Objective To investigate the regulatory role and mechanism of lobetyolin(LBT,a poly-acetylene glycoside isolated from the roots of Codonopsis pilosula)in the proliferation and apop-tosis of brain glioma cells based on the Akt/GSK-3β/Snail signaling pathway.Methods Human brain glioma cell line U-373MG was randomly divided into normal,SC79(Akt activator),LBT,and LBT+SC79 groups.After corresponding interventions,CCK-8 assay,colony formation assay,and flow cytometry were used to detect the proliferation and apoptosis of the cells.Western blot-ting was employed to measure the protein expression levels of the molecules related to prolifera-tion,apoptosis,and Akt/GSK-3β/Snail signaling pathway.After tumor xenograft nude mouse model of U-373MG cells was established,followed by grouping and interventions as above cell experiments,the tumor weight and volume were measured.Immunohistochemical assay and TUNEL assay were performed to detect the proliferation and apoptosis of tumor cells.Western blotting was applied to detect Akt/GSK-3β/Snail signaling pathway related proteins in the nude mouse groups.Results In the LBT+SC79 group,cell viability,number of formed colonies,pro-tein levels of cyclin D1,Bcl-2 and Snail,p-Akt/Akt and p-GSK-3β/GSK-3β,tumor weight and vol-ume,and positive ratios of Ki67,cyclin D1 and Bcl-2 in transplanted tumors were increased(P＜0.05),and cell apoptotic rate[(3.20±1.14)％vs(46.15±1.52)％,P＜0.05],Bax protein level(0.51±0.07 vs 0.89±0.06,P＜0.05),and positive ratios of TUNEL[(51.56±7.13)％vs(74.95±8.61)％,P＜0.05]and Bax[(32.71±5.43)％vs(41.86±4.90),P＜0.05]in transplanted tumors were declined when compared with the LBT group.Conclusion LBT can induce apoptosis and inhibit proliferation of brain glioma cells in vitro and in vivo by blocking activation of the Akt/GSK-3β/Snail signaling pathway.

Objective To investigate the regulatory role and mechanism of lobetyolin(LBT,a poly-acetylene glycoside isolated from the roots of Codonopsis pilosula)in the proliferation and apop-tosis of brain glioma cells based on the Akt/GSK-3β/Snail signaling pathway.Methods Human brain glioma cell line U-373MG was randomly divided into normal,SC79(Akt activator),LBT,and LBT+SC79 groups.After corresponding interventions,CCK-8 assay,colony formation assay,and flow cytometry were used to detect the proliferation and apoptosis of the cells.Western blot-ting was employed to measure the protein expression levels of the molecules related to prolifera-tion,apoptosis,and Akt/GSK-3β/Snail signaling pathway.After tumor xenograft nude mouse model of U-373MG cells was established,followed by grouping and interventions as above cell experiments,the tumor weight and volume were measured.Immunohistochemical assay and TUNEL assay were performed to detect the proliferation and apoptosis of tumor cells.Western blotting was applied to detect Akt/GSK-3β/Snail signaling pathway related proteins in the nude mouse groups.Results In the LBT+SC79 group,cell viability,number of formed colonies,pro-tein levels of cyclin D1,Bcl-2 and Snail,p-Akt/Akt and p-GSK-3β/GSK-3β,tumor weight and vol-ume,and positive ratios of Ki67,cyclin D1 and Bcl-2 in transplanted tumors were increased(P＜0.05),and cell apoptotic rate[(3.20±1.14)％vs(46.15±1.52)％,P＜0.05],Bax protein level(0.51±0.07 vs 0.89±0.06,P＜0.05),and positive ratios of TUNEL[(51.56±7.13)％vs(74.95±8.61)％,P＜0.05]and Bax[(32.71±5.43)％vs(41.86±4.90),P＜0.05]in transplanted tumors were declined when compared with the LBT group.Conclusion LBT can induce apoptosis and inhibit proliferation of brain glioma cells in vitro and in vivo by blocking activation of the Akt/GSK-3β/Snail signaling pathway.

