ObjectiveTo investigate the mechanism of modified Shenhong Tongluo prescription on cell apoptosis in rats with myocardial ischemia-reperfusion injury （MIRI）. MethodSixty Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， low-， medium-， and high-dose groups of modified Shenhong Tongluo prescription， and a simvastatin group. Except for the blank group， a rat model of MIRI was prepared by ligating the left anterior descending coronary artery. Starting from the first day after successful modeling， the blank group （1.0 mL·kg^-1 physiological saline）， model group （1.0 mL·kg^-1 physiological saline）， low-， medium-， and high-dose groups of modified Shenhong Tongluo prescription （1.031， 2.063， and 4.126 g·kg^-1 Shenhong Tongluo prescriptiona standard concentrate）， and simvastatin group （0.71 mg·kg^-1 simvastatin） were orally administered once daily for 2 weeks. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of cardiomyocytes. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of serum creatine kinase isoenzyme （CK-MB）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）. TdT-mediated dUTP nick-end labeling（TUNEL） staining was used to detect the apoptosis rate of rat cardiomyocytes. Western blot was used to detect the expression levels of apoptosis-related proteins B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and caspase-3. ResultCompared with the blank group， in the model group， HE staining showed disturbed arrangement of cardiomyocytes， incomplete fibers， focal necrosis of cardiomyocytes， and inflammatory cell infiltration； serum CK-MB， IL-6， and TNF-α levels were significantly increased （P<0.05）； apoptosis rate of cardiomyocytes was significantly increased （P<0.01）， with significantly increased expression levels of Bax and Caspase-3 proteins， and significantly decreased Bcl-2 expression （P<0.05）. Compared with the model group， the low-， medium-， and high-dose groups of modified Shenhong Tongluo prescription significantly reduced CK-MB， IL-6， and TNF-α levels （P<0.05）， significantly downregulated cardiomyocyte apoptosis rate （P<0.05）， significantly decreased Bax and Caspase-3 proteins， and significantly increased Bcl-2 expression levels （P<0.01）. In the modified Shenhong Tongluo prescription groups， the expression levels of Bax and Caspase-3 proteins significantly decreased with increasing dosage， while the expression level of Bcl-2 significantly increased with increasing dosage of modified Shenhong Tongluo prescription （P<0.05）. ConclusionShenhong Tongluo prescription can alleviate myocardial tissue pathological damage and reduce myocardial cell apoptosis， possibly by inhibiting Caspase-3 and Bax expression and promoting Bcl-2 expression.

Objective To explore the feasibility and effectiveness of the artificial intelligence(AI)diagnostic model for bone age imaging in the radiology information system-picture archiving and communication system(RIS-PACS)environment operation.Methods The optimized bone age AI model was integrated into the RIS-PACS platform.The bone age imaging data of 88 038 patients aged 0-18 years old were automatically evaluated.The reference bone age was determined by the consensus of two experienced radi-ologists based on GP map,with an error of±1.0 year old.The success rate,accuracy,system compatibility,stability,and influen-cing factors of results were further analyzed.Results The time for bone age AI evaluation of each case did not exceed 3 seconds,and the success rate of automatic evaluation reached 100%.AI model of bone age and RIS-PACS in hospital could be well integrated.Accord-ing to the readings evaluated by pediatric radiologists based on GP maps,the accuracy rate was 93.05%for girls and 89.53%for boys,with a mean absolute error(MAE)of(0.42±0.54)years old for girls and(0.45±0.60)years old for boys,respectively.The AI model could run efficiency in the RIS-PACS,which significantly reduced the burden of radiologists.The factors that affect the accuracy of the model were image position,exposures,multiple images in a single sequence and hand deformity,etc.Conclusion The bone age imaging AI diagnostic model can be seamlessly embedded into RIS-PACS in hospital,achieving one click bone age imaging diagnosis.

