ObjectiveTo construct a large language model （LLM）-based intelligent pre-consultation system for traditional Chinese medicine （TCM） to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function， BLEU-4， and ROUGE-L metrics， through which training convergence， text generation quality， and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content， TCM pharmacist licensure content， TCM symptom terminology recognition， and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy， consultation rounds， and consultation duration. ResultsAfter 100 000 iterations， the training loss value was gradually stabilized at about 0.7±0.08， indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L， suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms， 505 relationships between diseases and syndromes， 1011 relationships between diseases and main symptoms， and 1 303 600 relationships among different symptoms， and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners， licensed pharmacists of Chinese materia medica， recognition of TCM symptom terminology， and meridian recognition were 94.09%， 78.00%， 87.50%， and 68.80%， respectively. In clinical tests， the syndrome differentiation accuracy of the system reached 88.33%， with fewer consultation rounds and shorter consultation time compared to the attending physicians （P＜0.01）， suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language， it collects all the patient's symptom through guided questioning， thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.

ObjectiveBased on the TCM theory of "Yang transforms materials to Qi while Yin constitutes material form"， this paper explored the effects of Zuogui Wan and Yougui Wan on the molecular mechanism of mitochondrial biogenesis during the adipogenic differentiation process of rat bone marrow mesenchymal stem cells （BMSCs） by mediating peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and peroxisome proliferators-activated receptor γ （PPARγ）， providing theoretical support for the prevention and treatment of postmenopausal osteoporosis （PMOP） using Zuogui Wan and Yougui Wan. MethodsBMSCs were divided into a blank group， Zuogui Wan （ZGW） group， Yougui Wan （YGW） group， and Progynova group. Cell identification was performed using flow cytometry. The growth curves of BMSCs were plotted using the methylthiazolyldiphenyl-tetrazolium bromide （MTT） method， and the effects of Zuogui Wan and Yougui Wan on the proliferation of BMSCs were detected. The Oil red O staining method was used to detect lipid droplet formation. The Western blot method was used to detect the expression of adipogenesis-related factors PPARγ， CCAAT/enharcer-binding protein （C/EBP）α， C/EBPβ， lipoprotein lipase （LPL） protein， brown adipose tissue-related （BAT） proteins PGC-1α， uncoupcing protein 1 （UCP1）， PR domdin-containing protein 16 （PRDM16）， mitochondrial biogenesis-related PGC-1α， nuclear respiratory factor 1 （Nrf1）， nuclear factor E₂-related factor 2 （Nrf2）， and mitochondrial transcription factor A （TFAM）. The expression of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， LPL genes， and the copy number of cytochrome B （CytoB mtDNA） gene was detected using real-time polymerase chain reaction （Real-time PCR）. Mitochondrial ultrastructure was detected using transmission electron microscopy. ResultsCompared with that in the blank group， the proliferation ability of BMSCs in each treatment group increased continuously as the intervention progressed， and lipid droplets significantly decreased after the drug intervention. The mRNA and protein expression levels of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， and LPL were significantly downregulated （P<0.01）， while those of the BAT-related factors PGC-1α， UCP1， PRDM16 were significantly upregulated （P<0.01）. The number of mitochondria increased， accompanied by reduced swelling. The double membrane and cristae structure were clear， and the internal cristae rupture was reduced. The copy number of CytoB mtDNA in each treatment group was significantly increased （P<0.01）. The protein expression levels of mitochondrial biogenesis-related PGC-1α， Nrf1， Nrf2， and TFAM in each treatment group were significantly increased （P<0.01）. ConclusionBoth Zuogui Wan and Yougui Wan can prevent and treat PMOP by intervening in mitochondrial biogenesis in BMSCs through PGC-1α/PPARγ.

