1.IDH3A Inhibits Cardiomyocyte Hypertrophy via Elevating α-Ketoglutarate Level
Huayan WU ; Yihong WEN ; Hengli ZHAO ; Yuan GAO ; Chuanmeng ZHOU ; Ya WANG ; Jiening ZHU ; Zhixin SHAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):275-283
ObjectiveTo investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A (IDH3A) on cardiomyocyte hypertrophy. MethodsThe expression of IDH3A in the myocardium of healthy volunteers (n=10) and patients with heart failure (HF) (n=10), and in the myocardium of mice subjected to transverse aortic constriction (TAC) surgery and sham operation, as well as in phenylephrine (PE)-induced neonatal rat ventricular cardiomyocytes (NRVCs), was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay. The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated. The effect of IDH3A on NRVCs area was examined by phalloidin staining assay. A mutant of IDH3A with abolished enzymatic activity, IDH3A_D208A, was generated through site-directed mutagenesis. The impact of this IDH3A mutant on the hypertrophic phenotype, ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity. The effect of exogenous α-ketoglutaric acid (AKG) on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay, respectively. ResultsIDH3A was significantly decreased in the myocardium of HF patients, in the myocardium of TAC-operated mice, and in PE-induced NRVCs (P = 0.005 2,P = 0.026 6,P = 0.041 3 and P = 0.006 6, respectively). Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs (P < 0.000 1, P = 0.000 1 and P = 0.000 2, respectively). The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs (P = 0.001 2 and P<0.000 1, respectively), whereas the enzymatically inactive IDH3A mutant lacked this effect. Exogenous AKG provision could, but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy. ConclusionIDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level, providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.
2.Efficacy and Safety of Acupuncture Combined with Levodopa in the Treatment of Parkinson's Disease: A Randomized Controlled Trial
Jingyun ZHU ; Xiyan GAO ; Linlin WANG ; Zhixin REN ; Guiling WANG ; Jing GUO ; Yanrong WU
Journal of Traditional Chinese Medicine 2025;66(14):1456-1462
ObjectiveTo evaluate the clinical efficacy and safety of acupuncture combined with levodopa in the treatment of Parkinson's disease(PD). MethodsA total of 60 patients with PD were enrolled and randomly assigned to test group or control group, with 30 patients in each group. The control group received levodopa only, starting at 100 mg per dose, three times daily, with gradual increases not exceeding a maximum daily dose of 800 mg. The test group received acupuncture three times per week in addition to levodopa. Both groups were treated for 12 weeks. Assessments were conducted before treatment, after 6 and 12 weeks treatment, using the Unified Parkinson's Disease Rating Scale(UPDRS), Wearing-Off Questionnaire-9(WOQ-9), Montreal Cognitive Assessment(MoCA), Mini-Mental State Examination(MMSE), Depression Rating Scale(DRS), Hamilton Depression Scale(HAMD), Hamilton Anxiety Scale(HAMA), PD Questionnaire-39(PDQ-39), and Pittsburgh Sleep Quality Index(PSQI). Repeated measures ANOVA was utilized to evaluate the effects of time, group, and their interaction on each index. Spearman correlation analysis was conducted to examine the relationships between combined treatment and outcome scores. Adverse events in both groups were recorded throughout the study. ResultsBoth groups showed significant improvements after 6 and 12 weeks treatment, with decreases in UPDRS total score, WOQ-9 total score, DRS score, HAMD score, HAMA score, PDQ-39 score, and PSQI score, and increases in MoCA and MMSE scores(P<0.05). Compared with the control group, the test group demonstrated significantly greater improvements in all the above indicators after 6 and 12 weeks (P<0.05). Repeated measures ANOVA showed significant time main effects, group main effects, and their interaction across all outcome measures(P<0.01). Spearman correlation analysis revealed that combined therapy was significantly negatively correlated with UPDRS, WOQ-9, DRS, HAMD, HAMA, PDQ-39, and PSQI scores, while positively correlated with MoCA and MMSE scores after 12 weeks of treatment(P<0.05). Both groups did not experience any serious adverse events and did not affect treatment. ConclusionAcupuncture combined with levodopa is more effective than levodopa alone in improving motor function, non-motor symptoms, cognitive function, depression and anxiety, quality of life, and sleep quality in patients with PD, with good safety.
