1.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
2.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
3.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
4.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
5.Research on application of ICF-guided case-based learning in teaching internship of rehabilitation medicine undergraduates
Yinhua ZHENG ; Zhaohong YAN ; Shuang MA
Chinese Journal of Medical Education Research 2024;23(7):915-919
Objective:To explore the application of case-based learning (CBL) guided by the International Classification of Functioning, Disability and Health (ICF) in teaching internship of rehabilitation medicine undergraduates.Methods:According to the implementation time of ICF-guided CBL teaching (February 2023), 55 students who interned before February 2023 were included in the control group and received routine teaching, and 54 students who interned after February 2023 were enrolled in the observation group and received ICF-guided CBL teaching. The assessment score, professional identity score, learning adaptability score, communication ability score, and critical thinking score were evaluated before and after teaching. SPSS 23.0 was used for t-test and chi-square test. Results:After teaching, the assessment score, professional identity score, learning adaptability score, communication ability score, and critical thinking score of both groups of students significantly increased. Compared with the control group, the observation group showed significantly higher assessment score [(166.01±14.21) vs. (150.19±13.73)], professional identity score [(124.50±12.73) vs. (103.94±10.42)], learning adaptability score [(71.93±7.43) vs. (57.69±6.71)], communication ability score [(23.77±4.21) vs. (19.97±3.94)], and critical thinking score [(150.03±11.20) vs. (129.38±10.57)].Conclusions:ICF-guided CBL teaching can help to improve the professional identity and learning adaptability of rehabilitation medicine undergraduates, enhance their skill of communication with patients and critical thinking ability, and increase their professional theoretical knowledge and practical ability. Therefore, ICF-guided CBL is a beneficial exploration of teaching internship of rehabilitation medicine undergraduates.
6.Influence of muscle regions of meridians needling method combined with auricular point sticking on pain and range of motion in patients with chronic nonspecific low back pain
Yunping SHAN ; Yinhua MA ; Baoqing SU ; Kaiwei ZHANG
Journal of Acupuncture and Tuina Science 2024;22(5):381-386
Objective:To observe the effects of muscle regions of meridians needling method combined with auricular point sticking on pain and lumbar range of motion in patients with chronic nonspecific low back pain. Methods:A total of 100 patients with chronic nonspecific low back pain were randomly divided into a control group and an observation group,with 50 patients in each group.Both groups received auricular point sticking treatment,while the control group received additional conventional acupuncture treatment,and the observation group received additional muscle regions of meridians needling method.The total effective rate of the two groups was compared after 4 weeks of treatment.Before treatment and after 1 week and 4 weeks of treatment,the visual analog scale(VAS)score was used to assess the degree of low back pain,and the modified-modified Schober(MMS)score was used to evaluate the lumbar range of motion. Results:There was statistical significance in comparing the total effective rate between the two groups(P<0.01).During the treatment process,as the number of treatments increased,the VAS score gradually decreased,and the MMS score gradually increased in both groups.After 1 week and 4 weeks of treatment,the VAS score in the observation group was lower than that in the control group(P<0.01),and the MMS score in the observation group was higher than that in the control group(P<0.01).During the treatment period,no serious adverse reactions occurred in either group. Conclusion:Based on auricular point sticking treatment,muscle regions of meridians needling method is more effective than conventional acupuncture in treating chronic nonspecific low back pain since it is able to significantly reduce the pain and improve the lumbar range of motion.
