1.The Impact of Pcdh15 Deficiency on Cellular Energy Metabolism and Oxidative Stress, and Its Role and Mechanism in Hearing Loss
Ying LAN ; Yang WU ; Shijie ZHAO ; Jun TANG ; Xingming LIANG ; Tao HOU ; Lu PENG ; Yongpeng LI ; Xinxing ZHAO ; Shihua YIN
Clinical and Experimental Otorhinolaryngology 2026;19(2):129-144
Objectives:
. This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice.
Methods:
. CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays.
Results:
. Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage.
Conclusion
. Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.
2.Analysis of clinical and cardiac MR characteristics of cardiac sarcoidosis
Fanming KONG ; Kai YANG ; Gang YIN ; Jinghui LI ; Shihua ZHAO ; Minjie LU
Chinese Journal of Radiology 2025;59(8):923-929
Objective:To investigate the clinical characteristics and cardiac magnetic resonance (CMR) features of cardiac sarcoidosis (CS).Methods:This retrospective study included 8 consecutive patients with pathologically confirmed CS by endomyocardial biopsy from Fuwai Hospital, Chinese Academy of Medical Sciences, between January 2012 and September 2024. All patients underwent comprehensive CMR examinations including cine imaging and late gadolinium enhancement (LGE) imaging. Clinical data, including electrocardiographic findings, were collected. CMR phenotyping was performed based on imaging characteristics, and cardiac structure and function parameters were evaluated. LGE analysis was conducted using the American Heart Association 17-segment model to assess the distribution patterns and involvement sites.Results:The most common clinical symptoms were chest tightness (4 patients), palpitations (4 patients), and shortness of breath (6 patients). Electrocardiographic abnormalities included atrioventricular block in 4 patients, right bundle branch block in 2 patients, left bundle branch block in 2 patients, frequent premature ventricular contractions in 4 patients, and non-sustained ventricular tachycardia in 5 patients. CMR phenotyping revealed hypertrophic cardiomyopathy pattern in 3 patients, with 2 patients maintaining normal biventricular function and 1 patient showing significantly reduced biventricular systolic function. Dilated cardiomyopathy pattern was identified in 4 patients, all demonstrating significantly impaired biventricular systolic function. One patient exhibited another phenotype with preserved biventricular systolic function. LGE analysis demonstrated that the anterior wall and anterior septum (segments 1, 2, 7, 8) were the most frequently involved regions, followed by the lateral and inferior walls (segments 5, 6, 11, 12). Subepicardial involvement was the predominant pattern of myocardial enhancement.Conclusions:Cardiac sarcoidosis exhibits diverse clinical manifestations and heterogeneous imaging characteristics. CMR not only provides a comprehensive assessment of cardiac structure and function but also reveals distinctive myocardial tissue characteristics, particularly the extent and distribution patterns of LGE involvement. These findings have significant reference value for early identification of CS and differential diagnosis from other cardiomyopathies.
3.Full free-breathing cardiac MR: feasibility and efficacy assessment
Fei TENG ; Wenli ZHOU ; Gang YIN ; Xinling YANG ; Jing AN ; Kai YANG ; Shihua ZHAO ; Minjie LU
Chinese Journal of Radiology 2025;59(10):1142-1148
Objective:To explore the feasibility and effectiveness of full free-breathing cardiac magnetic resonance (CMR) in clinical practice.Methods:The study prospectively included patients who underwent full free-breathing CMR and traditional breath-holding cine imaging between June 1 and June 30, 2024. An analysis and comparison were conducted on the image acquisition time, image quality, and left ventricular function parameters under two scanning methods, including left ventricular ejection fraction (LVEF), left ventricular cardiac output (LVCO),left ventricular end diastolic volume (LVEDV), left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume (LVESV), left ventricular end systolic volume index (LVESVI), left ventricular stroke volume (LVSV), and left ventricular mass (LVM). In addition, the study conducted both quantitative and qualitative analyses of other sequences in full free-breathing CMR, including T 1 mapping, T 2 mapping, flow imaging, and late gadolinium enhancement (LGE). Group comparisons were performed using the Wilcoxon signed-rank test or paired t-test. Consistency assessments included Bland-Altman analysis, intraclass correlation coefficient ( ICC), and linear regression analysis. Results:Totally, 150 patients were recruited into the study. The average acquisition time of full free-breathing CMR was (22.1±3.1) min, with an average short axis cine sequence examination time of (2.7±0.4) min; The average acquisition time of short axis images in a breath-holding state was (4.9±1.4) min, which was significantly longer than the cine scan in the free-breathing state ( P0.001). The cine and LGE images quality scores obtained from full free-breathing CMR were 4 (4, 4) points and 5 (4, 5) points, respectively, while the cine image quality score obtained in a breath-holding state was 5 (4, 5) points. Compared with traditional breath-hold CMR, free-breathing CMR measurements showed slightly higher LVESV, and LVESVI, while LVEDV, LVEDVI, LVSV, LVCO, LVEF, and LVM were slightly lower, except for LVSV and LVCO, which showed no statistically significant difference, the differences in other cardiac function parameters were statistically significant ( P0.05). However, the two methods demonstrated good consistency( ICC0.947) and correlation (0.808 r0.993, P0.001). The Bland-Altman analysis showed that the bias for all cardiac function parameters was within 8.0%. The Native T 1 and T 2 values for free-breathing CMR were (1 277.5±57.0) ms and 40.1 (38.5, 41.4) ms, respectively, and the results of flow imaging and echocardiography were basically consistent. Conclusions:Free-breathing CMR is feasible and effective in clinical practice, showing a high level of consistency with left ventricular functional parameters obtained from traditional breath-hold scanning. It significantly shortens examination time and holds great clinical value for the promotion and widespread use of CMR.
