1.Research on the value of narrative medicine in bridging differences in shared decision-making
Shan LUO ; Dabin WANG ; Jiawen ZHANG ; Fang XIE ; Hong LIU
Chinese Medical Ethics 2025;38(6):679-686
Shared Decision-Making (SDM) is a crucial concept in modern medicine, emphasizing the joint participation of doctors and patients in the medical decision-making process. However, the authoritative position of doctors and the passive role of patients in traditional medical models often overlook the personal wishes and needs of patients, leading to tense doctor-patient relationships and medical disputes. By listening to and understanding their stories, narrative medicine helps doctors gain a more comprehensive understanding of patients’ situations and balances medical advice with patient needs in the decision-making process. Through systematic literature analysis and theoretical exploration, this paper investigated the application effects and mechanisms of narrative medicine in different medical contexts, as well as analyzed its specific role in the process of SDM. The aim is to explore the value of narrative medicine in bridging differences in SDM, revealing its role in promoting doctor-patient communication, enhancing decision-making participation, and improving medical outcomes. Researches had found that narrative medicine enhanced doctors’ “narrative ability”, promoted emotional communication and trust between doctors and patients, reduced conflicts and misunderstandings in decision-making, and improved patients’ sense of participation and trust, thus playing an important role in SDM. Therefore, by enhancing doctor-patient communication and understanding, promoting SDM and treatment selection between doctors and patients, personalized care and treatment optimization, advocating for doctor-patient co-construction, improving consultation efficiency, restoring the patient’s subject position, and other methods, it can bridge doctor-patient differences, promote communication and enhance decision-making participation, and improve medical outcomes and patient satisfaction.
2.Four Weeks of HIIT Modulates Lactate-mediated Synaptic Plasticity to Improve Depressive-like Behavior in CUMS Rats
Yu-Mei HAN ; Zi-Wei ZHANG ; Jia-Ren LIANG ; Chun-Hui BAO ; Jun-Sheng TIAN ; Shi ZHOU ; Huan XIANG ; Yong-Hong YANG
Progress in Biochemistry and Biophysics 2025;52(6):1499-1510
ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, Smax) alternated with one minute at low speed (50%-55% Smax), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.
3.Effects of Kidney-Tonifying and Blood-Activating Acupuncture on Mitochondrial Membrane Potential and SIRT1/PGC-1α Axis in Hippocampal Tissue of SAMP8 Mice
Dan REN ; Ting ZHANG ; Jiangxi XU ; Hong ZHU ; Ruomeng LI
Journal of Traditional Chinese Medicine 2025;66(13):1378-1385
ObjectiveTo explore the potential mechanisms of kidney-tonifying and blood-activating acupuncture for Alzheimer's disease. MethodsMale SAMP8 mice were randomly divided into a model group, acupuncture group, non-acupoint group, and donepezi group, with 10 mice in each group, and 10 SAMR1 mice as normal group. The acupuncture group received acupuncture at Baihui (GV 20), Xuehai (SP 10), Shenshu (BL 23), and Geshu (BL 17). Xuehai (SP 10), Shenshu (BL 23), and Geshu (BL 17) were stimulated on the left side first and then on the right side alternately, once a day. The non-acupoint group received acupuncture at fixed bilateral non-meridian, non-acupoint points under the ribs, once a day. The model and normal groups underwent equivalent handling and restraint stress without acupuncture. The donepezi group received 1 mg/kg donepezil via gastric gavage daily. All groups were treated for 4 weeks. After treatment, Morris water maze tests (to record orientation sailing latency, number of traverses through the platform quadrant) and open field (to record distance travelled) were used to evaluate learning and memory abilities; hippocampal neuronal damage was analyzed via HE and Nissl staining; mitochondrial membrane potential and reactive oxygen species (ROS) were measured using assay kits; Western blot and qRT-PCR were performed to detect silencing information regulator 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and mRNA expression levels. ResultsCompared with the normal group, mice in the model group and non-acupoint group showed elevated orientation sailing latency and relative multiplicity of ROS in hippocampal tissues, and reduced number of traverses through the platform quadrant, distance of movement in the open-field experiment, number of Nissl-staining-positive cells in the hippocampal tissues, mitochondrial membrane potential, and protein levels and mRNA expression of SIRT1, PGC-1α (P<0.01); HE staining showed that the hippocampal tissues of the mice was loosely arranged, with reduced number of neurons and vacuolar degeneration; Nissl staining showed that pyramidal neurons in the hippocampal region were not neatly arranged, and the number of Nissl bodies in the cytoplasm was less and the staining was lighter. Compared with the model group, mice in the acupuncture group and donepezil group had lower orientation sailing latency and relative multiplicity of ROS in the hippocampal tissue, higher number of traverses through the platform quadrant, distance of movement in the open-field experiment, number of Nissl-stained positive cells in the hippocampal tissue, mitochondrial membrane potential, and protein levels and mRNA expression of SIRT1 and PGC-1α (P<0.01), and HE staining and Nissl staining showed significant improvement in hippocampal histopathological damage. Compared with the donepezil group, the orientation sailing latency shortened in the acupuncture group of mice (P<0.01). ConclusionKidney-tonifying and blood-activating acupuncture method can alleviate the SIRT1/PGC-1α signalling pathway in the hippocampal tissue and improve the mitochondrial function, thus alleviating the neuronal damage, which is one of the possible mechanisms for its treatment of Alzheimer's disease.
