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.

To verify whether chaperones can promote the soluble expression of PlpE in Escherichia coli and whether the expressed protein is active,prokaryotic expression and Western blot detection were performed.The results showed that:The PlpE prokaryotic expression vector pET-32a(+)-plpE was expressed as inclusion body,and the expression form was not changed by changing the concentration of inducer,induction time and temperature.The companion proteins pG-KJE8,pGro7,pKJE7 and pG-Tf2 were co-expressed with pET-32a(+)-plpE in Eschierichia coli expres-sion system,respectively.When the final concentration of IPTG of 0.5 mmol/L,L-arabinose of 0.5 g/L or tetracycline of 5.0 μg/L were added as inducers and induced at 37 ℃ for 8 h,the results showed that the molecular companion pGro7 could change the expression of rp-PlpE from inclu-sion body to soluble expression.pG-KJE8,pKJE7 and pG-Tf2 had no effect on the expression of rp-PlpE.The soluble rp-PlpE can react specifically with the positive serum of Mannheimia haemolyti-ca.Therefore,the study showed that the co-expression of the chaperone protein pGro7 can make the rp-PlpE protein express in a soluble form,and the purified protein exhibits reactogenicity.These findings lay the foundation for the establishment of a subunit vaccine and serological diagno-sis methods for Mannheimia haemolytica.

Objectives:To investigate the clinical value of cardiac magnetic resonance imaging(CMR)feature-tracking strain analysis in risk stratification of diabetic heart failure with preserved ejection fraction(HFpEF).Methods:In this retrospective study,a total of 215 patients with diabetic HFpEF who underwent CMR at Chinese Academy of Medical Sciences Fuwai Hospital from January 2012 to December 2018 were included.Myocardial strain parameters were calculated using CMR feature-tracking technology.Patients were followed up by medical records or telephone calls.Composite endpoint event,all-cause death or heart failure hospitalization during follow-up were recorded.Patients were divided into event group and event-free group.Univariable and multivariable Cox proportional hazard regression analyses were performed to determine the risk factors for the outcomes in diabetic HFpEF.The effects of hypertension and obesity on the prognosis of diabetic HFpEF patients and whether they affect the prognostic value of CMR feature-tracking strain analysis were also analyzed.Results:During a follow-up of(7.1±1.8)years,93(43.3%)patients had endpoint events(event group),including 28 all-cause deaths and 65 heart failure hospitalization.Compared with the event-free group(n=122),patients in the event group had significantly lower left ventricular ejection fraction,higher prevalence and extent of late gadolinium enhancement,and significantly reduced global longitudinal strain(GLS),global circumferential strain,global radial strain,and global systolic longitudinal strain rate(all P<0.05).The absolute GLS value was significantly lower in event group than in event-free group,regardless of the presence of hypertension and obesity.Multivariate Cox regression analysis showed that estimated glomerular filtration rate(HR=0.983,95%CI:0.972-0.993,P=0.001),left atrial volume index(HR=1.015,95%CI:1.005-1.026,P=0.004),and GLS(HR=1.142,95%CI:1.060-1.231,P<0.001)were independent risk factors for adverse cardiovascular events in diabetic HFpEF patients.However,adjusted N-terminal pro-brain natriuretic peptide was not an independent prognostic factor.The cut-offvalue of GLS to predict outcome was-14.09%from ROC curve analysis.The Kaplan-Meier curve showed that in patients with and without hypertension and obesity,patients with the GLS>-14.09%had lower event-free survival compared to patients with GLS≤-14.09%(all P<0.05),and the ability of GLS to predict adverse outcomes was not affected by hypertension and obesity.Conclusions:GLS obtained by CMR feature-tracking strain analysis is an independent predictor of adverse outcomes in diabetic HFpEF,and its ability to predict adverse outcomes is independent of hypertension and obesity.

