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.A Case Report of Jansen-de Vries Syndrome Caused by PPM1D Gene Mutation and Literature Review
Mei XUE ; Bo PANG ; Xiaoqian ZHANG ; Ziyu GAO ; Bo ZHOU ; Zhixin ZHANG
JOURNAL OF RARE DISEASES 2025;4(3):355-360
Jansen-de Vries syndrome, also known as intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, is a rare autosomal dominant disorder characterized by multisystem involvement. This article reports the case of a young child who presented with global developmental delay, gastrointestinal dysfunction, intellectual disability, and short stature. Distinct facial features included a broad forehead, low nasal bridge, thin upper lip, and widely spaced and misaligned teeth. Additional phenotypic findings involved small hands and feet, as well as digital anomalies. Through whole-exome sequencing (WES) and copy number variation (CNV) analysis, a pathogenic variant was identified in the 
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.Novel 18F-FES PET/CT in Non-invasive Functional Diagnosis of Delayed Lung Metastasis Presented with Horner Syndrome in a Metastatic Breast Cancer Patient
Ru YAO ; Zhixin HAO ; Yang QU ; Chao ZHANG ; Weijia LI ; Jie LANG ; Bo PAN ; Yidong ZHOU ; Qiang SUN ; Li HUO
Medical Journal of Peking Union Medical College Hospital 2024;15(3):702-707
Hormonal receptor positive human epidermal receptor 2 negative (HR+/HER2-) is the commonest molecular subtype of breast cancer (BC). Patients with HR+/HER2- BC may manifest clinically a late recurrence whose BC metastasizes 10-15 years post-operatively. We report one case who presented with pulmonary mass in upper lobe of lung and Horner syndrome 16 years after BC surgery. FDG PET/CT suggested pulmonary malignancy but could not differentiate between primary or metastatic cancer when invasive biopsy was quite risky. Novel 18F-FES PET/CT facilitated the non-invasive functional diagnosis of estrogen-receptor positive (ER+) pulmonary metastasis of BC, and the patient experienced partial response (PR) after CDK4/6 inhibitor and aromatase inhibitor as endocrine therapy. This article reviews the diagnosis and treatment process of this case, to provide guidance for non-invasive global evaluation of ER status among metastatic HR+/HER2- BC patients with 18F-FES PET/CT.
5.The nursing care of a patient with large skin ulcers caused by EBV positive T/NK-cell lymphoproliferative diseases based on TIME Clinical-Decision-Support-Tool
Zhixin WANG ; Cong LI ; Junjie ZHANG ; Yongping MA ; Wenhua ZHOU
Chinese Journal of Practical Nursing 2024;40(31):2461-2466
		                        		
		                        			
		                        			To summarize the nursing experience of a patient with large skin ulcers caused by EBV positive T/NK-cell lymphoproliferative diseases based on TIME Clinical-Decision-Support-Tool. The main points of nursing care were as follows: early identification of the cause of ulceration and active treatment of the underlying disease; accurate and continuous assessment of patients and their wounds; multidisciplinary consultation to ensure the integrity and comprehensiveness of diagnosis and treatment; active identification of obstacle factors and risk control; providing different dressing change programs according to different wound healing stages; evaluation of treatment effects at any time; timely pain management; improving the nutritional status of patients; providing health education and psychological nursing care. After 367 days of wound dressing, the patient′s wound was fully healed, and EBV-DNA was not detected in genetic examination after hematopoietic stem cell transplantation.
		                        		
		                        		
		                        		
		                        	
6.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 . 
		                        		
		                        		
		                        		
		                        	
7.Clinical treatment guideline for pulmonary blast injury (version 2023)
Zhiming SONG ; Junhua GUO ; Jianming CHEN ; Jing ZHONG ; Yan DOU ; Jiarong MENG ; Guomin ZHANG ; Guodong LIU ; Huaping LIANG ; Hezhong CHEN ; Shuogui XU ; Yufeng ZHANG ; Zhinong WANG ; Daixing ZHONG ; Tao JIANG ; Zhiqiang XUE ; Feihu ZHOU ; Zhixin LIANG ; Yang LIU ; Xu WU ; Kaican CAI ; Yi SHEN ; Yong SONG ; Xiaoli YUAN ; Enwu XU ; Yifeng ZHENG ; Shumin WANG ; Erping XI ; Shengsheng YANG ; Wenke CAI ; Yu CHEN ; Qingxin LI ; Zhiqiang ZOU ; Chang SU ; Hongwei SHANG ; Jiangxing XU ; Yongjing LIU ; Qianjin WANG ; Xiaodong WEI ; Guoan XU ; Gaofeng LIU ; Junhui LUO ; Qinghua LI ; Bin SONG ; Ming GUO ; Chen HUANG ; Xunyu XU ; Yuanrong TU ; Liling ZHENG ; Mingke DUAN ; Renping WAN ; Tengbo YU ; Hai YU ; Yanmei ZHAO ; Yuping WEI ; Jin ZHANG ; Hua GUO ; Jianxin JIANG ; Lianyang ZHANG ; Yunfeng YI
Chinese Journal of Trauma 2023;39(12):1057-1069
		                        		
		                        			
		                        			Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.
		                        		
