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.Relationship between the levels of serum neuron-specific enolase,tumor necrosis factor-α and the prognosis of children with epilepsy secondary to viral encephalitis
Pei JI ; Lijun SUN ; Hongmei XU ; Chunmei HOU
Journal of Xinxiang Medical College 2024;41(10):962-967
Objective To investigate the relationship between the levels of serum neuron-specific enolase(NSE)and tumor necrosis factor alpha(TNF-α)and the attack stage and prognosis of children with epilepsy secondary to viral encephalitis(VE).Methods A total of 96 children with VE admitted to the People's Hospital Affiliated to Inner Mongolia Medical University from January 2015 to January 2020 were selected as the research subjects,and they were divided into the control group(children with VE,n=30)and the observation group(children with epilepsy secondary to VE,n=66).In addition,30 healthy children who underwent physical examination in the hospital during the same period were selected as the health group.The levels of serum NSE and TNF-α in the health group,control group and observation group were compared.Children in the observation group were further divided into the 24h relapse group(n=48)and 24h non-relapse group(n=18)according to the attack of disease within 24h after admission.The levels of serum NSE and TNF-α were compared between the two groups.Pearson correlation was used to analyze the relationship between the levels of NSE,TNF-α and the attack stage of epilepsy secondary to VE.Children in the observation group were divided into the good prognosis group(n=45)and the poor prognosis group(n=21)according to the Glasgow Outcome Scale score at discharge.The serum levels of NSE,TNF-α and other possible prognostic factors were compared between the two groups.Multivariate logistic regression analysis was used to explore the prognostic factors of children with epilepsy secondary to VE,and the predictive value of serum NSE and TNF-αlevels on the prognosis of children with epilepsy secondary to VE was analyzed by drawing the receiver operating characteristic curve.Results The level of serum NSE in the control group was significantly higher than that in the health group(P<0.05),and there was no significant difference in the level of serum TNF-α between the control group and the health group(P>0.05).The serum levels of NSE and TNF-α in the observation group were significantly higher than those in the control group(P<0.05).The serum levels of NSE and TNF-α in the observation group were significantly higher than those in the control group(P<0.05).The levels of serum NSE and TNF-α in the 24 h relapse group were significantly higher than those in the 24 h non-relapse group(P<0.05).The proportion of severe abnormal EEG,severe abnormal brain images and complicated respiratory failure,and serum levels of c-reactive protein,NSE and TNF-α in the good prognosis group were lower than those in the poor prognosis group(P<0.05);there were no significant differences in sex,age,body mass,brain injury site,fever,hypokalemia,hyponatremia,previous convulsions,stress hyperglycemia,complicated organ dysfunction,viral infection,first episode of epilepsy,Glasgow Coma Scale score at admission,duration of convulsion,length of hospital stay,white blood cell count,aspartate transaminase,creatine kinase and cardiac troponin levels between the two groups(P>0.05).The results of multivariate logistic regression analysis showed that complicated respiratory failure,serum NSE and TNF-α levels were correlated with the prognosis of children with epilepsy secondary to VE(P<0.05).The area under the curve(AUC)of serum NSE and TNF-α levels in predicting the prognosis of children with epilepsy secondary to VE was 0.724(95%confidence interval:0.672-0.776)and 0.689(95%confidence interval:0.637-0.734),respectively,with a sensitivity of 82.22%and 75.56%and a specificity of 76.19%and 71.43%;the AUC of the combination of the two in predicting the prognosis of children with epilepsy secondary to VE was 0.826(95%confidence interval:0.774-0.873),with a sensitivity of 73.33%and a specificity of 80.95%.Conclusion The serum levels of NSE and TNF-α are abnormally high in children with epilepsy secondary to VE.Both of them are factors affecting the prognosis of children with epilepsy secondary to VE,showing a good predictive value for the prognosis of epilepsy secondary to VE.
6.Hygienic investigation and analysis of escape room-style venues in Yangpu District, Shanghai
Huabin SONG ; Chunmei TAO ; Yan YANG ; Zhe SUN ; Chen ZHANG ; Xue HAN
Shanghai Journal of Preventive Medicine 2024;36(6):570-573
ObjectiveTo investigate and analyze the public health status of escape room-style venues in Yangpu District, Shanghai. MethodsReferring to the hygiene standards and testing methods for public places, an investigation of the current situation and environmental monitoring were conducted in 15 escape room-style venues in Yangpu District, which involved exploring the changes in physical, chemical, and microbial indicators before and after the game. ResultsThe hygiene condition of escape room-style venues in Yangpu District was generally good, with all 19 monitoring indicators not exceeding the indoor standards. The indoor carbon dioxide (CO2) and formaldehyde concentrations increased significantly after the game but did not exceed the standards. ConclusionThe hygiene condition of escape room-style venues in Yangpu District is good. However, potential public health risks were identified in four aspects: site selection and design, length of the game, cross-contamination, and training and management.