Aim This study aims to investigate the therapeutic effect and underlying mechanism of Todda-lia asiatica in the treatment of ischemic stroke(IS),utilizing network pharmacology,molecular docking technology,and animal experiments.Methods To screen the chemical components of Toddalia asiatica and its targets related to IS,a database was utilized.A protein-protein interaction(PPI)network was con-structed,followed by KEGG pathway enrichment anal-ysis.Molecular docking was performed to investigate the interaction between the components and target pro-teins.Finally,the effects of the drug on the PI3K/AKT/mTOR pathway and autophagy were validated through animal experiments.We established a middle cerebral artery occlusion(MCAO)rat model and di-vided the rats into the model group,Donepezil hydro-chloride group,Toddalia asiatica group,and sham op-eration group randomly.Observed the pathological changes in neurons of the rat hippocampal and cortical regions induced by the drug,performed immunohisto-chemical analysis to detect and localize mTOR expres-sion,and used Western blot to assess the expression levels of PI3K,p-PI3K,AKT,p-AKT,mTOR,as well as autophagy markers(LC3-Ⅱ and p62).Re-sults A total of 22 active ingredients from Toddalia asiatica,including AKT1 and MAPK3,were identified through screening.Additionally,194 signaling path-ways,such as PI3K/AKT and MAPK,were analyzed.The active compounds in Toddalia asiatica demonstra-ted stable binding affinity with targets associated with ischemic stroke.The results of the animal experiment indicated that,compared to the sham-operated group,the neuronal distribution in the hippocampal and corti-cal regions of the model group rats became sparser and more disorganized.There was a decrease in the number of Nissl bodies and cytoplasmic vacuolization.The ex-pression of mTOR-positive cells in the hippocampal and cortical regions was reduced.Additionally,the ex-pression levels of p-PI3K,p-AKT,mTOR,and p62 in the rat hippocampal tissue decreased(P＜0.05,P＜0.01),while the expression of LC3-Ⅱ increased(P＜0.01).Compared with the model group,the rats in the Toddalia asiatica and the Donepezil hydrochloride groups effectively improved the aforementioned indica-tors in rats.Conclusions Network pharmacology a-nalysis has revealed the promising potential of Toddalia asiatica in treating ischemic stroke,attributed to its di-verse components,targets,and pathways.The animal experiment showed that Toddalia asiatica can protect the neuronal structure in the hippocampal and cortical regions,which may be related to the inhibition of ex-cessive autophagy mediated by the PI3 K/AKT/mTOR pathway.

Objective To investigate the expression and prognostic value of spindle and kinetochore-associated complex subunit 2(SKA2)in cervical cancer tissues,as well as its impact on the proliferation,migration and invasion of cervical cancer cells.Methods The expression of SKA2 in cervical cancer tissues was analyzed by bioinformatics database and immunohistochemical SP method,and the relationship between SKA2 expression level and clinicopathological features of cervical cancer patients and its prognostic value was analyzed.The mRNA expression of SKA2 in human normal cervical cells(HcerEpic)and cervical cancer cells(HeLa,SiHa,CaSki,C-33A)was detected by RT-qPCR.Cervical cancer cells SiHa with higher SKA2 expression level was selected for further study.SiHa cell model with down-regulated SKA2 expression was constructed,and its knockdown effect was verified.Cell proliferation capacity was detected by CCK-8 method,cell migration capacity was detected by cell scratch wound healing assay,and cell migration and invasion capacity was detected by Transwell assay.Results Compared with normal cervical tissues and cells,the expression levels of SKA2 mRNA and protein were higher in cervical cancer tissues and cells,and the differences were statistically significant(P<0.05).High SKA2 expression was associated with FIGO staging in patients with cervical cancer.Furthermore,SKA2 knockdown could inhibit the proliferation,migration and invasion of SiHa cells in cervical cancer(P<0.05).Conclusion SKA2 is up-regulated in cervical cancer tissues and cells,and can promote the proliferation,migration and invasion of cervical cancer cells.The expression level of SKA2 is associated with the progression of cervical cancer,and the prognosis of cervical cancer patients with high SKA2 expression is worse.

