Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Buyang Huanwu Decoction(BYHWD), as one of the classic formulas in traditional Chinese medicine(TCM) for the treatment of cerebral ischemic stroke(CIS), has demonstrated definite effects in clinical practice. However, the material basis and mechanism of treatment have not been systematically elucidated. This study employed network pharmacology and molecular docking to analyze the potential targets and mechanisms of blood-and brain-penetrating active components of BYHWD in reducing cell apoptosis in CIS. Cell experiments were then carried out to validate the prediction results. In the experiments, five active components including hydroxysafflor yellow A( HSYA), tetramethylpyrazine( TMP), astragaloside Ⅳ( AS-Ⅳ), amygdalin( AMY), and paeoniflorin(PF) were selected to explore the pharmacological effects of BYHWD. HT22 cells were treated with BYHWD, and the cell counting kit-8(CCK-8) method was employed to examine the toxic and side effects of BYHWD. A cell model of oxygen-glucose deprivation/reoxygenation( OGD/R) was constructed, with apoptosis and pyroptosis as the main screening indicators. The levels of lactate dehydrogenase(LDH) and glutathione(GSH) were measured to assess the cell membrane integrity. Flow cytometry was employed to detect apoptosis, and the activities of caspase-3 and caspase-1 were measured to clarify the status of apoptosis and pyroptosis. ELISA was employed to determine the levels of interleukin(IL)-1β and IL-18 to confirm pyroptosis. HSYA and AMY were identified in this study as the active components regulating apoptosis and pyroptosis. TUNEL was employed to detect the apoptosis rate, and Western blot was employed to determine the expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3, which confirmed that the anti-apoptotic effect of the combined component group was superior to that of the single component groups. The molecular docking results revealed strong binding affinity of HSYA and AMY with SDF-1α and CXCR4.AMD3100, a selective antagonist of CXCR4, was then used for intervention. The results of Western blot showed alterations in the expression levels of apoptosis-associated proteins, SDF-1α, and CXCR4. In conclusion, HSYA and AMY influence cellular apoptosis by modulating the SDF-1α/CXCR4 signaling cascade.
Drugs, Chinese Herbal/chemistry* ; Apoptosis/drug effects* ; Animals ; Neurons/cytology* ; Mice ; Molecular Docking Simulation ; Cell Line ; Glucose/metabolism* ; Humans ; Neuroprotective Agents/pharmacology*

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE T o explore the prevention and control measures for the hospital-acquired pulmonary mu-cormycosis caused by Cunninghamella bertholletiae.METHODS One case of patient with pulmonary mucormyco-sis caused by Cunninghamella bertholletiae who was treated in pediatric intensive care unit(PICU)of a three-A general hospital was enrolled in the study,the process of clinical diagnosis and treatment was summarized.A ret-rospective survey regarding four aspects including people,machine,materials and environment was conducted.The related factors leading to the hospital-acquired infections in the patient were analyzed.RESULTS The child was diagnosed with severe aplastic anemia and underwent hematopoietic stem cell transplantation,the child was treated with various invasive procedures during the treatment period and was infected with pulmona-ry mucormycosis caused by the rare Cunninghamella bertholletiae.The occurrence of the pulmonary mucormyco-sis was associated with the poor management of medical textile,insufficient environmental cleaning and disinfec-tion and nonstandard invasive procedures.CONCLUSIONS The Cunninghamella bertholletiae infection is less com-mon,but the risk of death is high.It is necessary for the medical institutions to complete the prevention and con-trol measures and intensify the health care workers'capabilities in identification of the pathogenic fungus so as to reduce the incidence of pulmonary mucormycosis caused by the pathogen.