As a non-invasive imaging modality,cardiac magnetic resonance(CMR)enables a"one-stop"in vivo assessment of cardiac morphology,structure,functional status and histological features,plays an irreplaceable role in the diagnosis,prognosis and risk stratification of cardiovascular diseases.In 2024,CMR has made continuous progress towards precision medicine.Upgraded technologies such as tissue characterization imaging and myocardial strain analysis,are gradually transformed into standard clinical practice.Artificial intelligence and other new algorithms have improved the quality and efficiency of CMR.The application of CMR in non-ischemic heart disease,ischemic heart disease and other areas is highly valued in the new version of various guidelines,highlighting the importance of CMR in the clinical management of cardiovascular diseases.This article aims to systematically review representative achievements of CMR in 2024 from the perspectives of both technological innovation and clinical translation,providing the latest update in this field.

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.

To verify whether chaperones can promote the soluble expression of PlpE in Escherichia coli and whether the expressed protein is active,prokaryotic expression and Western blot detection were performed.The results showed that:The PlpE prokaryotic expression vector pET-32a(+)-plpE was expressed as inclusion body,and the expression form was not changed by changing the concentration of inducer,induction time and temperature.The companion proteins pG-KJE8,pGro7,pKJE7 and pG-Tf2 were co-expressed with pET-32a(+)-plpE in Eschierichia coli expres-sion system,respectively.When the final concentration of IPTG of 0.5 mmol/L,L-arabinose of 0.5 g/L or tetracycline of 5.0 μg/L were added as inducers and induced at 37 ℃ for 8 h,the results showed that the molecular companion pGro7 could change the expression of rp-PlpE from inclu-sion body to soluble expression.pG-KJE8,pKJE7 and pG-Tf2 had no effect on the expression of rp-PlpE.The soluble rp-PlpE can react specifically with the positive serum of Mannheimia haemolyti-ca.Therefore,the study showed that the co-expression of the chaperone protein pGro7 can make the rp-PlpE protein express in a soluble form,and the purified protein exhibits reactogenicity.These findings lay the foundation for the establishment of a subunit vaccine and serological diagno-sis methods for Mannheimia haemolytica.

As a non-invasive imaging modality,cardiac magnetic resonance(CMR)enables a"one-stop"in vivo assessment of cardiac morphology,structure,functional status and histological features,plays an irreplaceable role in the diagnosis,prognosis and risk stratification of cardiovascular diseases.In 2024,CMR has made continuous progress towards precision medicine.Upgraded technologies such as tissue characterization imaging and myocardial strain analysis,are gradually transformed into standard clinical practice.Artificial intelligence and other new algorithms have improved the quality and efficiency of CMR.The application of CMR in non-ischemic heart disease,ischemic heart disease and other areas is highly valued in the new version of various guidelines,highlighting the importance of CMR in the clinical management of cardiovascular diseases.This article aims to systematically review representative achievements of CMR in 2024 from the perspectives of both technological innovation and clinical translation,providing the latest update in this field.

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.

