ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

Traditional Chinese medicine （TCM） pharmacology （PTCM） is a discipline that studies the interactions between Chinese medicines and the human body， as well as their underlying mechanisms， under the guidance of TCM theories while employing modern scientific techniques and methods. This article reviews the historical development and achievements of the PTCM discipline at the Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences， and outlines the reform measures undertaken in recent years to advance the construction of the graduate course system in PTCM. Building upon the foundation of the "Special Topics in PTCM" course， the curriculum has been expanded through reforms to include a series of self-designed courses， such as foundational advanced courses， experimental pharmacology courses， pharmacological research tools courses， and applied TCM research courses. Along with enriching the graduate course system， the study explores innovative approaches and methods for graduate education and teaching in PTCM， and reflects on the challenges in course system construction and teaching， serving as a reference for improving the quality of graduate training， promoting the development of the PTCM discipline， and advancing teaching reform practices.

Objective To identify the N6-methyladenosine (m6A)-related characteristic genes analyzed by gene clustering and immune cell infiltration in myocardial ischemia-reperfusion injury (MI/RI) after cardiopulmonary bypass through machine learning. Methods The differential genes associated with m6A methylation were screened by the dataset GSE132176 in GEO, the samples of the dataset were clustered based on the differential gene expression profile, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differential genes of the m6A cluster after clustering were performed to determine the gene function of the m6A cluster. R software was used to determine the better models in machine learning of support vector machine (SVM) model and random forest (RF) model, which were used to screen m6A-related characteristic genes in MI/RI, and construct characteristic gene nomogram to predict the incidence of disease. R software was used to analyze the correlation between characteristic genes and immune cells, and the online website was used to build a characteristic gene regulatory network. Results In this dataset, a total of 5 m6A-related differential genes were screened, and the gene expression profiles were divided into two clusters for cluster analysis. The enrichment analysis of m6A clusters showed that these genes were mainly involved in regulating monocytes differentiation, response to lipopolysaccharides, response to bacteria-derived molecules, cellular response to decreased oxygen levels, DNA transcription factor binding, DNA-binding transcription activator activity, RNA polymerase Ⅱ specificity, NOD-like receptor signaling pathway, fluid shear stress and atherosclerosis, tumor necrosis factor signaling pathway, interleukin-17 signaling pathway. The RF model was determined by R software as the better model, which determined that METTL3, YTHDF1, RBM15B and METTL14 were characteristic genes of MI/RI, and mast cells, type 1 helper lymphocytes (Th1), type 17 helper lymphocytes (Th17), and macrophages were found to be associated with MI/RI after cardiopulmonary bypass in immune cell infiltration. Conclusion The four characteristic genes METTL3, YTHDF1, RBM15B and METTL14 are obtained by machine learning, while cluster analysis and immune cell infiltration analysis can better reveal the pathophysiological process of MI/RI.

ObjectiveTo identify the chemical constituents of Ruyi Zhenbaowan in vitro and in vivo. MethodThe chemical constituents of Ruyi Zhenbaowan were identified based on UHPLC-Q Exactive Orbitrap HRMS. A total of 12 male SD rats were randomized into two groups： control （pure water） and Ruyi Zhenbaowan （1.8 g·kg^-1）. The rats were administrated with the suspension of Ruyi Zhenbaowan or pure water by gavage. After 1.5 h， the plasma and cerebrospinal fluid were collected. Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C₁₈ column （2.1 mm × 150 mm， 1.7 μm） with a mixture of 0.1% formic acid aqueous solution （A） and acetonitrile （B） as the mobile phase. Gradient elution was carried out according to the procedure of 0~15 min，97%~80%A；15~30 min ，80%~60%A；30~40 min，60%~30%A；40~45 min，30%~5%A. The ion source was electrospray ionization， and scan range was m/z 100-1 500. The prototype components and the components in the plasma and cerebrospinal fluid were analyzed qualitatively by scanning in positive and negative ion modes and identified by comparison with the data in published literature and the information of standard substances. ResultA total of 126 chemical constituents were identified from the 80% methanol solution of Ruyi Zhenbaowan， and 14 and 7 prototype constituents were detected in the plasma and the cerebrospinal fluid， respectively. In addition， the fragmentation rules of apigenin， apigenin-7-O-glucuronide， galangin， liquiritin， piperine， glycyrrhizic acid， eugenol， gallic acid， and cholic acid were deduced. ConclusionThis study achieved rapid multicomponent characterization and identification of Ruyi Zhenbaowan in vitro and in vivo， providing theoretical support for exploring active substances and performing quality control.l.