4.Autologous hematopoietic stem cell transplantation with TBE conditioning in patients with primary central nervous system lymphoma
Junli CHEN ; Yi MA ; Ruiqing ZHAO ; Xiubin XIAO ; Xilin CHEN ; Shunzong YUAN ; Shihua ZHAO ; Yun LU ; Honghao GAO ; Yueqi WANG ; Hua YIN ; Nana CHENG ; Pan FENG ; Xiaoran BAI ; Wenrong HUANG
Chinese Journal of Hematology 2025;46(11):1038-1043
Objective:To assess the safety and efficacy of thiotepa, busulfan, and etoposide (TBE) conditioning followed by autologous hematopoietic stem-cell transplantation (TBE auto-HSCT) in primary central nervous system lymphoma (PCNSL) patients.Methods:Clinical data from 27 PCNSL patients who received TBE auto-HSCT at the Fifth Medical Center of PLA General Hospital between November 1, 2021, and April 30, 2024, were retrospectively analyzed.Results:Twenty-seven patients [16 males, 11 females; median age 57 (23–72) years] were included, with 12 (44.4%, 12/27) over 60. Twenty-five had newly diagnosed PCNSL and 2 were relapsed. Median time from diagnosis to transplantation was 6.9 (5.0–10.0) months. TBE auto-HSCT increased complete remission (CR) rate from 63.0 to 96.3% ( P= 0.005), and 9 of 10 patients in partial remission achieving CR post-transplant. Median follow-up was 24.5 months (range 2.0–36.0). Two-year progress-free and OS rates were (87.2±6.9) % and (88.6±6.2) %, respectively. Common grade 3 nonhematologic adverse events were diarrhea (18.5%, 5/27) and bacterial infections (14.8%, 4/27). One patient (64 years old) died from carbapenem-resistant Enterobacteriaceae infection within 2 months post-transplant, yielding a 100-day treatment-related mortality of 3.7% (1/27) . Conclusion:TBE-conditioned high-dose chemotherapy with auto-HSCT is effective, safe, and well-tolerated in PCNSL patients, including the elderly.
5.Advancements of cardiac MR feature tracking for assessing right heart strain
Chinese Journal of Medical Imaging Technology 2025;41(7):1158-1162
Right heart dysfunction is a key impact factor of prognosis of various cardiovascular diseases,yet the assessment of right heart function has long been overlooked in management of cardiovascular diseases.Cardiac MR feature tracking(CMR-FT)is an emerging technique that enables quantitative analysis of global and regional strain without the need for additional imaging sequences.The advancements of CMR-FT for assessing right heart strain were reviewed in this article.
6.Status of Clinical Practice Guideline Information Platforms
Xueqin ZHANG ; Yun ZHAO ; Jie LIU ; Long GE ; Ying XING ; Simeng REN ; Yifei WANG ; Wenzheng ZHANG ; Di ZHANG ; Shihua WANG ; Yao SUN ; Min WU ; Lin FENG ; Tiancai WEN
Medical Journal of Peking Union Medical College Hospital 2025;16(2):462-471
Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.
7.Longitudinal association between compulsive behaviour and smartphone addiction in middle school students
Chinese Journal of School Health 2025;46(5):638-641
Objective:
To explore the potential causal association between adolescent compulsive behaviour and smartphone addiction based on longitudinal data, so as to provide reference for the establishment of adolescent smartphone addiction interventions.
Methods:
A preliminary survey and follow-up were conducted on 8 907 middle and high school students in a district of Shenzhen in 2022 and 2023, respectively. Compulsive behaviours were measured by using the Mental Health Inventory for Middle School Students-60 Items (MMHI-60), smartphone addiction was assessed by using the Smartphone Addiction Scale-Short Version ( SAS- SV), and the associations between compulsive behaviours and smartphone addiction were analysed by using multilevel mixed-effects models and subgroup analyses.
Results:
Smartphone addiction detection rates among middle school students were significantly associated with genders, father s education level, mother s education level, study load subgroups, and whether or not they were single-parent families, and there were statistical differences ( χ 2=17.21-175.34, P <0.05). Students with compulsive behaviours were 2.98 times more likely to develop smartphone addiction than those without compulsive behaviours ( OR=2.98, 95%CI=2.77-3.22, P <0.05). Subgroup analysis of middle school students without smartphone addiction in the first year found that compulsive behaviours significantly predicted smartphone addiction ( OR= 1.76 , 95%CI=1.54-2.01, P <0.05).
