1.Effects of the prolyl hydroxylase 2 inhibitor cpd17 on mouse osteogenic precursor cells
Zhongqiu DU ; Xiaoyang QI ; Ping YANG ; Jianglin YU ; Yixin CHEN ; Linjian ZHANG ; Xusheng QIU
Chinese Journal of Tissue Engineering Research 2025;29(2):238-244
BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.
2.Biological characteristics of spontaneous ovarian cancer in Microtusfortis.
Junkang ZHOU ; Tianqiong HE ; Yixin WEN ; Qian LIU ; Wenling ZHI ; Lingxuan OUYANG ; Yushan QI ; Xin GAO ; Zikang ZHOU ; Zhijun ZHOU
Journal of Central South University(Medical Sciences) 2025;50(1):11-22
OBJECTIVES:
Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer.
METHODS:
The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes.
RESULTS:
Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm.
CONCLUSIONS
Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female
;
Ovarian Neoplasms/metabolism*
;
Animals
;
Carcinoma, Ovarian Epithelial
;
Disease Models, Animal
;
Humans
;
Neoplasms, Glandular and Epithelial/metabolism*
;
Ovary/pathology*
3.Cinnamic acid ameliorates doxorubicin-induced myocardial injury in mice by attenuating cardiomyocyte ferroptosis via inhibiting TLR4.
Qi YUN ; Ruoli DU ; Yuying HE ; Yixin ZHANG ; Jiahui WANG ; Hongwei YE ; Zhenghong LI ; Qin GAO
Journal of Southern Medical University 2025;45(9):1946-1958
OBJECTIVES:
To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice.
METHODS:
Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining.
RESULTS:
Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference.
CONCLUSIONS
CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals
;
Ferroptosis/drug effects*
;
Toll-Like Receptor 4/metabolism*
;
Myocytes, Cardiac/metabolism*
;
Mice, Inbred C57BL
;
Mice
;
Male
;
Doxorubicin/adverse effects*
;
Cinnamates/pharmacology*
;
Signal Transduction
;
Reactive Oxygen Species/metabolism*
4.AO/OTA 31-A3 intertrochanteric fracture intramedullary nail therapy: comparison of the efficacy of long and short nails
Jianglin YU ; Yifan TANG ; Zhongqiu DU ; Xiaoyang QI ; Hongfei SHI ; Jin XIONG ; Yixin CHEN ; Xusheng QIU
Chinese Journal of Orthopaedics 2024;44(3):161-168
Objective:To explore the efficacy of long intramedullary nails versus short intramedullary nails in the treatment of AO/OTA 31-A3 intertrochanteric fractures.Methods:A retrospective analysis was conducted on 60 patients with AO/OTA 31-A3 intertrochanteric femur fractures treated between March 2019 and August 2022. The patients were randomly divided into two groups (the long nail group and the short nail group). Thirty-four patients were treated with long intramedullary nails, including 16 males and 18 females, aged 68.41±17.84 years old (range 31-96 years). Twenty-six patients were treated with short intramedullary nails, including 13 males and 13 females, aged 72.23±13.97 years old (range 31-90 years). The causes of injury, fracture classification (AO/OTA classification), intraoperative blood loss, operation time, fracture healing time, imaging indexes (fracture reduction quality, postoperative neck trunk angle, and medial support), Harris score of the hip joint at the last follow-up, one-year mortality rates and complications were compared between the two groups.Results:The follow-up time was 24.26±6.67 months in the long nail group and 24.31±5.60 months in the short nail group, and the general information of the two groups were comparable. Between the long nail and short nail group, the intraoperative blood loss was 281.47±235.28 ml vs. 121.92±84.14 ml and the operation time was 110.44±24.63 min vs. 81.15±28.54 min with significant differences ( P<0.05). While the length of hospital stay was 12.35±4.81 d vs. 10.89±4.30 d, the good rate of fracture reduction was 55.9% vs. 61.53%, the fracture healing time was 120.44±16.43 d vs. 128.07±18.33 d, the presence rate of medial support was 67.6% vs. 79.4%, and the excellent rate of Harris score was 65.4% vs. 65.4% with no significant difference between the two groups ( P>0.05). One-year mortality rates was 5.3% vs. 7.1% and complications was 11.7% vs. 15.4% with no significant difference between the two groups ( P>0.05). Conclusion:Both long intramedullary nails and short intramedullary nails are effective in the treatment of AO/OTA 31-A3 intertrochanteric femur fractures. However, surgical time and intraoperative blood loss was less in the short nail group.