Objective:To comprehensively evaluate the changes in pulmonary artery hemodynamics in patients with repaired tetralogy of Fallot (rTOF) using four-dimensional flow (4D Flow) MRI, and to explore the value of viscous energy loss (EL) as an evaluation parameter of the right heart in patients with rTOF.Methods:A total of 30 rTOF patients who were prospectively admitted at Fuwai Hospital between October 2017 and November 2019, and 19 healthy controls who were prospectively recruited on March 2023, were enrolled in this study. All participants underwent a comprehensive 4D Flow MRI evaluation, and indicators of comparison between the two groups including quantitative flow analysis, wall shear stress (WSS) assessment, and EL evaluation in four planes: the right ventricular outflow tract (RVOT), main pulmonary artery (MPA), right pulmonary artery (RPA), and left pulmonary artery (LPA). The correlation between EL and traditional right ventricular (RV) function parameters, as well as WSS, was analyzed.Results:The RV function was generally decreased in rTOF patients, with an RV ejection fraction of 41.42 (35.85, 43.33) %. Compared with healthy controls, the volumes of backward flow, peak velocities, and both axial and circumferential WSS at the RVOT, MPA, RPA, and LPA were significantly increased in rTOF patients (all P<0.05). The EL in the pulmonary artery was extremely low in healthy controls, with the maximum EL values for the MPA-RPA and MPA-LPA segments during cardiac cycle being 0.51 (0.42, 0.73) and 0.68 (0.40, 0.94) mW, respectively. However, in rTOF patients, the EL values were as high as 63.63 (35.35, 82.15) and 56.41 (34.96, 88.76) mW, respectively. There was a significant moderate negative correlation between EL and RV ejection fraction, and a moderate to high positive correlation between EL with RV volume index, regurgitation fraction, as well as peak velocities (all P<0.05). Additionally, there was a significant positive correlation between EL and axial and circumferential WSS, with the correlation coefficients at MPA ranging from 0.67 to 0.88 (all P<0.05). Conclusions:Disordered flow in the pulmonary artery is common in patients with rTOF and should not be overlooked. The extensive viscous EL is closely associated with traditional RV function parameters and WSS. EL is expected to become an crucial parameter for evaluating right heart function in rTOF patients.

Objective To explore the influencing factors of self injury or suicide in adolescent patients with depression.Methods A total of 96 adolescents who were diagnosed with depressive disorder at Yunnan Psychiatirc Hospital and Kunming Psychiatirc Hospital from January 2023 to May 2024 were selected for the study.The case group consisted of 61 adolescents who had self-injury or suicidal behaviors within 30 days,while the control group consisted of 35 adolescents who had no self-injury or suicidal behaviors within at least 30 days.Assessments were performed using the Patient Health Questionnaire-9(PHQ-9),Millon Screening Inventory for Borderline Personality Disorder(MSI-BPD),House-Tree-Person Drawing Test(HTP),and the Columbia Suicide Severity Rating Scale(C-SSRS).Among these,72 subjects underwent skin pressure pain threshold testing using the Algometer HP-50,with 12 in the self-harm or suicide group within 2 days and 60 in the group beyond 2 days.Results(1)Analysis of gender and age between the two groups showed statistically significant differences(P<0.05),with a higher proportion of females and younger ages in the 30-day group;(2)The PHQ-9 score for the 30-day group was(19.59±5.99),with a score of(2.41±0.97)for item 9("Thoughts that it would be better to be dead or to hurt oneself in some way"),and an MSI-BPD score of(7.43±1.61).The scores for the group over 30 days were(10.89±7.99),(1.00±1.11)for item 9,and(5.40±3.13)for MSI-BPD.Independent samples t-test analysis showed significant differences(P<0.01);(3)In the 30-day group,five drawing characteristics from the 47 HTP characteristics(shift of center of gravity,hair not disheveled or no hair,no mountains,no sun,and no flowers or grass)were found to occur at a higher rate,with statistical significance(P<0.05);(4)In the binary logistic regression analysis of 96 patients with the 30-day suicide or self-injury behavior as the dependent variable,the absence of flowers and PHQ-9 question 9 score are the risk factors for adolescent depression patients to have self-injury or suicide behavior within 30 days(OR no flowers=7.934,OR score on PHQ-9 question 9=3.554).(5)Among the 72 subjects the skin pressure pain threshold for adolescents who exhibited self-injure or suicide behaviors within 2 days(8.83±4.27 N)was significantly higher than that for patients beyond 2 days(6.48±3.00 N),with statistical significance(t=-2.201,P<0.05).Additionally,the score for item 9 of the PHQ-9 was higher(2.50±0.67 vs 1.87±0.95),also showing statistical significance(t=-2.201,P<0.05).Conclusion The absence of flowers or grass in HTP painting,and stronger suicidal ideation or suicide attempt are risk factors for self-injury or suicidal behavior in adolescents with depression.Furthermore,those who self-injure or commit suicide within 2 days have a higher pain threshold compared to those beyond 2 days.