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.Evaluation of the effect of campus tray design on salt intake control among boarding students in Guizhou Province
QIU Yujie, DU Zhixin, YUAN Fan, ZHAO Hang, LIU Ailing
Chinese Journal of School Health 2025;46(7):956-960
Objective:
To explore the effect of replacing rice bowls with trays on controlling the salt intake among school aged children, providing new evidence and insights for salt reduction intervention.
Methods:
From April to May 2024, 373 students from grades 4-9 at a boarding school in Guizhou Province were enrolled through stratified random cluster sampling, with one intervention class and one control class per grade. During the intervention period for one month, and the types of meals provided, pricing standards, and dining procedures shall remain consistent with daily operations, the intervention group ( n =181) compartmentalized trays for lunch and dinner, while the control group ( n =192) still used a rice bowl. Pre and post intervention assessments included 24 hour urine collection, questionnaire surveys, and physical measurements. The difference in differences analysis combined with multiple linear regression was used to analyze the changes in sodium intake and to evaluate the net effect of the intervention.
Results:
The post intervention 24 hour sodium intake in the intervention group was ( 2 222.6 ±1 013.6) mg, an increase of 94.6 mg from baseline, with no statistically significant difference ( t=1.10, P >0.05). In contrast, the post intervention 24 hour sodium intake in the control group was (2 080.5±895.7) mg, a decrease of 190.8 mg from baseline, showing a statistically significant difference ( t=-2.39, P <0.05). The difference in differences results indicated that after adjusting the model for factors such as gender, grade and dietary behaviors affecting sodium intake, the intervention group showed a net increase of 232.5 mg [ β(95%CI )=232.5(-40.3-505.2)] in 24 hour sodium intake compared to the control group, with no statistically significant net effect ( P >0.05).
Conclusions
Merely changing tableware is insufficient to control children s salt intake effectively. Based on continuous practical explorations and evidence based research grounded in the nudge theory, multi dimensional measures such as salt reduction education and the construction of a supportive environment should be integrated to form an intervention system that achieves synergistic and enhanced effects.
3.Characteristics of gut microbiota determine effects of specific probiotics strains in patients with functional constipation.
Haohao ZHANG ; Lijuan SUN ; Zhixin ZHAO ; Yao ZHOU ; Yuyao LIU ; Nannan ZHANG ; Junya YAN ; Shibo WANG ; Renlong LI ; Jing ZHANG ; Xueying WANG ; Wenjiao LI ; Yan PAN ; Meixia WANG ; Bing LUO ; Mengbin LI ; Zhihong SUN ; Yongxiang ZHAO ; Yongzhan NIE
Chinese Medical Journal 2024;137(1):120-122
4.Evaluation of Simulated Weightlessness Model of Hindlimb Unloading Miniature Pigs and Their Tissue Damage
Yingxin TU ; Yilan JI ; Fei WANG ; Dongming YANG ; Dongdong WANG ; Zhixin SUN ; Yuexin DAI ; Yanji WANG ; KAN GUANGHAN ; Bin WU ; Deming ZHAO ; Lifeng YANG
Laboratory Animal and Comparative Medicine 2024;44(5):475-486
Objective To establish a weightlessness simulation animal model using miniature pigs, leveraging the characteristic of multiple systems’ tissue structures and functions similar to those of humans, and to observe pathophysiological changes, providing a new method for aerospace research. Methods Nine standard-grade miniature pigs were selected and randomly divided into an experimental group (n=7) and a control group (n=2). The experimental group was fixed using customized metal cages, with canvas slings suspending their hind limbs off the ground, and the body positioned at a -20° angle relative to the ground to simulate unloading for 30 days (24 hours a day). Data on body weight, blood volume, and blood biochemistry indicators were collected at different time points for statistical analysis of basic physiological changes. After the experiment, the miniature pigs were euthanized and tissue samples were collected for histopathological observation of the cardiovascular, skeletal and muscle systems HE and Masson staining. Statistical analysis was also conducted on the thickness of arterial vessels and the diameter of skeletal muscle fibers. Additionally, western blotting was employed to detect the expression levels of skeletal muscle atrophy-related proteins, including muscle-specific RING finger protein 1 (MuRf-1) and muscle atrophy F-box (MAFbx, as known as Atrogin-1), while immunohistochemistry was used to detect the expression of glial fibrillary acidic protein (GFAP), an indicator of astrocyte activation in the brain, reflecting the pathophysiological functional changes across systems. Results After hindlimb unloading, the experimental group showed significant decreases in body weight (P<0.001) and blood volume (P<0.01). During the experiment, hemoglobin, hematocrit, and red blood cell count levels significantly