1.Study on the effect and mechanism of Xinyang Tablet on myocardial ferroptosis in mice with chronic heart failure
Jinhua KANG ; Pengpeng LIANG ; Xiaoxiong ZHOU ; Ao LIU ; Zhongqi YANG ; Hongyan WU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):516-528
Objective:
Exploring the effect and mechanism of Xinyang Tablet on reduction of ferroptosis in myocardial cells from mice with chronic heart failure.
Methods:
Sixty C57BL/6J mice were randomly assigned to the sham, model, Xinyang Tablet low-dose (0.34 g/kg), Xinyang Tablet medium-dose (0.68 g/kg), Xinyang Tablet high-dose (1.36 g/kg), and perindopril (0.607 mg/kg) groups using a random number table method (10 mice in each group). Except for the sham group, all other groups underwent aortic arch constriction surgery to construct a chronic heart failure model. On the third day after completion of the modeling, each treatment group was administered the corresponding medication by gavage, while the sham and model groups were administered equal volumes of water by gavage once a day for eight consecutive weeks. After treatment, cardiac ultrasound was used to detect the structure and function of the mouse heart. Hematoxylin and eosin staining was used to detect pathological changes in mouse heart tissue. Masson staining was used to detect the proportion of fibrotic area of mouse heart tissue. Realtime fluorescence PCR was used to detect the mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen 3α (Col3α), and myosin heavy chain 7 (MYH7) in mouse myocardial tissue. Transmission electron microscope was used to detect the ultrastructure of myocardial cell mitochondria. Reactive oxygen species (ROS) staining was used to detect the mean fluorescence intensity of ROS in myocardial tissue. Micro-determination was used to detect superoxide dismutase (SOD) activity in myocardial tissue. An immunofluorescence assay was used to detect the mean fluorescence intensity of phosphorylated histone deacetylase 2 (p-HDAC2) in myocardial cell. Western blotting was used to detect the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), p-HDAC2, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), glutathione peroxidase 4 (GPX4), and cystine glutamate reverse transporter (xCT) in mouse myocardial tissue.
Results:
Compared to the sham group, the model group showed a decrease in left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), an increase in left ventricular end-systolic diameter(LVESD) and left ventricular end-diastolic diameter (LVEDD), an increase in the proportion of cardiac fibrosis area, an increase in relative expression levels of ANP, BNP, Col3α, and MYH7 mRNA, an increase in ROS mean fluorescence intensity, a decrease in SOD activity, an increase in mean fluorescence intensity of p-HDAC2, an increase in relative expression levels of p-HDAC2 and NOX1 proteins, and a decrease in relative expression levels of Nrf2, GPX4, and xCT proteins (P<0.05). Myocardial fibrosis lesions are obvious, with disordered mitochondrial arrangement, decreased volume and shrinkage, increased membrane density, and reduced mitochondrial cristae. Compared to the model group, the LVEF and LVFS of mice in each dose group of Xinyang Tablet and the perindopril group increased, LVESD and LVEDD decreased, the proportion of fibrotic area of heart tissue decreased, the relative expression levels of ANP, BNP, Col3α, MYH7 mRNA decreased, ROS mean fluorescence intensity decreased, SOD activity increased, mean fluorescence intensity of p-HDAC2 decreased, relative expression levels of p-HDAC2 and NOX1 proteins decreased, and relative expression levels of Nrf2 and xCT proteins increased (P<0.05). Myocardial fibrosis was reduced, the mitochondrial arrangement was more regular, the mitochondria enlarged, the membrane density was reduced, and mitochondrial cristae increased. Compared to the model group, the relative expression level of the GPX4 protein in myocardial tissue increased in the Xinyang Tablet medium-, high-dose, and the perindopril groups (P<0.05).
Conclusion
Xinyang Tablet can improve ferroptosis and ventricular remodeling in mice with chronic heart failure by regulating the HDAC2-mediated Nrf2 antioxidant pathway.