4.Effectiveness of acceptance and commitment therapy in improving depression, anxiety, psychological flexibility and return-to-school rate among adolescents with school absenteeism
Yanshan ZHANG ; Zhifang CHEN ; Ke ZHENG ; Guobang WU ; Fushan XU ; Maorong HU
Sichuan Mental Health 2025;38(3):198-203
BackgroundThe issue of school absenteeism due to school refusal in adolescents has become increasingly prominent. Acceptance and Commitment Therapy (ACT) has been applied successfully to improve depression, anxiety, and psychological flexibility in adolescents, while few studies have tested the effect of ACT intervention on above-mentioned psychological aspects and return-to-school rate in adolescents with school absenteeism. ObjectiveTo explore the effect of ACT on depression, anxiety, psychological flexibility and return-to-school rate in school absenteeism adolescents, and to provide a broader evidence base for clinical interventions. MethodsFrom May to June 2024, a sample of 50 adolescents with Shenzhen school registration who had been suspended from school for more than a consecutive month for school refusal were recruited based on Wechat official account platform. The adolescents were divided into study group and control group by random number table method. Both groups received psychological education with the theme of 'Causes and Coping Strategies of School Refusal', and study group added a 6-week ACT intervention with weekly 1-hour sessions. At baseline and after treatment, Patients’ Health Questionnaire Depression Scale-9 item (PHQ-9), Generalized Anxiety Disorder Scale-7 item (GAD-7) and Comprehensive assessment of Acceptance and Commitment Therapy processes (CompACT) were used for the clinical evaluation. ResultsA total of 45 (90.00%)adolescents completed the study, including 25 in study group and 20 in control group. Analysis revealed that study group scored higher on PHQ-9 and GAD-7, while lower on total CompACT score, openness dimension and awareness dimension compared with control group, with statistical significance (F=7.786, 10.334, 12.922, 14.374, 3.075, P<0.05 or 0.01). After intervention, the rate of return-to-school was higher in study group than in control group (40.00% vs 10.00%, χ²=5.114, P<0.05). ConclusionACT intervention for adolescents with school absenteeism may alleviate depression and anxiety, improve their psychological flexibility and increase return-to-school rate.[Funded by the "14th Five Year Plan" for Social Sciences Project in Jiangxi Province (number, 24JY41D); Science and Technology Planning Project of Shenzhen Municipality (number, 20210617155253001)]
5.Effects of Huoxue Xiaoyi Formula (活血消异方) on Tfh Cells and the JAK/STAT Pathway in Ectopic Tissues of Ovarian Endometriosis Model Rats
Weisen FAN ; Yongjia ZHANG ; Yaqian WANG ; Hong LEI ; Huiting YAN ; Ruijie HOU ; Xin WANG ; Yu TAO ; Ruihua ZHAO
Journal of Traditional Chinese Medicine 2025;66(14):1473-1480
ObjectiveTo explore the potential mechanism of Huoxue Xiaoyi Formula (活血消异方, HXF) in treating ovarian endometriosis (OEM) from the perspective of T follicular helper (Tfh) cells and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. MethodsForty-five female SD rats with normal estrous cycles were randomly divided into three groups, HXF group, model group, and normal group, with 15 rats in each group. A rat model of OEM was established by autologous endometrial tissue implantation. After successful modeling, the treatment group received HXF at 5.85 g/(kg·d) by gavage for 14 consecutive days. The model group and normal group received 1 mL/d of normal saline by gavage. RNA-sequencing data from human proliferative-phase endometriotic and normal endometrial tissues were downloaded from the GEO database. Transcriptomic sequencing was used to analyze gene expression in rat ovarian ectopic