ObjectiveTo investigate the material basis of the pathogenesis of cerebral ischemic injury with blood stasis and toxin syndrome and to explore the protective effects of Huayu Jiedu prescription （HYJDP） on neutrophil extracellular trap-related cell death （NETosis） in cerebral ischemic injury following acute cerebral infarction. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly divided into six groups （n=12 per group）： sham operation （Sham） group， blood stasis and toxin model （Model） group， low-， medium-， and high-dose HYJDP groups （HYJDP-L， HYJDP-M， and HYJDP-H； 9， 18， and 36 g·kg^-1， respectively）， and butylphthalide （NBP） group （0.06 g·kg^-1）. Except for the Sham group， rats in all other groups were subjected to carrageenan/dry yeast combined with a modified intraluminal filament method to establish a focal cerebral ischemia model of the middle cerebral artery with blood stasis and toxin syndrome. Neurological function was evaluated at 24 h after modeling using the Zea-Longa neurological deficit score. Cerebral infarction rate was assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Pathological morphology of brain tissue was observed using hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to determine serum levels of interleukin-8 （IL-8）， myeloperoxidase-DNA complexes （MPO-DNA）， and citrullinated histone H3 （CitH3）. Protein expression of phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （p-Akt）， mammalian target of rapamycin （p-mTOR）， sequestosome 1 （p62）， and CitH3 in brain tissue was detected by Western blot. Immunofluorescence （IF） was used to detect the expression of neutrophil-specific marker Ly6G， CitH3， and neuron-specific nuclear protein （NeuN） in brain tissue. ResultsCompared with the Sham group， neurological deficit scores and cerebral infarction rates in the model group were significantly increased （P<0.01 for both）. HE staining showed varying degrees of neuronal degeneration and necrosis， characterized by blurred neuronal structures， nuclear pyknosis and fragmentation， cytoplasmic dissolution into a vacuolated reticular pattern， and mild glial cell proliferation. ELISA results showed that serum levels of IL-8， MPO-DNA， and CitH3 were significantly increased （P<0.01）. Western blot analysis demonstrated decreased expression of p-PI3K， p-Akt， p-mTOR， and p62， while CitH3 expression was significantly increased （P<0.01）. IF results showed an increased number of NETs⁺ cells and a significant decrease in NeuN⁺ cells （P<0.01）. Compared with the Model group， neurological deficit scores in the HYJDP-H group were significantly decreased （P<0.05）， and cerebral infarction rates in the HYJDP-H and NBP groups were significantly reduced （P<0.01）. HE staining showed that brain tissue damage was markedly alleviated in the HYJDP-H group. ELISA results showed that levels of IL-8， MPO-DNA， and CitH3 were significantly decreased in the HYJDP-M， HYJDP-H， and NBP groups （P<0.01）. Western blot analysis showed that expression of p-PI3K， p-Akt， p-mTOR， and p62 was significantly increased in the HYJDP-H and NBP groups， while CitH3 expression was significantly reduced in all drug intervention groups （P<0.01）. IF results showed that the number of NETs⁺ cells was significantly decreased and the number of NeuN⁺ cells was significantly increased in all drug intervention groups （P<0.01）. ConclusionNETs may be the material basis of the pathogenesis of cerebral ischemic injury characterized by blood stasis and toxin. HYJDP can regulate the PI3K/Akt/mTOR signaling pathway， reduce the release of pro-inflammatory mediators and NETosis-related products， alleviate cerebral ischemic injury caused by autophagy-dependent NETosis， and thereby exert a neuroprotective effect.

Objective To analyze the effects of postoperative radiotherapy and other factors on the prognosis of metastatic sarcomatoid renal cell carcinoma(sRCC)so as to provide reference for the clinical decision-making.Methods Data of all sRCC patients during 2004-2018 were extracted from the American Surveillance,Epidemiology,and End Results(SEER)database,and 337 patients were ultimately enrolled.Patients were divided into the postoperative non-radiotheropy group(n=255)and postoperative radiotherapy group(n=82)based on different treatment modalities.Baseline data were compared between the two groups.The 1-year overall survival(OS)and cancer-specific survival(CSS)rates were calculated.Kaplan-Meier(K-M)survival curves were plotted.The prognostic factors were identified with univariate and multivariate Cox regression analyses.Results No significant differences were observed in baseline data between the two groups(P＞0.05).The 1-year OS(25.6％vs.30.1％)and CSS(26.2％vs.30.8％)in the postoperative radiotherapy group were lower than those in the postoperative no-radiotheropy group,but the differences were not statistically significant(P＞0.05).Multivariate Cox regression analysis showed that year of diagnosis,patients' age,tumor size,T stage,N stage and chemotherapy were independent prognostic factors of sRCC(P＜0.05).Patients diagnosed in 2015-2018 and treated with chemotherapy had a good prognosis,while patients＞61 years,with tumor size＞147 mm,tumor stage T3-T4,and stage N1 had a poor prognosis.Conclusion The year of diagnosis,patients'age,tumor size,tumor stage and chemotherapy were independent prognostic factors,and postoperative radiotherapy did not significantly improve the prognosis of metastatic sRCC patients.

