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.One case of severe cardiac arrhythmias caused by Huoxiang Zhengqi liquid
Yinping ZHAO ; Xiaoyu XIN ; Guibo XIE ; Huayan LI ; Yuan YAN
Chinese Journal of Pharmacoepidemiology 2024;33(4):476-480
A 22-year-old male self-administered Huoxiang Zhengqi liquid(10 mL,bid)orally due to abdominal pain and diarrhea.The symptoms improved significantly on the same day.Palpitations occurred about 30 minutes after 10 mL Huoxiang Zhengqi Liuquid administration in the morning and afternoon of the next day and in the morning of the third day,respectively,which was spontaneously relieved.Electrocardiogram showed that multiple arrhythmias alternated,including disordered atrial rhythm,paroxysmal atrial fibrillation,paroxysmal supraventricular tachycardia,frequent premature ventricular contractions,junctional premature contractions,atrioventricular block,and sinus bradycardia.After admission,the patient was given electrocardiography monitoring,polarizing fluid,verapamil injection,and other treatment methods to relieve symptoms,after 12 days of treatment,the patient's condition improved,and the electrocardiogram showed sinus rhythm.This case suggests that as an over-the-counter drug,the safety of Huoxiang Zhengqi liquid should be paid more attention by clinic and public.If patients manifest palpitation symptoms while using Huoxiang Zhengqi liquid,it is imperative to consider the potential for drug-induced serious arrhythmia and get medical treatment promptly.
3.Exploring the high-quality development path of public hospitals based on five core indicators
Hao CHEN ; Xiaozhe XIA ; Zhaoxin QIAN ; Huayan ZHOU ; Hong ZHAO
Chinese Journal of Hospital Administration 2024;40(1):7-11
The five core indicators(the case mix index, the proportion of level-4 surgery, the proportion of technical service income in medical income, the proportion of personnel expenditure in business expenditure, and the proportion of fixed part in personnel salary) and target values determined by the pilot goal of high-quality development of high-level public hospitals jointly built by National Health Commission and Provincial Government had become the core indicators for evaluating the quality and efficiency of public hospital development. The authors proposed the optimization and improvement measures for the five core indicators one by one from the internal reform and innovation in hospitals, as well as the synergetic development and governance of " insurance-medical-medicine linkage", combined with the current situation of a pilot hospital. The authors also proposed the starting points and driving force for promoting the high-quality development of public hospitals through the synergetic development and governance of " insurance-medical-medicine linkage", including implementing government investment responsibilities, streamlining the price evaluation of medical services, deepening the reform of medical insurance payment, accelerating the expansion of drug and consumable procurement, and promoting the application of advanced technologies and products, in order to provide reference for the in-depth promotion of high-quality development of public hospitals.