decreased (P<0.05) but gradually recovered. The expression levels of alanine aminotransferase and γ-glutamyltransferase initially decreased (P<0.05) before rebounding, while albumin significantly decreased (P<0.001) and globulin significantly increased (P<0.01). Creatinine significantly decreased (P<0.05). The average diameter of gastrocnemius muscle fibers in the experimental group significantly shortened (P<0.05), with a leftward shift in the distribution of muscle fiber diameters and an increase in small-diameter muscle fibers. Simultaneously, Atrogin-1 expression in the gastrocnemius and paravertebral muscles significantly increased (P<0.05). These changes are generally consistent with the effects of weightlessness on humans and animals in space. Furthermore, degenerative changes were observed in some neurons of the cortical parietal lobe, frontal lobe, and hippocampal regions of the experimental group, with a slight reduction in the number of Purkinje cells in the cerebellar region, and a significant enhancement of GFAP-positive signals in the hippocampal area (P<0.05). Conclusion Miniature pigs subjected to a -20° angle hind limb unloading for 30 days maybe serve as a new animal model for simulating weightlessness, applicable to related aerospace research.
5.Evaluation of Coefficients of Variation for Clinical Chemistry Tests Based on Internal Quality Control Data Across 5,425 Laboratories in China From 2013 to 2022
Wei WANG ; Zhixin ZHANG ; Chuanbao ZHANG ; Haijian ZHAO ; Shuai YUAN ; Jiali LIU ; Na DONG ; Zhiguo WANG ; Fengfeng KANG
Annals of Laboratory Medicine 2024;44(3):245-252
Background:
Clinical chemistry tests are most widely used in clinical laboratories, and diverse measurement systems for these analyses are available in China. We evaluated the imprecision of clinical chemistry measurement systems based on internal QC (IQC) data.
Methods:
IQC data for 27 general chemistry analytes were collected in February each year from 2013 to 2022. Four performance specifications were used to calculate pass rates for CVs of IQC data in 2022. Boxplots were drawn to analyze trends of CVs, and differences in CVs among different groups were assessed using the Mann–Whitney U-test or Kruskal– Wallis test.
Results:
The number of participating laboratories increased significantly from 1,777 in 2013 to 5,425 in 2022. CVs significantly decreased for all 27 analytes, except creatine kinase and lipase. Triglycerides, total bilirubin, direct bilirubin, iron, and γ-glutamyl transferase achieved pass rates > 80% for all goals. Nine analytes with pass rates < 80% based on 1/3 allowable total error were further analyzed; the results indicated that closed systems exhibited lower CVs than open systems for all analytes, except total protein. For all nine analytes, differences were significant between tertiary hospitals and non-tertiary hospitals and between accredited and non-accredited laboratories.
Conclusions
The CVs of IQC data for clinical chemistry have seen a continuous overall improvement in China. However, there is ample room for imprecision improvement for several analytes, with stricter performance specifications.
6.Characterization of Escherichia coli lytic phage vB_EcoP-R1 and its anti-biofilm activity
Zhixin SHI ; Zexuan LI ; Litao ZHANG ; Xin HONG ; Jing LIU ; Zhe ZHAO ; Genyan LIU
Chinese Journal of Clinical Laboratory Science 2024;42(4):261-266
Objective To isolate E.scherichia coli-specific bacteriophages from hospital waste water,analyze their biological character-istics and detect their cleavage effects on bacterial biofilms.Methods The phages were isolated and purified by double-layer agar plate method and their morphology was observed by transmission electron microscopy.Their one-step growth curve,in vitro lysis curve,tem-perature and acid-base stability were determined.Whole genome sequencing was used to analyze the genome composition and character-istics of bacteriophages.The crystal violet staining was used to evaluate the scavenging effects of phage on host biofilms.Results A novel Escherichia coli-specific bacteriophage named vB_EcoP-R1 was isolated from hospital sewage.Transmission electron microscopy revealed that the morphology of vB_EcoP-R1 was similar to that of Podoviridae,a member of Caudovirales,and it could survive stably in the temperature range of-20 ℃ to 50 ℃ and pH 5.0 to 11.0.The total length of the vB_EcoP-R1 genome was 40 875 bp and the GC content was 49.94%.There were no virulence genes and drug resistance genes in the phage genome.vB_EcoP-R1 was capable of lysing clinically isolated Escherichia coli and showed high species and genus specificity.After the phage acted on the host bacteria preformed biofilm for 4 h,the clearance rate of the biofilm reached 80.16%.Conclusion vB_EcoP-R1 should be a novel Escherichia coli-specif-ic bacteriophage with strong lysis and high specificity for species and genus.The bacteriophage could lyse the biofilm formed by the host bacteria,and is expected to be used as an alternative treatment for Escherichia coli infection.