2.Galangin improves cardiac remodeling and dysfunction after myocardial infarction via inhibiting cardiomyocyte apoptosis and inflammation
Jixian GAO ; Ming LI ; Bing WU ; Xiaoxiong LIU ; Hao XIA
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(1):71-75
Objective To investigate the effect of galangin on cardiac remodeling and cardiac func-tion after myocardial infarction(MI).Methods A total of 32 male C57/BL6 mice(8-10 weeks old)were subjected for MI modeling,and finally 24 mice were assigned into control group[sham operation+hydroxycellulose sodium(CMC-Na)],model group(MI+CMC-Na),and experimental group(MI+galangin),with 8 mice in each group.After MI modeling,the mice of the experimen-tal group were given 40 mg/kg galangin by gavage for 4 weeks,and those of the control group and the model group were given the same volume(0.4 ml)of CMC-Na solution.HE staining was used to observe the size of the infarct area.The mRNA levels of inflammatory factors in the heart were detected by qRT-PCR,and protein levels of related signaling pathway proteins were measured with Western blotting.Immunofluorescence(IF)assay was applied to detect the infiltration of in-flammatory cells in the infarct border zone.TUNEL staining was employed to detect cell apoptosis in the infarct border zone.Results At 4 weeks after modeling,larger infarct size,enhanced expression levels of IL-1β,IL-6,TNF-α,p-P65,p-IκBα and Bax,elevated apoptotic rate,decreased cardiac function indicators such as FS and LVEF,and reduced Bcl-2 expression level were observed in the model group than the control group(P<0.05).The experimental group had sig-nificant smaller myocardial infarct size[(11.64±0.64)%vs(21.84±1.94)%],less CD3 positive T cells[(3.10±0.46)%vs(6.28±0.24)%],F4-80 positive macrophages[(1.98±0.50)%vs(5.35±0.62)%]and LY6G positive neutrophils[(6.33±0.67)%vs(11.33±1.77)%],decreased expression levels of IL-1β,IL-6,TNF-α,p-P65,p-IκBα and Bax,reduced apoptotic rate[(21.45± 1.62)%vs(35.68±0.88)%],and increased FS and LVEF values and Bcl-2 expression level when compared with the model group(P<0.05).Conclusion Galangin improves myocardial remode-ling and cardiac dysfunction after MI by inhibiting inflammatory response and cell apoptosis.
3.Mechanism of salidroside in tumor suppression through the miRNA-mRNA signaling axis
Xiaoxiong WU ; Zhendong ZHANG ; Xiaoping WANG
Journal of Central South University(Medical Sciences) 2024;49(5):810-817
With the rapid development of traditional Chinese medicine and the continuous discovery of various anticancer effects of salidroside(sal),it is known that sal inhibits tumor proliferation,invasion and migration by inducing apoptosis and autophagy,regulating the cell cycle,modulating the tumor microenvironment,and controlling cancer-related signaling pathways and molecules.The microRNA(miRNA)-mRNA signaling axis can regulate the expression of target mRNAs by altering miRNA expression,thereby affecting the growth cycle,proliferation,and metabolism of cancer cells.Studies have shown that sal can influence the occurrence and progression of various malignant tumors through the miRNA-mRNA signaling axis,inhibiting the progression of lung cancer,gastric cancer,and nasopharyngeal carcinoma,with a notable time and dose dependence in its antitumor effects.Summarizing the specific mechanism of sal regulating miRNA-mRNA signaling axis to inhibit tumors in recent years can provide a new theoretical basis,diagnosis,and therapeutic methods for the research on prevention and treatment of tumors.