3.AngioJet-assisted catheter-directed thrombolysis versus catheter-directed thrombolysis alone in the treatment of acute deep venous thrombosis of lower extremity: a mid-term controlled clinical study
Xinqing LI ; Aimin QIAN ; Chenglong LI ; Xiaobin YU ; Yeqing ZHANG ; Fengrui LEI ; Liwei ZHU ; Zhixin CAI ; Hongfei SANG
Chinese Journal of General Surgery 2024;39(2):110-114
Objective:To compare the mid-term clinical effects of AngioJet rheolytic thrombectomy assisted catheter-directed thrombolysis (ART+CDT) with catheter-directed thrombolysis (CDT) in the treatment of acute deep venous thrombosis of lower extremities.Methods:Ninety-one patients admitted to the Department from Jan 2016 to Dec 2017 were placed with inferior vena cava filters and divided into ART+CDT group (30 cases)and CDT group (61 cases). Total urokinase dosge, thrombolytic time, operative cost, length of hospital stay, detumescence rate, thrombus clearance rate, cumulative patency rate of lower limb veins, Villalta score at 2 years and 5 years, thrombosis recurrence rate and chronic venous insufficiency quality of life questionnaire were compared between the two groups.Results:The success rate of surgery was 100% in both groups, there was no mortality. There were significant differences in the short-term postoperative outcomes between the two groups in terms of total dosage of urokinase, thrombolysis time, total cost of surgery, length of hospital stay, detumescence rate, venous patency scores before and after treatment, and venous patency rate (all P<0.05). For the mid- and long-term postoperative outcomes of 2 and 5 years, there were no significant differences in the incidence of PTS, recurrence rate of thrombus, chronic venous function scale, and cumulative patency rate at 2 years (all P>0.05). Conclusions:ART+CDT has a significant advantage over CDT alone in terms of early efficacy and early reopening of blood flow in patients. Both ART+CDT and CDT have a low incidence of PTS and a low recurrence rate of thrombus in the mid-term follow-up, and both have satisfactory performance in the mid- and long-term efficacy of interventional treatment of deep venous thrombosis of lower limbs.
4.Clinical characteristics and management status of Turner syndrome in 1 089 children
Yan LIANG ; Haiyan WEI ; Ruimin CHEN ; Zhixin ZHANG ; Xinran CHENG ; Na TAO ; Chunlin WANG ; Yu YANG ; Ying XIN ; Xin FAN ; Xingxing ZHANG ; Geli LIU ; Shengquan CHENG ; Min ZHU ; Hongwei DU ; Yan SUN ; Linqi CHEN ; Lanwei CUI ; Xiaoping LUO
Chinese Journal of Pediatrics 2024;62(10):962-968
Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.
5.An investigation of frequency of radiation services in medical institutions in Hangzhou, China, 2020
Qian QIAN ; Haihua WANG ; Yong YANG ; Bo ZHU ; Jiamian YU ; Liyan JING ; Luting YANG ; Peiyi QIAN ; Zhixin ZHAO
Chinese Journal of Radiological Health 2023;32(2):125-130
Objective To investigate radiation resources in medical diagnosis and treatment and their use frequency in medical institutions in Hangzhou, China, and to provide a basis for relevant departments to rationally allocate and scientifically supervise the resources. Methods From April 1, 2019 to March 31, 2020, a survey was conducted on the basic information, radiation staff, equipment configuration, and frequency of radiation diagnosis and treatment of all medical institutions in Hangzhou using a questionnaire. Results There were 1001 institutions with radiation services in Hangzhou, with 6714 radiation staff members and 2742 pieces of radiation equipment. The frequency of conventional X-ray diagnosis was 788.43 per 1000 population. The frequency of computed tomography diagnosis was 531.93 per 1000 population. The frequency of mammography and dental photography diagnosis was 246.34 per 1000 population. The frequency of interventional diagnosis and treatment was 10.01 per 1000 population. The frequency of radiotherapy was 2.39 per 1000 population. The frequency of nuclear medicine diagnosis was 8.90 per 1000 population. The frequency of nuclear medicine treatment was 0.99 per 1000 population. Conclusion Medical institutions have developed rapidly in Hangzhou, but with an unbalanced situation. In order to better protect the health of examinees, we recommend relevant departments optimize resource allocation and strengthen supervision on radiation protection in medical institutions.
6.Preparation of 4-sulfonylcalix6arene-modified cotton for uranium contamination removal
Haoxin GUO ; Yilong WANG ; Zebao ZHENG ; Kunlu LIU ; Rongqing HUANG ; Zhibing ZHENG ; Bo HUANG ; Zhixin WANG ; Meiyu WANG ; Benbo LIU ; Guo CHEN ; Xu WANG ; Zhihua YANG ; Maoxiang ZHU
Chinese Journal of Radiological Health 2023;32(6):603-610
Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.