Objective To explore the effect of a phased rehabilitation training programme to relieve shoulder dys-function in patients after neck dissection and to provide effective solutions for postoperative shoulder joint function recov-ery of patients.Methods This study has been reviewed and approved by the Ethics Committee,and informed consent has been obtained from patients.A phased rehabilitaiton training programme for the shoulder after neck dessection was developed through literature review and discussion,and 70 eligible patients from Hospital of Stomatology,Sun Yat-sen University from December 2020 to April 2021 were selected and randomly divided into the test group and control group(35 patients in each group).The control group underwent motor rehabilitation training from 6 weeks postoperative to 1 year after surgery,such as shoulder mobility and coordination training and small range of motion training of the neck,while the test group took part in a rehabilitation training program that included familiarization maneuver training,protective rehabilitation,exercise rehabilitation,and resistance training in the following four stages:preoperative,postop-erative general anesthesia and awake until the removal of stitches,the removal of stitches until 6 weeks after surgery,and 6 weeks after surgery until 1 year after surgery.The frequency of training in both groups was at least 3 days per week,and the length of each training session was 10-15 min.The intensity of exercise was 2-3 points on the Borg Conscious Ex-ercise Intensity Scale(i.e.,mild-to-moderate tachypnea or fatigue).The neck dissection injury index(NDII)was used to evaluate the quality of life related to shoulder joint function at four time points:preoperative,postoperative 3 months,postoperative 6 months,and postoperative 12 months.The higher the score,the better the quality of life.Results 28 cases in the test group and 32 cases in the control group completed a one-year follow-up.At 3 and 6 months postopera-tive,the NDII of the test group was significantly higher than that of the control group[3 months postoperative:test group(93.48±9.36)vs.control group(80.00±11.34)(P＜0.001),6 months postoperative:test group(98.21±4.76)vs.control group(90.70±9.12)(P＜0.001)];12 months after surgery,the NDII of the test group(97.23±4.88)was still higher than that of the control group(96.33±4.49),but the difference was not statistically significant(P=0.458).The difference in NDII scores among subjects at 3,6,and 12 months after surgery was statistically significant in each group(P＜0.001).Conclusion The application of the phased rehabilitation training method in neck dissection patients has a feasibility and could improve the quality of life of patients'shoulder joint function within 6 months after surgery.

This paper reviewed the concept of organizational silence, elaborated on the content, evaluation methods, reliability, validity, characteristics, and other aspects of nurse organizational silence assessment tools, and compares the basic characteristics, content, and application of each tool. The aim was to provide reference for selection of appropriate assessment tools to identify nurse organizational silence, as well as for the development of comprehensive assessment tools and the early formulation of management strategies.

Objective:To understand the current situation of psychological crisis vulnerability among elderly individuals with multimorbidity and analyze the factors that influence it, to provide insights for improving their coping abilities.Methods:A cross-sectional survey design was conducted at Renmin Hospital of Wuhan University from May 1 to November 30, 2022.The attitudes toward aging, sense of meaning of life, and vulnerability to psychological crisis were analysed among outpatients and inpatients.Statistical analysis was performed on the questionnaire results, and the influencing factors of vulnerability to psychological crisis in elderly patients with co-morbidities were analyzed using one-way linear regression and multivariate linear regression.Additionally, the correlation between aging attitudes, sense of meaning of life, and vulnerability to psychological crisis was examined using Pearson correlation analysis.Results:A total of 685 questionnaires were distributed, and 602 valid questionnaires were collected, resulting in a valid recovery rate of 87.9%.The total score for the sense of meaning of life in elderly co-morbid patients was(39.2±8.3), while the total score for aging attitudes was(80.2±13.5).The total score for psychological crisis vulnerability was(69.4±12.8), indicating a medium-high level of vulnerability.The results of multiple linear regression analysis revealed that the factors influencing psychological crisis vulnerability in elderly multimorbidity, in descending order, were residence status, economic situation, marital status, age, type of chronic disease, and hospitalization history in the past six months.Psychological crisis vulnerability in elderly multimorbidity showed a negative correlation with the sense of meaning of life and the attitude of aging( r=-0.315, -0.264, both P<0.01), while the attitude of aging exhibited a positive correlation with the sense of meaning of life( r=0.515, P<0.01). Conclusions:The vulnerability of elderly individuals with multimorbidity to psychological crises is influenced by several factors.Healthcare professionals should prioritize individuals who are elderly, residing in nursing institutions, widowed, financially disadvantaged, experiencing multiple illnesses, and not currently hospitalized.