ObjectiveTo investigate the current status and development needs of evidence-based medicine （EBM） capability in ethnic minority medicine， and explore effective strategies to enhance EBM capability in this field. MethodsThe questionnaire survey was conducted in various ethnic minority medical institutions and research organisations. The questionnaire covered three dimensions， firstly， perceptions and attitudes towards evidence-based medicine； secondly， advantages and challenges in the development of ethnic minority medicine； thirdly， demands and recommendations for enhancing evidence-based medicine capability in ethnic minority medicine. ResultsA total of 501 valid questionnaires were collected， of which 103 questionnaires were collected by re-sending to minority medicine regions with insufficient participation. The questionnaires included 354 responses （70.66%） from practitioners of minority medicine， including Tibetan medicine， Mongolian medicine， Uyghur medicine， Zhuang medicine， and Korean medicine. Among the 501 questionnaires， 146 respondents （29.14%） indicated that they knew about EBM， 355 respondents （70.86%） had either a "general understanding" or had "not heard about" EBM before， and 469 respondents （93.61%） believed that introducing ECM could promote the development of ethnic minority medicine. The primary challenge in promoting EBM in the field of ethnic minority medicine is the lack of professionals in EBM and a lack of understanding of how to apply it into clinical practice （442 respondents， 88.22%）. In the 9-point importance rating for enhancing evidence-based abilities， high scores were achieved in standardization of clinical practice guidelines （7.50±1.90） and methods for sample sizes in clinical research （7.45±1.90）. Regarding the demand for improving clinical research literacy， expert academic lectures， and experience sharing （404 respondents， 80.64%） and evidence-based methodology monographs on ethnic minority medicine （401 respondents， 80.04%） were emphasized. ConclusionsPractitioners in ethnic minority medicine hold a positive attitude towards integrating EBM. However， there remains substantial room for the education and dissemination of EBM. Enhancing evidence-based capabilities can be achieved through specific measures such as cultivating or recruiting talents in EBM， establishing evidence-based support platforms for clinical research， organizing regular academic lectures and exchanges， and strengthening the construction of theoretical frameworks and evaluation systems tailored to ethnic minority medicine， thereby following a path of evidence-based practices aligned with the unique characteristics of ethnic minority medicine.

Objective To investigate the effect of mesenchymal stem cells(MSCs)combined with immunosuppressants(IS)on immune rejection in a rat model of liver transplantation.Methods F344 rats were divided into Normal group(without any intervention),PS group(injected with an equal volume of normal saline),MSC group(injected with MSC),IS group(injected with IS),and MSC+IS group(injected with MSC and IS),with 8 rats in each group.For all rats except those in the Normal group,the Kamada's double-cuff method was used to establish a model of orthotopic liver transplantation,without reconstruction of the hepatic artery.HE staining and Masson staining were performed for rat liver tissue,and the degree of liver fibrosis was analyzed;immunohistochemical experiments were used to measure the infiltration of T cells and NK cells,and immunofluorescence assay was used to analyze macrophage M2 polarization.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.The Kaplan-Meier method was used to plot survival curves,and the log-rank test was used for survival analysis.Results Compared with the PS group,the MSC+IS group had a significantly prolonged survival time(P＜0.01),and the MSC group,the IS group,and the MSC+IS group had a significant improvement in the histological structure of the liver and a significant reduction in the degree of liver fibrosis(all P＜0.000 1),as well as a significant reduction in the infiltration of NK and T cells(all P＜0.000 1)and a significant increase in the degree of macrophage M2 polarization(all P＜0.000 1).The MSC+IS group had a significantly better effect than the MSC group and the IS group.Conclusion MSCs combined with IS can improve liver histopathology,reduce inflammatory cell infiltration,promote macrophage M2 polarization,and exert an immunosuppressive effect in rats after liver transplantation.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To preliminarily analyze the expression of angiotensin-converting enzyme 2 (ACE2) and to investigate its potential regulatory mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP).Methods:Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from February 2020 to May 2021 were selected, including 17 males and 6 females, aging from 23 to 66 years old. Expression of ACE2 was evaluated via immunohistochemical staining in controls with non-chronic rhinosinusitis, non-eosinophilic CRSwNP (non-ECRSwNP), and eosinophilic CRSwNP (ECRSwNP) tissue, respectively. Correlations between ACE2 and the indicated Th1/Th2-related cytokines (IFN-γ, IL-4, IL-5, IL-13, IL-25, IL-33, TSLP and periostin) were analyzed based on GSE72713 dataset. Protein-protein interaction (PPI) network was constructed via string database, immune infiltration of GSE72713 dataset was evaluated using cibersort algorithm. ACE2 was comprehensively analyzed by microRNA regulatory network, gene set enrichment analysis (GSEA) and pharmacological analysis. Statistical analysis was performed using GraphPad 7.0 and SPSS 20.0 software.Results:ACE2 was up-regulated in non-ECRSwNP compared with ECRSwNP. Microarray analysis showed that ACE2 was positively correlated with IFN-γ while inversely correlated with IL-5, IL-13 and periostin significantly. Analysis of immune infiltration suggested that ACE2 expression correlated positively with the number of M1 macrophage while negatively with M2 macrophage. GSEA demonstrated that interferon-related signaling pathways were up-regulated in non-ECRSwNP, and miRNA-200B/miRNA-200C/miRNA-429 pathways targeting ACE2 were enriched in ECRSwNP. Results of pharmacological analysis indicated that ampicillin was able to promote the expression of ACE2 whereas acetaminophen could down regulated the expression of ACE2.Conclusion:Expression pattern of ACE2 is varied in non-ECRSwNP and ECRSwNP, which may be related to the different infiltration of indicated cytokines and different regulatory pathways of miRNA.