tissues and normal uterine tissues, and comparisons were made with human data to verify JAK/STAT pathway activation in proliferative-phase ectopic tissues. Immunohistochemistry was used to detect the positive expression of CXC chemokine receptor 5 (CXCR5) and interleukin-21 (IL-21) in rat ovarian ectopic and normal uterine tissues. Western Blotting was performed to detect the protein levels of IL-21, IL-21 receptor (IL-21R), Janus kinase 1 (JAK1), signal transducer and activator of transcription 6 (STAT6), and B-cell lymphoma 2 (Bcl-2). Tfh cell infiltration was analyzed using immune cell infiltration methods. ResultsGene set enrichment analysis showed that the JAK/STAT pathway was significantly activated in human proliferative-phase endometriotic tissues compared to normal endometrial tissues. Similarly, the JAK/STAT pathway was markedly activated in rat ovarian ectopic tissues in the model group compared to the normal group, but suppressed in the HXF group compared to the model group. Compared with normal uterine tissues, ovarian ectopic tissues in the model group showed increased Tfh cell infiltration scores, higher CXCR5 and IL-21 expression, and elevated levels of IL-21, IL-21R, JAK1, STAT6, and Bcl-2 proteins. Compared with the model group, HXF group showed reduced CXCR5 and IL-21 expression and decreased protein levels of IL-21, IL-21R, JAK1, STAT6, and Bcl-2. ConclusionHXF may suppress activation of the JAK/STAT signaling pathway in ovarian endometriotic tissues by inhibiting IL-21 secretion from Tfh cells.
6.Literature analysis of the differences in the occurrence of urinary epithelial carcinoma after kidney transplantation between northern and southern China
Pengjie WU ; Runhua TANG ; Dong WEI ; Yaqun ZHANG ; Hong MA ; Bin JIN ; Xin CHEN ; Jianlong WANG ; Ming LIU ; Yaoguang ZHANG ; Ben WAN ; Jianye WANG
Journal of Modern Urology 2025;30(5):432-437
Objective: To investigate the regional differences in the incidence of urothelial carcinoma among kidney transplant recipients between northern and southern China,so as to provide reference for early diagnosis of this disease. Methods: A comprehensive search was conducted across multiple databases,including CNKI,Wanfang,CBM,and PubMed,using the keywords “kidney transplantation” and “tumor” to collect clinical data from qualified kidney transplant centers.The latest and most complete literature data published by 17 transplant centers in northern China and 14 in southern China were included.Statistical analyses were performed to compare the incidence of post-transplant urothelial carcinoma and non-urothelial malignancies. Results: A total of 37 475 kidney transplant recipients were included,among whom 837 (2.23%) developed post-transplant malignancies,including urothelial carcinoma (366/837,43.73%),non-urothelial carcinoma (444/837,53.05%),and malignancies with unspecified pathology (27/837,3.23%).The incidence of malignancies was significantly higher in northern China than in southern China [(2.82±1.39)% vs. (1.67±0.83)%,P=0.011],with a particularly pronounced difference in the incidence of urothelial carcinoma [(1.68±1.12)% vs. (0.32±0.32)%,P<0.001].No significant difference was observed in the incidence of non-urothelial carcinoma between the two regions [(1.11±0.56)% vs. (1.35±0.65)%,P=0.279].Additionally,female transplant recipients exhibited a higher incidence of malignancies than males in both regions (southern China:2.38% vs. 1.80%; northern China:8.93% vs. 2.52%). Conclusion: The incidence of urothelial carcinoma following kidney transplantation is significantly higher in northern China than in southern China,underscoring the importance of implementing regular tumor screening for kidney transplant recipients,particularly for female patients in northern China,to facilitate early diagnosis and timely intervention.