4.Mechanism of Qingre Lishi Huazhuo Method(Modified Simiaosan) on Chronic Gouty Arthritis of Dampness-heat Obstruction Syndrome Based on NLRP3/IL-1β Signaling Pathway
Mingrui DU ; Zhe ZHAO ; Huayan LI ; Xin WANG ; Yan CUI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(11):133-140
ObjectiveTo study the clinical efficacy of the Qingre Lishi Huazhuo method on patients with chronic gouty arthritis of dampness-heat obstruction syndrome and the effect on nucleotide-binding oligomerization domain-like receptor 3(NLRP3)/interleukin-1β (IL-1β) signaling pathway to preliminarily explore its mechanism. MethodSixty patients with chronic gouty arthritis of dampness-heat obstruction syndrome were enrolled and divided into a treatment group (30 cases) and a control group (30 cases) according to the random number table method. Thirty people were assigned to the healthy group. Patients in the control group were treated with oral Febuxostat, while those in the treatment group were treated with modified Simiaosan combined with Febuxostat. Treatment lasted four weeks. The general clinical data, traditional Chinese medicine (TCM) syndrome scores, serum uric acid (UA), serum creatinine (SCr), blood urea nitrogen (BUN), fasting blood glucose (FPG), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) of patients were recorded. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of IL-1β,TNF-α, and IL-6,and the levels of NLRP3,cysteinyl aspartate-specific protease-1 (Caspase-1), and apoptosis-associated speck-like protein containing a CARD (ASC) were detected by Western blot. ResultBefore treatment, the levels of body mass index (BMI), systolic blood pressure (SBP),diastolic blood pressure (DBP),UA,SCr,BUN,FPG,LDL,TG,and TC in both groups significantly increased (P<0.05,P<0.01),and the levels of HDL significantly decreased as compared with those in the healthy group(P<0.05). Additionally, the levels of IL-1β, TNF-α, and IL-6 in both groups significantly increased before treatment (P<0.01). Compared with the results before treatment, patients in the two groups had significant reductions in tube pain, joint tenderness, joint swelling,joint fever, activity disorders, body fatigue, sliminess, bitter mouth, yellow and red urine, and tongue manifestation scores (P<0.05,P<0.01). Compared with patients in the control group after treatment, those in the treatment group had a significant decrease in joint fever, body fatigue, sliminess, bitter mouth,sticky stool,yellow and red urine, tongue manifestation score, and pulse score (P<0.05). The total effective rate in the treatment group was 80.0% (24/30), higher than 56.7% (17/30)in the control group(χ2=11.916,P<0.05). Compared with the results before treatment, BMI, SBP, DBP, UA, SCr, BUN, FPG, LDL, TG, TC, ESR,CRP, IL-1β, TNF-α, IL-6 levels, and VAS score in both groups significantly decreased (P<0.05,P<0.01). Compared with patients in the control group after treatment, those in the treatment group had decreased DBP,ESR, IL-1β levels, and VAS score (P<0.05). Western blot results showed that before treatment, the protein expression of NLRP3, Caspase-1, and ASC in peripheral blood mononuclear cells (PBMCs) of patients in both groups were higher than those in the healthy group (P<0.01). Compared with the results before treatment, the protein expression of NLRP3, Caspase-1, and ASC in PBMCs in patients of both groups after treatment decreased (P<0.05,P<0.01). Compared with the control group after treatment, the treatment group showed decreased expression levels of NLRP3 and Caspase-1(P<0.05). ConclusionThe Qingre Lishi Huazhuo method can effectively improve the clinical symptoms and reduce inflammation of chronic gouty arthritis of dampness-heat obstruction syndrome with good safety. The mechanism may be related to the inhibition of the NLRP3/IL-1β signaling pathway.
5.Clinical study of radiation exposure from atrial fibrillation catheter ablation guided by magnetic navigation system and cryoballoon
Xiaoyu LIU ; Jie ZHENG ; Kulin LI ; Huayan YOU ; Xiaoyan LI ; Shipeng DANG ; Xiaoxi ZHAO ; Ruxing WANG
Chinese Journal of Radiological Medicine and Protection 2023;43(7):547-553
Objective:To identify the method to reduce X-ray exposure during ablation of atrial fibrillation (AF) by comparing the cryoballoon (CRYO) ablation and remote magnetic navigation (RMN) ablation.Methods:A retrospective analysis was conducted on 144 patients undergoing CRYO ablation (CRYO group) and 121 patients undergoing RMN ablation (RMN group) in our hospital. Entrance surface doses at reference points online, exposure time during procedure and outcomes were analyzed for different types of patients.Results:Compared with the RMN group, the procedure time for the CRYO group significantly decreased [(165.0±23.6), (97.8±18.4) min, t=26.05, P<0.001]. However, the entrance surface dose value [(232.3±130.7), (669.0±387.5) mGy, Z=-12.29, P<0.001] and X-ray exposure time [(8.1±3.1), (23.4±6.2) min, t=-24.57, P<0.001] increased significantly for the CRYO group. No significant difference was found between the two groups in the proportion of maintaining sinus rhythm during follow-up of patients (71.9%, 75.7%, P=0.618). Multiple regression analysis showed that obese patients, patients with non-paroxysmal AF and patients with variant pulmonary veins were associated with an increase in entrance surface dose values in the CRYO group ( t=5.47, 2.23, 3.39, P<0.05). The X-ray exposure time for the three types patients above in the CRYO group also increased ( t=2.87, 3.86, 3.25, P<0.05) in the CRYO group. However, only obese patients in the RMN group had an increase in entrance surface dose value ( Z=-4.15, P<0.001) and no increase in exposure time. For the three types of patients above, there was no significant difference in proportion of maintaining sinus rhythm between the CRYO group and the RMN group during follow-up ( P>0.05). Conclusions:Compared with RMN ablation, the radiation exposure of CRYO AF ablation significantly increased, especially in obese patients, patients with non-paroxysmal AF and patients with pulmonary veins variation. The use of RMN for these types of patients may reduce the radiation exposure without affecting the procedure outcomes.
