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.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。
3.Automatic synthesis and in vivo imaging of Al 18F-NOTA-FAPI-04
Xiao JIANG ; Xiaoxiong WANG ; Taipeng SHEN ; Yutang YAO ; Xiuli LI ; Jiaqi SHEN ; Ying KOU ; Meihua CHEN ; Shirong CHEN ; Dingqiong XIAO ; Meng ZHAO ; Hao LU ; Jiayu LI ; Shengyan HU ; Xiaoping HU ; Zhifu LUO ; Xing ZHOU ; Chuan LI ; Zhuzhong CHENG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(1):31-35
Objective:To automatically synthesize Al 18F-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04, perform PET/CT imaging in vivo, and evaluate its diagnostic efficacy on tumors. Methods:Al 18F-NOTA-FAPI-04 was produced in All-in-one automatic synthesis module and its quality control was conducted by high performance liquid chromatography (HPLC) equipped with a radioactive detector. Al 18F-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice ( n=3) and 4T1 breast cancer models ( n=3) to determine its biodistribution. Then Al 18F-NOTA-FAPI-04 and 18F-FDG PET/CT imaging were performed in a hepatocellular carcinoma patient (male, 51 years old). Results:The synthesis time of Al 18F-NOTA-FAPI-04 was about 35 min, and the radiochemical yield was (25.2±1.9)% (attenuation correction, n=3). The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (46.11±3.07) GBq/μmol (attenuation correction, n=3). The radiochemical purity was above 99.0% and was still above 98.0% at room temperature after 6 h. PET/CT imaging in mice showed that physiological uptake of Al 18F-NOTA-FAPI-04 was mainly in biliary system and bladder, and Al 18F-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that Al 18F-NOTA-FAPI-04 obtained high tumor background ratio (TBR) values of 4.1, 8.9, 5.4, 4.8, 2.2 in parasternal lymph nodes, anterior diaphragmatic lymph nodes, hilar lymph nodes, pancreaticoduodenal ligament lymph nodes, abdominal aortic lymph nodes, respectively, while TBR values were 1.0, 2.8, 5.0, 2.1, 1.1 by 18F-FDG. Conclusions:Al 18F-NOTA-FAPI-04 can be synthesized with short time, high radiochemical yield and good stability using All-in-one module. Al 18F-NOTA-FAPI-04 PET/CT imaging has high contrast and excellent diagnostic efficacy on tumors.
4.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.
5.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.
6.Retrospective analysis of clinical characteristics of 18 pregnant women infected with dengue virus in Ruili City, Yunnan Province
Wenshuang JIA ; Man LI ; Jiayuan SHEN ; Zhongping YANG ; Jiarong MAO ; Xiaoxiong YIN ; Yonghua LIU ; Yangsiqi LI ; Hongning ZHOU
Chinese Journal of Endemiology 2021;40(9):752-755
Objective:To understand the clinical characteristics of pregnant women infected with dengue virus (DENV) in Ruili City, Yunnan Province, so as to provide basis for formulating effective diagnosis and treatment protocol of dengue fever in pregnant women.Methods:A total of 18 pregnant women infected with DENV hospitalized in Ruili People's Hospital in 2017 and 2018 were selected as observation group, and 18 non-pregnant women infected with DENV were selected as control group according to the age range of the observation group, and epidemiological and clinical data of patients in the two groups were retrospectively collected. Epidemiological characteristics, clinical symptoms and laboratory biochemical indexes of the two groups were compared and analyzed.Results:There were no significant differences ( t = - 0.032, 0.495, P > 0.05) in age [(27.9 ± 5.3) vs (27.9 ± 5.1) years old] and hospitalization stay [(6.8 ± 1.6) vs (6.6 ± 2.0) d] between the observation group and control group. One pregnant woman in observation group had early pregnancy abortion. Patients of both groups had fever in 18 cases (100.0%), headache, muscle aches, and chills in 14 cases (77.8%), anorexia in 15 cases (83.3%), and nausea and vomiting in 5 cases (27.8%); fatigue in 14 cases (77.8%) and 16 cases (88.9%), respectively; there was 1 case of rash in observation group (5.6%), and no rash in control group. There were no significant differences in the above mentioned clinical symptoms distribution between the two groups ( P > 0.05). On the first day of admission, the reduction proportions in red blood cells [61.1% (11/18) vs 5.6% (1/18)], hemoglobin [50.0% (9/18) vs 16.7% (3/18)], and hematocrit [61.1% (11/18) vs 16.7% (3/18)] in observation group were significantly higher than those in control group ( P < 0.05); on the fifth day of admission, the reduction proportions in hemoglobin [33.3% (6/18) vs 5.6% (1/18)] and hematocrit [33.3% (6/18) vs 5.6% (1/18)] in observation group were significantly higher than those in control group ( P < 0.05). Conclusions:The red blood cells, hemoglobin and hematocrit of pregnant women infected with DENV are significantly reduced, and there is a risk of miscarriage in early pregnancy. It is suggested that relevant departments should strengthen the training of medical staff to diagnose and treat pregnant women infected with DENV early.
