CCK-8.The migration and invasion of hepatoma Hep3B cells were detected by Transwell assay.The expression levels of proliferation-related proteins proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)related proteins(E-cadherin,N-cadherin and Vimentin),and CMTM6 proteins in hepatoma Hep3B cells were detected by Western blotting experiments.Results Compared with those in BC group,there were no significant differences in the proliferation,migration and invasion abilities of Hep3B cells,or the expression levels of PCNA,EMT related proteins(E-cadherin,N-cadherin and Vimentin)and CMTM6 protein in NC group(P＞0.05).Compared with NC group,LBJJP,MBJJP and HBJJP drug-containing serum inhibited the proliferation,migration and invasion of Hep3B cells,downregulated the protein expression of PCNA;MBJJP and HBJJP upregulated the protein expression of E-cadherin.The protein expressions of N-cadherin,Vimentin and CMTM6 were downregulated,with significant differences(P＜0.05).Compared with pcDNA3.1 group,the protein expression of CMTM6,cell proliferation,migration,invasion,PCNA protein expression,N-cadherin protein expression,and Vimentin protein expression in Hep3B cells in pcDNA3.1-CMTM6 group were significantly upregulated,while the protein expression of E-cadherin was significantly downregulated(P＜0.05).Compared with NC+pcDNA3.1 group,the proliferation,migration and invasion abilities of Hep3B cells in MBJJP+pcDNA3.1 group were decreased,the expression levels of PCNA,Vimentin and N-cadherin protein were decreased,while the expression level of E-cadherin protein was increased.Compared with NC+pcDNA3.1-CMTM6 group,MBJJP+pcDNA3.1-CMTM6 group had the same results in the proliferation,migration and invasion abilities of Hep3B cells and the protein expression levels of PCNA,Vimentin,N-cadherin and E-cadherin.The differences were statistically significant(all P＜0.05).Conclusion BJJP may inhibit the proliferation,migration,invasion and EMT of hepatoma Hep3B cells by regulating the expression of CMTM6.

Objective To elucidate the effects and mechanisms of Biejiajian pill(BJJP)-containing serum on the malignant biological behaviors of hepatocellular carcinoma Huh7 cells.Methods This research knocked down CKLF-like MARVEL transmembrane domain containing 6(CMTM6)expression using a CMTM6-specific small interfering RNA(siRNA).Healthy Sprague-Dawley rats were used to prepare normal rat serum and low-(0.55 g/kg),medium-(1.1 g/kg),and high-(2.2 g/kg)BJJP-containing.Huh7 cells were cultured with normal fetal bovine serum(BC),normal rat serum(NC),and low-,medium-,and high-dose BJJP serum(LBJJP,MBJJP,and HBJJP,respectively).BJJP-containing serum and si-CMTM6 were applied to Huh7 cancer cells,and the proliferation,migration,and invasion abilities were evaluated by CCK-8 and Transwell assays,respectively.Protein expression levels of proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)markers,and CMTM6 were detected by Western blot.Results CMTM6 knockdown significantly reduced the mRNA and protein expression level of CMTM6 in Huh7 cells(P＜0.05).There were no significant differences between the BC and NC groups in terms of cell proliferation,migration,invasion,expression levels of PCNA,EMT markers,and CMTM6(all P＞0.05).BJJP-containing serum markedly inhibited Huh7 cell proliferation,migration,and invasion(P＜0.05),downregulated PCNA,CMTM6,N-cadherin,and Vimentin expression,and upregulated E-cadherin compared with the NC group(all P＜0.05).CMTM6 knockdown suppressed malignant behaviors,with reduced PCNA,Vimentin,and N-cadherin and elevated E-cadherin expression(all P＜0.05).Conclusions BJJP-containing serum can significantly inhibit Huh7 cell growth,invasion,migration,and EMT progression,potentially mediated via CMTM6 suppression.

Objective To investigate the application effect of biofeedback electrical stimulation combined with Kegel exercises using vaginal dumbbell in pelvic floor muscle strength rehabilitation of patients with postpartum pelvic floor dysfunction(PFD).Methods A prospective study was conducted on 70 PFD patients who were divided into control group(n=34)and combined group(n=36)according to random numbers generated by Excel.Control group received Kegel exercises using vaginal dumbbell,while combined group was given biofeedback electrical stimulation on this basis.Both groups underwent 3 months of continuous treatment.GRRUG method was adopted to assess pelvic floor muscle strength after treatment;a low-frequency neuromuscular stimulation therapy device was used to detect the pelvic floor muscle fiber electromyography value and fatigue value;and female sexual function index(FSFI)was utilized to evaluate the quality of sexual life.The pelvic floor function impairments in two groups were also recorded and compared.Results After treatment,compared with control group,combined group had greater proportions of above grade Ⅲ muscle strength of class Ⅰ and class Ⅱ muscle fibers(P<0.05),higher mean pelvic floor electromyography values of class Ⅰ and class Ⅱ muscle fibers(P<0.05),and lower fatigue value of pelvic floor muscle(P<0.05).In addition,combined group had higher FSFI scores for sexual desire,sexual arousal,vaginal lubrication,orgasm,satisfaction and dyspareunia,and the total score than control group(P<0.05),and the incidence rates of frequent and urgent urination,lumbosacral pain,and vaginal relaxation were lower in combined group as compared with control group(P<0.05).Conclusion The combination of biofeedback electrical stimulation and Kegel exercises using vaginal dumbbell in the treatment of patients with postpartum PFD can significantly improve pelvic floor muscle strength,alleviate symptoms such as frequent and urgent urination,lumbosacral pain and vaginal relaxation,and improve the quality of sexual life.