7.Application of visual mind mapping based on Mini-CEX evaluation in the practical teaching of nursing students in department of general surgery
Meiying SHEN ; Yinhua MA ; Ping WANG ; Zeyu ZHANG ; Huihui LIANG
Chinese Journal of Medical Education Research 2022;21(3):363-367
Objective:To explore the effect of visual mind mapping based on Mini-CEX evaluation combined with case-based learning (CBL) on improving the learning ability and teaching satisfaction of nursing students in department of general surgery.Methods:A total of 120 nurses rotating in the Department of General Surgery, Panzhihua Central Hospital (Clinical Medical College of Panzhihua University) from September 2019 to July 2020 were selected as research objects, and randomly divided into a control group and a study group, with 60 nurses in each group. The control group used traditional teaching, and the study group used visual mind mapping based on Mini-CEX evaluation combined with CBL. After the training, the clinical comprehensive ability of the nurses was evaluated by theoretical and practical assessment, and the self-learning ability and teaching satisfaction of the nurses were analyzed through self-made questionnaire survey. SPSS 22.0 was used for t test and chi-square test. Results:The theoretical and practical assessment scores of nursing students in the study group were significantly higher than those in the control group[(95.01±3.52) vs. (83.26±4.05); (96.14±3.22) vs. (81.17±4.30)] ( P=0.001). Before the rotation training, there was no statistical difference between the study group and the control group in the scores of self-motivation beliefs, task analysis, self-monitoring and adjustment, and self-evaluation ( P>0.05). After the rotation training, the scores of above 4 aspects were significantly higher in study group than the control group ( P<0.05). The nurse trainees in the study group were significantly superior to those in control group in the following 7 aspects: reasonable arrangement of the teaching plan, novelty of the teaching mode, improvement of clinical nursing skills, improvement of the nurse-patient communication ability, improvement of the emergency response ability, and overall teaching satisfaction ( P=0.001). Conclusion:Visual mind mapping based on Mini-CEX evaluation combined with CBL applied to clinical teaching training of nursing students in the department of general surgery can effectively improve the effectiveness of nursing teaching and teaching satisfaction, improve the learning ability of nurses, and improve the nursing level of nursing students in the department of general surgery.
8.Current situation on drug resistance and influencing factors of multidrug-resistance in newly treated pulmonary tuberculosis patients in Gansu province
Ling MA ; Jixiu GU ; Qing LI ; Yinhua LI ; Dongdong WANG ; Jian HE ; Hongyan SI
Chinese Journal of Epidemiology 2022;43(7):1093-1098
Objective:In order to provide the precise prevention and control strategy of drug resistance TB in Gansu province, we analyzed the status and risk factors of new drug resistance pulmonary tuberculosis patients.Methods:New pulmonary tuberculosis patients were enrolled from 30 tuberculosis-specialized medical institutions (drug resistance monitoring stations) in Gansu province between first September 2014 to 31 th August 2017, and filled in the survey questionnaire. The isolated Mycobacterium tuberculosis (MTB) strains were implemented 10 drugs drug- susceptibility tes, including isoniazid (INH), rifampicin (RFP), ethambutol (EMB), streptomycin (Sm), kanamycin (Km), amikacin (Am), ofloxacin (Ofx), capreomycin (Cm), propithio-iso-nicotinamide (Pto).The risk factors were analyzed by logistic regression model. Results:One patient was corresponding one clinical isolates among 1 815 patients. The rate (95% CI) of total drug-resistance, single drugresistance, multiple drug- resistance, multidrug-resistance and extensively drug-resistant were 25.45% (23.45%-27.46%), 11.40% (9.94%-12.87%),6.23% (5.11%-7.34%), 7.82% (6.59%-9.06%) and 0.28% (0.03%-0.52%) respectively. Among 142 multidrug-resistant TB patients, the farmers, young adults aged 20-59 and low-income group were 90.85%, 62.68% and 31.69%, respectively. The results of univariate and multivariate analysis showed that the male, non-Han, treatment less than 1 month group and treatment less than 1 month and withdrawal less than 2 month group were risk factors of new multidrug-resistant pulmonary TB. Conclusions:Compared with the Chinese national baseline level of TB resistance, the total drug resistance rate of new TB patients in Gansu province was low, but the multidrug-resistance rate was high. The health assistance for rural low-income TB patients was still an important strategy to prevent and control multidrug-resistant in Gansu province. And measures must implement to stop irregular treatment and poor compliance, as the risk factors of multidrug-resistance in new PTB patients.
9.Automated function imaging for predicting severe stenosis of left anterior descending coronary artery
Yinhua CHEN ; Yong CHEN ; Yong MA ; Jing YUAN ; Haidi YU ; Fei YANG ; Xiuxiu WU
Chinese Journal of Medical Imaging Technology 2017;33(10):1501-1505
Objective To explore the value of automated function imaging (AFI) based on two-dimensional speckle tracking imaging (2D-STI) technique longitudinal strain for predicting severe stenosis of left anterior descending (LAD) coronary artery in patients with suspected coronary heart disease (CHD).Methods Ninety-two patients with suspected CHD were divided into two groups according to the coronary angiography (CAG) results.There were 49 cases in group A (LAD stenosis rate <70%) and 43 cases in group B (LAD stenosis rate ≥70%).The two dimensional gray scale dynamic images were obtained in apical four-chamber view,apical two-chamber view and long axis of left ventricle (LV) view.Eighteen segments of LV longitudinal peak systolic strain,global longitudinal strain (GLS) and territorial longitudinal strain (TLS) supplied with LAD were measured with AFI software.The conventional ultrasonic parameters and the two-dimensional longitudinal strain parameters were compared between the two groups and ROC curve analysis of these parameters was used to predict LAD severe stenosis.Results There was no significant difference in the conventional ultrasonic parameters between the two groups (all P>0.05).The group B had lower GLS,TLS than group A (both P<0.001).GLS and TLS showed the highest area under ROC curve (0.715 and 0.705) for predicting LAD severe stenosis.The cut-off value,sensitivity and specificity for predicting LAD severe stenosis were-19.58 %,63.3 %,67.4 % in TLS,and-20.85 %,74.4 %,61.2 % in GLS respectively.Conclusion The longitudinal strain parameters measured with AFI based on 2D-STI technique can be used to predict LAD severe stenosis in patients with CHD,and GLS is more sensitive than TLS.