Objective:To investigate the expression and cellular provenance of interleukin 17A (IL-17A) in non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP), and to analyze the possible reasons for its different expression.Methods:Samples were collected from 14 patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and 28 patients with nECRSwNP, who underwent functional endoscopic sinus surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to May 2018, including 33 males and 9 females, with the age ranging from 18 to 65 years old. Enzyme linked immune sorbent assay (ELISA) and flow cytometry were used to investigate the expression and cellular origins of IL-17A in the nasal tissue of ECRSwNP and nECRSwNP groups. Then the difference of quantity and differentiation ability of the major cells producing IL-17A between ECRSwNP and nECRSwNP groups were analyzed by flow cytometry. Finally, the expressions of IL-6, transforming growth factor-β(TGF-β), and IL-23, which were considered as the important factors in promoting Th17/Tc17 differentiation in CRSwNP and their correlation with IL-17A, were analyzed by ELISA. Statistical analysis was performed using IBM SPSS 20.Results:The IL-17A protein levels and IL-17A +lymphocyte percentages were higher in nECRSwNP group compared with that of the ECRSwNP group (158.56 (167.76) pg/ml ( M( QR)) vs. 9.42 (11.33) pg/ml, 10.21%±1.54% ( ± s) vs. 3.93%±0.80%, Z=2.95, t=3.62, all P<0.01). Tc17 cells (CD8 +T cells producing IL-17A) and Th17 cells (CD4 +T cells producing IL-17A) were major IL-17A producers in both ECRSwNP and nECRSwNP group. Further analysis revealed that there was no significant difference in quantity of CD8 +and CD4 +T cells between ECRSwNP and nECRSwNP group, but the differentiation ability about CD8 +and CD4 +T cells differentiating into Tc17 and Th17 in nECRSwNP group was stronger than that in ECRSwNP. The high expressions of IL-6 and TGF-β, which were considered as the important factors in promoting Th17/Tc17 differentiation were also found in nECRSwNP group compared with ECRSwNP (56.07 (234.25) pg/ml vs. 8.27 (12.51) pg/ml, (5.44±0.34) pg/ml vs. (4.17±0.22) pg/ml, Z=2.426, t=2.29, all P<0.05). But the difference in expression of IL-23 was not significant difference between the two groups. Moreover, the expression of IL-17A showed significantly positive correlation with IL-6 ( r=0.615, P=0.009). No positive correlation between IL-17A and TGF-β or IL-23 was observed. Conclusions:The expression of IL-17A in nasal mucosa of nECRSwNP patients is significantly higher than that of ECRSwNP, which is due to the increase of expression and differentiation of Tc17/Th17 cells. IL-17A shows positive correlation with IL-6 in CRSwNP, which is the important factor in promoting Th17/Tc17 differentiation.