BACKGROUND:In recent years,artificial intelligence has gradually emerged and has been applied in various fields such as spinal cord nerve injury and repair,which has a positive impact on clinical treatment. OBJECTIVE:To study the application progress of artificial intelligence in the diagnosis,treatment,and rehabilitation of spinal cord nerve injury and repair,clarify the research hotspots and shortcomings in this field,and provide suggestions for future research work. METHODS:Relevant literature on artificial intelligence in the field of spinal cord nerve injury and repair was retrieved on the Web of Science core collection database until 2023.CiteSpace 6.1.R6 and VOSviewer 1.6.19 software was used to perform general literature analysis,co-citation of literature,co-citation of journals,double image overlay of journals,keyword clustering,and other visual analysis on the literature data. RESULTS AND CONCLUSION:(1)A total of 1 713 articles were selected,and the annual publication volume in this field showed a fluctuating upward trend,with the United States taking the lead,and Kadone and Hideki being the authors with the highest publication volume.ARCH PHYS MED REHAB was the journal with the highest number of citations.(2)Keyword co-occurrence and cluster analysis showed that after removing keywords similar to the search terms,the main keywords were divided into three main clusters:Exoskeleton and exercise rehabilitation(the largest core hotspot);machine learning and neural plasticity;robotics and rehabilitation training.(3)Keyword burst analysis showed that deep learning and artificial intelligence had become burst terms in the past five years.(4)The results of in-depth analysis of co cited and highly cited literature showed that the hotspots of artificial intelligence in the field of spinal cord nerve injury and repair were mainly focused on powered exoskeletons,gaits,electrical nerve stimulation,intracortical brain-computer interface(IBCI),robots,and polymer biomaterials,and neural stem cell.(5)The research on artificial intelligence in the field of spinal cord nerve injury and repair has shown an upward trend in recent years.The focus of this field had gradually shifted from single treatment methods such as exoskeletons and electrical stimulation to intelligent,precise,and personalized directions.(6)There were some limitations in this field,such as the consequences of missing or imbalanced data,low data accuracy and reproducibility,and ethical issues(such as privacy,research transparency,and clinical reliability).Future research should address the issue of data collection,requiring large sample,high-quality clinical datasets to establish effective artificial intelligence models.At the same time,the research on genomics and other mechanisms in this field is very weak.In the future,various machine learning technologies such as brain chips can be used,and gene editing therapy,single-cell spatial transcriptome and other methods can be used to study the basic mechanisms of regeneration-related gene upregulation and axon growth structural protein production.

Objectives:To explore the value of non-invasive myocardial work combined with myocardial contrast echocardiography(MCE)in the early diagnosis of coronary artery disease and its efficacy in stratifying the severity of coronary vessel lesions.Methods:A total of 130 patients with suspected coronary artery disease admitted to the First Affiliated Hospital of Dalian Medical University from June 2024 to January 2025 were enrolled in this study.All patients underwent echocardiography and MCE after admission,and coronary angiography(CAG).Based on CAG results,patients were divided into non-CAD group(n=45,coronary artery stenosis<50%)and CAD group(n=85,coronary artery stenosis≥50%).Patients in CAD group were further divided into low-score CAD group(≤49 points,n=43)and high-score CAD group(>49 points,n=42)according to the median of Gensini score(49 points).Non-invasive MW indices and quantitative MCE parameters were assessed.A binary logistic regression model was used to construct a combined diagnostic model,and the value of each parameter in diagnosing CAD and evaluating the severity of coronary lesions was calculated.The receiver operating characteristic(ROC)curve of subjects was estimated,and the area under the curve(AUC)was calculated to evaluate its sensitivity and specificity for early diagnosis of coronary heart disease.Results:Compared with the non-CAD group,the global longitudinal strain,global work index(GWI),and global constructive work(GCW)in both low-score and high-score CAD groups were significantly lower(all P<0.05),and the global work efficiency in the high-score CAD group was significantly reduced(P<0.05).MCE indices in both low-score and high-score CAD groups were significantly lower than those in the non-CAD group(all P<0.05).The multivariate logistic stepwise regression analysis and ROC curve showed that GWI(OR=0.997,95%CI:0.995-0.999,P=0.003)and A value(representing the peak intensity of the curve,reflecting myocardial blood volume(OR=0.415,95%CI:0.246-0.698,P=0.001)were independent predictors of low-score CAD.The combined diagnostic sensitivity and specificity for low-score coronary artery disease were 72.1%and 88.9%respectively,with an AUC of 0.851.GCW(OR=0.997,95%CI:0.995-1.000,P=0.019)and β-value(OR=0.000,95%CI:0.000-0.003,P<0.001)were independent predictors of high-score CAD.The combined diagnostic sensitivity and specificity for high-score coronary artery disease were 88.1%and 88.9%respectively,with an AUC of 0.934.Conclusions:Both non-invasive myocardial work parameters and MCE parameters have high diagnostic efficacy for coronary artery lesions of various degrees.The combined application of the two methods significantly improves the accuracy of coronary artery disease diagnosis,with improved sensitivity and specificity than single technique.Our results provide a new non-invasive comprehensive diagnostic model for clinical early diagnosis and risk stratification of coronary artery disease.