7.Impact of maternal stress during pregnancy on placental glucose transporters
Qi SONG ; Zhixin DU ; Liping YANG ; Junlin HOU ; Jiajia ZHAO ; Yongye WU ; Yaohui WANG ; Xiaolin LI
Acta Laboratorium Animalis Scientia Sinica 2024;32(7):828-835
Objective To investigate the effect of fear-induced stress during pregnancy on the expression of glucose transporters(GLUT)in the placenta,providing evidence for the theory of fetal damage caused by fear-induced stress during pregnancy.Methods Twenty pregnant Wistar rats were randomly divided into a control group and a model group of 10 rats each.In the model group,a fear-induced stress model was established using the modified bystander electroshock method for 20 days.After the experiment,the number of offspring and the weights of the placenta and fetal rats were measured,and the placental efficiency was calculated.Transmission electron microscopy was used to observe the morphological changes of placental cells.Bioinformatics analysis was performed to screen for differential genes in placentas affected by pregnancy stress-phobia,and gene set enrichment analysis was performed.Protein immunoblotting(Western Blot),Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR),and immunohistochemistry were used to detect the expression levels of GLUT1,GLUT3,GLUT6,and GLUT7 proteins and genes.Results The placental efficiency was significantly reduced in the model group compared with that in the control group.The result of transmission electron microscopy in the model group showed that the placental microvilli were sparse and short and that the mitochondria and endoplasmic reticulum were swollen.Gene set enrichment analysis revealed that placental genes were significantly enriched in cellular glucose homeostasis in the model group compared with those in the control group.The result of Western Blot,Real-time PCR,and immunohistochemistry indicated a decrease in both the protein and gene expression levels of GLUT1,GLUT6,and GLUT7 in the placenta of pregnant rats.Conclusions Prenatal exposure to fear-induced stress may lead to adverse pregnancy outcomes.These adverse outcomes are potentially associated with reduced levels of three key GLUTs in the placenta:GLUT1,GLUT6,and GLUT7.
8.Construction and Verification of a Risk Prediction Model for Death From Dissection Rupture in Patients With Acute Aortic Dissection During Emergency Treatment
Zhixin ZHANG ; Tao LIANG ; Yanmin YANG ; Chen ZHANG ; Yunxia HAO ; Yanjuan ZHANG ; Rui ZHAO ; Ran PANG ; Jing YANG
Chinese Circulation Journal 2024;39(9):903-909
Objectives:To explore the risk factors for death from ruptured acute aortic dissection during emergency treatment,construct and validate a risk prediction model for death from ruptured acute aortic dissection during emergency treatment. Methods:A total of 301 cases of acute aortic dissection patients who were admitted to Chinese Academy of Medical Sciences Fuwai Hospital from January 2018 to August 2021 were included in this study.Patients were divided into survival subgroup(n=239)and death subgroup(n=62)according to whether dissection rupture occurred in the acute stage of the disease.Univariate and multivariate analyses were performed.Logistic regression analysis was used to establish the risk prediction model.The Hosmer-Lemeshow test was conducted to assess the model's goodness of fit,and the receiver operating characteristic curve(ROC curve)was used to evaluate the model's predictive performance.A prospective validation was performed on 129 cases of acute aortic dissection patients admitted to our hospital's emergency department from September 2021 to September 2022. Results:Among the 301 cases of acute aortic dissection patients,there were 62 cases of rupture and death,with an incidence rate of 20.6%.The results of multivariate analysis showed that age(OR=1.066,95%CI:1.034-1.099),type A dissection(OR=0.045,95%CI:0.006-0.364),history of hypertension(OR=0.377,95%CI:0.167-0.850),and concomitant hypotension(OR=4.424,95%CI:1.467-13.340)were determinants of deaths.The model formula was Z=-5.624+0.064×age-0.976×history of hypertension(yes=1,no=0)-3.104×type(Type A=0,Type B=1)+1.487×concomitant hypotension(yes=1,no=0).The Hosmer-Lemeshow test result showed χ2=9.328,df=8,P=0.315,the area under the ROC curve was 0.874,sensitivity was 79.0%,specificity was 81.6%,and the maximum Youden index was 0.606.The model validation result showed that the area under the ROC curve was 0.722,sensitivity was 73.7%,specificity was 69.1%,and accuracy was 89.9%. Conclusions:Age,history of hypertension,dissection type,and combined hypotension are predictors of the risk prediction model for death from dissection rupture in patients with acute aortic dissection during emergency treatment.The model constructed in this study has good predictive performance,which can provide reference for medical staffto quickly identify high-risk patients for death from ruptured acute aortic dissection and timely predictive measures could be highlighted in indicated cases.