BACKGROUND:Immune cells are correlated with various metabolic bone diseases,yet the specific immunological mechanisms and causal relationships remain elusive.OBJECTIVE:To investigate the causal relationship between immune cells and the risk of metabolic bone diseases through two-sample Mendelian randomization.METHODS:Genome-wide association study(GWAS)data on 731 immune cells and metabolic bone diseases(osteonecrosis,osteomalacia,osteoporosis,and osteoporosis combined with pathological fracture)were obtained from publicly available databases.Genetic variants related to immune cells were employed as instrumental variables.The inverse variance weighting method was utilized as the primary analytical approach,while MR-Egger and weighted median methods were applied to assess the causal relationships between immune cells and the risk of metabolic bone diseases.In addition,MR-PRESSO,MR-Egger regression,Cochran's Q test,and the leave-one-out method were implemented to evaluate genetic polymorphisms and the heterogeneity of instrumental variables,and MR Steiger method was used to exclude reverse causality.RESULTS AND CONCLUSION:(1)The analysis revealed that IgD-CD38dim％B cells,HLA DR on CD14+CD16-monocytes,and HLA DR on CD14+monocytes were significantly and causally associated with an increased risk of osteoporosis(P＜6.8x10-5).Sensitivity analyses confirmed the reliability and stability of these results.Furthermore,among the immune cell types studied,28 demonstrated potential causal associations with osteonecrosis,23 with osteomalacia,46 with osteoporosis,and 45 with the combined condition of osteoporosis and pathologic fracture(P＜0.05).(2)This study provides a comprehensive assessment of the causal influence of immune cells on metabolic bone diseases,highlighting the significant role of immune factors in the pathogenesis of these conditions,particularly osteoporosis.The findings contribute valuable insights into the relationship between immune traits and bone metabolism,laying a foundation for future research in this domain.This study utilized an international database to analyze the European population,which offers a reference for Chinese biomedical research in the realm of metabolic bone diseases,and facilitates the conduction of relevant studies for the Chinese population,thereby promoting the enhancement of the prevention and treatment of metabolic bone diseases.

ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

Objective To analyze the effects of postoperative radiotherapy and other factors on the prognosis of metastatic sarcomatoid renal cell carcinoma(sRCC)so as to provide reference for the clinical decision-making.Methods Data of all sRCC patients during 2004-2018 were extracted from the American Surveillance,Epidemiology,and End Results(SEER)database,and 337 patients were ultimately enrolled.Patients were divided into the postoperative non-radiotheropy group(n=255)and postoperative radiotherapy group(n=82)based on different treatment modalities.Baseline data were compared between the two groups.The 1-year overall survival(OS)and cancer-specific survival(CSS)rates were calculated.Kaplan-Meier(K-M)survival curves were plotted.The prognostic factors were identified with univariate and multivariate Cox regression analyses.Results No significant differences were observed in baseline data between the two groups(P＞0.05).The 1-year OS(25.6％vs.30.1％)and CSS(26.2％vs.30.8％)in the postoperative radiotherapy group were lower than those in the postoperative no-radiotheropy group,but the differences were not statistically significant(P＞0.05).Multivariate Cox regression analysis showed that year of diagnosis,patients' age,tumor size,T stage,N stage and chemotherapy were independent prognostic factors of sRCC(P＜0.05).Patients diagnosed in 2015-2018 and treated with chemotherapy had a good prognosis,while patients＞61 years,with tumor size＞147 mm,tumor stage T3-T4,and stage N1 had a poor prognosis.Conclusion The year of diagnosis,patients'age,tumor size,tumor stage and chemotherapy were independent prognostic factors,and postoperative radiotherapy did not significantly improve the prognosis of metastatic sRCC patients.