5.Research Progress on the Role of HMGB1 in Regulating the Function of Osteoarthritis Chondrocytes
Xin QI ; Xiaogang ZHANG ; Haiyang YU ; Xin CHEN ; Wenbo AN ; Zhipeng WANG ; Duoxian WANG ; Pengfei LUO ; Yixin CHEN ; Jiaojiao MA ; Wei QI ; Ziyang HU ; Jianjun LIU
Medical Journal of Peking Union Medical College Hospital 2024;15(1):141-146
Osteoarthritis (OA) is a chronic degenerative joint disease whose main characteristic is the destruction of articular cartilage, causing pain and disability in patients and seriously affecting their quality of life. OA can be induced by a variety of causes, and pathological changes in articular cartilage are considered to be one of the key driving factors for the occurrence of OA. High mobility group box-1 protein (HMGB1), as a non-histone protein in eukaryotic cells, can participate in regulating the inflammation and apoptosis process of OA chondrocytes, thus leading to the occurrence of OA. This article reviews the research on the mechanism of HMGB1 in OA chondrocytes, with a view to providing new ideas for the clinical prevention and treatment of OA.
6.Design of a fully integrated multi-channel implantable brain-computer interface electrical stimulation system
Qi TANG ; Yixin XUE ; Zhaohui BU ; Qibin ZHENG ; Jiayu LIU
International Journal of Biomedical Engineering 2024;47(2):123-130
Objective:To design a fully integrated multi-channel implantable brain-computer interface electrical stimulation system.Methods:The human-computer interaction interface of the upper computer was set by users, and the data was packaged via a self-built protocol. When parameters were transmitted to the field programmable gate array (FPGA) chip through the Bluetooth module, the stimulation chip was controlled after the parameter analysis was completed. Eventually the user-set current stimulation was output. To verify the system feasibility, the accuracy of the single-channel stimulation waveform, the multi-channel output capability, and the adjustable range of the parameter were tested separately.Results:It realized 16 channels of time-sharing differential stimulation current output, the output stimulation current waveform was dual-phase equal-width pulse, the amplitude ranged within 4~1 000 μA, the pulse single-phase width range was 10~1 000 μs, the cycle time was 1~1 000 ms, thus the current parameters could be accurately adjusted.Conclusions:A fully integrated multi-channel implantable brain-computer interface electrical stimulation system was completed.
7.Prevention and treatment of cross infection of novel coronavirus pneumonia in thoracic surgery ward
WANG Qi ; KUANG Wan ; PING Wei ; GAO Yi ; HAO Zhipeng ; CAI Yixin ; LI Yangkai ; ZHANG Ni ; FU Xiangning
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(04):371-375
Objective By summarizing the clinical characteristics of perioperative patients with cross infection of novel coronavirus in thoracic surgery ward, to guide the prevention and treatment of nosocomial infection during the anti-epidemic period. Methods The clinical data of 451 patients with chest diseases in the Department of Thoracic Surgery of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 1st to 24th, 2020 were analyzed and followed up. There were 245 surgical patients and 206 non-surgical patients. Results In the department, 7 patients (7/451, 1.55%) were infected with the novel coronavirus and all of them were surgical patients, whose preoperative imaging data did not reveal the imaging changes of novel coronavirus. There were 5 males and 2 females, aged 56 to 68 years. The patients with old age, smoking, surgery, coronary heart disease, chronic liver disease and tumor history were more susceptible to infection. From the spatial distribution of patient beds, it was found that the distance among infected patients was greater than 1 m, and no cross infection was found in the other patients of the same ward. During follow-up, two family members of noninfected patients were found to be infected one week after discharge. However, there was no overlap of spatiotemporal distribution between the family members and the infected patients during the hospitalization period. Conclusion The novel coronavirus pneumonia rate in the department of thoracic surgery is low, which may be opportunistic infection. At the same time, a good control and prevention of epidemic disease can reduce the occurrence of cross infection in the department of thoracic surgery.
