Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

Objective To quantitatively evaluate structural changes in the TMD disc using magnetic resonance T2 mapping technology at open and closed mouth positions,and assess its significance.Methods 127 newly diagnosed patients with TMD and 51 controls in the Department of Oral and Maxillofacial Surgery of the Affiliated Hospital of Yunnan University from June 2023 to January 2024 were prospectively collected.All subjects underwent routine TMJ sequence and T2 mapping sequence scans.After scanning,the pseudo-color images were processed,and T2 values of the joint disc(anterior and posterior bands)were measured at open and closed mouth positions to analyze their correlation with TMD disc displacement.Results The T2 values of the posterior zone of the joint disc in both open and closed positions were higher than those in the anterior zone of the joint disc in the case group(P<0.05);for different anterior displacement degrees of the joint disc,T2 values showed a progressive increase from the normal position group to the mild and moderate anterior displacement groups,while the severely displaced group demonstrated a decreasing trend(P<0.01);joint clicking and occlusal abnormalities were independent risk factors for non-reducible anterior joint disc displacement in TMD patients.Conclusion Scans during both mouth-opening and closing positions can be used to assess joint disc injury in TMD;T2 mapping technology can quantitatively and sensitively reflect changes in the biochemical composition of joint disc microstructure.

Objective Analysing the risk factors for the occurrence of pre-frailty or frailty of the community elderly in Chengdu and constructing a risk prediction model.Methods The general information questionnaire,MNA-SF scale,Changsha version of the MoCA scale,PSQI scale,FRAIL scale,and Traditional Chinese Medicine Constitution Scale for the elderly were used in the cross-sectional survey.A total of 400 elderly people who completed community physical examinations in Chengdu from April 2022 to April 2023 were selected as the research objects.Based on multivariate Logistic regression analysis,the independent influencing factors were determined,and RStudio software was used to construct a risk prediction model nomogram.The physical examination data of 200 elderly people collected in Deyang City from June 2023 to October 2023 were used for external verification.The area under the ROC curve,Hosmer-Lemeshow test and calibration curve,and decision curve were used to evaluate the discrimination,calibration,and clinical practicability of the model.Results Age,abdominal circumference,number of chronic diseases,PSQI score,allergy history,and balanced constitution were independent influencing factors for pre-frailty/frailty in the elderly in the community(P<0.05),and the regression equation was as follows:Logit(P)=0.063×age+0.025×abdominal circumference-1.006×allergy history+0.300×number of chronic diseases+0.082×PSQI-1.013×balanced constitution-8.269.The area under the ROC curve of the modeling group was 0.779(95%CI:0.733-0.825),the sensitivity was 67.1%,the specificity was 76.3%,and the maximum Youden index was 0.434.The area under the ROC curve of the external validation group was 0.783(95%CI:0.709-0.856),the sensitivity was 62.0%,the specificity was 95.0%,and the maximum Youden index was 0.570.The Hosmer-Lemeshow goodness of fit test results of the two groups were χ2=3.285,P=0.915 and χ2=8.376,P=0.398,and the calibration curve fit was good.DCA showed that the threshold probability of clinical benefit was 5%-99%and 21%-98%.Conclusions The pre-frailty/frailty risk prediction model established in this study has good predictive efficacy for the elderly in the community,and the use of this model for screening and early intervention of high-risk populations can be clinically beneficial.

Objective To analyze the research status,hot directions and frontier trends of traditional Chinese medicine in the prevention and treatment of diseases by regulating Notch signaling pathway based on bibliometrics.Methods Based on Citespace and Vosviewer,the literature on the regulation of Notch signaling pathway by traditional Chinese medicine in CNKI and WoSCC was visually analyzed.Results 362 and 85 related literatures were published in Chinese and English respectively until January 2024.Since 2013,the number of literatures published in this field has shown a fluctuating increasing trend.China is the country with the most publications;Hunan University of Chinese Medicine were the institutions with the most publications in the Chinese database,and Beijing University of Chinese Medicine was the institution with the most publications in the English literature database.Combined with the research direction of each research team and keyword clustering and burst analysis,the research hotspots of traditional Chinese medicine regulating Notch signaling pathway are focused on cerebral ischemia,myelosuppression and hepatic fibrosis.Diseases such as Asthma,colorectal cancer have become emerging research directions in recent years.Electroacupuncture therapy to promote stem cell proliferation and treat neurological diseases is one of the frontier research trends in this field.Conclusion Recent years have seen a rapid development of traditional Chinese medicine's disease prevention and treatment that targets Notch signaling pathway.Various expert teams have obtained rich research results,and the research hotspots show a diversified trend.In-depth exploration of this can provide strong evidence for the molecular mechanism of traditional Chinese medicine in the treatment of various diseases.

