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.Explorations of Clinical Teaching and Training Model for Refresher Anesthesiologists
Manjiao MA ; Lulu MA ; Ruiying WANG ; Xiuhua ZHANG
Medical Journal of Peking Union Medical College Hospital 2024;15(2):462-465
6.Effect and Mechanism of Nongsuo Dangguiwan in Relieving Oxidative Stress in Premature Ovarian Insufficiency Rats Based on Nrf2/HO-1 Signaling Pathway
Jiaqi LUO ; Xiaoli DU ; Dongmei CHEN ; Miao CHEN ; Na HU ; Shasha XING ; Wenzhao LIU ; Ruiying TIAN ; Li YANG ; Jing WANG ; Rui HE ; Huiming MA
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):1-9
ObjectiveTo investigate the effect and mechanism of Nongsuo Dangguiwan in improving ovarian oxidative stress in rats with ovarian dysfunction. MethodThirty-six adult female SD rats were randomly divided into normal group, model group, positive drug group (Femoston, 0.3 mg·kg-1), and high-, medium-, and low-dose groups of concentrated Nongsuo Dangguiwan (2.08, 4.16, 8.32 g·kg-1), with six rats in each group. Rats, except for those in the normal group, were injected with 80 mg·kg-1 vinyl cyclohexene dioxide (VCD) per day for 14 consecutive days to induce ovarian dysfunction. From the 15th day, rats were treated with corresponding drugs by gavage, while those in the model group received 2 mL·kg-1 saline, once daily for 28 consecutive days. The ovarian index, levels of related hormones including estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-mullerian hormone (AMH) in serum, as well as superoxide dismutase (SOD) activity and glutathione (GSH) content in serum were measured by enzyme-linked immunosorbent assay (ELISA). The malondialdehyde (MDA) content in serum was detected by the thiobarbituric acid (TAB) method. Ovarian morphology was observed by hematoxylin-eosin (HE) staining. The expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), SOD2, and SOD1 in ovarian tissues was detected by immunohistochemistry (IHC) and Western blot. ResultCompared with the normal group, the model group showed a significant reduction in growing follicles in the ovary, loose arrangement of granulosa cells in the follicle, decreased body weight, ovarian index, and serum AMH and E2 levels, increased LH and FSH levels (P<0.01), reduced levels of SOD and GSH in serum (P<0.01), and increased MDA level (P<0.01). Compared with the model group, the groups with drug intervention showed increased ovarian index (P<0.05, P<0.01), increased serum E2 level (P<0.05, P<0.01), decreased FSH, AMH, and LH levels (P<0.05, P<0.01), increased number of growing follicles in the ovary, potentiated SOD activity in serum, increased GSH content, decreased MDA content (P<0.05, P<0.01), and up-regulated expression levels of Nrf2, HO-1, SOD2, and SOD1 proteins in ovarian tissues (P<0.05, P<0.01). ConclusionNongsuo Dangguiwan can regulate serum hormone levels, increase the expression of Nrf2, HO-1, SOD2, and SOD1 in ovarian tissues, and improve ovarian antioxidant capacity to resist oxidative stress injury, thereby improving ovarian reserve function.
7.A qualitative study on the construction of the re-certification evaluation index system for the qualifications of intravenous therapy specialist nurses
Wei WANG ; Ruiying MA ; Nan ZHANG ; Ying SU ; Huiying HUANG
Chinese Journal of Modern Nursing 2023;29(20):2716-2722
Objective:To construct the recertification evaluation index system for the qualifications of intravenous therapy specialist nurses based on the perspective of specialist nurses, so as to provide a reference basis for the construction of a re-certification management scheme for specialized nurses in China.Methods:Using the purpose sampling method, a total of 12 intravenous therapy specialist nurses from 3 tertiary hospitals in Fangshan District, Beijing were selected as the research objects from February to July 2021 for semi-structured in-depth interviews. Subject analysis method was used to analyze the interview data and extract the evaluation indexes of qualification re-certification.Results:The re-certification evaluation index system of intravenous therapy specialist nurses included 8 topics (professional practice ability, professional theoretical knowledge, professional innovation and development ability, critical thinking ability, communication and coordination ability, professional attitude, legal practice and ethical practice ability, nursing management ability) and 29 sub-topics.Conclusions:The qualification re-certification evaluation index system for specialized nurses based on qualitative interviews with intravenous therapy specialist nurses includes 8 ability themes, which can provide reference for the establishment of a re-certification management system for intravenous therapy specialist nurses.
