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.Evaluation of the therapeutic effect of dupilumab combined with 2% cleboride ointment in the treatment of moderate to severe atopic dermatitis
Baojun ZHANG ; Shuangxing FU ; Xiaobo FANG ; Yinhua PENG ; Yaguang WU ; Zhifang ZHAI
Chongqing Medicine 2025;54(10):2309-2312
Objective To evaluate the efficacy and safety of dupilumab combined with 2%cleboride ointment in the treatment of moderate to severe atopic dermatitis,as well as its impact on serological indica-tors.Methods A retrospective analysis was conducted on the clinical data of 67 patients with moderate to se-vere atopic dermatitis(AD)admitted to the Department of Dermatology of Shaoxing University Affiliated Hospital from March 2021 to December 2024.The study subjects were divided into an experimental group(n=35)and a control group(n=32)according to the treatment method.The experimental group was treated with Dupilumab injection and 2%Cleboride ointment,while the control group was treated with ebastine tab-lets and 2%cleboride ointment.Clinical and related serological indicators of patients after 16 weeks of treat-ment were collected,and the itch digital scale score,eczema area and severity(EASI)score,IL-4,IL-13 levels,and incidence of local skin adverse reactions were analyzed before and after treatment in both groups.Results The total effective rate of the experimental group after treatment was 94.29%(33/35),which was higher than the control group[53.13%(17/32)],and the difference was statistically significant(x2=12.862,P<0.001).There was no statistically significant difference in symptom scores,IL-4,and IL-13 levels between the two groups before treatment(P>0.05).After treatment,the symptom scores of the experimental group were lower than those of the control group,and the difference was statistically significant(P<0.05).The lev-els of IL-4 and IL-13 in the experimental group were lower than those in the control group,and the difference was statistically significant(P<0.05).The incidence of adverse reactions in the experimental group was 2.86%(1/35),significantly lower than the 34.38%(11/32)in the control group,and the difference was sta-tistically significant(x2=9.252,P=0.002).Conclusion The combination of dupilumab injection and 2%cleboride ointment is effective in relieving skin symptoms,regulating cellular immune function,reducing in-flammatory reactions,and minimizing local skin adverse reactions in patients with moderate to severe AD.It is worthy of clinical promotion and use.
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.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.
6.Rubusoside protects against myocardial injury in gestational diabetes mellitus rats via the endoplasmic reticulum stress-ferroptosis pathway
Yinhua YUAN ; Qi GUAN ; Shanshan ZHANG
Chinese Journal of Endocrinology and Metabolism 2024;40(11):956-965
Objective:To explore effect of rubusoside(RS) on myocardial injury in gestational diabetes mellitus(GDM) rats and its mechanism.Methods:Pregnant SD rats were divided into control, GDM model, insulin treatment(INS), RS, endoplasmic reticulum stress inhibitor 4-phenylbutyric acid(4-PBA), and RS+ endoplasmic reticulum stress inducer thapsigargin(THA) groups. Glycolipid metabolism, cardiac function, serum LDH, cTnI, and CK-MB levels, myocardial tissue morphology, SOD, GSH, MDA, Fe 2+ content were assessed. ROS levels were assessed using DHE staining, and iron ion deposition was evaluated via Prussian blue staining. The expression of endoplasmic reticulum stress and ferroptosis related proteins in myocardial tissue after intervention was analyzed through Western blot and immunohistochemistry. Results:Compared with control rats, GDM model rats showed increased body weight, FBG, TC, TG, abnormal cardiac function, significant myocardial damage, elevated serum LDH, cTnI, CK-MB, reduced SOD and GSH, increased MDA, Fe 2+, ROS, and iron ions, along with altered protein expression indicating endoplasmic reticulum stress and ferroptosis. RS and 4-PBA mitigated these changes, reducing myocardial injury. THA reversed RS′s protective effects via the endoplasmic reticulum stress-ferroptosis pathway. Conclusion:RS improves glycolipid metabolism and alleviates myocardial injury in GDM rats by inhibiting endoplasmic reticulum stress and reducing ferroptosis.
7.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.