7.Solitary pulmonary capillary hemangioma of adult: a series of 10 cases
Yiming ZHOU ; Jie DAI ; Xiaoxiong XU ; Yuming ZHU ; Gening JIANG ; Liping ZHANG
Chinese Journal of Surgery 2021;59(1):66-70
Objective:To examine the clinical features, diagnostic and therapeutic strategy of solitary pulmonary capillary hemangioma (SPCH).Methods:The data of 10 SPCH cases who underwent surgical operations from June 2017 to June 2020 in Shanghai Pulmonary Hospital, Tongji Universitywere retrospectively reviewed. There were 4 males and 6 females, aged (49.8±13.6) years (range: 26 to 66 years). The clinical manifestations, imaging manifestations, treatment and pathological diagnosis were analyzed. Results:All patients were asymptomatic, and all nodules were detected by CT. The size of nodule was (14.9±5.8) mm (range: 8 to 30 mm). Seven of 10 cases showed the mixed ground-glass nodule appearance and 2 cases showed solid nodule and 1 case showed cystic solid nodule appearance in CT findings. The growth speed was very slow. The follow-up time was 4.5(21.5) months before surgery. Histologically, SPCH manifested as a solitary lesion composed of densely proliferating and dilated capillaries without cytologic atypia within the alveolar septa. Immunohistochemically, capillaries of SPCH uniformly expressed endothelial markers, such as CD31, CD34. The patients were followed up for 15.0(22.0) months after surgery and all recovered well.Conclusions:SPCH is probably an unrecognized benign capillary proliferative disease. SPCH lesions mimic early lung cancer on CT as mixed ground-glass nodule, may be misdiagnosed as other nonspecific benign lesions. With careful histologic examination, SPCH can be successfully diagnosed using CD34 or CD31 immunohistochemistry staining.
8.Solitary pulmonary capillary hemangioma of adult: a series of 10 cases
Yiming ZHOU ; Jie DAI ; Xiaoxiong XU ; Yuming ZHU ; Gening JIANG ; Liping ZHANG
Chinese Journal of Surgery 2021;59(1):66-70
Objective:To examine the clinical features, diagnostic and therapeutic strategy of solitary pulmonary capillary hemangioma (SPCH).Methods:The data of 10 SPCH cases who underwent surgical operations from June 2017 to June 2020 in Shanghai Pulmonary Hospital, Tongji Universitywere retrospectively reviewed. There were 4 males and 6 females, aged (49.8±13.6) years (range: 26 to 66 years). The clinical manifestations, imaging manifestations, treatment and pathological diagnosis were analyzed. Results:All patients were asymptomatic, and all nodules were detected by CT. The size of nodule was (14.9±5.8) mm (range: 8 to 30 mm). Seven of 10 cases showed the mixed ground-glass nodule appearance and 2 cases showed solid nodule and 1 case showed cystic solid nodule appearance in CT findings. The growth speed was very slow. The follow-up time was 4.5(21.5) months before surgery. Histologically, SPCH manifested as a solitary lesion composed of densely proliferating and dilated capillaries without cytologic atypia within the alveolar septa. Immunohistochemically, capillaries of SPCH uniformly expressed endothelial markers, such as CD31, CD34. The patients were followed up for 15.0(22.0) months after surgery and all recovered well.Conclusions:SPCH is probably an unrecognized benign capillary proliferative disease. SPCH lesions mimic early lung cancer on CT as mixed ground-glass nodule, may be misdiagnosed as other nonspecific benign lesions. With careful histologic examination, SPCH can be successfully diagnosed using CD34 or CD31 immunohistochemistry staining.