6.Value of short-time transcutaneous carbon dioxide and oxygen pressure monitoring in critically ill preterm infants
Yuejyu CAI ; Xiaolan LI ; Xiao RONG ; Weineng LU ; Huayan ZHANG ; Xiaopeng ZHAO
Chinese Journal of Perinatal Medicine 2023;26(8):658-663
Objective:To investigate the value of short-time transcutaneous carbon dioxide pressure (TcPCO 2) and transcutaneous oxygen pressure (TcPO 2) monitoring in critically ill preterm infants. Methods:From January to December 2018, 62 critically ill neonates receiving respiratory support at Guangzhou Women and Children's Medical Center were retrospectively enrolled. A total of 348 sets of paired data including TcPCO 2/TcPO 2 and arterial carbon dioxide pressure (PaCO 2)/arterial oxygen partial pressure (PaO 2) were analyzed. The patients were divided into different groups based upon birth weight (23 cases>1 000 g-≤1 500 g, 129 sets of paired data; 18 cases≤1 000 g, 130 sets of paired data) and gestational age (16 cases born at ≤28 gestational weeks, 127 sets of paired data; 29 cases born at 28-34 gestational weeks, 159 sets of paired data) and the differences between groups were compared. The correlation and consistency of TcPCO 2/TcPO 2 and PaCO 2/PaO 2 were evaluated using Pearson's correlation and Blan-Altman scatter plots. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic efficacy of TcPCO 2 in neonates with hypercapnia. Results:There was a positive correlation between TcPCO 2 and PaCO 2 in all patients ( r=0.913, 95% CI:0.894-0.929, P<0.05). In patients whose birth weight was>1 000 g-≤1 500 g or≤1 000 g, TcPCO 2 and PaCO 2 were positively correlated and the consistency were good ( r=0.909, 95% CI:0.874-0.935; r=0.934, 95% CI:0.908-0.953; both P<0.05), and the same finding was also observed in patients born at≤28 gestational weeks or 28-34 weeks of gestation ( r=0.938, 95% CI:0.913-0.956; r=0.871, 95% CI: 0.827-0.904; both P<0.05). The sensitivity, specificity and area under curve of TcPCO 2 in the diagnosis of hypercapnia were 90.91%, 85.85%, and 0.942, respectively. There was a poor correlation between TcPO 2 and PaO 2 in all patients and those with birth weight >1 000 g-≤1 500 g or gestational age 28-34 weeks (all r<0.75, all P<0.05). There was no correlation between TcPO 2 and PaO 2 in the birth weight ≤1 000 g and gestational age ≤28 weeks groups (both P>0.05). Conclusions:Short-time TcPCO 2 monitoring can accurately assess PaCO 2 in critically ill neonates requiring respiratory support and is of high diagnostic value for hypercapnia. However, TcPO 2 has limitation in evaluating PaO 2 and other indicators may need to be involved.