Objective:To investigate the effects of phillyrin(PHN)on the proliferation,invasion,and epithelial-mesenchymal transition(EMT)of glioma U251 cells by adjusting the high mobility group protein B1(HMGB1)/receptor of advanced glycation endproduct(RAGE)signaling pathway.Methods:Human glioma U251cells were assigned into the PHN-0 group(treated with 0 μmol/L PHN),the low,medium,and high-dose PHN groups(PHN-50、PHN-100、PHN-200 groups,treated with 50,100,and 200 μmol/L PHN respectively),the PHN+pcDNA-NC group(treated with 200 μmol/L PHN after transfection of pcDNA-NC plasmid),and the PHN+HMGB1 group(treated with 200 μmol/L PHN after transfection of overexpressed HMGB1 plasmid).The proliferation ability of cells in each group was detected by the CCK-8 method and the clone formation assay.The apoptosis level of cells in each group was detected by flow cytometry.The migration and invasion abilities of cells in each group were detected by the Transwell assay.ELISA was used to detect the IL-8 secretion level of cells in each group.Immunofluorescence was used to detect the positive rates of N-cadherin and E-cadherin in cells of each group.WB assay was performed to detect the expression levels of Toll like receptor 4(TLR4),nuclear factor-kappa B(NF-κ B),HMGB1,RAGE,N-cadherin,E-cadherin,cell cycle protein D1(cyclin D1),cyclin dependent kinase 2(CDK2),B-lymphoblastoma-2(Bcl-2),Bcl-2 associated X protein(BAX)proteins in cells of each group.Results:Compared with those in the PHN-0 group,the proliferation activity,the number of clone formation,the numbers of invasion and migration,IL-8 secretion levels,the positive rate and protein expression of N-cadherin,and the expressions of TLR4,NF-κB,HMGB1,RAGE,cyclin D1 and CDK2 protein in the PHN-50,PHN-100,and PHN-200 groups decreased significantly(all P<0.05);and the apoptosis rate,the positivity rate and protein expression of E-cadherin,and the BAX/Bcl-2 ratio increased significantly(all P<0.05).At the same time,overexpression of HMGB1 could reverse the inhibitory effects of PHN on the proliferation,migration,invasion and EMT of U251 cells,as well as its promoting effect on the apoptosis(all P<0.05).Conclusion:PHN inhibits the proliferation,invasion and EMT progression of glioma U251 cells through the HMGB1/RAGE signaling pathway.

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 investigate the impact of silymarin(SM)on the malignant growth of glioma cells and the regulatory mechanism on the miR-124-3p/WEE1 axis.Methods Glioma U87 cells were grouped into control,SM low,medium,and high concentration groups,and SM high concentration + miR-124-3p inhibitor group(SM high + miR-124-3p inhibitor group).CCK-8 was used to measure the proli-feration rate of cells;Transwell? assay was applied to assay the migration and invasion of cells;cell cycle progression was detected by flow cytometry;Western blotting was applied to measure the expression of cyclin D1 and apoptosis-related proteins;the levels of miR-124-3p and WEE1 mRNA were determined by qRT-PCR;and a luciferase activity test was applied to verify the targeting relationship between miR-124-3p and WEE1;in addition,the establishment,administration,and analysis of a NOD/SCID mouse model of intracranial trans-planted tumor were conducted.Results Compared with the control group,the cell proliferation,the numbers of migrating and invading cells,the expression of cyclin D1,and the level of WEE1 mRNA in the various SM treatment groups decreased,the number of cells in G0/G1 phase,the expression of cleaved caspase-8,cleaved caspase-9,cleaved caspase-3 and miR-124-3p increased(P＜0.05);furthermore,transfection of miR-124-3p inhibitor reversed the inhibitory effect of SM on the malignant behavior of glioma cells.In vivo experiments with mice showed that the weights and volumes of tumors in the SM treatment group were lower than those in the model group(P＜0.05),and there was no discernible change in the weight of the mice(P＞0.05).Conclusion SM can inhibit the malignant growth of glioma cells by upregulating miR-124-3p and downregulating WEE1.

