1.Therapeutic effect of ticagrelor on acute ST elevation myocardial infarction and its influence on short-term prognosis
Jiayong HU ; Haoyue YU ; Zhaojun CHEN ; Xiaofeng TANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2017;26(1):74-77
Objective:To explore therapeutic effect of ticagrelor on patients with acute ST elevation myocardial in‐farction (STEMI) and its influence on short‐term prognosis .Methods :A total of 180 STEMI patients undergoing e‐mergency percutaneous coronary intervention (PCI) were selected ,randomly divided into clopidogrel group (n=90) and ticagrelor group (n=90) .Clinical therapeutic effect was compared between two groups ;platelet function ,inci‐dence of major adverse cardiovascular events (MACE) ,adverse reactions and bleeding events were observed in two groups .Results:Total effective rate of ticagrelor group was significantly higher than that of clopidogrel group (93.4% vs .87.8% ,P=0.036);compared with clopidogrel group on 24h and 7d after operation ,there were signif‐icant reductions in platelet aggregation rate [24h :(62.1 ± 5.2)% vs . (56.5 ± 5.4)% ,7d:(47.3 ± 6.1)% vs . (38.7 ± 5.2)% ] and P2Y12 reaction unit [24h:(218.1 ± 12.3) U vs . (201.3 ± 11.1) U ,7d:(173.4 ± 11.8) U vs . (152.6 ± 12.6) U] in ticagrelor , P< 0.05 all;there were no significant difference in incidence rates of MACE ,adverse reactions and bleeding events between two groups , P>0. 05 all .Conclusion:Compared with clopi‐dogrel ,ticagrelor can better reduce platelet aggregation rate and improve clinical therapeutic effect without increas‐ing incidence of adverse reactions and bleeding events .
3.Transplantation of autologous bone marrow mesenchymal stem cells modified with AKT1 for treating pig ischemic cardiomyopathy
Yunsheng YU ; Shiqiang GUO ; Guiping YU ; Wenxue YE ; Haoyue HUANG ; Yihuan CHEN ; Fei HUA ; Yongquan GU ; Zhenya SHEN
Chinese Journal of Tissue Engineering Research 2009;13(49):9616-9624
BACKGROUND: A great quantity of cell loss in early stage following stem cell transplantation can significantly affect transplantation effect. Presently, it is confirmed that overexpression of AKT1 gene significantly inhibit cell apoptosis. OBJECTIVE: To explore whether AKT1 gene overexpression can block stem cell apoptosis under hypoxic condition following pig autologous bone marrow mesenchymal stem cell (BMSC) transplantation, and the effect of repairing damaged myocardium. DESIGN, TIME AND SETTING: The randomized controlled animal study was performed at the Soochow University from August 2005 to February 2007.MATERIALS: A total of 24 healthy male Meishan pigs were supplied by the Animal Experimental Center of Soochow University. METHODS: The CDS (regulation domin of AKT1) AKT1-cDNA fragment was amplified. Lentivector Packaging Kit was used to transfect BMSCs after synthesized with pCDH1-AKT1 shuttling plasmid. Following BrdU labeling, models of myocardial infarction were constructed by occluding the distal left anterior descending coronary artery in pigs with gelatin sponge. 4 weeks later, pigs were randomly divided into four groups: the model control group, the DMEM group, the BMSCs group, and the AKT-transfected group. In model control group, there was no other injection after occluding the left anterior descending coronary artery. In the DMEM group, 5 mL DMEM was injected into the coronary artery. 5 mL BMSCs (1×10~7 cells) were infused into the coronary artery in the BMSCs group. 