BACKGROUND:Immune cells are correlated with various metabolic bone diseases,yet the specific immunological mechanisms and causal relationships remain elusive.OBJECTIVE:To investigate the causal relationship between immune cells and the risk of metabolic bone diseases through two-sample Mendelian randomization.METHODS:Genome-wide association study(GWAS)data on 731 immune cells and metabolic bone diseases(osteonecrosis,osteomalacia,osteoporosis,and osteoporosis combined with pathological fracture)were obtained from publicly available databases.Genetic variants related to immune cells were employed as instrumental variables.The inverse variance weighting method was utilized as the primary analytical approach,while MR-Egger and weighted median methods were applied to assess the causal relationships between immune cells and the risk of metabolic bone diseases.In addition,MR-PRESSO,MR-Egger regression,Cochran's Q test,and the leave-one-out method were implemented to evaluate genetic polymorphisms and the heterogeneity of instrumental variables,and MR Steiger method was used to exclude reverse causality.RESULTS AND CONCLUSION:(1)The analysis revealed that IgD-CD38dim％B cells,HLA DR on CD14+CD16-monocytes,and HLA DR on CD14+monocytes were significantly and causally associated with an increased risk of osteoporosis(P＜6.8x10-5).Sensitivity analyses confirmed the reliability and stability of these results.Furthermore,among the immune cell types studied,28 demonstrated potential causal associations with osteonecrosis,23 with osteomalacia,46 with osteoporosis,and 45 with the combined condition of osteoporosis and pathologic fracture(P＜0.05).(2)This study provides a comprehensive assessment of the causal influence of immune cells on metabolic bone diseases,highlighting the significant role of immune factors in the pathogenesis of these conditions,particularly osteoporosis.The findings contribute valuable insights into the relationship between immune traits and bone metabolism,laying a foundation for future research in this domain.This study utilized an international database to analyze the European population,which offers a reference for Chinese biomedical research in the realm of metabolic bone diseases,and facilitates the conduction of relevant studies for the Chinese population,thereby promoting the enhancement of the prevention and treatment of metabolic bone diseases.

Objective To explore the research current situation of TCM regulation of mesenchymal stem cells through visualization analysis;To summarize the research direction and hotspots.Methods The research literature on TCM regulation of mesenchymal stem cells was retrieved from CNKI,VIP and Wanfang Data from 2003 to 2022.CiteSpace 6.1.R6 software was used to visually analyze the authors,institutions and keywords of the research literature,and clustering analysis and emergence analysis of keywords were carried out.CNKI database was used to make statistics on literature citations.Results A total of 2 404 articles were included in this study,and the research literature on TCM regulation of mesenchymal stem cells showed an overall increasing trend.The main research institutions were Guangzhou University of Chinese Medicine,Gansu University of Chinese Medicine and Liaoning University of Traditional Chinese Medicine,etc.The main authors were Liu Yongqi,Chen Dongfeng and Fan Yingchang,etc.The high-frequency keywords included osteogenic differentiation,proliferation,rat,osteoporosis and icariin.Conclusion The effects of TCM monomer and compounds on the proliferation and differentiation of stem cells is the hot research area in this field,and the osteogenic differentiation of mesenchymal stem cells is an important research trend at present.

Objective:To investigate the diagnosis of dual-energy X-ray absorptiometry(DXA)for osteoporosis(OP)of postmenopausal patients with rheumatoid arthritis(RA)in Qinghai region and the risk factors of them.Methods:A total of 200 postmenopausal female RA patients who admitted to Qinghai Hospital of Traditional Chinese Medicine from May 2022 to April 2023 were selected.All patients were tested for bone mineral density(BMD)after admission,and lumbar spines L1-L4,whole lumbar,large trochanter,Ward's triangle area,whole body and whole forearm were measured by DXA.According to the results of BMD test,patients whose BMD T values of all body parts-2.5 SD were less or equal to-2.5 were included in the OP group(121 cases),and patients whose BMD T value of all body parts were larger than-2.5 SD were included in the non-OP group(79 cases).The BMD T value of different body parts between two groups of RA patients were compared and analyzed.The area under curve(AUC)of receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficiency of BMD T value for OP.The logistic regression method was adopted to analyze the risk factors that postmenopausal RA patients of Qinghai region occurred OP.Results:The BMD T values of L1,L2,L3,L4,whole lumbar,large trochanter,Ward's triangular area,whole body and whole forearm of OP group were obviously lower than those of the non-OP group.In analysis of ROC curve,the sensitivities of BMD T values of L1,L2,L3,L4,whole lumbar,large trochanter,Ward's triangle area,whole body and forearm were respectively 96.20%,95.22%,90.16%,96.03%,92.01%,89.36%,99.26%,90.02% and 96.03% in diagnosing OP,and the specificities of them were respectively 81.00%,82.19%,85.22%,83.06%,83.06%,90.22%,80.06%,86.23%,83.09%,and the AUC values of them were respectively 0.908,0.905,0.896,0.906,0.903,0.879,0.918,0.901 and 0.906.The results of the logistic-regression analysis showed that advanced age,long disease course,rheumatic activity scores of 28 joints,erythrocyte sedimentation rate and Calcium supplementation were the risk factors of occurring OP in postmenopausal RA patients in Qinghai region.Conclusion:The DXA method that detects BMD of RA patients who occur OP can be used as gold standard to assess OP,and there are many risk factors that affect the occurrence of OP in postmenopausal RA patients of Qinghai region.The clinical work should combine with relative factors to formulate reasonable measure so as to reduce the incidence of OP.