7.Meta-analysis of the effects of low-dose ionizing radiation on the thyroid of medical radiation workers
Yong YANG ; Qiang WANG ; Luting YANG ; Aiqing YU ; Zhixin ZHAO ; Bo ZHU ; Liyan JING
Chinese Journal of Radiological Medicine and Protection 2023;43(6):447-456
Objective:To assess the effects of low-dose ionizing radiation on the thyroid of medical radiation workers.Methods:Based on the inclusion and exclusion criteria, 27 articles, involving 22 937 individuals, were screened finally from relevant literature published from 1996 to 2022. Meta-analysis was carried out using Stata 16.0 for serum levels of triiodothyronine (T 3), free triiodothyronine (FT 3), thyroid hormone (T 4), free thyroid hormone (FT 4), thyrotropin-stimulating hormone (TSH) and thyroid nodule rates. As well, subgroup analysis were carried out of thyroid function in different types of radiation workers. Results:The standardized mean difference (SMD) at T 3 and T 4 levels for radiation workers was -0.19 (-0.37, -0.01) and -0.34 (-0.38, -0.30), lower than that of control group ( Z=2.07, -16.06, P<0.05). The SMD at FT 4 levels for radiation workers was 0.22 (0.06, 0.39), higher than control group ( Z=2.61, P<0.05). The relative risk of thyroid nodules in radiation workers was 1.47 (1.19, 1.82), higher than that of control group ( Z=-3.58, P<0.05). The analysis result for subgroup showed that the SMD for T 3, T 4 and TSH levels in the interventional radiology workers were -0.29 (-0.51, -0.07), -0.31 (-0.47, -0.15) and -0.43 (-0.73, -0.13) ( Z=-2.55, -3.86, -2.82, P<0.05), respectively, and the SMD for T 4 levels in the nuclear medicine workers was -0.26 (-0.45, -0.07), which meaned a reduced risk compared to the control group ( Z=-2.70, P<0.05). Conclusions:Long-term low doses of ionising radiation may have adverse effects on thyroid hormone and thyroid nodule in radiation workers, particularly in interventional radiology workers, and attention should be focused on their radiation protection.
8.HucMSC-cm protects lipopolysaccharide-induced acute lung injury by activating AMP-activated protein kinase
Haiyang CHEN ; Hongfeng YANG ; Jiaqi SHEN ; Wei ZHU ; Zhixin YU
Chinese Journal of Emergency Medicine 2022;31(5):636-643
Objective:To investigate the protective effect of human umbilical cord mesenchymal stem cell conditioned medium (HucMSC-cm) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and relevant mechanism of action.Methods:Forty 6-week-old male C57BL/6 mice were selected and randomized (random number) into the sham group, LPS group, LPS + HucMSC-cm (LPS+cm) group, and LPS+HucMSC-cm+Compound C (LPS+cm+cc) group, with 10 mice in each group. Mice were intratracheally injected with LPS (5 mg/kg) to establish ALI model, and intratracheally injected with hucMSC-CM (50 μL) 4 h after LPS treatment. Mice in the LPS+cm+cc group were intraperitoneally treated with Compound C (15 mg/kg) prior to LPS treatment. Neutrophils in peripheral blood were counted with the automated hematology analyzer 72 h after LPS administration. After that, mice were sacrificed, and the lung tissue pathology was observed using hematoxylin eosin (HE) staining. Besides, the expressions of IL-6, ICAM-1, VCAM-1 and P-AMP-activated protein kinase (P-AMPK) in the lung tissues were analyzed by Western blot and immunohistochemical assay. In vitro, human lung microvascular endothelial cells (HuLEC-5a) were cultured and divided into three groups: control group, LPS group (10 μg/ mL), and LPS + HucMSC-cm group. After 24 h of treatment, the expressions of p-AMPK and AMPK were detected by Western blot, and the expressions of IL-6 and IL-8 were detected by real-time fluorescence quantitative PCR. Oneway analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between two groups were performed using the Tukey’s multiple comparison test. Results:Compared with the sham group, the LPS group showed lungs with congestion and swelling, thickened pulmonary septum, and inflammatory cell infiltration. Moreover, in the LPS group, the protein expressions of IL-6 ( P=0.003), ICAM-1 ( P<0.001) and VCAM-1 ( P=0.001) were increased significantly, while the expression of p-AMPK was decreased ( P=0.013), accompanied by an increase in the proportion of neutrophils in peripheral blood ( P<0.001). Compared with the LPS group, the LPS+HucMSC-cm group demonstrated eased congestion, edema and pathological injury of lung tissue, reversed protein expressions of IL-6 ( P=0.003), ICAM-1 ( P=0.002), VCAM-1 ( P=0.006) and P-AMPK ( P=0.002), as well as decreased proportion of neutrophils in peripheral blood ( P<0.005). Compared with the LPS+HucMSC-cm group, the LPS+cm+cc group exhibited more severe lung histopathological injury, significantly increased protein expressions of IL-6, ICAM-1 and VCAM-1 in lung tissues, as well as decreased expression of P-AMPK protein. The results of immunohistochemistry were consistent with those of protein. In vitro experiment, after LPS treatment, the mRNA expressions of IL-6 ( P<0.001) and IL-8 ( P=0.027) were increased and p-AMPK protein expression ( P=0.005) was decreased as compared with the control group. In comparison with the LPS group, the LPS+HucMSC-cm group showed decreased mRNA expression levels of IL-6 ( P=0.003) and IL-8 ( P=0.002), but increased protein level of p-AMPK ( P=0.003). Conclusions:HucMSC-cm has a protective effect against LPS-induced acute lung injury, which is mainly attributed to the inhibited expression of adhesion molecules and inflammatory factors under the activation of AMPK.