5 mL BMSCs transfected with the AKT1 gene were injected in the AKT-transfected group MAIN OUTCOME MEASURES: Western blot analysis and real time RT-PCR were used to test the plasmid. The cardiac function was evaluated by magnetic resonance image. Histological characteristics of the myocardium were observed using immunohistochemistry. Serum vascular endothelial growth factor and transforming growth factor β1 levels were determined by ELISA. RESULTS: AKT1-cDNA was cloned into pCDH1-MCS1-EF1-copGFP and the sequence was confirmed in comparison with the published one. AKT mRNA expression could be detected distinctly 24 and 48 hours after transfecting cells. The expression of AKT1 intensity in MSCs remained strong 2 weeks later with detected by real time RT-PCR and Western blot analysis. AKT1-mRNA transcriptional levels were 120 times of primary cells. Before the cell implantation, the left ventricular end-diastolic dimension increased and the stroke volume decreased in the myocardial infarction hearts. The cardiac function was significantly improved after cell implantation, and the implanted MSCs prevented the infarct region from thinning and expanding, improved contraction and increased perfusion in all groups relative to the control hearts. The left ventricular chamber size was smaller in the hearts with being transplanted cells than that in the control hearts. Moreover, the improvement was even markedly greater in AKT-transfected group (P < 0.05). Hematoxylin-eosin staining results showed that fibering was significant in the model control group and DMEM group. Island-like myocardium was observed in the infarct zone of the BMSCs group and AKT-transfected group, and plenty of small vessels-shape structure was detected in the AKT-transfected group. Immunohistochemistry demonstrated that Von Willebrand Factor (vWF) and Cx-43 expression was determined in the myocardium in the BMSCs group and AKT-transfected group, and the proportion of BrdU and Cx-43-positive cells to BrdU-positive cells was significantly greater in the AKT-transfected group compared with the BMSCs group 4 weeks following transplantation (P < 0.05). Following cell transplantation, vascular endothelial growth factor levels were gradually increased, peaked at 1 week, gradually decreased, and reached a normal level at 4 weeks. Transforming growth factor p1 levels were gradually reduced, and significantly less than the model control group, DMEM group 4 weeks later (P < 0.05), and significantly lower than that pretransplantation (P < 0.05).CONCLUSION: Using lentiviral vector to construct with AKT1 gene could stably make BMSCs overexpress AKT1. The BMSCs engraftment in host myocardium might improve the left ventricle function by attenuating the contractile dysfunction and pathologic thinning in this model of left ventricular wall infarction. AKT1 overexpression can significantly improve cardiac function following infarction.
4.Prognostic predictive value of detecting minimal residual disease in acute myeloid leukemia after 2 courses of hypomethylating agents combined with low-dose induction chemotherapy
Haoyue CHEN ; Chunhua LIU ; Qiaoyan HAN
Journal of Leukemia & Lymphoma 2023;32(4):215-220
Objective:To explore the prognostic predictive value of detecting minimal residual disease (MRD) after 2 courses of hypomethylating agents (HMA) combined with low-dose induction chemotherapy in patients with acute myeloid leukemia (AML).Methods:The data of 43 newly diagnosed AML patients treated by HMA combined with low-dose induction chemotherapy in Jingjiang People's Hospital of Jiangsu Province from January 2016 to January 2021 were retrospectively analyzed, and the bone marrow MRD levels were detected by multiparametric 10-color flow cytometry (MFC) after 1 course and 2 courses of chemotherapy. Patients were divided into three groups according to MRD levels: the group with negative MRD after 1 course of induction chemotherapy (MRD-1 group), the group with negative MRD after 2 courses of induction chemotherapy (MRD-2 group), and the group without negative MRD after 2 courses of induction chemotherapy (MRD+ group). Kaplan-Meier method was used to draw the progression-free survival (PFS) and overall survival (OS) curves of all patients and each group, and log-rank test was performed to compare them; the influencing factors for OS were analyzed using