7.Effect of ursodeoxycholic acid on symptoms after severe acute respiratory syndrome coronavirus 2 infection in patients with primary biliary cholangitis and their family members
Gui JIA ; Chunmei YANG ; Xiufang WANG ; Juan DENG ; Ruiqing SUN ; Linhua ZHENG ; Yulong SHANG ; Ying HAN
Journal of Clinical Hepatology 2024;40(7):1370-1374
Objective To investigate the effect of ursodeoxycholic acid(UDCA)on the symptoms after severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in patients with primary biliary cholangitis(PBC)and their family member.Methods A questionnaire survey was conducted to collect related information from 171 PBC patients who attended The First Affiliated Hospital of Air Force Medical University before March 22,2023 and 128 family members,including demographic information,comorbidities,UDCA administration,SARS-CoV-2 infection,vaccination,symptoms,therapeutic medication,and the changes in liver disease-related symptoms.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.Results The median age was 51 years in the PBC patients and 49 years in the family members,with no significant difference between the two groups(P>0.05).Compared with the family member group,the PBC group had significantly lower body mass index(22.2±2.4 kg/m2 vs 23.3±2.9 kg/m2,P<0.001)and proportion of male individuals(10%vs 55%,P<0.001).All PBC patients received UDCA at a dose of 13—15 mg/kg,and SARS-CoV-2 infection rate was 100%in both groups.The family members had a significantly higher SARS-CoV-2 vaccination rate than the PBC patients(91%vs 57%,P<0.001).Compared with the family members,the PBC patients had significantly milder symptoms of sneezing,nasal obstruction,chest pain,and abnormal taste(P<0.05).Compared with the family members,the PBC patients had significantly lower rates of use of compound cold medicine(11%vs 20%,P<0.05)and Lianhua Qingwen capsules(12%vs 21%,P<0.05).For the PBC patients after SARS-CoV-2 infection,the liver disease-related symptoms such as fatigue,abdominal distension,dry mouth and dry eyes,pruritus,and yellow skin were aggravated by 37%,2%,27%,10%,and 3%,respectively.Conclusion Compared with the immediate family members of PBC patients who do not take UDCA,the PBC patients receiving UDCA do not show a reduction in SARS-CoV-2 infection rate,but UDCA may have a certain effect on alleviating infection-related symptoms in such patients.PBC patients may still experience the aggravation of liver disease-related symptoms after SARS-CoV-2 infection,and the long-term effect on PBC patients after SARS-CoV-2 infection should be taken seriously in clinical practice.
8.Risk factors for pulmonary embolism in patients with acute spinal cord injury
Yijing LI ; Supeng YAN ; Yanxia SHAO ; Yuan YUAN ; Chunmei JIANG ; Shuyu PU ; Wei SUN
Journal of Army Medical University 2024;46(18):2130-2137
Objective To investigate the risk factors for pulmonary embolism (PE)in patients with acute spinal cord injury (ASCI).Methods A case-control design was adopted in this study.Basic information,injury cause,injury site,imaging and laboratory examination results and other relevant data of 840 ASCI patients admitted to 3 affiliated hospitals of Army Medical University from January 2018 to August 2023 were collected.According to occurrence of PE or not,these patients were divided a PE group (n=83) and a non-PE group (n=757).Univariate analysis was performed on 37 risk factors including gender,age,length of hospital stay,length of intensive care unit (ICU)stay,cause of injury,and so on,and then multivariate logistic regression analysis was applied to analyze these selected significant variables.Results Univariate analysis showed that 24 factors such as age,length of hospital stay,lower limb fracture,pulmonary contusion and infection,shock and number of operations were related to the occurrence of PE in ASCI patients (P<0.05).Binary logistic regression analysis indicated that age (P=0.000,OR=1.957,95%CI:1.532~2.499),length of ICU stay (P=0.000,OR=2.561,95%CI:1.728~3.794),number of operations (P=0.015,OR=1.814,95%CI:1.124~2.927),spinal fixation (P=0.004,OR=0.370,95%CI:0.189~0.724),restrictive position (P=0.000,OR=21.269,95%CI:5.276~85.740),platelet count (P=0.000,OR=1.553,95%CI:1.236~1.951),D-dimer level (P=0.000,OR=1.600,95%CI:1.376~1.860)and prothrombin time (P=0.025,OR=2.756,95%CI:1.138~6.670)were independent risk factors for PE in the patients.Conclusion The mortality of the ASCI patients with PE is significantly higher than those without.Age,length of ICU stay,number of operations,spinal fixation,restrictive position,platelet count,D-dimer level and prothrombin time are closely associated with PE in ASCI patients.
