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.Study on the Quality Regionalization of Forsythia suspensa(Thunb.)Vahl in Shanxi Province Based on MaxEnt Model and ArcGIS
Xiaoxiong SUO ; Caixia LIU ; Yimeng ZHAO ; Chenhui DU ; Lili PING ; Haixian ZHAN ; Runli HE ; Cailing SHANG ; Xiaobo ZHANG ; Tingting SHI ; Xiangping PEI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(10):1-7
Objective To establish ecological suitability zone of Forsythia suspensa(Thunb.)Vahl in Shanxi Province;To study the quality regionalization of Forsythia suspensa(Thunb.)Vahl from different producing areas in Shanxi Province;To provide reference for reasonable planting and wild tending of Forsythia suspensa(Thunb.)Vahl.Methods Maximum entropy(MaxEnt)model and ArcGIS software were used to study the ecological suitability of Forsythia suspensa(Thunb.)Vahl in Shanxi Province;By screening the main environmental factors and combining them with the content of forsythoside and forsythoside A in Forsythia suspensa(Thunb.)Vahl of different regions,a quality zoning of Forsythia suspensa Thunb.Vahl medicinal materials in Shanxi Province based on forsythoside,forsythoside A and environmental factors was constructed.Results The ecological suitable areas of Forsythia suspensa Thunb.Vahl in Shanxi Province were mainly distributed in the southern part of Shanxi Province,mainly in Linfen,Yuncheng,Changzhi,and Jincheng.The general contents of forsythoside and forsythoside A in the Forsythia suspensa(Thunb.)Vahl medicinal material were gradually reduced from southern part to northern part of Shanxi Province.The comprehensive quality was high in southern part of Shanxi Province,mainly in Linfen,Changzhi,Yuncheng and Jincheng.Conclusion The results of this study are consistent with the actual survey.The southern part of Shanxi province is a suitable planting area for high quality Forsythia suspensa(Thunb.)Vahl,which provides a reference for the standardized planting and wild tending of Forsythia suspensa(Thunb.)Vahl.
4.Clinical and electrocardiographic characteristics of carriers with SCN5A mutations and non-SCN5A mutations in fever-induced Brugada syndrome
Keqin SHEN ; Zhonghe ZHANG ; Ganxiao CHEN ; Xiaoxiong LIU ; Guohua FAN ; Jinqiu LIU ; Hao XIA ; Hong JIANG ; Dan HU
Chinese Journal of Cardiology 2024;52(12):1377-1382
Objective:To investigate the differences in clinical and electrocardiographic characteristics between carriers of SCN5A mutations and non-SCN5A mutations in fever-induced Brugada syndrome.Methods:This study is a retrospective cohort study. A total of 263 patients with fever-induced Brugada syndrome who were admitted to Renmin Hospital of Wuhan University from January 2000 to December 2023 were selected. Their clinical manifestations, electrocardiographic characteristics, and major adverse cardiovascular events (MACE) at the time of diagnosis and during the follow-up period were collected. Among them, 200 patients underwent next-generation sequencing. Based on the genetic variation results, after excluding other mutations, they were divided into SCN5A mutation group, non-SCN5A sodium-related mutation group, potassium/calcium mutation group, and no mutation group. Comparisons were made among these groups in terms of their clinical and electrocardiographic characteristics.Results:Among the 263 patients with fever-induced Brugada syndrome, the mean age was (41.9±17.6) years, with 80.6% (212/263) being male. The median follow-up duration was 53.0 months, and 13.7% (36/263) of the patients experienced MACE. The rate of SCN5A mutation was 34.5% (69/200), while the rates of non-SCN5A sodium-related mutations and potassium/calcium-related mutations were 4.5% (9/200) and 3.5% (7/200), respectively. The SCN5A mutation group was younger than the non-SCN5A sodium-related mutation group and the no mutation group (ages were (33.8±14.7), (49.8±11.6), (44.6±15.7) years, respectively, P<0.001). The SCN5A mutation group also had a longer PR interval than the no mutation group ((176.8±32.3) ms vs. (163.9±28.6) ms, P=0.034). The incidence of MACE was higher in the non-SCN5A sodium-related mutation group than that in the no mutation group (55.6% (5/9) vs. 9.1% (9/99), P=0.002). Conclusions:Fever-induced Brugada syndrome patients carrying non-SCN5A mutations exhibit distinct clinical and electrocardiographic characteristics compared to those with SCN5A mutations. These differences warrant attention in clinical practice.