Objective To use multiple model integration to predict the potential distribution of suitable areas for Hedysari Radix in China and the main environmental factors affecting its distribution.Methods Based on 119 geographical distribution points obtained from species distribution databases,and incorporating 19 bioclimatic and topographic factors,a species distribution model was constructed using the Biomod2 software package 3.5-1 version ensemble modeling platform,integrating six algorithms including generalized linear model,gradient boosting machine,random forest,and others.Geographic information system spatial analysis methods were used to quantitatively assess the distribution characteristics of suitable habitats of Hedysari Radix under current climate conditions and under future climate scenarios,while identifying the primary environmental drivers of its distribution.Results The ensemble model showed significantly superior predictive performance.TSS value and AUC value were 0.924 and 0.992,respectively.Key environmental factors significantly influencing the distribution of Hedysari Radix included slope,aspect,daily average temperature difference,isothermity,seasonal variation coefficient of temperature,lowest temperature in the coldest month,annual precipitation,driest month precipitation,and seasonal variation coefficient of precipitation.Under current climate conditions,suitable habitats for Hedysari Radix were primarily concentrated in the regions of Longnan and Dingxi in Gansu Province,covering an area of approximately 26.17×104 km2.Under future climate scenarios,suitable habitats will gradually shift toward the northwest into lower temperature zones,with a significant reduction in area.Conclusion The habitat suitability model developed in this study provides a basis for the conservation and sustainable utilization of Hedysari Radix genetic resources,while also offering a methodological reference for ecological adaptability studies of medicinal plants.

AIM:To investigate the modulatory effects of electroacupuncture(EA)on spinal cord neurons au-tophagy in rats with bone cancer pain.METHODS:(1)Verification of autophagy-related protein expression at different time points in a bone cancer pain model:a total of 56 female Sprague-Dawley(SD)rats were randomly divided into a sham-operated(sham)group and a model group.The model group was further subdivided into 6 subgroups corresponding to time points of 3,6,9,12,15,and 18 d,with 8 rats per subgroup.Thermal and mechanical pain thresholds,tibial bone destruction,and spinal neuron marker neuronal nuclear antigen(NeuN)co-localized with LC3B,Beclin1,and P62 were examined in rats at each designated time point.(2)Changes in spinal autophagy proteins following EA intervention:an additional 40 rats were randomly assigned to sham group,model group,EA group,sham EA(SEA)group,and autoph-agy agonist rapamycin(Rap)group,with 8 animals per group.EA was administered to the rats in EA group beginning on day 6 after modeling,the rats in SEA group received needle insertion without electrical stimulation,while those in Rap group received intraperitoneal injections of rapamycin(5 mg/kg).Thermal pain thresholds were assessed at designated in-tervals,followed by mechanical pain threshold assessments conducted on the subsequent day.Treatment continued until day 21,with rapamycin administered at the end of each intervention day.Tibial bone destruction was evaluated using he-matoxylin-eosin(HE)staining.Expression levels of LC3B Ⅱ/LC3B I,Beclin1,and P62 proteins in the spinal cord were determined by Western blot and immunohistochemistry.RESULTS:(1)Compared with the Sham group,thermal and mechanical pain thresholds were significantly decreased in the model group starting from day 6(P<0.01).Rat tibial bones exhibited notable damage,with severity progressively increasing over time.Protein expression levels of LC3B Ⅱ/LC3B I,Beclin1,and P62 were significantly elevated in the spinal cord at various time points(P<0.01),and these pro-teins were co-localized with spinal cord neurons.(2)Compared with the model group,mechanical and thermal pain thresholds in the EA and Rap groups gradually increased,with statistically significant differences observed from days 8 and 6 onward,respectively(P<0.01).In addition,LC3B Ⅱ/LC3B I and Beclin1 protein expression levels were signifi-cantly upregulated(P<0.01),whereas P62 expression was markedly downregulated(P<0.01).Immunohistochemical analysis demonstrated significantly enhanced positive staining for LC3B Ⅱ/LC3B I and Beclin1 and significantly decreased positive staining for P62 in the spinal cord of rats in the EA and Rap groups(P<0.05).Notably,no significant differences were observed in the SEA group(P>0.05).CONCLUSION:EA promotes spinal cord neurons autophagy in rats with bone cancer pain.The enhancement of autophagy may represent a potential mechanism underlying the analgesic effect of EA in bone cancer pain.