7.Neonatal transaldolase deficiency: a case report
Yuanjing LI ; Huayan ZHANG ; Jin HAN ; Xiuzhen LI ; Xiaopeng ZHAO
Chinese Journal of Perinatal Medicine 2022;25(4):294-297
We report a neonate with transaldolase deficiency caused by compound heterozygous variation of the TALDO1 gene. A pregnant woman, who had an adverse pregnancy history, was found with multiple fetal abnormalities on prenatal ultrasound and the following whole exon sequencing indicated a likely pathogenic heterozygous variation of c.462-2A>G and c.574C>T(p.R192C) in TALDO1 gene in the fetus. A body was born at 38 +1 weeks and presented dysmorphic features (cutis laxa/wrinkled skin and low-set ears, etc.), splenomegaly, anemia, abnormal liver function and coagulation. In combination with the prenatal testing results, transaldolase deficiency was diagnosed. The patients still had cutis laxa/wrinkled skin on the back of both hands and neck at one year and three months old. Therefore, for babies with hepatosplenomegaly, anemia, thrombocytopenia, coagulation dysfunction, at the same time with dysmorphic features such as cutis laxa, low-set ears, attention should be paid to the investigation of transaldolase deficiency.
8.A Chromosome-level Genome Assembly of Wild Castor Provides New Insights into Its Adaptive Evolution in Tropical Desert
Lu JIANJUN ; Pan CHENG ; Fan WEI ; Liu WANFEI ; Zhao HUAYAN ; Li DONGHAI ; Wang SEN ; Hu LIANLIAN ; He BING ; Qian KUN ; Qin RUI ; Ruan JUE ; Lin QIANG ; Lü SHIYOU ; Cui PENG
Genomics, Proteomics & Bioinformatics 2022;20(1):42-59
Wild castor grows in the high-altitude tropical desert of the African Plateau,a region known for high ultraviolet radiation,strong light,and extremely dry condition.To investigate the potential genetic basis of adaptation to both highland and tropical deserts,we generated a chromosome-level genome sequence assembly of the wild castor accession WT05,with a genome size of 316 Mb,a scaffold N50 of 31.93 Mb,and a contig N50 of 8.96 Mb,respectively.Compared with cultivated castor and other Euphorbiaceae species,the wild castor exhibits positive selection and gene family expansion for genes involved in DNA repair,photosynthesis,and abiotic stress responses.Genetic variations associated with positive selection were identified in several key genes,such as LIG1,DDB2,and RECGI,involved in nucleotide excision repair.Moreover,a study of genomic diversity among wild and cultivated accessions revealed genomic regions containing selection signatures associated with the adaptation to extreme environments.The identification of the genes and alleles with selection signatures provides insights into the genetic mechanisms under-lying the adaptation of wild castor to the high-altitude tropical desert and would facilitate direct improvement of modern castor varieties.
9.Histological Validation of Cardiovascular Magnetic Resonance T1 Mapping for Assessing the Evolution of Myocardial Injury in Myocardial Infarction:An Experimental Study
Lu ZHANG ; Zhi-gang YANG ; Huayan XU ; Meng-xi YANG ; Rong XU ; Lin CHEN ; Ran SUN ; Tianyu MIAO ; Jichun ZHAO ; Xiaoyue ZHOU ; Chuan FU ; Yingkun GUO
Korean Journal of Radiology 2020;21(12):1299-1309
Objective:
To determine whether T1 mapping could monitor the dynamic changes of injury in myocardial infarction (MI) and be histologically validated.
Materials and Methods:
In 22 pigs, MI was induced by ligating the left anterior descending artery and they underwent serial cardiovascular magnetic resonance examinations with modified Look-Locker inversion T1 mapping and extracellular volume (ECV) computation in acute (within 24 hours, n = 22), subacute (7 days, n = 13), and chronic (3 months, n = 7) phases of MI. Masson’s trichrome staining was performed for histological ECV calculation. Myocardial native T1 and ECV were obtained by region of interest measurement in infarcted, peri-infarct, and remote myocardium.