8.Spatial characteristics analysis of hand, foot and mouth disease in Pudong New Area of Shanghai, 2015-2018
Zou CHEN ; Lihong WANG ; Dan LIU ; Yuanping WANG ; Weiping ZHU ; Qi ZHAO ; Yixin ZHOU
Journal of Public Health and Preventive Medicine 2020;31(2):50-53
Objective To understand the spatial epidemic characteristics of hand-foot-mouth disease in Pudong New Area of Shanghai from 2015 to 2018, and to provide reference for prevention and control. Methods SPSS 21.0 software was used for statistical analysis of the reported incidence of hand-foot-mouth disease, ArcGIS 10.2 software was used to make geographic distribution map, and OpenGeoDa software was used to make spatial autocorrelation analysis. Results The global Moran's I autocorrelation coefficient of the reported incidence rate of hand-foot-mouth disease in various streets and towns in Pudong New Area of Shanghai was 0.38, which was statistically significant (P=0.001). Local spatial autocorrelation analysis found that 5 streets were in high-high area. Conclusion The geographical distribution of reported incidence of hand-foot-mouth disease in various streets and towns of Pudong New Area in Shanghai was spatially aggregated, and the reported incidence decreased from north to south.
9.circRNA_001569 affects the malignant biological behavior of breast cancer cells through the miR-145/HBXIP axis
DONG Jiangmeng ; WANG Yong ; QI Yixin ; JIA Wei
Chinese Journal of Cancer Biotherapy 2020;27(11):1220-1228
[摘 要] 目的:探讨circRNA_001569通过miR-145/HBXIP轴在乳腺癌细胞增殖、侵袭、迁移中发挥的作用。方法:收集2016年1月至2019年1月期间衡水市人民医院收治的30例乳腺癌患者的癌组织和癌旁组织。qPCR检测circRNA_001569在乳腺癌组织、癌旁组织以及细胞系中的表达。生物信息学工具预测miR-145的靶基因,RNA免疫沉淀(RNA immunoprecipitation,RIP)和双荧光素酶报告基因实验检测miR-145或靶基因之间的相互作用;向乳腺癌MDA-MB-231和MCF-7细胞中转染si-circRNA_001569、miR-145 mimics或miR-145 inhibitor,建立基因过表达或沉默的细胞模型,qPCR和Western blotting分别检测转染对相关基因和蛋白表达的影响,CCK-8法、Transwell实验检测转染对细胞增殖、侵袭和迁移的影响。结果:在乳腺癌组织和乳腺癌细胞中,circRNA_001569和HBXIP均呈高表达、miR-145呈低表达。RIP分析和双荧光素酶实验证实了miR-145与circRNA_001569和HBXIP之间的靶向关系;circRNA_001569或HBXIP过表达促进MDA-MB-231和MCF-7细胞的增殖、侵袭和迁移(均P<0.01),而miR-145过表达起相反的作用(均P<0.01)。结论:circRNA_001569可能通过下调miR-145的表达、上调HBXIP的表达从而促进乳腺癌细胞的增殖、侵袭和迁移。
10.Progress of clinical application of microperimetry in ocular fundus diseases
Jing MING ; Like XIE ; Xiaofeng HAO ; Rui QIN ; Zhifang ZHANG ; Yixin QI ; Huilan SUN ; Xiaoyu LI
Chinese Journal of Ocular Fundus Diseases 2019;35(4):408-413
Microperimetry is a procedure to assess retinal sensitivity while fundus is examined directly.It is a psychophysical method which is rapid,safe and non-invasive.It combines analysis of function and morphology and has an eye tracking system that can improve the fixation stability of patient with eccentric fixation and fixation instable.Microperimetry is supplement to visual function,perimetry,and other visual function parameters.As deepening of research,its clinical application value in ocular fundus diseases including age-related macular degeneration,diabetic retinopathy,retinitis pigmentosa,Stargardt's disease,macular hole,rhegmatogenous retinal detachment and central serous chorioretinopathy needs to be further explored.


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