4.The status of homologous recombination deficiency and BRCA1/2 gene mutation in ovarian cancer patients in the Yunnan region and their clinical significance
CAI Jingjing ; LIU Xin ; LI Zhuoying ; HAN Tingting ; GUO Yinjin ; MA Luyao ; WANG Xiaoxiong ; LI Hongsheng ; LI Quan ; DU Yaqian ; LAN Yunyi ; SHEN Shaocong ; YANG Ruijiao ; WU Shunxian ; LIU Junxi ; ZHOU Yong
Chinese Journal of Cancer Biotherapy 2023;30(12):1082-1087
[摘 要] 目的:采用基于中国人群单核苷酸多态性位点开发的同源重组缺陷(HRD)检测工具评估云南地区卵巢癌患者的HRD状态和BRCA1/2基因突变频率并探讨其临床意义。方法:共纳入2021年1月至2023年5月间在云南省肿瘤医院收治的卵巢癌患者248例,HRD状态采用基因组瘢痕评分法(GSS)(主要依据拷贝数的长度、类型、位置及基因组断片)或HRD评分法(杂合性缺失、端粒等位基因失衡及大片段移位等基因组不稳定事件的总和)进行评估,当组织样本的GSS≥50分或HRD评分≥42分者或检测到有害的BRCA1/2基因突变时HRD被定义为阳性。分析患者HRD状态与临床病理特征的关系。结果:248名卵巢癌患者中70.97%的患者HRD呈阳性,其中BRCA1/2基因突变率为30.65%。Ⅲ~Ⅵ期、高级别浆液腺癌的卵巢癌患者具有更高的HRD阳性率(均P<0.01),HRD评分更高的患者其合并其他基因突变的频率也越高(P<0.05)。HRD状态与卵巢癌的病理类型、临床分期和其他基因突变均有关联(均P<0.01)。结论:云南地区卵巢癌患者HRD阳性率较高,HRD阳性的卵巢癌患者可以从聚ADP核糖聚合酶(PARP)抑制剂治疗中获得更大的收益。
5.Progress of Research on Long Noncoding RNA in Digestive System Tumors
Xiang LI ; Maosheng CHEN ; Duolin NIU ; Xinyi ZHAO ; Xiaoxiong WU ; Xiaolan CAO ; Xiaoping WANG
Chinese Journal of Gastroenterology 2023;28(10):631-635
The incidence and mortality of digestive system tumors are high,and the trend is increasing year by year,and the early onset is hidden,difficult to detect,and seriously threaten human health.In recent years,it has been found that long noncoding RNA(lncRNA),as a new class of non-coding RNA,plays an important role in the occurrence and development of tumors,influencing the occurrence and development of tumors by regulating the malignant biological characteristics of tumor cells such as proliferation,invasion and metastasis.Further study on the role of lncRNA in digestive system tumors can further discover its diagnosis and treatment methods,and provide new ideas for reducing the incidence and mortality of digestive system tumors.This article reviewed the progress of research in lncRNA in digestive system tumors.
6.Progress of Research on Long Noncoding RNA in Digestive System Tumors
Xiang LI ; Maosheng CHEN ; Duolin NIU ; Xinyi ZHAO ; Xiaoxiong WU ; Xiaolan CAO ; Xiaoping WANG
Chinese Journal of Gastroenterology 2023;28(10):636-640
The incidence and mortality of digestive system tumors are increasing year by year,which seriously threatens human life and health.In recent years,it has been found that long noncoding RNA(lncRNA)is involved in regulating the proliferation,migration,and invasion of digestive system tumors.This article reviewed the progress of research on lncRNA in digestive system tumors.
7. Outcomes of 33 patients with anaplastic large cell lymphoma treated after hematopoietic stem cell transplantation
Ning LU ; Xiaofan LI ; Yujun DONG ; Yini WANG ; Xiaorui FU ; Yamei WU ; Yuhang LI ; Maihong WANG ; Nainong LI ; Hanyun REN ; Zhao WANG ; Mingzhi ZHANG ; Xiaoxiong WU ; Liangding HU ; Yao LIU ; Wenrong HUANG
Chinese Journal of Hematology 2020;41(2):117-122
Objective:
To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) .
Methods:
The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis.