10.Value of real-time three-dimensional echocardiography in evaluating right ventricular structure and hemodynamic parameters of patients with pulmonary hypertension
Yong CHEN ; Yong MA ; Jing YUAN ; Haidi YU ; Fei YANG ; Yinhua CHEN ; Xiuxiu WU
Chinese Journal of Medical Ultrasound (Electronic Edition) 2017;14(9):664-670
Objective To explore the value of real-time three-dimensional echocardiography (RT-3DE) in evaluating right ventricular structure and hemodynamic parameters of patients with pulmonary hypertension (PH).Methods A total of 89 PH patients in Subei People′s Hospital from July 2014 to December 2016 were selected as PH group, and 49 subjects with health examination were designed as control group. According to pulmonary arterial systolic pressure (PASP), the 89 patients with PH were divided into mild PH group (n=29), moderate PH group (n=32) and severe PH group (n=28). The indexes of right heart structure such as right ventricular diameter (RVTD), left ventricular diameter (LVTD), right ventricular end diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV) and right ventricular ejection fraction (RVEF) as well as hemodynamic parameters such as pulmonary systolic pressure (SPAP), pulmonary artery diastolic pressure (DPAP), mean pulmonary artery pressure (MPAP) and right ventricular output (RCO) were detected by RT-3DE in all the subjects. The indexes of right heart structure and hemodynamic parameters were compared by independent-samplet test between PH group and control group, and indexes of right heart structure and hemodynamic parameters were compared by variance analysis among different PH groups. The SNK-q test was used for the further comparison between any two groups.Results The RVTD, EDV and ESV in the PH group were significantly higher than those in the control group, while LVTD, SV and RVEF were significantly lower than those in the control group (t=-2.73,P=0.003;t=-4.37,P=0.001;t=-4.57,P=0.002;t=-3.49,P=0.039;t=-2.01,P=0.043;t=6.36,P=0.001). The RVTD, EDV and ESV in moderate PH group and severe PH group were significantly higher than those in the mild PH group, while the LVTD, SV and RVEF were significantly lower than those in the mild PH group (q=4.318, 4.713, 3.873, 3.921, 5.127, 5.347, 5.618, 5.903, 4.318, 4.501, 5.327, 5.981, allP<0.05). The LVTD, EDV, ESV, SV, RVEF in the severe PH group were significantly lower than those in the moderate PH group, while the RVTD was significantly higher than the moderate PH group (q=3.708, 3.249, 4.807, 3.953, 3.197, 3.764, allP<0.05). The SPAP, DPAP and MPAP in PH group were significantly higher than those in control group, while RCO was significantly lower than that that in the control group (t=0.637,P=0.001;t=0.875,P=0.001;t=0.783, P=0.001;t=0.691,P=0.035). The SPAP, DPAP and MPAP in moderate PH group and severe PH group were significantly higher than those in the mild PH group, and the SPAP in the severe PH group was significantly higher than that in the moderate PH group (q=4.349,P=0.041;q=5.871,P=0.039;q=4.201,P=0.042;q=4.869,P=0.043;q=3.981,P=0.034;q=3.991,P=0.035;q=0.421,P=0.039). There were no significant differences in DPAP and MPAP between the moderate PH group and the severe PH group. The RCO decreased gradually in the mild PH group, the moderate PH group and the severe PH group, and there were significant differences between any two groups (q=3.541,P=0.033;q=3.204,P=0.030;q=0.391,P=0.043). Conclusion In PH patients, the right ventricular function declined, and RT-3DE can accurately evaluate the right ventricular function in patients with different degrees of pulmonary hypertension.

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