8.Progress on the relationship between environmental risk factors during maternal pregnancy and childhood allergic diseases
International Journal of Pediatrics 2024;51(8):537-542
Allergic diseases are one of the most common chronic non-infectious diseases in childhood,primarily resulting from genetic and environmental interactions.Evidence suggests that maternal exposure to risk factors during pregnancy can impact the fetus through the placenta,leading to immune dysregulation,disruptions in gut microbiota composition,and ultimately contributing to the development of allergic diseases in children.Therefore,maternal pregnancy represents a critical period for preventing allergic diseases in children.This article provides an overview of research advancements regarding the influence of environmental risk factors during pregnancy on allergic diseases in children,focusing on aspects such as maternal diet,medication usage,maternal illnesses during pregnancy,and allergen exposure,so as to provide new strategies for preventing childhood allergic diseases.
9.Effect of Intrauterine Perfusion of Granulocyte Colony-Stimulating Factor on Endometrium and Blood Flow Parameters in Patients With Thin Endometrium:A Prospective Controlled Clinical Trial
Shaorong XU ; Qianhong MA ; Yao ZHANG ; Yinhua AN ; Wei HE ; Ying MA ; Junlin LI ; Dan LI ; Wei LU ; Qinqin MA ; Jiajia YONG ; Ting LAI ; Lian SU ; Hong XIANG
Journal of Sichuan University (Medical Sciences) 2024;55(3):574-579
Objective To investigate the effects of intrauterine perfusion with granulocyte colony-stimulating factor(G-CSF)on the endometrial thickness,volume,and blood flow parameters of patients with thin endometrium and their clinical outcomes.Methods We designed a prospective non-randomized synchronous controlled trial and recruited patients with thin endometrium who underwent frozen-thawed embryo transfer(FET)at Mianyang Central Hospital between September 1,2021 and September 1,2023.They were divided into two groups,an experimental group of patients who received the experimental treatment of intrauterine perfusion with G-CSF and a control group of patients who did not receive the experimental treatment.The general data and the clinical outcomes of the two groups were analyzed and compared.The endometrial thickness,volume and blood flow parameters of patients in the experimental group before and after intrauterine perfusion with G-CSF were analyzed.Results The clinical data of 83 patients were included in the study.The experimental group included 51 cases,while the control group included 31 cases.There were no significant differences in the baseline data between the two groups.The clinical pregnancy rate of the experimental group(56.86% )was higher than that of the control group(50.00% )and the rate of spontaneous abortion in the experimental group(27.59% )was lower than that in the control group(37.50% ),but the differences were not statistically significant(P>0.05).In the experimental group,the postperfusion endometrial thickness([0.67±0.1]cm)was greater than the preperfusion endometrial thickness([0.59±0.09]cm),the postperfusion([1.84±0.81]cm3)was greater than the preperfusion endometrial volume([1.54±0.69]cm3),and the postperfusion vascularization flow index(VFI)(1.97±2.82)was greater than the preperfusion VFI(0.99±1.04),with all the differences being statistically significant(P<0.05).Conclusion Intrauterine perfusion with G-CSF can enhance the endometrial thickness,volume,and some blood flow parameters in patients with thin endometrium.
10.Construction of evidence-based pneumonia prevention and nursing plan for acute stroke patients
Yuxian GUAN ; Hongbo YAN ; Pingjing SUN ; Yonghua TUO ; Yinhua SONG ; Ping ZHANG
Chinese Journal of Modern Nursing 2023;29(24):3254-3262
Objective:To construct a scientifically standardized and promotable pneumonia prevention and nursing plan for acute stroke patients to guide clinical nursing practice.Methods:According to the evidence-based retrieval strategy, we systematically searched the domestic and foreign clinical decision support system, guideline networks, professional association websites and relevant databases. All databases were searched from January 2012 to November 2022. A preliminary pneumonia prevention and nursing plan for acute stroke patients was formulated after literature quality evaluation, evidence extraction, evidence integration and evaluation. The plan was further revised and improved through three rounds of Delphi expert consultation.Results:In the three rounds of expert consultation, the enthusiasm of experts was 100.0%, 100.0%, 83.3%, the authority coefficient of experts were 0.967, 0.967, 0.937, the coefficient of variation were 0.048 to 0.363, 0 to 0.177, 0 to 0.144, and the Kendal harmony coefficient were 0.221, 0.139, 0.339 ( P<0.001) . The final nursing plan included 8 modules, including pneumonia risk prediction, general nursing, swallowing and dietary management, airway management, oral management, position and exercise, condition observation, and health education, with a total of 30 items. Conclusions:The evidence and Delphi method based pneumonia prevention and nursing plan for acute stroke patients is scientific, reliable and applicable, which can provide a basis for nursing practice.

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