Objective:To explore the clinical efficacy of immediately adding mifepristone tablets after medical abortion in improving the complete abortion rate.Methods:This study was a randomized controlled trial. A total of 300 patients with medical abortion in Family Planning Center of Hangzhou Women's Hospital from January 2022 to December 2023 were randomly divided into high-dose group, low-dose group and control group by the digital table method, with 100 cases in each group. The low-dose group was given mifepristone tablets 25 mg bid×5 d immediately after medical abortion; the high-dose group was given mifepristone tablets 50 mg bid×5 d immediately after medical abortion; the control did not use mifepristone after medical abortion. The complete abortion rate, the duration of vaginal bleeding, the amount of vaginal bleeding and the incidence of adverse events such as complications were compared among the three groups.Results:For the three indicators of complete abortion rate, duration of vaginal bleeding and the proportion of vaginal bleeding volume exceeding the individual's customary menstrual flow, they were 92.0% (92/100), (9.0±2.8) d and 0% respectively in the low-dose group, 89.0% (89/100), (10.8±3.0) d and 0% respectively in the high-dose group, and 67.0% (67/100), (16.5±2.6) d and 11.0% (11/100) respectively in the control. The complete abortion rate in the high-dose group and low-dose group was significantly higher than that in the control (all P<0.001), while the duration and the proportion of vaginal bleeding volume exceeding the individual's customary menstrual flow were significantly lower than those in the control (all P<0.001), and the differences were statistically significant. The incidence of complications and the occurrence level of other adverse events were similar between the high-dose and low-dose groups and the control, and the differences were not statistically significant (all P>0.05). Conclusion:Immediately giving mifepristone tablets after medical abortion can effectively improve the complete abortion rate, significantly reduce the amount and duration of vaginal bleeding in patients, and the security of the medication is good.

BACKGROUND:Mongolian medicine Echinops sphaerocephalus L.is a commonly used medicine for bone injury in Mongolian medicine.It is effective for tendon injury,fracture,bone nonunion,bone fever,tingling,sore and other diseases.Our previous studies have confirmed that Mongolian medicine Echinops sphaerocephalus L.can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,but its effect on angiogenesis in the process of bone defect repair is unknown.OBJECTIVE:To investigate the effect of Echinops sphaerocephalus L.on in vitro angiogenesis in human umbilical vein vascular endothelial cells and to explore the angiogenesis-promoting active ingredients and their mechanisms of action of Echinops sphaerocephalus L.using network pharmacology technology.METHODS:The ethanol extract of Echinops sphaerocephalus L.was prepared and preserved by freeze-drying.The proliferation,migration,chemotaxis and angiogenesis of human umbilical vein endothelial cells were observed after treatment with different concentrations(1 000,100,and 10 μg/mL)of Echinops sphaerocephalus L.The active components and possible signaling pathways that promoted angiogenesis were enriched and analyzed by network pharmacology.RESULTS AND CONCLUSION:(1)The effect of Echinops sphaerocephalus L.on angiogenesis was regulated by its mass concentration:at low mass concentration(10 μg/mL),Echinops sphaerocephalus L.could promote the proliferation,migration,chemotaxis and angiogenesis of human umbilical vein vascular endothelial cells;on the contrary,Echinops sphaerocephalus L.inhibited the proliferation,migration,and chemotaxis of human umbilical vein endothelial cells at high mass concentration(1 000 μg/mL).However,the inhibitory effect of Echinops sphaerocephalus L.on angiogenesis was not significant at high mass concentration due to the limitation of experimental time.10 μg/mL Echinops sphaerocephalus L.could up-regulate the mRNA expression of angiogenesis-associated factors,including kinase insert domain receptor,vascular endothelial growth factor A,and hypoxia-inducible factor α,and thereby influenced angiogenesis during bone repair.(2)Network pharmacological analyses indicated that Echinops sphaerocephalus L.may bind to eight core targets(TGFB1,TNF,IL-6,STAT3,CTNNB1,IL-1B,AKT1,and HIF-1A)through four core active components(apigenin,caffeic acid,quercetin,and chlorogenic acid)to exert an effect on angiogenesis,atherosclerosis,multiple viral infections,and tumor angiogenesis-related signaling pathways.