Aortic dissection is a catastrophic cardiovascular disease with a high mortality rate. The healthy behavior of patients with aortic dissection plays an important role in the outcome, and patients must pay attention to the management of healthy behavior outside the hospital. This article reviews the influencing factors and intervention strategies of the health promotion behaviors of patients with aortic dissection, and proposes suggestions for intervention programs to improve the management of patients ' health behaviors, so as to provide a reference for related research on health behavior management of patients with aortic dissections.

Objective:The storage of medical data has been digitized in China, but a unified and structured model has not yet been established. The standardized collection, analysis and sorting of tumor clinical data is the foundation of improving the standard of tumor diagnosis and treatment. Therefore, establishing a database platform of gastric cancer (GC) is an urgent need to integrate data resources and improve the level of diagnosis and treatment. The population economics indexes of GC patients in the last 20 years are analyzed in a single-center GC database. The medical records were structured by natural language processing technology. Authors aim to investigate the clinical pathological characteristics, staging and survival of the GC patients with gastrectomy.Method:A retrospective cohort study was carried out. Clinicopatological data of patients receiving surgical treatment from 2000 to 2019 were retrospectively collected. According to the gastric cancer TNM staging guidelines from the Union for International Cancer Control and the American Joint Committee on Cancer (UICC/AJCC) 8th edition, the structured gastric cancer clinicopathological data were re-evaluated and interpreted. The Kaplan-Meier method and the log-rank test were used to compare survival rate among different groups of patients with complete follow-up data of 2010-2016.Results:Clinicopathological data of 13 492 GC patients were enrolled. The ratio of men to women in the whole group was 3.25:1.00, including 10 320 men with average onset age of 59.68 years, which was basically stable in recent 20 years, and 3172 women with average onset age of 55.93 years, which presented a trend of average increasement of 0.17 year per year. The average hospitalization duration for GC patients showed a decreasing trend year by year, which was 13.87 days in 2019. Average hospitalization cost for GC patients was increasing year by year, with a peak of 83 600 CNY in 2017 and 75 400 CNY in 2019. By natural language identification and exclusion criteria screening, a total of 7218 GC patients obtained structured clinicopathological information. Analysis on clinicopathological characteristics of 3626 GC patients in the last 5 years showed that the average diameter of tumor was (4.44±2.61) cm; the average number of harvested lymph node was 24.30±13.29; the proportion of surgical methods were as following: open surgery in 1398 cases (38.55%), laparoscopic surgery in 1856 cases (51.19%) and robotic surgery in 372 cases (10.26%). The postoperative pathological stage was as following: IA in 658 cases (18.15%), IB in 318 cases (8.77%), IIA in 559 cases (15.42%), IIB in 543 (14.98%), III A in 632 (17.43%), III B in 612 cases (16.88%), III C in 276 cases (7.61%), and IV in 28 cases (0.77%). Complete follow-up data of 3431 patients from 2010 to 2016 were presented. The 1-, 3- and 5-year survival rates were 82%, 69% and 60%, respectively for the whole group. The 1-, 3- and 5-year survival rates for patients undergoing laparoscopic surgery were 83%, 70% and 64%, respectively, and for those undergoing open surgery were 81%, 67% and 56%, respectively, and the difference between the two groups was not statistically significant ( P=0.109). The 5-year survival rate of GC patients with different AJCC stages was as following: 88% in IA, 77% in IB, 70% in II A, 62% in II B, 44% in III A, 32% in III B, 22% in III C, and 17% in IV. Conclusion:This study provides basic data for the establishment of comprehensive diagnosis and treatment model of multicenter, shedding light on the improvement of comprehensive treatment of GC in China.