9.Research progress in Chaihu Jia Longgu Muli Decoction in treating perimenopausal insomnia
Wenxin LIANG ; Yawen SUN ; Chunmei LIU
International Journal of Traditional Chinese Medicine 2024;46(9):1245-1248,F3
Chaihu Jia Longgu Muli Decoction can effectively improve the sleep quality of perimenopausal insomnia patients, reduce negative emotions, regulate the neuroendocrine system, improve the other perimenopausal symptoms, and has higher safety. Chaihu Jia Longgu Muli Decoction can play a role in perimenopausal insomnia by correcting hormone levels, regulating a variety of neurotransmitters and cytokines, regulating intestinal flora and other ways.
10.The effect of mindfulness-based stress reduction on renal function and quality of life in uremic hemodialysis patients
Juan SUN ; Chunmei YUAN ; Jinyu SUN ; Yang SONG
Chinese Journal of Practical Nursing 2023;39(12):881-887
Objective:To construct a mindfulness-based stress reduction (MBSR) intervention program suitable for uremic hemodialysis patients, and analyze the impact of the program on renal function and quality of life in uremic hemodialysis patients.Methods:This was a randomized controlled trial. The convenience sampling method was used to select 92 uremic patients who underwent hemodialysis in the First People's Hospital of Lianyungang City from March 2018 to March 2019. They were divided into routine group (46 cases, routine care) and MBSR group (46 cases, MBSR of face-to-face guidance combined with WeChat platform supervision) by random number table method. Both groups were intervened for 8 weeks. The Chinese version of the European Five-Dimensional Scale (EQ-5D-3L) was used to evaluate the quality of life of the patients, and the quality of life of the two groups before and after the intervention was compared; and the blood creatinine (Scr) and estimated glomerular filtration rate (eGFR), urea nitrogen (BUN), cystatin C (CysC) levels of the two groups before and after the intervention were analyzed.Results:Before the intervention, there was no significant difference in the levels of Scr, eGFR, BUN, and CysC between the two groups ( P>0.05); after 8 weeks of intervention, the levels of Scr, eGFR, BUN, and CysC were (201.81±14.77) μmol/L, (35.30 ± 2.02) ml/min and (11.47 ± 2.66) mmol/L, (2.41 ± 0.28) mg/L in the MBSR group, (218.37 ± 14.90) μmol/L, (33.99 ± 1.95) ml/min, (12.50 ± 0.76) mmol/L, (2.76 ± 0.30) mg/L in the routine group, the differences were statistically significant between the two groups ( t values were 2.53-5.79, all P<0.05). Before the intervention, there was no significant difference in EQ-5D-3L scores between the two groups ( P>0.05); after 8 weeks of intervention, the pain (discomfort), anxiety (depression), Vasual Analogue Scale (VAS) scores were (1.17 ± 0.34), (1.02 ± 0.35), (88.57 ± 20.28) points in the MBSR group, and (1.46 ± 0.63), (1.30 ± 0.32), (62.69 ± 18.79) points in the routine group, the differences were statistically significant between the two groups ( t=2.75, 4.00, 6.35, all P<0.05). Scr level was negatively correlated with self-care, pain (discomfort), anxiety (depression), mobility, daily activity ability, and VAS ( r values were -0.481 - -0.214, all P<0.05); eGFR level was positively correlated with self-care, pain (discomfort), anxiety (depression), mobility, daily activity ability, and VAS ( r values were 0.199-0.492, all P<0.05). But BUN and CysC levels were not correlated with EQ-5D-3L score (all P>0.05). Conclusions:MBSR can effectively improve the renal function and quality of life of uremic hemodialysis patients, and it is worthy of clinical application.

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