Objective To develop the Ego Depletion Scale for Type 2 Diabetes Patients and evaluate its reliability and validity,and to provide a specific assessment tool for evaluating ego-depletion in self-management.Methods Guided by the self-control strength model,the initial scale was constructed through literature review,semi-structured interviews,2 rounds of expert consultation,and a pilot survey.A convenience sampling method was employed to recruit 460 patients with Type 2 Diabetes from the endocrinology department of a tertiary hospital in Wuhan,Hubei Province,between April and July 2024.They were randomly divided into 2 subsets for exploratory factor analysis and confirmatory factor analysis.Results A total of 451 valid questionnaires were collected.Exploratory factor analysis extracted 6 common factors,with a cumulative variance contribution of 73.231％.In confirmatory factor analysis,an item was deleted due to failing to meet the standardized loading value criterion.The revised Ego Depletion Scale for Type 2 Diabetes Patients comprised 6 dimensions and 22 items.The total Cronbach's α coefficient was 0.911;split-half reliability was 0.744;the content validity index was 0.860.Correlation coefficients between the total score and scores of each dimension of the scale and the total score of the Self-Regulatory Fatigue Scale ranged from 0.558 to 0.946(P＜0.001).Conclusion The scale exhibits robust reliability and validity,serving as a scientifically instrument for assessing ego depletion in patients with Type 2 Diabetes.

Aim To study the role and mechanism of ML210 in glioma.Methods The cell viability was detected by CCK8 assay.The percentage of dead cells was detected by SYTOXstaining.The role of ferroptosis-signaling pathway in gliomas was detected bygenomics.Cell proliferation was observed by EdU staining and clone formation assay.Cell migration ability was detec-ted by scratch healing assay.The apoptosis was detec-ted by flow cytometry.Cell mitochondrial function was assesses by JC-1 staining.The mechanism of action of ML210 was detected by molecular docking coupled with immunoblotting assay(Western blot).The levels of ROS,MDA were observed by ELISA.Results Compared with the control group,ML210 treatment dose-dependently decreased glioma cell viability,in-hibited cell proliferation,migration,and increased cell apoptosis and mitochondrial dysfunction,which were reversed by ferroptosis antagonists.Gene microarray screening showed that 688 genes of the ferroptosissig-naling pathway were aberrant and 10 signaling path-ways were altered in gliomas.Molecular docking re-sults showed that ML210 binding to GPX4 significantly inhibited the protein expression level of GPX4 and pro-moted the elevation of ROS and MDA levels.Conclu-sions ML210 produces anti-glioma cells via GPX4-mediated ferroptosis pathway.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Objective:To explore the effect of remote motor imagery therapy on rehabilitation of patients with severe coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:This randomized con-trolled study enrolled 164 patients with severe CHD undergoing PCI who admitted in the First Affiliated Hospital of Hebei North University between January 2022 and January 2024.Patients were divided into control group(n=82)and intervention group(n=82).Patients in the control group was given conventional home nursing intervention comparing to those in the intervention group receiving additional remote motor imagery therapy.Both groups were intervened for 8 weeks.Indexes of pain,psychological emotion,ability of daily living,motor function and fall were compared between two groups.Results:Compared to those in control group after intervention,patients in interven-tion group had significant lower scores of visual analogue scale(VAS)[(2.03±0.81)points vs.(5.14±0.84)points],the Hospital anxiety and depression scale(HADS)anxiety subscale(HADS-A)[(4.89±0.84)points vs.(9.05±0.78)points],HADS depression subscale(H ADS-D)[(5.31±1.10)points vs.(10.13±0.82)points],HADS total score[(10.20±1.39)points vs.(19.18±1.18)points](P＜0.001 all),and significant higher 6-min walking distance(6MWD)[(439.31±16.51)m vs.(364.94±12.76)m],peak oxygen uptake(VO2 peak)[(20.28±2.40)ml·kg-1·min-1 vs.(17.26±1.35)ml·kg-1·min-1],anaerobic threshold oxygen consumption(VO2AT)[(17.04±1.18)ml·kg-1·min-1 vs.(13.62±1.16)ml·kg-1·min-1],scores of Chinese modified Fall Efficacy Scale(MFES)[(107.28±4.84)points vs.(87.41±4.73)points],ability of daily living(ADL)scale[(78.95±3.92)points vs.(68.00±4.10)points]and Barthel index[(85.83±2.50)points vs.(69.79±3.42)points](P＜0.001 all).We detected significant lower incidence of falling(7.50％vs.21.25％)in the intervention group compared to control group(P=0.013).Conclusion:Remote motor imagery therapy may strengthen motor function and ability of daily living,and relieve pain and negative emotions in patients with severe CHD after PCI.