Osteoporosis is a common senile bone metabolism disease， clinically characterized by decreased bone mass， destruction of bone microstructure， increased bone fragility， and easy fracture. It tends to occur in the elderly and postmenopausal women， seriously threatening the quality of life and physical and mental health of the elderly. At present， the treatment of osteoporosis is mainly based on oral western medicines， such as calcium， Vitamin D， and bisphosphonates. Still， there are drawbacks such as a long medication cycle and many adverse reactions. In recent years， due to the advantages of multi-component， multi-pathway， and multi-target， some traditional Chinese medicines and effective ingredients can regulate the osteogenic and osteoclastic differentiation process in both directions and are widely used in the prevention and treatment of osteoporosis. Hippophae rhamnoides is a commonly used herbal medicine， and its fruits are rich in flavonoids， polyphenols， fatty acids， vitamins， and trace elements， which have been proven to have a good anti-osteoporosis effect. Isorhamnetin is the main effective ingredient of Hippophae rhamnoides fruits， which has many pharmacological effects such as anti-inflammation， anti-oxidative stress， anti-aging， and anti-tumor. Studies have shown that isorhamnetin can participate in the regulation of bone metabolism and has a good anti-osteoporosis effect. However， the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis have not been systematically summarized. Therefore， this paper reviewed the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis by referring to relevant literature to provide more basis for the development and application of isorhamnetin.

As the cornerstone of modern medical diagnosis,pathology is facing multiple challenges such as workforce shortages,strong diagnostic subjectivity,and inefficient workflows.With advantages in image recognition,pattern analysis,and big data processing,artificial intelligence(AI)is increasingly being integrated into the field of pathological diagnosis,driving its transition toward digitization and intelligence.This article systematically reviews the development of AI in pathology,from early supervised learning validation to weakly supervised learning overcoming annotation bottlenecks,and the recent rise of self-supervised and multimodal foundation models.It demonstrates the broad applications of AI in improving diagnostic consistency,optimizing workflows,and predicting molecular features and prognoses.AI not only enhances the objectivity and efficiency of pathological diagnosis but also promotes the development of emerging interdisciplinary fields such as computational pathomics,providing strong support for precision medicine.Although challenges such as data standardization and regulatory approval remain in clinical implementation,the deep integration of AI and pathology is ushering in a new era of human-machine collaboration and intelligent diagnostics.

Objective To identify co-expressed genes and potential comorbidity mechanisms between Alzheimer's disease(AD)and epilepsy with publicly available single-cell transcriptome sequencing data from human brains,fol-lowed by functional validation in APP/PS1 double transgenic AD mouse models expressing the chimerical Mo/HuAPP695swe amyloid precursor protein and mutant PS1-dE9 presenilin 1.Methods The single-cell transcriptome sequencing data of brain tissue from AD and epilepsy patients were collected from gene expression omnibus(GEO)database followed by cell clustering,differential expression analysis and gene ontology(GO)func-tional enrichment analysis using R-based tools such as Seurat and cluster Profiler and video electroencephalogram (vEEG)monitoring and Western blot experiments.Results A total of eight major brain cell types were identified,with neurons and glial cells exhibiting shared differentially expressed genes between AD and epilepsy.These co-ex-pressed genes were significantly clustered in pathways related to metal ion homeostasis,synaptic transmission,oxi-dative stress,and immune activation,which suggested common pathological mechanisms involving in synaptic dys-function and neuro-inflammation in both disorders.The vEEG recordings of APP/PS1 mouse model of AD showed 30％of mice exhibited high-frequency epileptic seizures,while 70％showed low-frequency seizure activity.Subse-quent validation in the prefrontal cortex of AD mice confirmed up-regulated expression of key molecular markers(HES5,c-FOS,and RPL10A)identified through single-cell sequencing analysis.Conclusions AD and epilepsy share gene co-expression profiles and functional pathways in specific cell types.The results of research provide a theoretical support for further elucidating their comorbidity mechanisms and developing targeted therapeutic strategy.