univariate and multivariate Cox proportional hazards models.Results:Among the 43 patients, 17 patients (39.5%) were in the MRD-1 group, 14 patients (32.6%) were in the MRD-2 group, and 12 patients (27.9%) were in the MRD+ group. There were no statistical differences among the 3 groups in gender, age, hemoglobin level at initial diagnosis, white blood cell count, platelet count, lactate dehydrogenase level, disease subtype, WT1 expression, karyotype, and genetic risk stratification (all P > 0.05). The median follow-up was 15 months (1-67 months). Survival analysis showed a median OS time of 21 months (95% CI 15 months -not reached) in 43 patients and a median PFS time of 12 months (95% CI 9-18 months) in 29 patients included in the PFS analysis; PFS and OS in the MRD-1 and MRD-2 groups were better than those in the MRD+ group (all P < 0.01), and the differences in PFS and OS between the MRD-1 and MRD-2 groups were not statistically significant (both P > 0.05); the median PFS time was 5 months (95% CI 2 months-not reached) in the MRD+ group, the median PFS time was 15 months (95% CI 7 months-not reached) in the MRD-1 group, and the median PFS time was 18 months (95% CI 11 months-not reached) in the MRD-2 group; the median OS time in the MRD+ group was 9 months (95% CI 7 months-not reached), the median OS time was not reached in the MRD-1 group, and the median OS time was 38 months (95% CI 38 months-not reached) in the MRD-2 group. Multivariate Cox regression analysis showed that age ( HR = 1.080, 95% CI 1.004-1.160, P = 0.038), MRD status (MRD-1 vs. MRD+: HR = 0.125, 95% CI 0.031-0.507, P = 0.004; MRD-2 vs. MRD+: HR = 0.146, 95% CI 0.037-0.577, P = 0.006) were independent influencing factors for OS in AML patients. Conclusions:The survival is good in AML patients with MRD negative conversion after both 1 course and 2 courses of HMA combined with low-dose induction chemotherapy, and both are better than that in patients with positive MRD after 2 courses of chemotherapy.
5.Sj?gren's syndrome with cerebral venous sinus thrombosis:a case report
Xue CHEN ; Haoyue WANG ; Mingming LI ; Zhaoming GE
Chinese Journal of Cerebrovascular Diseases 2024;21(9):629-631,637
Cerebral venous sinus thrombosis(CVST)is a special type of cerebrovascular disease,and the common autoimmune diseases that can cause CVST are systemic lupus erythematosus and antiphospholipid syndrome,and the combination of CVST with Sj?gren's syndrome is not common in clinical practice.The authors reported the case data of a patient with Sj?gren's syndrome combined with CVST and discussed the possible pathogenesis,treatment and prognosis,with the aim of providing some guidance for the diagnosis and treatment of this type of patient.
6.Role of different phenotype tumor-associated macrophages in tumor progression
Haoyue GUO ; Rui MAO ; Ran WANG ; Erjia ZHU ; Donglai CHEN
Chinese Journal of Clinical Oncology 2018;45(9):482-486
Innate immune cells are highly represented in the tumor microenvironment,and among the most abundant of these are macrophages.However,macrophages are broadly categorized as"classically activated"pro-inflammatory M1 macrophages and"alter-natively activated"anti-inflammatory M2 macrophages,which might be too simplified to describe the various phenotypes and func-tions of tumor-associated macrophages(TAMs).Most TAMs are now reclassified into CD68+TAM,CD163+TAM,CD204+TAM,CD169+TAM,and CCL18+TAM,among others,according to the different expression of surface proteins.These surface proteins have different types of ligands and regulate different signaling pathways and cytokines.Therefore,even if these subtypes of TAMs have similar ef-fects of promoting or inhibiting tumors,the mechanisms involved and the induced clinical manifestations are different.In this paper, the effects of various phenotypes of TAMs on tumor growth,metastasis,prognosis,and clinical relevance are reviewed.