Conclusion
There is a potential causal association between obsessive-compulsive behaviours and smartphone addiction in middle school students, and obsessive-compulsive behaviours in middle school students could significantly predicted the occurrence of smartphone addiction.
9.The predictive value of cardiac MRI for the first episode of malignant ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy
Zhixiang DONG ; Yanyan SONG ; Xuan MA ; Jiaxin WANG ; Shujuan YANG ; Yun TANG ; Pengyu ZHOU ; Kai YANG ; Xiuyu CHEN ; Xinxiang ZHAO ; Shihua ZHAO
Chinese Journal of Cardiology 2025;53(7):784-791
Objective:To explore the value of cardiac magnetic resonance imaging (CMR) derived left ventricular late gadolinium enhancement (LV LGE) for the primary prevention of malignant ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients.Methods:This was a single-center retrospective study. Consecutive ARVC patients who underwent CMR at Fuwai Hospital between January 2016 and September 2020, with no history of malignant ventricular arrhythmias at diagnosis, were enrolled. Clinical data and CMR characteristics were collected. The primary endpoint was defined as new-onset malignant ventricular arrhythmias related events, including sustained ventricular tachycardia, ventricular fibrillation/flutter, sudden cardiac death, cardiac arrest, and appropriate implantable cardioverter-defibrillator discharge. Follow-up via telephone interviews and medical records was conducted to confirm endpoint occurrences, and patients were categorized into event-free and event groups based on endpoint status. Univariable and multivariable Cox regression analysis were performed to identify independent risk factors for malignant ventricular arrhythmias in ARVC patients. Subgroup analyses were conducted based on the ARVC 5-year risk score (cutoff: 25%) and the median value of LV LGE percentage (cutoff: 13%). Kaplan-Meier curves were plotted, and log-rank tests were used to compare the difference in the incidence of primary endpoint events between subgroups. Receiver operating characteristic curves and likelihood ratio test were used to evaluate the incremental prognostic value of LV LGE percentage beyond the ARVC 5-year risk score.Results:A total of 172 ARVC patients were enrolled, aged (39.0±16.6) years, including 73 females (42.4%). During a follow-up of 53.1 (25.4, 76.9) months, 51 patients (29.7%) experienced malignant ventricular arrhythmias related events, including 3 cases of sudden cardiac death, 1 cardiac arrest, 33 sustained ventricular tachycardia and 14 appropriate implantable cardioverter-defibrillator discharges. Multivariable Cox regression analysis indicated that the ARVC 5-year risk score ( HR=1.028, 95% CI 1.015-1.041, P<0.001) and LV LGE percentage ( HR=1.059, 95% CI 1.032-1.087, P<0.001) were independent risk factors of the primary endpoint events. Kaplan-Meier analysis using composite stratification (ARVC 5-year risk score cutoff: 25%; LV LGE percentage cutoff: 13%) demonstrated that patients with both high risk scores (≥25%) and extensive LV LGE (≥13%) had the highest risk of primary endpoint events. Notably, among patients with ARVC 5-year risk scores <25%, those with LV LGE≥13% had a higher incidence of primary endpoint events than those without (log-rank P=0.037). The composite prediction model combining the 5-year risk score and left ventricular LGE percentage demonstrated significantly improved predictive performance (area under the curve ( AUC)=0.82, 95% CI 0.75-0.90; likelihood ratio test all P<0.001) compared to single-variable models (left ventricular LGE percentage alone: AUC=0.71, 95% CI 0.63-0.82, P=0.01; 5-year risk score alone: AUC=0.71, 95% CI 0.62-0.81, P=0.02). Conclusion:LV LGE percentage independently predict new-onset malignant ventricular arrhythmias in ARVC patients and provided incremental prognostic value based on the existing ARVC 5-year risk score.
10.A stem cell and integrative medicine system for chronic diseases:a conceptual framework
Chunhua ZHAO ; Yunfei JI ; Shihua WANG ; Xingyan AN
Basic & Clinical Medicine 2025;45(12):1692-1696
This article focuses on the clinical need for curative interventions in chronic diseases.It proposes an inte-grated medical framework that combines"quantum prediction,prevention and control through Traditional Chinese and Western Medicine,and stem cell repair"and details its path to clinical application.To address the complex,multi-target pathology of diseases like diabetes,this research integrates multiple disciplines:stem cell technology,the holistic philosophy of Traditional Chinese Medicine(TCM),the evidence-based rigor of Western Medicine,and the cutting-edge concepts of quantum biology.The goal is to create a new diagnostic and therapeutic model that syn-thesizes disease and syndrome classification while bridging macro and micro perspectives,ultimately driving break-throughs in chronic disease management.Theoretically,the study proposes a strategy to rejuvenate cells and remodel the microenvironment using pluripotent stem cells combined with synergistic TCM-Western Medicine approaches.Practically,it establishes a seamless system—from molecular early-warning and dynamic prevention to tissue re-pair—supported by standardized protocols,preclinical validation,multi-center clinical trials,and an intelligent health management platform.


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