Objective:To analyze the distribution characteristics of prognostic factors affecting recurrence in peripheral T-cell lymphoma(PTCL)patients with different levels of histone deacetylase(HDAC)based on latent class analysis.Methods:112 PTCL patients who were treated in our hospital from September 2012 to September 2019 were selected and divided into recurrence group and non-recurrence group.The clinical data of the two groups of patients were compared.Multivariate logistic regression was used to analyze the risk factors for recurrence.Latent class analysis was used to compare the distribution characteristics of prognostic factors affecting recurrence between the high-risk group and the low-risk group.Results:There were 87 patients(77.68％)in recurrence group and 25 patients(22.32％)in non-recurrence group.The result of multivariate logistic regression showed that ECOG score ≥2,Ann Arbor stage Ⅲ-Ⅳ,IPI score＞2,bone marrow involvement,elevated serum β2-microglobulin(β2-MG),short-term efficacy not reaching complete remission(CR)or partial remission(PR),and the high expression of HDAC were all independent risk factors for recurrence in patients with PTCL(P＜0.05).The recurrence rate of patients with high HDAC levels was significantly higher than that of patiens with low HDAC levels(P＜0.05).The results of cluster analysis showed that the risk of recurrence was obviously clustered,and the patients could be divided into high recurrence risk group(HDAC＞5 points)and low recurrence risk group(HDAC≤5 points).The results of latent class analysis showed that patients with multiple risk factors account for a higher proportion in the high recurrence risk group,compared with the low recurrence risk group(P＜0.05).Conclusion:There are differences in recurrence rates among PTCL patients with different HDAC levels and in distribution characteristics of risk factors between high recurrence risk and low recurrence risk groups.

Objective To design a nuclear emergency medical rescue simulation platform to solve the problmes in nuclear accident scenario simulation,fidelity of on-site medical treatment training and training organization.Methords A nuclear emergency medical rescue simulation platform was developed with the technologies of virtual reality(VR),augmented reality(AR),spatial positioning,full-body motion capture,gesture simulation and three-dimensional modeling,Unity3D platform,3D Studio Max software and Visual Studio,which mainly consisted of a hardware system and a software system.The hardware system was composed of the AR training equipment and VR training equipment,of which,the AR training equipment included a surface contamination detector simulator,an individual decontaminator simulator and AR glasses,and the VR training equipment was made up of VR glasses,large-space localization equipment,backpack computers,data gloves and full-body motion capture equipment.The software system involved in several modules for theoretical knowledge teaching and assessment,VR/AR practical teaching training and VR/AR evaluation.Results The system realized simulated collaborative training and evaluation for medical emergency response to nuclear accidents.Conclusion The platform constructed contributes to solving the practical problems in organizing and implementing education and training for nuclear emergency medical rescue,and the education and training are both enhanced greatly.[Chinese Medical Equipment Journal,2024,45(9):50-56]

Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

AIM To investigate the effects of Ginkgo biloba extract on hearing function,cochlear morphology and autophagy-related protein expression in a rat model of presbycusis.METHODS Forty-five rats were randomly divided into the control group,the model group and the low,medium and high dose G.biloba extract groups(10,20 and 30 mg/kg),with 9 rats in each group.The rat model of presbycusis was established by intraperitoneal injection of 500 mg/kg D-galactose(D-gal).Eight weeks after the corresponding administration,the rats had their changes of hearing threshold detected by the auditory brainstem evoked potential(ABR);their morphological changes of cochlear hair cells,stria vascularis(SV)and spiral ganglion cells observed by HE staining;their number of hair cells inside and outside the cochlea detected by immunofluorescence staining;their ultrastructure changes of cochlear hair cells observed by transmission electron microscopy;and their expression of autophagy-related proteins in cochlea tissue detected by Western blot.RESULTS Compared with the control group,the model group displayed increased ABR threshold(P<0.01);more severely damaged inner and outer hair cells,spiral ganglion cells and SV,decreased SV thickness and numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.01);decreased protein expressions of Beclin1 and LC3 Ⅱ and ratio of LC3 Ⅱ/LC3 Ⅰ in cochlear tissue(P<0.01),and higher P62 protein expression(P<0.01).Compared with the model group,the medium and high dose G.biloba extract groups shared decreased ABR thresholds(P<0.01);improved morphology of inner and outer hair cells and SV in the cochlea,normalized,morphology of spiral ganglion cells,and increased SV thickness and the numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.05,P<0.01);increased protein expressions of Beclin1 and LC3 Ⅱ and the ratio of LC3 Ⅱ/LC3 Ⅰ in the cochlea(P<0.01),and decreased P62 protein expression(P<0.01).CONCLUSION The protective effects G.biloba extract on hearing function and cochlear cells in the rat model of presbycusis may be associated with the up-regulated expression of Beclin1 and LC3 Ⅱ proteins and down-regulated P62 protein expression in cochlear tissues.