Objective To identify key patterns of programmed cell death(PCD)and core genes during ischemia-reperfusion injury(IRI)in kidney transplantation.Methods Kidney transplant datasets were obtained from gene expression database,and PCD-related differentially expressed genes were screened.The non-negative matrix factorization algorithm was used to classify patients and analyze subtype-specific biological functions and key PCD patterns.Machine learning models combined with univariate Cox regression and Kaplan-Meier survival analysis were employed to identify core PCD genes during IRI in kidney transplantation and explore their correlation with key PCD patterns.A rat kidney transplant model was used to assess IRI severity through hematoxylin-eosin staining,serum creatinine(Scr),blood urea nitrogen(BUN),and Western blotting for key gene protein expression.Results Fourteen PCD-related genes were identified.Patients were classified into metabolic(subtype 1)and inflammatory(subtype 2)subtypes.Subtype 2 activated four key PCD patterns:pyroptosis,necroptosis,apoptosis and immunogenic cell death.The optimal model(XGBoost-CV:10 fold+Lasso-CV:10 fold)and survival analysis identified MCL1,BAG3,and RHOB as core PCD genes during IRI in kidney transplantation,which were broadly correlated with key PCD patterns.Experimental results showed that compared to the sham group,rats in the model group had more severe tubular injury,higher Scr and BUN levels,and increased BAG3,RHOB and MCL1 protein expression(all P<0.001).Conclusions These four PCD patterns are crucial in the pathogenesis of IRI in kidney transplantation.MCL1,BAG3 and RHOB may serve as potential biomarkers and therapeutic targets for IRI in kidney transplantation.

AIM:To investigate the modulatory effects of electroacupuncture(EA)on spinal cord neurons au-tophagy in rats with bone cancer pain.METHODS:(1)Verification of autophagy-related protein expression at different time points in a bone cancer pain model:a total of 56 female Sprague-Dawley(SD)rats were randomly divided into a sham-operated(sham)group and a model group.The model group was further subdivided into 6 subgroups corresponding to time points of 3,6,9,12,15,and 18 d,with 8 rats per subgroup.Thermal and mechanical pain thresholds,tibial bone destruction,and spinal neuron marker neuronal nuclear antigen(NeuN)co-localized with LC3B,Beclin1,and P62 were examined in rats at each designated time point.(2)Changes in spinal autophagy proteins following EA intervention:an additional 40 rats were randomly assigned to sham group,model group,EA group,sham EA(SEA)group,and autoph-agy agonist rapamycin(Rap)group,with 8 animals per group.EA was administered to the rats in EA group beginning on day 6 after modeling,the rats in SEA group received needle insertion without electrical stimulation,while those in Rap group received intraperitoneal injections of rapamycin(5 mg/kg).Thermal pain thresholds were assessed at designated in-tervals,followed by mechanical pain threshold assessments conducted on the subsequent day.Treatment continued until day 21,with rapamycin administered at the end of each intervention day.Tibial bone destruction was evaluated using he-matoxylin-eosin(HE)staining.Expression levels of LC3B Ⅱ/LC3B I,Beclin1,and P62 proteins in the spinal cord were determined by Western blot and immunohistochemistry.RESULTS:(1)Compared with the Sham group,thermal and mechanical pain thresholds were significantly decreased in the model group starting from day 6(P<0.01).Rat tibial bones exhibited notable damage,with severity progressively increasing over time.Protein expression levels of LC3B Ⅱ/LC3B I,Beclin1,and P62 were significantly elevated in the spinal cord at various time points(P<0.01),and these pro-teins were co-localized with spinal cord neurons.(2)Compared with the model group,mechanical and thermal pain thresholds in the EA and Rap groups gradually increased,with statistically significant differences observed from days 8 and 6 onward,respectively(P<0.01).In addition,LC3B Ⅱ/LC3B I and Beclin1 protein expression levels were signifi-cantly upregulated(P<0.01),whereas P62 expression was markedly downregulated(P<0.01).Immunohistochemical analysis demonstrated significantly enhanced positive staining for LC3B Ⅱ/LC3B I and Beclin1 and significantly decreased positive staining for P62 in the spinal cord of rats in the EA and Rap groups(P<0.05).Notably,no significant differences were observed in the SEA group(P>0.05).CONCLUSION:EA promotes spinal cord neurons autophagy in rats with bone cancer pain.The enhancement of autophagy may represent a potential mechanism underlying the analgesic effect of EA in bone cancer pain.