BACKGROUND:Due to the very limited ability of articular cartilage to repair itself,articular cartilage defects caused by natural degeneration or trauma often cannot be repaired on their own,which triggers or aggravates osteoarthritis and even leads to severe disability.Therefore,the repair treatment after articular cartilage injury has become an urgent clinical problem. OBJECTIVE:To summarize the hot research topics and development trends in the field of articular cartilage repair using bibliometric analysis. METHODS:Literature related to articular cartilage repair was searched from the Web of Science Core Collection from 2000 to 2023,and bibliometric and visualization analyses were carried out using VOSviewer,Citespeace and Bibliometrix R-package. RESULTS AND CONCLUSION:The annual publication volume in the field of articular cartilage repair shows an overall increasing trend,with the United States,China,and Germany being the top three countries in terms of publication volume,and the research institutions focus on universities and hospitals,with Harvard University,New York Hospital for Special Surgery,and Shanghai Jiao Tong University being the top three institutions in terms of publication volume.AMERICAN JOURNAL OF SPORTS MEDICINE is the journal that publishes the most research literature in the field,and BIOMATERIALS is the journal with the highest number of citations in the field."Injectable hydrogels for cartilage and bone tissue engineering"is the most cited document published in the last decade,and the author with the most publications is Madry Henning,an active author in the field.The active authors in this field have formed a number of stable research teams with each other,and the cooperation between different teams needs to be further strengthened.Intra-articular injections,high tibial osteotomies,hydrogels,drug delivery,inflammation,cartilage regeneration,and scaffolds are the current hot topics of research in this field,and the application of 3D printing technology,bio-inks,silk proteins,injectable hydrogels,and exosomes in articular cartilage repair may be the frontier of research in this field.Integrating various innovative technologies and methods for more effective,durable and functional cartilage tissue regeneration and repair,and facilitating the clinical translation of the relevant technologies and methods by conducting more high-quality clinical studies may be the future research trend in this field.

With the acceleration of social rhythm， the progress of science and technology， and the increase of the number of phubbers， the incidence of cervical degenerative diseases is also increasing year by year. Cervical spondylotic radiculopathy（CSR）， as one of the diseases induced by cervical degeneration， has seriously affected people's quality of life and physical and mental health. Traditional Chinese medicine（TCM） is effective in the treatment of CSR， but the theoretical and basic experimental evidence is not sufficient， and the current formulation standard of animal model is not unified. Therefore， based on the clinical guidelines of Chinese and Western medicine for CSR and the characteristics of the disease and syndrome， the author systematically summarized and analyzed the existing animal models， and found that the existing models of microvascular clamp nerve root compression method had a poor agreement with the the Chinese and Western medical guidelines， while the modeling methods of spinal canal insertion， autologous bone insertion compression， stainless steel column compression， and fixed frame cervical degeneration reflected a high degree of agreement in the Western medical guidelines. However， the Chinese medical diagnostic criteria were poorly matched. This indicates that the existing animal models of this disease show few TCM syndrome elements， and lack information collection and evaluation in animal behavioral evaluation similar to the four diagnoses of TCM. In conclusion， this paper aims to systematically evaluate the current status of animal model establishment of CSR based on the concept of combination of disease and syndrome， so as to provide a theoretical basis for the model establishment of CSR that is more consistent with clinical characteristics and symptoms of Chinese and Western medicine.