7.Correlation of platelet recovery after complete remission of induction chemotherapy with minimal residual disease and clinical characteristics in acute myeloid leukemia
Haoyue CHEN ; Miao SUN ; Chunhua LIU ; Qiaoyan HAN ; Xiaorui LI
Journal of Leukemia & Lymphoma 2022;31(11):655-658
Objective:To investigate the correlation of excessive platelet (Plt) recovery at the first time of achieving morphologic complete remission (CR) after induction chemotherapy with minimal residual disease (MRD) and the clinical features of acute myeloid leukemia (AML).Methods:The clinical data of newly-treated 57 AML patients (except for acute promyelocytic leukemia) who achieved CR after induction chemotherapy in Jinjiang People's Hospital from January 2016 to December 2021 were retrospectively analyzed. A total of 57 newly diagnosed adult AML patients were divided into excessive Plt recovery group (Plt recovery>350×10 9/L) and normal Plt recovery group [Plt recovery: (100-350)×10 9/L] according to the Plt recovery. Meanwhile, the MRD was analyzed by using multiparameter flow cytometry (MFC) in patients achieving CR after receiving 1 course of standard treatment regimen or 1-2 courses of demethylation drugs combined with pre-conditioning regimen. The clinical features and negative rate of MRD between the two groups were compared. Results:Among 57 CR patients, 31 (54.4%) patients had CR with excessive Plt recovery and MFC-MRD negative rate was 67.7% (21/31); 26 (45.6%) had CR with normal Plt recovery and MFC-MRD negative rate was 38.5% (10/26); and the difference in the proportion of MRD negative patients between the both groups was statistically significant ( χ2 = 4.89, P = 0.027). There were no statistically differences in the proportions of patients with different gender, age, WBC at initial diagnosis, Plt, chemotherapy regimen and risk degree classification between the two groups (all P > 0.05). Conclusions:In AML patients, excessive Plt recovery at the first time of achieving morphologic CR after induction chemotherapy is associated with negative MRD, which has a certain value in the judgement of therapeutic effect.
8.Development and strategy analysis of Chinese herbal medicine in Germany
Haoyue LI ; Jing ZHAO ; Zijun ZHANG ; Xueyang ZHANG ; Xiaoying TONG ; Masseli CHRISTINE ; Yisheng ZHANG ; Chen LIU ; Haiyu XU ; Rongrong GAO
International Journal of Traditional Chinese Medicine 2022;44(11):1215-1220
Germany owns the largest herbal market in Europe and has the world's leading R&D capabilities for herbal medicine products. Chinese herbal medicine (CHM) spreaded to Germany hundreds of years ago. Since the beginning of the 20th century, China and Germany have signed a series of agreements to support traditional medicine cooperation, and the exchange of herbs between China and Germany has become more frequent, bringing opportunities for CHM to enter into Germany. In recent years, China and Germany have gained progress in the fields of CHM research and trade, etc. However, there are differences in the understanding of herbal medicines, quality standard evaluation, usage, and medication rules between the two countries. By doing SWOT analysis of the development of CHM in Germany, this paper suggested to promote Sino-German medical exchanges and build a community of common health for mankind through strengthening the clinical application of CHM, finding new ways of CHM entering into German market, and building an international talent team of traditional Chinese medicine.