Results:
Native T1 and ECV in peri-infarct myocardium differed from remote myocardium in acute (1181 ± 62 ms vs. 1113 ± 64 ms, p = 0.002; 24 ± 4% vs. 19 ± 4%, p = 0.031) and subacute phases (1264 ± 41 ms vs. 1171 ± 56 ms, p < 0.001; 27 ± 4% vs. 22 ± 2%, p = 0.009) but not in chronic phase (1157 ± 57 ms vs. 1120 ± 54 ms, p = 0.934; 23 ± 2% vs. 20 ± 1%, p = 0.109). From acute to chronic MI, infarcted native T1 peaked in subacute phase (1275 ± 63 ms vs. 1637 ± 123 ms vs. 1471 ± 98 ms, p < 0.001), while ECV progressively increased with time (35 ± 7% vs. 46 ± 6% vs. 52 ± 4%,p < 0.001). Native T1 correlated well with histological findings (R2 = 0.65 to 0.89, all p < 0.001) so did ECV (R2 = 0.73 to 0.94, all p < 0.001).
Conclusion
T1 mapping allows the quantitative assessment of injury in MI and the noninvasive monitoring of tissue injury evolution, which correlates well with histological findings.
10.Histological Validation of Cardiovascular Magnetic Resonance T1 Mapping for Assessing the Evolution of Myocardial Injury in Myocardial Infarction:An Experimental Study
Lu ZHANG ; Zhi-gang YANG ; Huayan XU ; Meng-xi YANG ; Rong XU ; Lin CHEN ; Ran SUN ; Tianyu MIAO ; Jichun ZHAO ; Xiaoyue ZHOU ; Chuan FU ; Yingkun GUO
Korean Journal of Radiology 2020;21(12):1299-1309
Objective:
To determine whether T1 mapping could monitor the dynamic changes of injury in myocardial infarction (MI) and be histologically validated.
Materials and Methods:
In 22 pigs, MI was induced by ligating the left anterior descending artery and they underwent serial cardiovascular magnetic resonance examinations with modified Look-Locker inversion T1 mapping and extracellular volume (ECV) computation in acute (within 24 hours, n = 22), subacute (7 days, n = 13), and chronic (3 months, n = 7) phases of MI. Masson’s trichrome staining was performed for histological ECV calculation. Myocardial native T1 and ECV were obtained by region of interest measurement in infarcted, peri-infarct, and remote myocardium.
Results:
Native T1 and ECV in peri-infarct myocardium differed from remote myocardium in acute (1181 ± 62 ms vs. 1113 ± 64 ms, p = 0.002; 24 ± 4% vs. 19 ± 4%, p = 0.031) and subacute phases (1264 ± 41 ms vs. 1171 ± 56 ms, p < 0.001; 27 ± 4% vs. 22 ± 2%, p = 0.009) but not in chronic phase (1157 ± 57 ms vs. 1120 ± 54 ms, p = 0.934; 23 ± 2% vs. 20 ± 1%, p = 0.109). From acute to chronic MI, infarcted native T1 peaked in subacute phase (1275 ± 63 ms vs. 1637 ± 123 ms vs. 1471 ± 98 ms, p < 0.001), while ECV progressively increased with time (35 ± 7% vs. 46 ± 6% vs. 52 ± 4%,p < 0.001). Native T1 correlated well with histological findings (R2 = 0.65 to 0.89, all p < 0.001) so did ECV (R2 = 0.73 to 0.94, all p < 0.001).
Conclusion
T1 mapping allows the quantitative assessment of injury in MI and the noninvasive monitoring of tissue injury evolution, which correlates well with histological findings.

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