ObjectiveTo investigate the distribution of traditional Chinese medicine （TCM） syndrome elements in type 2 diabetes mellitus （T2DM） patients based on maximum body mass index （maxBMI） and explore their association with complication risks. MethodsA retrospective cross-sectional study was used to collect clinical data from hospitalized T2DM patients， extracting age， gender， smoking history， alcohol consumption history， duration of disease， HbA1c level， complications， and TCM syndromes， and extracting the syndrome elements of disease location and disease nature based on their TCM syndromes. MaxBMI was calculated by telephone survey of patients' self-reported maximum body weight； patients with maxBMI ≥24 kg/m² were classified into spleen-heat syndrome group， and those with maxBMI ＜24 kg/m² were classified into consumptive-heat syndrome group. The distribution of TCM syndrome types and syndrome elements of patients in the two groups were analysed. Then the propensity score matching method was used to balance the baseline characteristics between the two groups and compare the differences in the distribution of syndrome types and syndrome elements and the risk of macrovascular and microvascular complications between the two groups. ResultsAmong the 1178 T2DM patients， syndrome elements in spleen-heat patients （1034 cases） were primarily located in the spleen （351 cases， 33.95%）， liver （240 cases， 23.21%）， and stomach （139 cases， 13.44%）， while in consumptive-heat patients （144 cases）， they were concentrated in the spleen （57 cases， 39.58%）， liver （34 cases， 23.61%）， and kidneys （17 cases， 11.81%）； regarding syndrome elements of disease nature， spleen-heat patients were predominantly characterized by qi deficiency （481 cases， 46.52%）， phlegm （353 cases， 22.73%）， and dampness （241 cases， 23.31%）， whereas consumptive-heat patients showed more qi deficiency （84 cases， 58.33%） and yin deficiency （44 cases， 30.56%）. After propensity score matching， 132 cases were included in each group， and no statistically significant differences were observed in the distribution of syndrome elements of disease location between the two groups （P＞0.05）， but the phlegm element was significantly more prevalent in spleen-heat patients than in consumptive-heat patients （P = 0.006）. Regarding the risk of complications， spleen-heat patients had a significantly higher risk of developing macrovascular complications compared to consumptive-heat patients （OR=2.04， P=0.010）， while no significant differences were found between groups in the occurrence of microvascular complications （P＞0.05）. ConclusionThe spleen-heat T2DM patients show a more frequent syndrome element of disease nature of phlegm， and a higher risk of developing macrovascular complications compared to consumptive-heat patients.

Accurate prediction of drug responses in cancer cell lines (CCLs) and transferable prediction of clinical drug responses using CCLs are two major tasks in personalized medicine. Despite the rapid advancements in existing computational methods for preclinical and clinical cancer drug response (CDR) prediction, challenges remain regarding the generalization of new drugs that are unseen in the training set. Herein, we propose a multimodal fusion deep learning (DL) model called drug-target and single-cell language based CDR (DTLCDR) to predict preclinical and clinical CDRs. The model integrates chemical descriptors, molecular graph representations, predicted protein target profiles of drugs, and cell line expression profiles with general knowledge from single cells. Among these features, a well-trained drug-target interaction (DTI) prediction model is used to generate target profiles of drugs, and a pretrained single-cell language model is integrated to provide general genomic knowledge. Comparison experiments on the cell line drug sensitivity dataset demonstrated that DTLCDR exhibited improved generalizability and robustness in predicting unseen drugs compared with previous state-of-the-art baseline methods. Further ablation studies verified the effectiveness of each component of our model, highlighting the significant contribution of target information to generalizability. Subsequently, the ability of DTLCDR to predict novel molecules was validated through in vitro cell experiments, demonstrating its potential for real-world applications. Moreover, DTLCDR was transferred to the clinical datasets, demonstrating satisfactory performance in the clinical data, regardless of whether the drugs were included in the cell line dataset. Overall, our results suggest that the DTLCDR is a promising tool for personalized drug discovery.

Objective To explore the application effect of the Mini-CEX evaluation model based on the OBE concept in the clinical Practice teaching of neurology.Methods We Selected 100 students who will Practice in the Department of Neurology from 2022 to 2023 as the research objects,and divided them into the experimental group(n=50)and the control group(n=50).Under the guidance of the OBE concept,the experimental group was guided by learning outcomes,refined the teaching objectives,and applied the Mini-CEX evaluation mode for evaluation and feedback.In contrast,the control group adopted the traditional teaching mode.Combined with the observation data,we analyzed and compared the data of various indicators of the two groups of students at the beginning and end of the internship.Results At the end of the internship,the scores of clinical consultation,Physical examination,humanistic medicine,clinical diagnosis,health consultation,organizational effect,and overall evaluation of the experimental group were significantly improved and were higher than those of the control group.After the Practice,in terms of skill test scores,the experimental group scored higher than the control group,the difference was statistically significant(P<0.05),and the experimental group also scored higher in satisfaction evaluation than the control group.Conclusion The Mini-CEX evaluation teaching model based on the concept of OBE is applied to the clinical practice teaching of the neurology department,which can enhance the training effect of students'clinical practice skills.