8.Meta-analysis on the safety and efficacy of very early mobilization intervention in patients with acute cerebral stroke
Gonglin XU ; Chengcheng LI ; Ruiying MA
Chinese Journal of Modern Nursing 2023;29(31):4261-4269
Objective:To evaluate the safety and efficacy of very early mobilization intervention in patients with acute cerebral stroke through a Meta-analysis.Methods:Randomized controlled trials (RCTs) investigating the efficacy and safety of very early mobilization intervention in acute cerebral stroke patients were searched in databases including PubMed, Cochrane Library, Embase, CNKI, Wanfang, VIP and SinoMed up until January 23, 2023. Two researchers independently screened the literature, extracted data, and assessed the quality of the included studies based on inclusion and exclusion criteria. Analysis was performed using RevMan 5.3.Results:A total of 13 studies involving 3 202 acute cerebral stroke patients were included. The Meta-analysis revealed that compared with conventional nursing methods, very early mobilization intervention effectively reduced the incidence of post-stroke complications [ RR=0.59, 95% CI (0.46, 0.75), P<0.001], enhanced patients' daily living abilities [ MD=6.63, 95% CI (2.99, 10.27), P<0.001], and shortened the length of hospital stay [ MD=-2.46, 95% CI (-3.86, -1.05), P<0.001]. The intervention did not increase the rates of mortality [ RR=1.11, 95% CI (0.85, 1.45), P>0.05], adverse events [ RR=0.85, 95% CI (0.60, 1.20), P>0.05], or disability [ RR=0.94, 95% CI (0.76, 1.15), P>0.05] in acute cerebral stroke patients. Subgroup analysis on the initiation time and frequency of the intervention showed a statistically significant reduction in mortality rate in the 24-72 h subgroup ( P<0.05), while no significant difference was found in the 0-24 h subgroup ( P>0.05). Both subgroups with activity frequencies of ≥1 time/day and ≥2 times/day showed significant improvements in daily living abilities compared to conventional care ( P<0.05), whereas no significant difference was found in the subgroup with uncertain daily activity frequency ( P>0.05) . Conclusions:Very early mobilization intervention can safely and effectively reduce the incidence of post-stroke complications in patients with acute cerebral stroke, improve daily living abilities, and shorten the length of hospital stay.
9.Effect of Jianpi Yishen Huazhuo Prescription on Ovarian Function in Rats with Polycystic Ovary Syndrome Based on NLRP3 Inflammatory Pathway
Miao CHEN ; Xiaoli DU ; Yahong FENG ; Xiaojing ZHANG ; Jiaqi LUO ; Jing WANG ; Nan NAN ; Wenzhao LIU ; Shasha XING ; Ruiying TIAN ; Li YANG ; Miao SUN ; Rui HE ; Dongmei CHEN ; Huiming MA
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(20):61-70
ObjectiveTo explore the mechanism of Jianpi Yishen Huazhuo prescription in the improvement of ovarian function in polycystic ovary syndrome (PCOS). MethodSeventy female SD rats in SPF grade were randomly divided into 6 groups, 15 in the blank group and 15 in the model group, 10 in the metformin group (0.1 g·kg-1·d-1), and 10 in the low (1.275 g·kg-1·d-1), medium (2.55 g·kg-1·d-1), and high-dose (5.10 g·kg-1·d-1) Jianpi Yishen Huazhuo prescription groups. The blank group was given normal saline (10 mL·kg-1·d-1) by gavage and ordinary feed, and the other groups were given letrozole (1 mg·kg-1·d-1) by gavage combined with high-fat feed for 21 days to induce the model of PCOS. After modeling, the blank group and model group were given equal volume normal saline by gavage, and each drug group was given the corresponding dose of the drug by gavage for 30 days. The changes in body mass and fasting blood glucose (FPG) of rats before and after modeling were compared. Hematoxylin eosin (HE) staining was used to observe the morphological change in the ovaries of rats in each group. The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-Mullerian hormone (AMH), and estradiol (E2) were measured by enzyme-linked immunosorbent assay (ELISA), and the LH/FSH ratio was calculated. Immunohistochemical staining (IHC) and Western blot were used to detect the protein expression levels of nucleoside binding oligomerization domain protein like receptor 3 (NALP3), apoptosis-associated speck-like protein (ASC), cysteine protease-1 (Caspase-1), nuclear transcription factor-κB (NF-κB), interleukin-1β (IL-1β), interleukin-18 (IL-18), and interleukin-6 (IL-6) in the rat ovaries. ResultAs compared with the blank group, large follicles with polycystic expansion were found in the ovaries of the model group, no dominant follicles were found, the granular layer of follicles decreased and arranged loosely, and the number of corpus luteum decreased significantly. Serum T, LH, AMH and LH/FSH increased in the model group (P<0.05, P<0.01), while FSH and E2 decreased (P<0.05, P<0.01). The relative protein expression levels of NALP3, ASC, Caspase-1, NF-κB, IL-1β, IL-18, and IL-6 increased (P<0.05, P<0.01) in the ovaries of the model group. Compared with the model group, the low, medium, and high-dose Jianpi Yishen Huazhuo prescription groups and the metformin group showed growing follicles and corpus luteum at all levels, the number of cystic expanding follicles decreased, the thickness of follicular granular layer increased, the number of follicular fluid increased, mature follicles were visible, and the local morphology of oocytes was complete. Serum T, LH, AMH, and LH/FSH in these groups decreased (P<0.05, P<0.01), while E2 and FSH increased (P<0.05). The relative protein expressions of NALP3, ASC, Caspase-1, NF-κB, IL-1β, IL-18, and IL-6 in the ovaries of these groups decreased (P<0.05, P<0.01). There was no significant difference among the treatment groups. ConclusionBy inhibiting the activation of NLRP3 inflammasome, Jianpi Yishen Huazhuo prescription reduces the release of NALP3, ASC, Caspase-1, NF-κB, IL-18, IL-1β, and IL-6 inflammatory factors in ovarian tissues, regulates endocrine level, and effectively reduces PCOS inflammatory statu, so as to play a role in improving ovarian function.
10.Research progress of capacity management of patients with heart failure
Chinese Journal of Modern Nursing 2021;27(7):841-845
Capacity overload is an important pathophysiological change in the development of acute and chronic heart failure and capacity management is a very important part in the management of heart failure. This article starts with the relationship between heart failure and capacity management and reviews the methods of capacity assessment and the commonly used nursing interventions for capacity management. It aims to emphasize the importance and necessity of capacity management for patients with heart failure and provide clinical nurses with the direction of capacity assessment and basis for formulating corresponding nursing measures.

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