9. The report of two cases infection with novel coronavirus (2019-ncov) after kidney transplantation and the association literature analyzation
Tao QIU ; Jingyue WANG ; Jiangqiao ZHOU ; Jilin ZOU ; Zhongbao CHEN ; Xiaoxiong MA ; Long ZHANG
Chinese Journal of Organ Transplantation 2020;41(0):E004-E004
Objective:
To investigate the clinical experience of patients with novel coronavirus (2019-ncov) infection after kidney transplantation.
Method:
Clinical data of two patients with 2019-nCoV infection after renal transplantationin Jan 2020 Renmin Hospital of Wuhan Universiyt were retrospectively analyzed.Case 1 was a 48-year-old male with CMV pneumonia secondary to 2019-nCoV infection at 4 months after transplantation. CT imaging showed multiple patchy ground-glass images of both lungs. Case 2 was a 59-year-old male, who was screened positive for 2019-nCoV nucleic acid due to fever at 9 days after renal transplantation and showed no clinical manifestations of pneumonia. After diagnosis, case 1 was transferred to a designated hospital for isolation. Treatment regimens: cefoperazone sulbactam sodium + linezolid to resist infection, gamma globulin to enhance immunity function, methylprednisolone to control inflammatory response, antiviral regimens including arbidol tablets + lopina-velitonavir tablets. Case 2 was treated with isolated treatment in a single room. The treatment plan included anti-infection (cefoperazone sulbactam sodium), enhancing immunity function (gamma globulin), antivirus therapy with arbidol and other symptomatic treatment.
Result:
Follow up with 3 weeks, case 1 recovered with renal dysfunction, nucleic acid test with nasopharyngeal swabs turned negative, and pulmonary imaging improved. Case 2 showed no obvious clinical symptoms, and the nucleic acid test of nasopharyngeal swabs turned negative for 3 times.
Conclusion
Renal transplant recipients should receive fine protection to avoid exposure to high-risk environments. Diagnosis should be defined with combination of clinical manifestations, nucleic acid test and pulmonary imaging. At present, there are no antiviral drugs and symptomatic treatment is the main choice.
10. Early efficacy of lateral unicondylar replacement for lateral compartment osteoarthritis of the knee
Bo ZHANG ; Yuan LIN ; Shixiang REN ; Jiang PAN ; Zhiwei WANG ; Liang WEN ; Tong CHEN ; Lei ZHOU ; Desi MA ; Xiaoxiong ZHAO ; Yang YU
Chinese Journal of Surgery 2020;58(2):125-130
Objective:
To discuss the surgical technique of lateral unicondylar knee replacement (UKR) for patients with lateral compartment osteoarthritis and evaluate its recent clinical efficacy.
Methods:
A retrospective analysis was conducted on 22 cases of lateral compartment osteoarthritis patients receiving lateral UKR at Orthopedic Department, Beijing Chao Yang Hospital, Capital Medical University from January 2016 to January 2019.There were 8 males (8 knees) and 14 females (14 knees), aged 65.7 years(range: 54 to 83 years).All patients completed preoperative imaging examination and excluded extra-articular deformity.Lateral parapelatellar approach was used for the operation and the tibial osteotomy was performed by extramedullary positioning.The residual cartilage of the external condyle was removed by pendulum saw to subchondral bone.Appropriate prosthesis were selected, and the tightness of the gap and the stability of the joints were repeatedly confirmed during the operation.The postoperative complications and the results of physical and imaging examinations were collected.The preoperative and postoperative Oxford knee Score (OKS) and knee society score (KSS) of patients were recorded and compared by paired


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