9.Antigen presentation and T cell activation by dendritic cells in radiation damage
Qian LI ; Shuang GENG ; Chengming YAN ; Haoxin GUO ; Zhixin WANG ; Meiyu WANG ; Benbo LIU ; Xu WANG ; Yilong WANG ; Zhihua YANG ; Maoxiang ZHU
Chinese Journal of Radiological Health 2022;31(6):657-662
Objective To explore dendritic cells (DCs)-mediated antigen presentation for radiation-injured cells by using the in vitro cell co-culture technology to simulate the in vivo microenvironment of the lung tissue. Methods 60Co γ-irradiated mouse lung epithelial cells (MLE-12) were cultured with bone marrow-derived DCs and/or splenic T lymphocytes for 48 hours. Flow cytometry was used to measure the expression levels of costimulatory molecules (CD80/86) and antigenic peptide recognition complexes (the major histocompatibility complex [MHC] class Ⅰ/Ⅱ) on DCs and T cell activation markers (CD69/28/152) as well as the numbers of CD4+ and CD8+ T cells. Results 60Co γ irradiation significantly increased the apoptosis rate of MLE-12 cells in a dose-dependent manner, and significantly stimulated the expression of CD80/86 and MHC Ⅱ on DCs, without direct activation of T cells. After γ (6 Gy)-irradiated MLE-12 cells were co-cultured with DCs and T lymphocytes for 48 h, there were significant increases in the expression of CD69 and CD28 on T cells, the numbers of CD4+ and CD8+ T cells, and the expression of CD86 and MHC I on DCs, as compared with the control groups. Conclusion Radiation-injured cells can stimulate antigen presentation by DCs and activate T cells.
10.Role of complement in radiation-induced lung injury
Shuang GENG ; Qian LI ; Tingting XI ; Meiyu WANG ; Haoxin GUO ; Zhixin WANG ; Xiaoguang BI ; Chengming YAN ; Zhihua YANG ; Yilong WANG ; Maoxiang ZHU
Chinese Journal of Radiological Health 2022;31(5):535-541
Objective To investigate the role of complement in radiation-induced lung injury in mice after chest irradiation with 60Co γ-rays at a single dose of 20 Gy. Methods C57BL/6 mice underwent chest irradiation with 60Co γ-rays at a single dose of 20 Gy, followed by observation for the inflammatory reaction of the lung tissue in the early stage (within 15 d) and pulmonary fibrosis in the later stage (30 and 180 d). Enzyme-linked immunosorbent assay was used to measure the levels of C2, C3a, C4, and C5b-9 in the lung tissues at 1, 3, 7, 15, 30, and 180 d after irradiation. The expression of complement mRNA in BEAS-2B cells after irradiation was determined using RT-PCR. Results Radiation-induced lung injury in micepresented as inflammatory response in the early stage and fibrosis in the late stage. Complement C2, C4, and C5b-9 complexes were increased in the early period (3 or 7 d) after irradiation (P < 0.05), which might be associated with the inflammatory response induced by irradiation. During 3 to 180 d, complement C3a was significantly higher in the irradiated mice than in the control mice, suggesting a close relationship between C3a and radiation-induced lung injury. The irradiated cells showed increased mRNA expression of C2 and C3, with no changes in the mRNA levels of C4 and C5. Conclusion Different complement proteins have varying responses to radiation-induced lung injury, among which C3a is closely related to radiation-induced lung injury, suggesting that regulating C3a and its receptors may be a new way to prevent and treat radiation-induced lung injury.


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