Objective Using the weighted gene co-expression network analysis(WGCNA)to explore the key genes of aging associated with Alzheimer's disease(AD).Methods GSE132903 was selected from GEO database as the analysis dataset.The differential expressed genes(DEGs)of AD were screened,and visualized with volcano and heat map.Aging and senescence-associated genes(ASAGs)were downloaded from MsigDB,Aging Altas and CellAge databases.WGCNA screened the gene modules with the highest correlation with AD,and genes of key modules subsequently performed with gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.AD age-related differential expressed genes(ARDEGs)were obtained by taking intersection genes of DEGs,key module genes of WGCNA and ASAGs.Protein-protein interaction(PPI)network analysis was performed using the STRING database to find key node genes.The co-expression networks and associated functions of key genes were analyzed using the GeneMANIA database.The key genes were validated in Alzdata database.Results 226 DEGs,606 ASAGs and 8 ARDEGs were obtained.The top 5 key genes selected by PPI were SYP,STXBP1,VAMP2,CPLX1 and STX1A.Alzdata database verified that the expressions of 5 key genes in other brain regions of AD were down-regulated,except for no significant changes of VAMP2 in hippocampus and STXBP1 in frontal cortex,as well as no expression of CPLX1 in frontal cortex.The differential expression of VAMP2,STXBP1 and STX1A appeared in the early stage of AD,and CPLX1 was related to the pathological process of Tau.SYP and STXBP1 were related to the pathological processes of amyloid β-protein and Tau.Conclusion SYP,STXBP1,VAMP2,CPLX1 and STX1A are ARDEGs,which are expected to be potential diagnostic and therapeutic targets for AD.

Objective To investigate the improvement effect and mechanism of Modified Kongsheng Zhenzhong Dan medicated serum on mitochondrial function of PC12 cells injured by oxygen-glucose deprivation/reperfusion(OGD/R)based on the SIRT1/PGC-1α pathway.Methods PC12 cells were used to construct OGD/R cell model in vitro.Cell grouping:normal group(10%FBS),model group(10%FBS),10%drug-containing serum group,5%drug-containing serum group(5%drug-containing serum+5%blank serum),10%blank serum group(control group).CCK-8 method was used to detect the cell survival rate,and the appropriate oxygen glucose deprivation time(2,4,6,8 hours)was screened.MTT assay was used to detect cell activity;mitochondrial stress test(MST)was used to detect the oxygen consumption rate(OCR).Apoptosis was detected by flow cytometry(Annexin V-PE/7-AAD double staining).The protein expression levels of SIRT1 and PGC-1α in PC12 cells were detected by Western Blot.Results Compared with the normal group,the activity of PC12 cells decreased significantly after oxygen-glucose deprivation for 2,4,6 and 8 hours(P＜0.05),and 6 hours of oxygen-glucose deprivation was selected as the time of subsequent experimental modeling.Compared with the normal group,the cell activity of the model group was significantly decreased(P＜0.05).The OCR values of basic respiration value,maximum respiration value,proton leakage,ATP production and standby respiration ability were significantly decreased(P＜0.05).The apoptosis rate was significantly increased(P＜0.05).The protein expression levels of SIRT1 and PGC-1α in cells were significantly decreased(P＜0.05).Compared with the model group,the cell activity of the Modified Kongsheng Zhenzhong Dan 10%and 5%drug-containing serum groups was significantly increased(P＜0.05).The OCR values of basal respiration value,maximum respiration value,proton leakage,ATP production and spare breathing ability were significantly increased(P＜0.05).The apoptosis rate was significantly decreased(P＜0.05).The protein expression levels of SIRT1 and PGC-1α in cells were significantly increased(P＜0.05).Conclusion The Modified Kongsheng Zhenzhong Dan medicated serum can improve mitochondrial dysfunction,inhibit neuronal apoptosis and promote neuronal survival in OGD/R-injured PC12 cells.The mechanism may be related to the activation of SIRT1/PGC-1α signaling pathway.