5.Application of a new residency training model for emergency medicine in the context of sub-specialty zoning
Xiaoxiong CHEN ; Yuanjuan JIANG ; Qiang XIANG ; Yajing SHEN ; Minghua LIU
Chinese Journal of Medical Education Research 2024;23(4):543-547
Objective:To investigate the application and teaching effect of a new residency training model for emergency medicine in the context of sub-specialty zoning.Methods:A total of 30 emergency medicine residents were randomly divided into experimental group and control group, with 15 residents in each group. The residents in the experimental group received teaching based on the sub-specialty zoning model, while those in the control group received traditional teaching. SPSS 26.0 software was used for the t-test and the chi-square test, and the two groups were compared in terms of demographic variables, training assessment scores, and teaching feedback. Results:There were no significant differences between the two groups in the demographic variables such as age, sex, education background, and years of clinical work, and there was also no significant difference between the two groups in the final assessment score of Chongqing ( P>0.05), but there was a significant difference between the two groups in the score of intra-department theoretical examination before the final assessment [(81.20±2.83) vs. (89.73±3.01), P<0.001]. The survey of teaching feedback showed that both groups had high confidence in independent duty and a high degree of satisfaction with teaching, with no significant differences between the two groups ( P>0.05); however, compared with the control group, the experimental group had a significantly higher recognition of the development of emergency sub-specialties and significantly better orientations of scientific research and self-development. Conclusions:The new residency training model for emergency medicine in the context of sub-specialty zoning may help with the long-term development of emergency medicine and should be further promoted and validated in emergency medicine residency training.
6.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。
7.Genetic safety evaluation of allogeneic bone marrow mesenchymal stem cells in hosts following traumatic brain injury
Sixian HUANG ; Zhiming FENG ; Yu XIE ; Xiaoxiong ZOU ; Kunlin LIU ; Shiting HUA ; Cong LI ; Yuxi ZOU ; Yingqian CAI ; Yanping TANG ; Xiaodan JIANG
Chinese Journal of Neuromedicine 2023;22(6):575-584
Objective:To investigate the genetic safety of allogeneic bone marrow mesenchymal stem cells (BMSCs) transplantation in traumatic brain injury (TBI).Methods:(1) In vivo experiment: BMSCs from male SD rats were isolated and cultured. Moderate TBI models were prepared by implanting and fixing micro-drug injection cannula into the left ventricle of 12 female SD rats, and 3 d after that, striking the right cerebral cortex of the rats with pneumatic precision percussion device was performed. Four h, and 3, 6, 9, and 12 d after modeling, TBI rats were given a single/multiple BMSCs infusion (2.5×10 5/time, total volume 10 μL) by cannula; 48 and 72 h, and 10 and 14 d after modeling, brain tissues of TBI rats (3 at each time point) were prepared into paraffin specimens. Immunofluorescent staining was used to detect the microglia activation, and RNAscope ? technology was used to detect the co-localization of astrocytes, neurons, microglia and transplanted BMSCs to observe whether the allogeneic BMSCs were integrated with the host brain cells after transplantation into TBI host. (2) In vitro experiment: the frozen and revived microglial cell line BV2 was transfected with green fluorescent protein (GFP)-positive lentiviral particles, and then, BMSCs prelabeled with pHrodo RED probe and BV2 cells pretreated with lipopolysaccharide were co-cultured in a certain ratio (BV2:BMSCs=1:1, 1:2, 2:1); after 36 and 72 h of co-culture, the phagocytosis between the 2 kinds of cells was observed under confocal fluorescence inverted microscope to observe the specific action forms of microglia on BMSCs. Results:(1) In vivo experiment: 48 and 72 h, and 10 and 14 d after modeling, no colocalization of transplanted BMSCs with astrocytes or neurons was found in paraffin sections of brain tissue in TBI rats; however, 10 and 14 d after modeling, microglia in TBI rats were obviously activated and migrated to the left lateral ventricle and choroid plexus, and co-localization of microglia with transplanted BMSCs was observed. (2) In vitro experiment: phagocytosis occurred after co-culture of BV2 cells at different proportions with BMSCs for 36 and 72 h. Conclusion:After transplantation, allogeneic BMSCs do not integrate with astrocytes or neurons of the TBI host, but they could be phagocytosed by microglia, indicating that allogeneic BMSCs transplantation for TBI is genetically safe.
8.Management of vascular complications after kidney transplantation caused by donor derived infection: a report of 6 cases
Long ZHANG ; Jiangqiao ZHOU ; Tao QIU ; Zhongbao CHEN ; Jilin ZOU ; Xiaoxiong MA ; Zeya JIN ; Yu XU ; Xiuheng LIU
Chinese Journal of Organ Transplantation 2022;43(6):340-345
Objective:To summarize the institutional experiences of treating vascular complications caused by donor-derived infection(DDI)after kidney transplantation(KT).Methods:From January 1, 2015 to December 31, 2020, clinical data were retrospectively reviewed for 6 cases of vascular complications caused by DDI.Age, gender, surgical approaches, immunity induction therapy, immune suppression therapy, infection prevention, onset time of complication, type of complications, infection pathogens, therapeutic protocols and prognoses were summarized.Results:Six patients developed vascular complications caused by DDI in 997 KT recipients with an overall morbidity rate of 0.6%.In 3 cases, carbapenem resistant Klebsiella pneumoniae were positive in culture of secretion and blood samples.And Candida albicans was detected by blood cultures and pathological examinations.One case of antibiotic resistant Staphylococcus aureus was detected by blood culture.Among 3 cases of transplant kidney artery pseudoaneurysm on interventional therapy, there were curing(1 case)and immediate recurrent infection(2 cases). The latter two eventually died by cardiac complications.In 2 cases of arterial hemorrhage, graft nephrectomy was followed by hemodialysis.One case of transplanted renal artery stenosis was successfully cured by artery stenting and survived with normal graft function so far.Conclusions:Interventional endovascular therapy and open surgery are indicated for vascular complications caused by DDI post-KT.Interventional therapy may boost the odds of rescuing transplant kidney.However, clinicians should watch out for the risk of recurrent infection.Open surgery is an effective tool of eliminating infected focus.Preserving transplant kidney or nephrectomy may be adopted on the basis of specific conditions.