7.Prediction of suitable habitats of Phlebotomus chinensis in Gansu Province based on the Biomod2 ensemble model
Dawei YU ; Yandong HOU ; Aiwei HE ; Yu FENG ; Guobing YANG ; Chengming YANG ; Hong LIANG ; Hailiang ZHANG ; Fan LI
Chinese Journal of Schistosomiasis Control 2025;37(3):276-283
Objective To investigate the suitable habitats of Phlebotomus chinensis in Gansu Province, so as provide insights into effective management of mountain-type zoonotic visceral leishmaniasis (MT-ZVL). Methods The geographical coordinates of locations where MT-ZVL cases were reported were retrieved in Gansu Province from 2015 to 2023, and data pertaining to 26 environmental variables were captured, including 19 climatic variables (annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest quarter, mean temperature of the coldest quarter, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, precipitation of the warmest quarter, and precipitation of the coldest quarter), five geographical variables (elevation, annual normalized difference vegetation index, vegetation type, landform type and land use type), and two population and economic variables (population distribution and gross domestic product). Twelve species distribution models were built using the biomod2 package in R project, including surface range envelope (SRE) model, generalized linear model (GLM), generalized additive model (GAM), multivariate adaptive regression splines (MARS) model, generalized boosted model (GBM), classification tree analysis (CTA) model, flexible discriminant analysis (FDA) model, maximum entropy (MaxEnt) model, optimized maximum entropy (MAXNET) model, artificial neural network (ANN) model, random forest (RF) model, and extreme gradient boosting (XGBOOST) model. The performance of 12 models was evaluated using the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS), and Kappa coefficient, and single models with high performance was selected to build the optimal ensemble models. Factors affecting the survival of Ph. chinensis were identified based on climatic, geographical, population and economic variables. In addition, the suitable distribution areas of Ph. chinensis were predicted in Gansu Province under shared socioeconomic pathway 126 (SSP126), SSP370 and SSP585 scenarios based on climatic data during the period from 1991 to 2020, from 2041 to 2060 (2050s), and from 2081 to 2100 (2090s) . Results A total of 11 species distribution models were successfully built for prediction of potential distribution areas of Ph. chinensis in Gansu Province, and the RF model had the highest predictive accuracy (AUC = 0.998). The ensemble model built based on the RF model, XGBOOST model, GLM, and MARS model had an increased predictive accuracy (AUC = 0.999) relative to single models. Among the 26 environmental factors, precipitation of the wettest quarter (12.00%), maximum temperature of the warmest month (11.58%), and annual normalized difference vegetation index (11.29%) had the greatest contributions to suitable habitats distribution of Ph. sinensis. Under the climatic conditions from 1991 to 2020, the potential suitable habitat area for Ph. chinensis in Gansu Province was approximately 5.80 × 104 km2, of which the highly suitable area was 1.42 × 104 km2, and primarily concentrated in the southernmost region of Gansu Province. By the 2050s, the unsuitable and lowly suitable areas for Ph. chinensis in Gansu Province had decreased by varying degrees compared to that of 1991 to 2020 period, while the moderately and highly suitable areas exhibited expansion and migration. By the 2090s, under the SSP126 scenario, the suitable habitat area for Ph. chinensis increased significantly, and under the SSP585 scenario, the highly suitable areas transformed into extremely suitable areas, also showing substantial growth. Future global warming is conducive to the survival and reproduction of Ph. chinensis. From the 2050s to the 2090s, the highly suitable areas for Ph. chinensis in Gansu Province will be projected to expand northward. Under the SSP126 scenario, the suitable habitat area for Ph. chinensis in Gansu Province is expected to increase by 194.75% and 204.79% in the 2050s and 2090s, respectively, compared to that of the 1991 to 2020 period. Under the SSP370 scenario, the moderately and highly suitable areas will be projected to increase by 164.40% and 209.03% in the 2050s and 2090s, respectively, while under the SSP585 scenario, they are expected to increase by 195.98% and 211.66%, respectively. Conclusions The distribution of potential suitable habitats of Ph. sinensis gradually shifts with climatic changes. Intensified surveillance and management of Ph. sinensis is recommended in central and eastern parts of Gansu Province to support early warning of MT-ZVL.
8.Evaluation of the safety and efficacy of ABO non-identical apheresis platelets with reduced plasma transfusion
Ronghua DIAO ; Qianying RUAN ; Lu BAI ; Hong ZHANG ; Zerong WANG ; Lei FU ; Shichun WANG
Chinese Journal of Blood Transfusion 2025;38(7):909-914
Objective: To evaluate the safety and efficacy of ABO non-identical platelets with reduced plasma (ABO-NPRP) transfusion in patients with hematological diseases. Methods: A retrospective analysis was conducted on 52 therapeutic doses of apheresis platelets with reduced plasma prepared at Chongqing Blood Center of the Chinese People's Liberation Army. The transfusion efficacy (24 h CCI) and the transfusion adverse reactions of these apheresis platelets were also observed in 35 patients with hematological diseases in First Affiliated Hospital of Army Medical University. Comparisons were made with a control group consisting of patients who received only identical apheresis platelets during the same period. Meanwhile, the effect of ABO-NPRP on the subsequent platelet transfusion efficacy was observed. Results: There was no statistically significant difference in PDW, MPV, and PLCR before and after the preparation of apheresis platelets with reduced plasma (P>0.05), while the difference in platelet count was statistically significant [(2.86±0.34)×10
per therapeutic dose vs (2.46±0.28)×10
per therapeutic dose, P<0.001]; there was no statistically significant difference in the 24 h CCI transfusion efficacy between conventional identical apheresis platelets and ABO-NPRP, with transfusion efficacy rates of 76.60% and 78.85%, respectively (P>0.05); there was no statistically significant difference in platelet transfusion efficacy between the group with ABO-NPRP and the group without ABO-NPRP (completely identical transfusion group), with transfusion efficacy rates of 77.78% and 75.25%, respectively (P>0.05). Conclusion: ABO-NPRP transfusion is safe, effective, demonstrating comparable efficacy to conventional identical transfusion. It can serve as an important complementary strategy to optimize the utilization of blood resources.