Objective To investigate the effect and mechanism of long chain non-coding RNA(ln-cRNA)SNHG16 regulating PAR1 on the proliferation,migration and invasion of lung cancer.Methods From March 2020 to August 2021,lung cancer tissues and adjacent tissues of 35 patients with lung cancer were col-lected,and lung cancer cell lines(HCC827,A549,SK-LU-1,A427)and normal lung cell lines(MRC5)were simultaneously cultured.The overexpression model of PAR1(pcDNA-PAR1)was constructed by using the expression vector pcDNA3.1.A549 cells were divided into four groups after transfection:si-SNHG16,si-PAR1,si-SNHG16+pcDNA-PAR1 and control(transfection with si-NC).The expression levels of lncRNA SNHG16 and PAR1 in lung cancer cell lines(HCC827,A549,SK-LU-1,A427),lung cancer tissues and adja-cent tissues were detected by real-time fluorescence quantitative reverse transcription-polymerase chain reac-tion(qRT-PCR),and the transfection efficiency of each group was verified.MTT assay and clonal formation were used to determine the proliferation of cells in each group,flow cytometry was used to detect the apopto-sis of cells in each group,cell scratch and Transwell test were used to detect the migration and invasion ability of cells in each group,and Western blot was used to detect the protein expression of PAR1.Results The ex-pression level of lncRNA SNHG16 in lung cancer tissue was higher than that in adjacent tissues(P＜0.05).The expression level of lncRNA SNHG16 in lung cancer cell lines(HCC827,A549,SK-LU-1,A427)was higher than that in normal lung cell lines(MRC5),with statistical significance(P＜0.05).The results of qRT-PCR showed that the expression level of lncRNA SNHG16 gene was(21.02±0.04)％of the control af-ter transfection of si-SNHG16,the expression level of PAR1 gene was(19.06±0.02)％of the control after transfection of si-PAR1,and the expression level of PAR1 gene was 2.70±0.00 folds of the control after transfection of pcDNA-PAR 1,the difference was statistically significant(P＜0.05).The results of Western blot showed that the expression level of transfected in each PAR1 protein was different from that of the con-trol(P＜0.05).Compared with the control,the activity of cells transfected with si-SNHG16 was lower,the a-bility of clone formation,cell migration and invasion was obviously inhibited,and the apoptosis rate was higher(P＜0.05),while pcDNA-PAR1 could weaken the influence of transfected si-SNHG16 on cell proliferation,apoptosis,migration and invasion(P＜0.05).lncRNA SNHG16 was positively correlated with the expression level of PAR1(r=0.61).Conclusion lncRNA SNHG16 can regulate the occurrence and development of lung cancer by targeting PAR1.

In order to establish the isolation,culture and identification method of cow bone marrow-derived macrophages,three different media(RPMI-1640,DMEM,DMEM/F12)were added with 20％fetal bovine serum(FBS),2.4％chlorine-streptomycin,1.2％glutamine(Gln),and M-CSF(20 ng/mL),respectively,to induce the monocytes extracted from the bone marrow of dairy cows to become macrophages.The induced M0 macrophages were polarized into M1-type macrophages by adding lipopolysaccharide(LPS).The morphology of macrophages was observed by optical mi-croscope at day 1,4 and 7,and the differences of differentiated macrophages between the three media were compared.The effects of prostaglandin D2(PGD2)-DP2 receptor pathway on the secre-tion of cytokines(IL-6,TNF-α)induced by Escherichia coli and phagocytosis of macrophages were also investigated.The results showed that the morphological changes of cells cultured in the medium of RPMI-1640 were the most obvious and the number was large.A large number of char-acteristic markers of mononuclear macrophages were detected(M0 markers:CD1 1b,CD14;M1 markers:CD11b,CD80)expression,M0 and M1 macrophage purity were 79.9％and 93.5％,re-spectively.COX-2 and H-PGDS gene expressions were significantly increased in E.coli group com-pared with the blank control group.The secretion of PGD2also increased significantly(P＜0.000 1).DP2 receptor inhibitors(CAY10471,CAY10595)could significantly inhibit the secretion of E.coli in-duced pro-inflammatory cytokines(IL-6,TNF-α)and significantly enhance the killing effect of macrophages on E.coli.The above results showed that the induced cells had the characteristic mor-phology and immunophenotype of macrophages.E.coli can induce the production of PGD2 in mac-rophages,and the PGD2-DP2 pathway regulates the secretion of cytokines in E.coli infected macro-phages.