		                        		
		                        		
		                        	
8.Experimental study on ultrasound/near-infrared dual-mode imaging and thrombolysis in vitro of phase-change mesoporous silicon nanoprobe
Zhiwen WANG ; Nan JIANG ; Juhong PAN ; Sheng CAO ; Zhixin JIANG ; Qing ZHOU ; Bo HU
Chinese Journal of Ultrasonography 2023;32(10):907-914
		                        		
		                        			
		                        			Objective:To explore the potential of thrombus-targeted nanoprobes for ultrasound/near-infrared bimodal imaging and their synergistic therapeutic effects on thrombosis in vitro.Methods:Nanoprobes loaded with arginine-glycine-aspartate peptide (RGD), perfluoropentane (PFP) and indocyanine green (ICG) were prepared by ultrasonic vibration and carbodiimide method with mesoporous silica nanoparticle (MSN) as the carrier. The probe morphology was observed by scanning and transmission electron microscopy. The loading of RGD and ICG was detected by Bicinchoninic Acid Assay (BCA) and UV-Visible-NIR spectroscopy respectively. The imaging performance and photothermal response of the nanoprobe under near infrared light (NIR) irradiation were studied in vitro. Its biological safety was tested by cytotoxicity test and hemolysis test. The phase transformation was studied under ultrasound and NIR irradiation. The nanoprobe was incubated with fresh arterial thrombus, and its target-seeking ability was observed by frozen section. Ultrasound and NIR irradiation were used to evaluate its thrombolytic ability by the weight changes of thrombus before and after irradiation.Results:The prepared nanoprobe had regular morphology and uniform size. The particle diameter was (156.83±5.05)nm, and the surface potential was (11.47±0.25)mV. The RGD coupling rate was (77.67±4.50)%, which could mediate the targeting of nanoprobe to fresh extracorporeal arterial thrombus. UV-Visible-NIR spectroscopy confirmed the successful loading of ICG, and its encapsulation rate was (80.47±0.05)%. After ultrasound and NIR irradiation, the nanoprobe could undergo acoustically induced phase transition, thermally induced phase transition and enhance the ultrasonic development effect. With the increase of the concentration of the nanoprobe solution, the NIR signal gradually increased, and the temperature rose in a concentration-dependent and intensity-dependent manner after NIR irradiation. The cytotoxicity test and hemolysis test showed that the nanoprobe had good biological safety, and it could play a thrombolytic role under the combined irradiation of ultrasound and NIR, and the weight of thrombus was significantly reduced after the treatment ( P<0.01). Conclusions:In this study, the nanoprobe (RGD/ICG/PFP@MSN) were successfully prepared possesses excellent dual mode imaging capabilities of ultrasound and NIR, excellent phase transition ability and photothermal conversion efficiency, as well as efficient targeted penetration and therapeutic effects against thrombosis. This study provides strong in vitro experimental evidence and new strategies for the integration of diagnosis and treatment of thrombotic diseases under the cooperation of ultrasound and NIR.
		                        		
		                        		
		                        		
		                        	
9.Advances in the treatment of hepatocellular carcinoma combined with hepatic vein tumor thrombus
Mengjian QI ; Liuxin ZHOU ; Qingxia SHI ; Wen WANG ; Xiaoxia SU ; Haining FAN ; Zhixin WANG
Chinese Journal of Hepatobiliary Surgery 2022;28(10):785-788
		                        		
		                        			
		                        			Hepatocellular carcinoma is one of the common malignant tumors in China, which seriously threatens the life and health of the nation. Hepatic vein tumor thrombosis (HVTT) is one of the common clinical manifestations. The prognosis of hepatocellular carcinoma combined with HVTT is extremely poor, and there is no unanimous opinion on its treatment in China and abroad. Currently, Asian guidelines recommend multidisciplinary treatment for patients with vascular invasion. This article reviewed the current progress in the treatment of hepatocellular carcinoma combined with HVTT.
		                        		
		                        		
		                        		
		                        	
10.Diagnosis and treatment of hepatic alveolar echinococcosis with intraperitoneal implantable metastasis
Jican YAN ; Zhiyu CHEN ; Wenhao YU ; Xinjian GUO ; Haijiu WANG ; Qian LU ; Liuxin ZHOU ; Haining FAN ; Zhixin WANG
Chinese Journal of Digestive Surgery 2021;20(9):1007-1010
		                        		
		                        			
		                        			Hepatic alveolar echinococcosis is a zoonotic parasitic disease caused by echinococcus multilocularis infection. The growth pattern of the lesions of hepatic alveolar echinococcosis is similar to that of liver malignant tumor showing invasive growth. Hepatic alveolar echinococcosis can not only directly invade the adjacent tissue structure, but also metastasize through the lymphatic tracts and blood vessels. Hepatic alveolar echinococcosis with intraperitoneal implantable metastasis is extremely rare. The authors introduce the diagnosis and treatment of 1 patient who had hepatic alveolar echinococcosis with intraperitoneal implantable metastasis.
		                        		
		                        		
		                        		
		                        	
            
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