Results:
The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK+ and 9 ones (27.3%) ALK-. Of them, 25 patients (19 ALK+ and 6 ALK-) underwent auto-HSCT and 8 cases (5 ALK+ and 3ALK-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS,
8. Clinical outcomes of hematopoietic stem cell transplantation for angioimmunoblastic T-cell lymphoma
Lingmin XU ; Nainong LI ; Zhao WANG ; Xiaoxiong WU ; Yujun DONG ; Xiaorui FU ; Yao LIU ; Liangding HU ; Xiaofan LI ; Yini WANG ; Yamei WU ; Hanyun REN ; Mingzhi ZHANG ; Maihong WANG ; Yuhang LI ; Wenrong HUANG
Chinese Journal of Hematology 2019;40(7):573-577
Objective:
To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) .
Methods:
From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively.
Results:
Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%
9.Clinical study on foscarnet prophylaxis and pre-emptive therapy for cytomegalovirus infection in hematopoietic stem cell transplantation
Yamei WU ; Yongbin CAO ; Xiaohong LI ; Lixin XU ; Bei YAN ; Songwei LI ; Haitao WANG ; Yahui GAO ; Tiantian ZHANG ; Yaqian ZHANG ; Li WANG ; Xiaoxiong WU
Journal of Leukemia & Lymphoma 2017;26(6):331-335
Objective To observe the clinical safety and efficacy of foscarnet prophylaxis and pre-emptive therapy for cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Ninety-six patients undergoing allo-HSCT from October 2014 to December 2016 were retrospectively analyzed. Plasma CMV-DNA was monitored with real-time quantitative polymerase chain reaction (RQ-PCR) from beginning to 180 days after transplantation. Foscarnet was used not only for prophylaxis but also for first-line pre-emptive therapy when plasma CMV-DNA turned to positive. Foscarnet was given 60 mg·kg-1·d-1 and 120 mg·kg-1·d-1 respectively in prevention and pre-emptive therapy. Incidences of CMV infection and CMV disease were observed, influencing factors on CMV in faction and the efficacy and safety of foscarnet prophylaxis were analyzed, and survival of patients treated by all-HSCT was evaluated. Results Of the total 96 patients, 42 cases (43.8%) had CMV infection with the median time of 42 days after allo-HSCT. CMV-DNA became negative in 36 patients (85.7%, 36/42) after pre-emptive therapy. Six patients (14.3 %, 6/42) developed CMV disease, including 5 patients with CMV negative and 1 patient died for CMV pneumonia. Haploidentical donor and grade Ⅱ-Ⅳacute graft versus host disease (GVHD) were the risk factors for CMV reactivation (χ2 = 3.834, P< 0.05; χ2 = 16.807, P< 0.001). The side effects of foscarnet prophylaxis were mild without hematologic toxicities. 12 patients (28.6 %) died in 42 patients with CMV infection, and 6 patients (11.1 %) died in 54 patients without CMV infection. The difference of survival rates between both groups was not statistically significant. Conclusion Foscarnet is an effective agent for prophylaxis and pre-emptive therapy in CMV infection after allo-HSCT with mild adverse reactions, especially for patients following with hematopoietic recovering.
10. Risk-factor analysis of poor graft function after allogeneic hematopoietic stem cell transplantation for severe aplastic anemia
Chenyan SHI ; A MAMAL ; Zenghui LIU ; Xiaoxiong WU ; Linghui XIA ; Danian NIE ; Yongrong LAI ; Fengqi DUAN ; Haowen XIAO ; Zujun JIANG ; Yonghua LI ; Yang XIAO
Chinese Journal of Hematology 2017;38(9):761-766
Objective:
To investigate the risk factors of poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (SAA) .
Methods:
Clinical data from 111 SAA patients who received allo-HSCT were analyzed retrospectively. Factors including age, gender, interval to transplantation, the level of serum ferritin before transplantation were analyzed by Cox multivariate regression analysis.
Results:
Among the 111 patients who underwent allo-HSCT, 16 developed PGF (14.4%) . Multivariate analysis showed donor type (


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