9.Analysis of the incidence and relevant factors of visual acuity abnormalities in preschool children undergoing kindergarten entrance physical examinations in Shannan City, Xizang, 2022
Sangzhu LABA ; Zhuoma QIONG ; Fei YANG ; Zhuoga SUOLANG ; Ruiqi ZHANG ; Jun CHEN ; Hui YIN ; Hong ZHOU
Shanghai Journal of Preventive Medicine 2025;37(6):535-539
ObjectiveTo investigate the incidence and relevant factors of visual acuity abnormalities in preschool children undergoing kindergarten entrance physical examinations in Shannan City, Xizang, in 2022, so as to formulate policies for protecting children’s visual acuity and provide a basis for optimizing the children’s health service system in this region. MethodsA cross sectional study was conducted among the children undergoing kindergarten entrance physical examinations in Shannan City in 2022. A diopter examination was performed for these children, and a questionnaire survey was administered to their caregivers. Additionally, factors affecting children’s visual acuity abnormalities were analyzed using the χ² test and binary logistic regression analysis. ResultsA total of 759 children were included in the analysis, with an incidence rate for visual acuity abnormalities of 11.20%. Univariate analysis showed that statistically significant differences were observed in the incidence rate for visual acuity abnormalities among preschool children in terms of different family monthly income (χ²=17.395, P<0.001), father’s education level (χ²=5.133, P=0.023), postnatal vitamin A and D supplementation (χ²=9.575, P=0.008), and feeding method within the first 6 months after birth (χ²=9.330, P=0.009). Multivariate analysis results indicated that family monthly income <5 000 yuan (OR=2.599, P=0.003), insufficient postnatal vitamin A and D supplementation (OR=1.912, P=0.011), and formula feeding (OR=2.131, P=0.010) were relevant factors for abnormal visual development in children. ConclusionThe incidence of visual acuity abnormalities in preschool children in Shannan City is slightly higher than that previously reported in other regions of Xizang. The occurrence of visual acuity abnormalities in children is related to factors such as family monthly income, postnatal vitamin A and D supplementation, and feeding method within the first 6 months after birth. Future interventions should be strengthened on the promotion and dissemination of knowledge related to eye use, such as improve parental awareness of eye care, promote timely vitamin A and D supplementation and encourage breast feeding for children after birth, more specifically, attentions need to be focused on the visual acuity problems of children from low-income families to safeguard the visual health in preschool children in Shannan City, Xizang.
10.Junctophilin-2 MORN-Helix Domain: Structural Basis for Membrane Binding and Hypertrophic Cardiomyopathy-associated Mutations
Jing-Xin WANG ; Zhi-Wei LI ; Wei LIU ; Wen-Qing ZHANG ; Jian-Chao LI
Progress in Biochemistry and Biophysics 2025;52(8):2103-2116
ObjectiveJunctophilin-2 (JPH2) is an essential structural protein that maintains junctional membrane complexes (JMCs) in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum, thereby facilitating excitation-contraction (E-C) coupling. Mutations in JPH2 have been associated with hypertrophic cardiomyopathy (HCM), but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus (MORN) repeat motifs remain incompletely understood. This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis. MethodsA recombinant N-terminal fragment of mouse JPH2 (residues1-440), encompassing the MORN repeats and an adjacent helical region, was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain. Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features. Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells. In addition, site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations, including R347C, was used to evaluate their effects on membrane interaction and subcellular localization. ResultsThe crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6 Å, revealing a compact, elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration, forming a continuous hydrophobic core stabilized by alternating aromatic residues. A C-terminal α-helix further reinforced structural integrity. Conservation analysis identified the inner groove of the MORN array as a highly conserved surface, suggesting its role as a protein-binding interface. A flexible linker segment enriched in positively charged residues, located adjacent to the MORN motifs, was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes. Functional assays demonstrated that mutation of these basic residues impaired membrane association, while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays, despite preserving the overall MORN-Helix fold in structural modeling. ConclusionThis study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2, highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions. The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis. These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.

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