Objective To study the mechanism of the amelioration of renal injury in immunoglobulin A nephropathy(IgAN)rats by multi-glycosides of Tripterygium wilfordii(GTW)based on the sphingosine kinase 1(Sphk1)/sphingosine 1-phosphate receptor 2(S1PR2)signalling pathway.Methods An IgAN rat model was established by means of bovine serum albumin gavage+castor oil and carbon tetrachloride subcutaneous injection+lipopolysaccharide tail vein injection.The rats were randomly divided into the model,control and experimental groups,with 9 rats in each group,and 10 normal rats were taken as the blank group.In the control group,6.25 mg·kg-1·d-1 prednisone was given by gavage;in the experimental group,9.375 mg·kg-1·d-1GTW was given by gavage;and in the blank and model groups,0.5 mL·100 g-1·d-1 0.9％NaCl was given by gavage,and the drugs were administered to the rats once a day in each group.At the end of the 15th week,urine samples were collected and blood albumin(ALB),blood urea nitrogen(BUN),24 hour-urine protein quantification(24 h-UTP),and urine erythrocyte counts were determined in each group,and the expression levels of Sphk1/S1PR2 proteins in each group were detected by Western blotting.Results The renal pathological changes in the control and experimental groups were significantly reduced compared with those in the model group by hematoxylin-eosin staining and immunofluorescence.The levels of ALB in the blank,model,control and experimental groups were(32.49±2.23),(22.98±0.51),(26.01±1.33)and(26.53±1.92)g·L-1;the levels of BUN were(6.11±1.71),(13.75±2.96),(6.71±1.35)and(4.77±0.99)mmol·L-1;the levels of 24 h-UTP were(5.72±1.96),(9.12±2.15),(5.78±2.05)and(4.75±1.50)mg·24 h-1;the urine erythrocyte counts were(9.73±2.40),(14.62±2.60),(9.90±1.59)and(9.46±2.94)cell·μL-1;the relative expression levels of Sphk1 protein were 0.85±0.02,1.47±0.02,1.06±0.02 and 1.09±0.02;the relative expression levels of S1PR2 protein were 0.27±0.02,0.88±0.01,0.43±0.02,and 0.42±0.02,respectively.The above indexes in the model group were statistically significant when compared with those of the control group and the experimental group(all P＜0.01).Conclusion GTW may reduce the proliferation of mesangial cells by inhibiting the Sphk1/S1PR2 signalling pathway,thus attenuating kidney injury in IgAN rats.

This study investigates whether compounds in Salvia miltiorrhiza Bunge can bind to the Toll like receptor 4/myeloid differentiation protein 2 (TLR4/MD2) protein complex and exhibit anti-inflammatory activity. Virtual screening of reported chemical components of Salvia miltiorrhiza Bunge against TLR4/MD2 was conducted in this study. The selected compound, neoprzewaquinone A (Neo A), was tested for its impact on the binding of lipopolysaccharide (LPS) to receptors on the cell membrane, its affinity for the protein, its influence on the dimerization of TLR4 and MD2 in LPS-induced cells, and its effects on the phosphorylation of nuclear factor-κB (NF-κB) p65 protein and the secretion of inflammatory cytokines in cells. Results indicate that Neo A in Salvia miltiorrhiza Bunge exhibited the highest virtual binding affinity with TLR4/MD2, with a value of -12.8 kcal·mol^-1. Neo A significantly inhibited the binding of LPS to receptors on the cell membrane (P < 0.01). Moreover, Neo A demonstrated affinity for rhTLR4/MD2, rhTLR4, and rhMD2, with K_D values of 267, 534, and 228 nmol·L^-1, respectively. Amino acid residues like TYR131 and PHE121 in TLR4/MD2 might play a role in the alkyl and π-alkyl hydrophobic interactions with Neo A. Neo A also significantly inhibited the dimerization of TLR4 and MD2 in LPS-mediated cells (P < 0.01) and markedly suppressed the phosphorylation of NF-κBp65 protein (P < 0.05). Furthermore, Neo A significantly or markedly inhibited the secretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in LPS-induced cells (P < 0.05, P < 0.01). In conclusion, Neo A exerts its anti-inflammatory effects by binding TLR4/MD2 then disrupting the binding of LPS to TLR4/MD2. It may serve as a TLR4/MD2 inhibitor with the potential to treat inflammation-related diseases targeting TLR4/MD2.