This study investigated the effect of arctigenin (Arc) on the cell activation, cytokines expression, proliferation, and cell-cycle distribution of mouse T lymphocytes. Mouse lymphocytes were prepared from lymph node and treated with Phorbol-12-myristate-13-acetate (PMA)/Ionimycin (Ion) and/or Arc. CD69, CD25, cytokines, proliferation and cell cycle were assayed by flow cytometry. The results showed that, at concentrations of less than 1.00 micromol x L(-1), Arc expressed non-obvious cell damage to cultured lymphocytes, however, it could significantly down-regulate the expression of CD69 and CD25, as well as TNF-alpha, IFN-gamma, IL-2, IL-4, IL-6 and IL-10 on PMA/Ion stimulated lymphocytes. At the same time, Arc could also inhibit the proliferation of PMA/Ion-activated lymphocytes and exhibited lymphocyte G 0/G1 phase cycle arrest. These results suggest that Arc possesses significant anti-inflammatory effects that may be mediated through the regulation of cell activation, cytokines expression and cell proliferation.

Objective To investigate the effects of docosahexaenoic acid (DHA) on action potential (AP)and transient outward potassium channel (Ito) in rat ventricular myocytes in order to evaluate the anti-arrhythmia mechanism of DHA. Method The rat ventricular myocytes were isolated by using enzyme digestion method. AP and Ito of individual ventricular myocyte were recorded by using patch-clamp technique in whole-cell configuration at room temperature. The effects of DHA on AP and Ito were observed when it was applied in 0 μmol/L, 20 μmol/L, 40 μmol/L, 60 μmol/L, 80 μmol/L, 100 μmol/L and 120μmol/L separaterly. Results The 25%,50% and 90% of action potential duration (APD25, APD50 and APD90) were gradually prolonged with the escalation of concentration of DHA ( P ＜ 0.05, n= 20). The effects of DHA of different concentrations on AP maximal velocity (Vmax), AP amplitude (APA) and AP overshoot (OS) did not produce significantly different results (P ＞ 0.05, n= 20). The degree of blockade of Ito was concentration-dependent as different concentrations of DHA were applied, and as the concentration of DHA was escalated, the I-V curves went downwards, the stably inactivated curves shifted to the lift, and the time taken for recovery from inactivation prolonged ( P ＜ 0.05, n =20). However, the different concentrations of DHA did not produce different effects on stably activated curves ( P＞ 0.05). The Itos were blocked to (2.61 ± 0.26)%, (21.79±4.85)%, (63.11 ± 6.57)%, 75.52±7.26 ) %, (81.82 ± 7.63) % and (84.33 ± 8.25) % by the above given concentrations of DHA respectively under given potential equaling to + 70 mV( P ＜ 0.05, n = 20), and the half-effect concentration (EC50) of DHA on Ito was(49.11±2.68) umol/L. Conclusions The effects of DHA on APD and Ito may be one of the anti-arrhythmia mechanism of DHA.

UNLABELLEDThis experiment was aimed to study the effects of different concentrations of medroxyprogesterone acetate (MPA) on proliferation, migration and apoptosis of endothelial progenitor cells (EPCs) in vitro and to provide experimental evidence for the use of MPA as anti-angiogenesis drug. We separated EPCs from bone marrow of a beagle dog and identified the expression of progesterone receptor (PR) in EPCs by immunocytochemistry. Proliferation tests (MTT analysis) were performed with EPCs in response to different concentration of MPA every 24 h for 7 consecutive days, the growth curve of these EPCs was obtained then. The inhibition rates were also obtained from MTT assay performed with EPCs exposed to different concentration of MPA. The migration tests were performed with EPCs in response to different concentrations of MPA. The cell cycle and apoptosis of EPCs exposed to different concentrations of MPA were analyzed by use of flow cytometry.

RESULTSImmunohistochemical staining showed that EPCs were positive to PR. High concentration of MPA had significant inhibition effect on the growth of EPCs. This effect was time- and dose-dependent. But the low concentration of MPA had not have such effect, EPCs exposed to high concentration of MPA were found arrested in S phase, and the apoptosis rate increased. The migration ability of EPCs exposed to high concentration of MPA was also damaged.

CONCLUSIONHigh concentration of MPA can induce EPCs' apoptosis and inhibit their growth and migration. All these biological effects of MPA may be achieved through PR on EPCs.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Apoptosis ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dogs ; Dose-Response Relationship, Drug ; Endothelial Cells ; cytology ; Female ; Medroxyprogesterone Acetate ; pharmacology ; Neovascularization, Physiologic ; drug effects ; Stem Cells ; cytology