Objective:The storage of medical data has been digitized in China, but a unified and structured model has not yet been established. The standardized collection, analysis and sorting of tumor clinical data is the foundation of improving the standard of tumor diagnosis and treatment. Therefore, establishing a database platform of gastric cancer (GC) is an urgent need to integrate data resources and improve the level of diagnosis and treatment. The population economics indexes of GC patients in the last 20 years are analyzed in a single-center GC database. The medical records were structured by natural language processing technology. Authors aim to investigate the clinical pathological characteristics, staging and survival of the GC patients with gastrectomy.Method:A retrospective cohort study was carried out. Clinicopatological data of patients receiving surgical treatment from 2000 to 2019 were retrospectively collected. According to the gastric cancer TNM staging guidelines from the Union for International Cancer Control and the American Joint Committee on Cancer (UICC/AJCC) 8th edition, the structured gastric cancer clinicopathological data were re-evaluated and interpreted. The Kaplan-Meier method and the log-rank test were used to compare survival rate among different groups of patients with complete follow-up data of 2010-2016.Results:Clinicopathological data of 13 492 GC patients were enrolled. The ratio of men to women in the whole group was 3.25:1.00, including 10 320 men with average onset age of 59.68 years, which was basically stable in recent 20 years, and 3172 women with average onset age of 55.93 years, which presented a trend of average increasement of 0.17 year per year. The average hospitalization duration for GC patients showed a decreasing trend year by year, which was 13.87 days in 2019. Average hospitalization cost for GC patients was increasing year by year, with a peak of 83 600 CNY in 2017 and 75 400 CNY in 2019. By natural language identification and exclusion criteria screening, a total of 7218 GC patients obtained structured clinicopathological information. Analysis on clinicopathological characteristics of 3626 GC patients in the last 5 years showed that the average diameter of tumor was (4.44±2.61) cm; the average number of harvested lymph node was 24.30±13.29; the proportion of surgical methods were as following: open surgery in 1398 cases (38.55%), laparoscopic surgery in 1856 cases (51.19%) and robotic surgery in 372 cases (10.26%). The postoperative pathological stage was as following: IA in 658 cases (18.15%), IB in 318 cases (8.77%), IIA in 559 cases (15.42%), IIB in 543 (14.98%), III A in 632 (17.43%), III B in 612 cases (16.88%), III C in 276 cases (7.61%), and IV in 28 cases (0.77%). Complete follow-up data of 3431 patients from 2010 to 2016 were presented. The 1-, 3- and 5-year survival rates were 82%, 69% and 60%, respectively for the whole group. The 1-, 3- and 5-year survival rates for patients undergoing laparoscopic surgery were 83%, 70% and 64%, respectively, and for those undergoing open surgery were 81%, 67% and 56%, respectively, and the difference between the two groups was not statistically significant ( P=0.109). The 5-year survival rate of GC patients with different AJCC stages was as following: 88% in IA, 77% in IB, 70% in II A, 62% in II B, 44% in III A, 32% in III B, 22% in III C, and 17% in IV. Conclusion:This study provides basic data for the establishment of comprehensive diagnosis and treatment model of multicenter, shedding light on the improvement of comprehensive treatment of GC in China.