Objective:To research access management method of evaluating medical consumables based on Kano performance classification model,so as to improve the quality of access management of medical consumables and clinical service level.Methods:The Better-Worse coefficient analysis method was adopted to analyze quantitative data,and a comprehensive performance evaluation was conducted on the basis of Kano model.And then,a classification management mode included access allocation of priority,evaluation dimensions of priority,standardization of access process and strengthening of dynamic supervision were formulated.A total of 120 kinds of medical consumables in clinical use of Jiangsu Province Hospital from January 2021 to December 2023 were selected.The expert performance evaluation model(expert performance evaluation)was adopted to conduct access management for medical consumables that were used during January 2021 and June 2022,and the Kano performance evaluation model(Kano performance evaluation)was adopted to conduct that for medical consumables that were used during July 2022 and December 2023.The performances of clinical service and operation quality of the two evaluation modes for the access of medical consumables were compared.Results:The Better coefficients of the consumables in outpatient department,emergency department and inpatient department,and consumables that were used in medical technique that adopted Kano performance evaluation mode were respectively 0.25±0.06,0.32±0.07,0.28±0.06 and 0.27±0.05,which were higher than those of that adopted expert performance evaluation mode,and the difference were statistically significant(t=4.791,4.241,5.667,5.996,P<0.05),respectively.The Worse coefficients of Kano performance evaluation mode were respectively 0.08±0.03,0.10±0.01,0.09±0.05 and 0.09±0.04,which were significantly lower than those of expert performance evaluation mode,and the differences of them were significant(t=3.431,3.049,3.324,2.979,P<0.05).The Better coefficients of operation quality performance of warehouse management,operating cost and supply of outside hospital of using Kano performance evaluation mode were respectively 0.44±0.08,0.40±0.09 and 0.22±0.06,which were higher than that of expert performance evaluation mode,and the differences were significant(t=4.052,3.563,4.792,P<0.05).The Worse coefficients of them of using Kano performance evaluation mode were respectively 0.18±0.05,0.16±0.06 and 0.10±0.04,which were lower than those of expert performance evaluation mode,and the differences were significant(t=3.347,3.438,4.092,P<0.05).Conclusion:The access management of evaluating medical consumables on the basis of Kano performance classification mode can improve the comprehensiveness and scientific nature of assessing the access of medical consumables,and enhance the level of clinical service of medical consumables,and improve the operation quality of supply management for medical consumables.

Objective:To explore the related risk factors contributing to re-fracture after hip surgery in elderly patients.Methods:This retrospective analysis was conducted on the clinical data of 2 415 elderly individuals who underwent surgical treatment for hip fractures and were discharged from Shanghai Sixth People's Hospital between January 2016 and December 2021.Patients were grouped into re-fracture and non-re-fracture cohorts based on whether a second fracture occurred within three years after surgery.Demographics, clinical data, and postoperative functional rehabilitation outcomes of the two groups were collected, and univariate and multivariate logistic regression analyses were applied to identify the independent risk factors for re-fractures after surgery.Results:A total of 2, 000 patients who completed follow-up were included in the final analysis, aged 60~91 years, with a mean age of (75.4±8.2) years.Among them, 855 were male(42.75%), and the postoperative re-fracture incidence was 28.25% (565/2 000). Univariate analysis indicated that advanced age, fracture type at first onset, lower Harris scores, insufficient rehabilitation training, osteoporosis, diabetes, cerebrovascular disorders, visual impairment, and syncope were all significantly associated with re-fracture (all P<0.05), while gender differences were not statistically significant ( P>0.05). Multivariate regression confirmed the following as independent risk factors: age ≥75 years, postoperative Harris score <80, non-standard rehabilitation training, combined osteoporosis, diabetes, cerebrovascular disease, visual impairment, and syncope ( OR、 RR>1). Conclusions:Elderly patients are prone to re-fracture after hip surgery, and its occurrence is closely related to advanced age, inadequate functional rehabilitation, osteoporosis, and multiple internal medical comorbidities.In clinical practice, attention should be paid to standardized postoperative rehabilitation, systematic anti-osteoporotic therapy, and active intervention of comorbidities to reduce the incidence of re-fracture and improve the long-term prognosis of patients.