9.Trends in clinicopathological characteristics of surgically-treated lung cancer: sex-based heterogeneity
Jie DAI ; Liangdong SUN ; Kaiqi JIN ; Xiaoxiong XU ; Zhao LI ; Xinsheng ZHU ; Linlin QIN ; Bin ZHOU ; Fujun YANG ; Yingran SHEN ; Ming LIU ; Xiaogang LIU ; Peng ZHANG ; Yuming ZHU ; Gening JIANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(7):396-401
Objective:To explore the sex-based heterogeneity in demographic and pathological trends of lung cancer during the past 30 years.Methods:Patients with primary lung cancer who received surgical treatment in the Department of thoracic surgery, Shanghai Pulmonary Hospital Tongji University from 1989 to 2018 were retrospectively analyzed. The differences between male and female patients in age, smoking history, pathological stage and type were compared. Mann- Kendall trend test was performed for trend analysis. Results:A total of 58 433 patients were included in this study, encompassing 30 729(52.6%) men and 27 , 704(47.4%) women. Compared with male patients, female patients were younger(56.0 years old vs. 59.7 years old), and had a higher proportion of non-smokers(98.3% vs. 52.3%), stage Ⅰ lung cancers(60.6% vs. 49.3%), and adenocarcinoma(93.7% vs. 56.1%, all P-values <0.001). Trend analyses revealed that the proportion of female patients increased year by year, and surpassed males in 2015, with the current ratio of male to female being 1∶1.5. After 2013, the age of onset in females was getting younger, and the average age decreased from 58.7 years old to 54.7 years old( P=0.02). The decrease in the proportion of smoking patients was mainly reflected by male patients(from 68.5% to 31.1%, P<0.01). Stage Ⅰ lung cancers in male and females outnumbered advanced stage in 2012 and 2010, respectively, with a much higher proportion in female patients. Among male patients, adenocarcinoma has replaced squamous cell carcinoma as the most common pathological type since 2012, while in female patients adenocarcinoma remained the most common pathological type of lung cancer, and its proportion continued to increase reaching over 98%. Conclusion:A dramatic change in gender distribution was noticed during the past 30 years. Female patients became the primary population in surgically-treated lung cancers, with a trend of getting younger. The proportion of smokers and squamous cell carcinoma decreased significantly in male patients, and adenocarcinoma has become the most common pathological type of lung cancer. The proportion of stage Ⅰ lung cancers was on a dramatic rise, with the popularization of CT screening for lung cancer.
10.Surgical management of pulmonary mucosa-associated lymphoid tissue-derived lymphoma: retrospective study of 86 cases
Xiaoxiong XU ; Ziwei WAN ; Hongcheng LIU ; Hao WANG ; Yuming ZHU ; Gening JIANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(10):599-603
Objective:To summarize our experience in diagnosis and treatment of patients with pulmonary mucosa-associated lymphoid tissue-derived(MALT) lymphoma and to explore the role of surgery.Methods:We retrospectively analyzed the clinical and follow-up data of 86 patients with pulmonary MALT lymphoma in Shanghai Pulmonary Hospital from January 2000 to December 2018. 86 cases were identified with 44 males and 42 females. The mean age was(56.7±10.6) years old. 38(44.2%) cases had symptoms mainly presenting as cough and sputum at diagnosis. The chest CT scan of the patients showed pulmonary consolidation in 39 cases, nodule/mass shadow in 37 cases, usually with air bronchogram. Only 8(9.3%) cases could be diagnosed by non-surgical approach. 58 cases received complete resection, 10 of which followed chemotherapy. 8 of 17 cases who received incomplete resection accepted chemotherapy. The rest 11 cases who experienced surgical biopsy because of uncertain diagnosis were treated by chemotherapy or radio-chemotherapy or just watch-to-wait.Results:The median follow-up of 83 cases was 64 months, ranged from 24 to 219 months. The estimated 5-year and 10-year OS rates were 95.0% and 76.8%, while 5-year and 10-year PFS were 75.7% and 35.1% respectively. Patients who received complete resectionhad better PFS( P<0.001)but similar OS( P=0.395), compared with those received incomplete resection. There were no significant difference in OS and PFS between patients who received complete resection accepted chemotherapy or not( P>0.05). Conclusion:Pulmonary MALT lymphoma has an indolent nature with an excellent long-term survival. Diagnosis is difficult to be made by non-surgical approach. Surgery plays an important role of treatment of pulmonary MALT lymphoma, due to significant improvement of diagnosis rate and radical treatment of localized disease by complete resection.


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