ObjectiveTo systematically evaluate the safety of Chinese medicines combined with Tripterygium wilfordii polyglycoside tablets/Tripterygium wilfordii tablets （TWPT/TWT） in the treatment of rheumatoid arthritis （RA）， and to explore the network regulatory mechanisms of enhancing efficacy and reducing toxicity of commonly used combination regimes. MethodThe literature involving the adverse reactions of TWPT/TWT in treating RA was searched and collected from three Chinese databases （CNKI， Wanfang Data， VIP） and three English databases （PubMed， Cochrane Library， Embase） from the inception of the databases to July 2021. All studies were assessed by the Cochrane risk of bias tool， and the data were extracted and analyzed by Stata 15.0. Furthermore， Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine 2.0 （TCMIP v2.0，http：//www.tcmip.cn/） was used to construct a "drug target-symptom gene of efficacy and toxicity" interaction network， to explore the underlying network regulatory mechanisms of enhancing efficacy and reducing toxicity of common T. wilfordii preparation combinations. ResultA total of 2 132 articles on Chinese medicines combined with TWPT/TWT in the treatment of RA were retrieved， and 18 of them were finally included. The systematic review showed that the adverse reactions of TWPT/TWT against RA mainly occurred in the digestive system， blood system， and reproductive system， of which digestive system had the highest incidence of damages. However， the combination with Chinese medicines effectively alleviated the adverse reactions caused by TWPT/TWT ［RR （95% CI）=0.45 （0.30， 0.66）， P<0.01］. In addition， the subgroup analysis indicated that the age of RA patients， course of disease， combination regimen， medication dosage and duration of treatment all affected the occurrence of adverse reactions of TWPT/TWT. It was found in clinical studies that total glucosides of paeony （TGP） and TWPT/TWT was most widely combined， and the effect of TGP in reducing TWPT/TWT-induced hepatotoxicity was also more significant than that of other Chinese medicines. Moreover， taking this combination regime as an example， this paper explored the "efficacy-toxicity" association mechanisms of TGP-TWPT/TWT against RA. The "drug target-symptom gene of efficacy and toxicity" interaction network revealed that the core network targets of TGP-TWPT/TWT enhanced efficacy and reduced toxicity mainly through regulating immunity-inflammation-related pathways， metabolic pathways and cell signal transduction. Especially， interleukin-4 （IL-4） and interleukin-13 （IL-13）， which were involved in the "immunity-inflammation" module， were the common targets of TGP-TWPT/TWT to enhance efficacy and reduce toxicity. The endogenous sterols， bile acids and bile salts， insulin secretion and other metabolic pathways in the "body metabolism" module were closely associated with the mechanisms of TWPT/TWT inducing hepatotoxicity and TGP reducing hepatotoxicity. While cell function regulation pathways， such as stem cell factor （SCF）/tyrosine kinase receptor （KIT） signaling pathway and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）signaling pathway were involved in both anti-RA effects and hepatotoxicity of TWPT/TWT. ConclusionClinical application of suitable Chinese medicines combined with TWPT/TWT in the treatment of RA can effectively improve the rheumatism and reduce the adverse reactions of TWPT/TWT， and TGP-TWPT/TWT has the most significant toxicity-reducing effect. Further biological network-based investigation indicates that the toxicity-reducing mechanism of TGP-TWPT/TWT may be related to the regulation of interleukin signaling pathway and bile acid metabolism pathway， and the synergistic efficacy-enhancing effect of the combination may be achieved by acting on interleukin signaling pathway and cell function regulation pathway.

ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets （TWPT） by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis （RA） and TWPT-induced liver injury. MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts， the "efficacy-toxicity" association network of TWPT was constructed， and the key network targets were identified by calculating the topological values of the nodes， including the degree， closeness and betweenness. After that， the biological functions and pathways of the key network targets were investigated by enrichment analysis. ResultA total of 119 differentially expressed genes （58 up-regulated and 61 down-regulated） between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics， and 49 differentially expressed proteins （36 up-regulated and 13 down-regulated） were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition， the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine， and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore， the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically， the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance， especially playing an important role in neutrophil degranulation， complement cascade reaction， and immune-inflammatory response mediated by protein post-translational modification. Notably， the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation， such as RAS and mitogen-activated protein kinase （MAPK） signaling pathway， and in several liver functional processes， such as glycogen metabolism and redox reaction. ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics， transcriptomics and proteomics， laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.