9.Exploration of Antidepressant Mechanism of Chaihu and Longgu Mulitang Based on cAMP/PKA/CREB/BDNF Signaling Pathway
Dike ZHAO ; Jun NIU ; Zhixin DU ; Chunyu ZHOU ; Shenao DING ; Xiaodan DU ; Liping YANG ; Mengdi MAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(3):17-25
ObjectiveTo observe the intervention effect of Chaihu and Longgu Mulitang (CLMT) on rat depression model prepared by chronic unpredictable mild stress (CUMS) based on cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling pathway. MethodSixty SD rats were divided into normal group, model group, and CLMT low-, medium- and high-dose groups and fluoxetine group (positive control) according to random number table. They, except the normal group, were treated with CUMS for 49 days to prepare the rat depression model. The CLMT low-, medium- and high-dose groups were given 2.89, 5.78 11.56 g·kg-1 of CHMD granules, respectively, and the fluoxetine group was given 2.06 mg·kg-1 of fluoxetine hydrochloride on the 29th day. The normal group and the model group received equal volume of normal saline for 21 days. The behavioral performance of rats were observed by open field test and forced swim test. The levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and cAMP in rat hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of PKA, CREB, and BDNF in rat hippocampus were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and the protein expressions of PKA and BDNF were detected by Western blot. Immunohistochemistry was used to determine the expression of CREB, and hematoxylin and eosin (HE) staining and Nissl staining were used to observe the morphological changes of hippocampus. ResultCompared with the conditions in the normal group, the immobility time of the model group in the forced swim test was increased (P<0.01) and the total movement distance, residence time in central area, number of entries in central area and movement distance in central area were decreased (P<0.01). Additionally, the contents of 5-HT, NE and cAMP in hippocampus of the model group as well as the protein expressions of PKA, BDNF and CRE,the mRNA expressions of BDNF and CREB were lower than those in the normal group (P<0.01). Compared with the model group, the CLMT groups had reduced immobility time (P<0.01), elevated total movement distance, residence time in central area, number of entries in central area and movement distance in central area (P<0.05, P<0.01), up-regulated contents of 5-HT, NE and cAMP in hippocampus (P<0.05, P<0.01), and up-regulated protein expressions of PKA, BDNF and CREB and mRNA expressions of BDNF and CREB (P<0.01). HE staining and Nissl staining showed that CLMT significantly improved the neuronal structure in rat hippocampus. ConclusionCLMT alleviates the anxiety and depression of rats. These effects may be mediated by regulating monoamine neurotransmitters 5-HT and NE in hippocampus of depressed rats, activating cAMP/PKA/CREB/BDNF signaling pathway, up-regulating the expression of BDNF and protecting hippocampal structure and function .
10.Advances in the application of three-dimensional visualization technique in hepatic alveolar echinococcosis
Dong ZHANG ; Zhixin WANG ; Qian ZHAO ; Xiaoxia SU ; Kai XU ; Mingming DONG ; Wei LI ; Lizhao HOU ; Haining FAN ; Haijiu WANG
Journal of Clinical Hepatology 2023;39(2):457-462
Hepatic alveolar echinococcosis (HAE) is a parasitic disease caused by Echinococcus multilocularis infection and has wide distribution and great harm in China. At present, ultrasound, CT, and MRI are the main radiological examination methods for HAE, with certain limitations in preoperative diagnosis and evaluation. This article introduces the guiding effect of three-dimensional visualization technique and its derivative technologies in the accurate diagnosis and preoperative evaluation of HAE, so as to provide help for the clinical diagnosis and treatment of HAE in the future.


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