Objective: To evaluate the predictive value of GRACE discharge score on the long-term out-of-hospital coronary thrombotic events (CTE) after percutaneous coronary intervention (PCI) with drug-eluting stents. Methods: Present study was a prospective, observational, single center study. 10 724 consecutive patients underwent PCI in Fuwai Hospital between January and December 2013 were included, stents were implanted with conventional method. After PCI, patients were prescribed aspirin 100 mg once daily indefinitely, and either clopidogrel 75 mg once daily or ticagrelor 90 mg twice daily for at least 1 year. A total of 9 782 patients were included in the final analysis after excluding patients who did not undergo successful stent implantation, who were not discharged on dual anti-platelet therapy (DAPT), who only underwent bare-metal stents, who experienced in-hospital major bleeding, stent thrombosis, myocardial infarction (MI) or death,and who lost follow up. Clinical data were collected from all patients. 9 543 patients with complete baseline data were further analyzed for risk stratification and predictive value of GRACE discharge score. CTE was defined as stent thrombosis or spontaneous myocardial infarction. All patients were followed through Fuwai Hospital Follow-up Center, and evaluated either by phone, letter, or clinic visits or at 1, 6, 12 and 24 months after PCI. Risk stratification was performed according to the GRACE discharge score, and the predictive value of the GRACE discharge score was assessed using the receiver operating characteristic (ROC) curve. Results: After 2 years follow-up, there were 95 CTE among the 9 782 patients. The patients were divided into 2 groups according to the presence or absence of CTE: CTE group (95 cases) and no CTE group (9 687 cases). GRACE discharge score was significantly higher in CTE group than no CTE group (82.98±27.58 vs. 75.51±22.46, t=-2.57, P=0.012). According to risk stratification of GRACE discharge score, the patients were divided into low-risk (≤88) group (n=6 902), moderate-risk (89-118) (n=2 988) and high-risk (>118) (n=343) groups. As compared to the low-risk group, CTE risk in moderate- and high-risk groups was 1.59 times (HR 1.59, 95%CI 1.01-2.52, P=0.046) and 3.89 times higher (HR 3.89, 95%CI 1.98-7.65, P<0.001), respectively. Further analysis showed that the GRACE score had predictive value in the total cohort for CTE (area under the receiver operating characteristic (AUROC) 0.576, 95%CI 0.512-0.640, P=0.012) and in the acute coronary syndromes(ACS) subgroup for CTE: (AUROC 0.594, 95%CI 0.509-0.680, P=0.019), but not in the non-ACS subgroup: (AUROC 0.561, 95%CI 0.466-0.657, P=0.187). Conclusion GRACE discharge score can predict the long-term out-of-hospital CTE in patients undergoing PCI with drug-eluting stents and treated with DAPT, and patients can be stratified into the low-, moderate- and high-risk groups of CTE by the GRACE discharge score.

Objective To study the clinical pathological features of Wegener's granulomatosis (WG) in middle-aged and elderly patients,and enhance understanding of this disease.Methods Totally 21 patients with WG (11 males,10 females,aged 45 to 76 years,mean age 58.1 years) in our hospial from February 1999 to July 2012 were selected.The clinical and pathological data of WG patients were retrospectively analyzed.34 biopsies including 2 autopsies from different organs were paraffin embedded and stained by hematoxylin and eosin and histochemistry.13 renal biopsies were all examined by immunofluorescence and electron microscope.Results The average time from the onset of clinical symptoms to the diagnosis was 5.3 months (from 24 days to 11.0 months).Eyes,nose and salivary glands were the most commonly involved parts at the beginning of Wegener's granulomatosis (52.4％,11 cases).The percentages of the skin,lung and renal involvement were 14.3％ (3 cases),81.0％ (17 cases) and 71.4％ (15 cases),respectively.Among 21 patients,18 patients were examined with anti-neutrophil cytoplasmic antibody (ANCA).c-ANCA was positive in 72.2 ％ patients (13 cases,13/18),p-ANCA was positive in 16.7％ patients (3 cases,3/18),and ANCA was negative in 11.1％ patients (2 cases,2/18).3 major pathological manifestations were observed:7 kinds of vasculitis including capillaritis,acute vasculitis,chronic vasculitis,fibrinoid necrosis in vasculitis,necrotizing granulomatous vasculitis,non-necrotizing granulomatous vasculitis and cicatricial vascular changes; 4 kinds of granulomatous inflammation including scattered giant cells,palisading histiocytes,poorly formed granulomas and microabscess surrounded by granulomatousinflammation;2 kinds of parenchymal necrosis including geographic necrosis and microabscess.13 kinds of histopathologic features in 3 major manifestations were found from 2 autopsies,but various kinds histopathologic features presented in small biopsy samples.Minor manifestations such as diffuse pulmonary hemorrhage were found at the periphery of WG.Conclusions The wide variation and broad spectrum of pathologic features can occur in WG.Vasculitis,granulomatous inflammation and parenchymal necrosis are the most important histopathological features.The correct diagnosis of WG requires careful correlation of pathology with complicated clinical features.