9.Observation on the effects and complications of mitral valve membrane replacement surgery with preserva-tion of mitral valve subvalvular structure on cardiac function and valve function
Yihuan CHEN ; Zhenya SHEN ; Yunsheng YU ; Haoyue HUANG ; Wenxue YE ; Fei HUA ; Yanqiu HU
The Journal of Practical Medicine 2024;40(15):2092-2097
Objective To investigate the effects and complications of mitral valve membrane replacement surgery with preservation of mitral valve subvalvular structure on cardiac and valve function.Methods A total of 84 patients receiving mitral valve membrane replacement surgery with preserved mitral valve subvalvular structure in the First Affiliated Hospital of Soochow University from August 2019 to July 2022 were selected as the observa-tion group,and 68 patients receiving mitral valve membrane replacement surgery without preservingmitral valve subvalvular structure were selected as the control group.The surgical indicators,comorbidities,preoperative and postoperative cardiac function,and mitral valve hemodynamic parameters were compared between the two groups.Results There was no statistically significant difference between the observation group and the control group in terms of surgical history,extracorporeal circulation time,aortic occlusion time,postoperative mechanical ventilation time,ICU retention time,and postoperative hospitalization time(P>0.05).At 1,3,and 6 months after surgery,the left ventricular end systolic diameter(LVESD)and left ventricular end diastolic diameter(LVEDD)in the observation group were significantly lower than those in the control group(P<0.05),while the left ventricular short axis shortening rate(LVFS)was significantly higher than that in the control group(P<0.05).There was no statistically significant difference in left ventricular ejection fraction(LVEF)between the observation group and the control group at 1,3,and 6 months after surgery(P>0.05).There was no statistically significant difference(P>0.05)in the peak mitral valve velocity(Vmax),maximum pressure gradient difference(PGmax),and mean pressure gradi-ent difference(PGmean)between the observation group and the control group at 1,3,and 6 months after surgery.There was no statistically significant difference in creatine kinase isoenzyme(CK-MB)and N-terminal precursor brain natriuretic peptide(NT-proBNP)between the observation group and the control group at 1,3,and 6 months after surgery(P>0.05).There was no statistically significant difference in the incidence of postoperative complica-tions between the observation group and the control group(P>0.05).Conclusion The preservation of the mitral valve subvalvular structure and mitral membrane replacement surgery improved patient cardiac function,while there was no significant difference in mitral valve orifice blood flow parameters and complications compared with surgery without preservation of the mitral valve subvalvular structure.
10.Mechanism of molecular hydrogen attenuating acute lung injury induced by lipopolysaccharid
Haoyue XUE ; Xinyi TANG ; Jinqiu DING ; Xiaobing CHEN ; Haoran CHEN ; Dian YU ; Xiaomin LI ; Yongpeng XIE
Chinese Journal of Emergency Medicine 2024;33(10):1413-1420
Objective:To investigate the role and mechanism of molecular hydrogen in lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods:Balb/c male mice were randomly(random number) divided into control group, control+H 2, LPS and LPS+H 2 group with 6 mice in each group. The levels of malondialdehyde (MDA) and Fe 2+ in lung tissue were detected by kits. The lung tissue morphology was observed. The infiltration levels of F4/80 positive macrophages in lung tissue were detected by immunofluorescence staining. A549 cells were divided into control, control+H 2, erastin and erastin+H 2 group. The reactive oxygen species (ROS), malondialdehyde, (MDA), lactate dehydrogenase (GSH), number of cell death and lactate dehydrogenase (LDH) release in each group were detected by kits. Nrf2, GPX4, and HO-1mRNA were quantified by real-time PCR, the protein expression level of Nrf2 was detected by western blot, and the nuclear translocation level of Nrf2 was observed by immunofluorescence. The chi-square test was performed before the measurement data were counted. One-way analysis of variance was used to compare differences between multiple groups. Results:Compared with the control group, the histopathological damage was aggravated, and the levels of MDA, Fe 2+ significantly increased in the LPS group, and F4/80 positive immune cells infiltration significantly increased (all P<0.05). Compared with LPS group, the degree of lung injury in LPS+H 2 group significantly reduced (all P<0.05). In vitro experiments, compared with the control group, the ROS, MDA levels, number of cell death and LDH release significantly increased in erastin group (all P<0.05), while GSH, and GPX4 mRNA levels decreased (all P<0.05). HO-1mRNA and Nrf2 nuclear translocation levels increased (all P<0.05). Compared with erastin group, ROS, MDA levels, cell death number and LDH release decreased in earstin+H 2 group (all P<0.05). The levels of GSH, GPX4 mRNA, Nrf2 mRNA, HO-1 mRNA and Nrf2 nuclear translocation levels increased (all P<0.05). Conclusions:Molecular hydrogen attenuates LPS-induced ALI by promoting Nrf2 nuclear translocation to inhibit ferroptosis of alveolar epithelial cells.