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.

Objective To analyze the therapeutic efficacy of low-temperature plasma surgery for children with obstructive sleep apnea-hypopnea syndrome(OSAHS)and its effects on inflammatory response,immune function,pain,and sleep quality for providing a basis for the rational treatment of OSAHS.Methods A prospective study was conducted on 92 children with OSAHS from January 2021 to December 2023,and they were randomly divided into control group(n=46)and pilot group(n=46).Control group were given conventional tonsil and adenoidectomy,while observation group were given low-temperature plasma tonsil and adenoid ablation.These patients in both groups were followed-up for 6 months after surgery,and there was no lost case during the follow-up period.The two groups were compared for the efficacy at 6 months after surgery,surgery-related indexes,scores of visual analogue scale for pain at 1,2,and 3 days after surgery,sleep quality before and at 6 months after surgery,inflammatory response,immune function,and the occurrence of complications during the 6 month follow-up period.Results Compared with control group,pilot group had higher overall effective rate at 6 months postoperatively(93.48%vs 78.26%,P<0.05),less intraoperative bleeding,and shorter operation and hospitalization time(P<0.05).The visual analog scale score gradually decreased in both groups at 1,2,3 days postoperatively,and the scores were lower in pilot group than in control group(P<0.05).Compared with those before surgery,apnea hypoventilation index and respiratory disturbance index were lower in both groups at 6 months postoperatively,with lower indicator values in the pilot group(P<0.05);while the lowest blood oxygen saturation increased in the two groups,with higher indicator values in the pilot group(P<0.05).Compared with those before surgery,serum procalcitonin,interleukin-1β,interleukin-6,high sensitive C-reactive protein,tumor necrosis factor-α,and whole-blood CD8+were lower in both groups at 3 days postoperatively,with lower indicator values in pilot group(P<0.05);while whole-blood CD3+,CD4+,CD4+/CD8+were higher in both groups at 3 days postoperatively,with higher indicator values in pilot group(P<0.05).The total complication rate within 6 months of follow-up was lower in pilot group than in control group(4.35%vs 17.39%,P<0.05).Conclusion Low-temperature plasma surgery is effective and safe in children with OSAHS,and it is considered that it might be related to its contributions to improvements in surgery-related indexes,inflammatory response,immune function,pain and sleep quality.

Objective To analyze the therapeutic efficacy of low-temperature plasma surgery for children with obstructive sleep apnea-hypopnea syndrome(OSAHS)and its effects on inflammatory response,immune function,pain,and sleep quality for providing a basis for the rational treatment of OSAHS.Methods A prospective study was conducted on 92 children with OSAHS from January 2021 to December 2023,and they were randomly divided into control group(n=46)and pilot group(n=46).Control group were given conventional tonsil and adenoidectomy,while observation group were given low-temperature plasma tonsil and adenoid ablation.These patients in both groups were followed-up for 6 months after surgery,and there was no lost case during the follow-up period.The two groups were compared for the efficacy at 6 months after surgery,surgery-related indexes,scores of visual analogue scale for pain at 1,2,and 3 days after surgery,sleep quality before and at 6 months after surgery,inflammatory response,immune function,and the occurrence of complications during the 6 month follow-up period.Results Compared with control group,pilot group had higher overall effective rate at 6 months postoperatively(93.48%vs 78.26%,P<0.05),less intraoperative bleeding,and shorter operation and hospitalization time(P<0.05).The visual analog scale score gradually decreased in both groups at 1,2,3 days postoperatively,and the scores were lower in pilot group than in control group(P<0.05).Compared with those before surgery,apnea hypoventilation index and respiratory disturbance index were lower in both groups at 6 months postoperatively,with lower indicator values in the pilot group(P<0.05);while the lowest blood oxygen saturation increased in the two groups,with higher indicator values in the pilot group(P<0.05).Compared with those before surgery,serum procalcitonin,interleukin-1β,interleukin-6,high sensitive C-reactive protein,tumor necrosis factor-α,and whole-blood CD8+were lower in both groups at 3 days postoperatively,with lower indicator values in pilot group(P<0.05);while whole-blood CD3+,CD4+,CD4+/CD8+were higher in both groups at 3 days postoperatively,with higher indicator values in pilot group(P<0.05).The total complication rate within 6 months of follow-up was lower in pilot group than in control group(4.35%vs 17.39%,P<0.05).Conclusion Low-temperature plasma surgery is effective and safe in children with OSAHS,and it is considered that it might be related to its contributions to improvements in surgery-related indexes,inflammatory response,immune function,pain and sleep quality.

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 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.

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.

Objective To investigate the clinical features of elderly patients with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)and the risk factors affecting the short-term prognosis of patients.Methods A retrospective analysis was performed for 417 patients with HBV-ACLF who were admitted to The General Hospital of Western Theater Command from January 2015 to January 2023,and related clinical data were collected,including general status,routine blood test results,biochemical parameters,and conditions of liver cirrhosis and decompensated events(ascites,hepatic encephalopathy,and their severities).The patients were followed up to observe 90-day survival.According to the age,the patients were divided into elderly group(with 106 patients aged≥60 years)and non-elderly group(with 311 patients aged＜60 years),and according to the 90-day survival,the elderly group were further divided into survival group with 41 patients and death/transplantation group with 65 patients.The independent-samples t test or the Mann-Whitney U test was used for comparison of quantitative data between two groups,and the chi-square test was used for comparison of qualitative data between two groups.The binary logistic regression analysis was used to determine the independent influencing factors for the risk of death within 90 days in elderly patients with HBV-ACLF,and a nomogram model was constructed for predicting the risk of death.The receiver operating characteristic(ROC)curve was used to investigate the value of the model in predicting the prognosis of HBV-ACLF patients in both the training set and the validation set.Calibration curve and decision curve were plotted for the models constructed in the training set and the validation set,and the model was assessed in terms of the degree of fitness and predicting benefits.Results The elderly patients had a significantly higher 90-day mortality rate than the non-elderly patients(P＜0.05),and compared with the non-elderly group,the elderly group had significantly higher incidence rate in female individuals,basic incidence rate of liver cirrhosis,incidence rate and grade of hepatic encephalopathy,incidence rate of ascites,and liver fibrosis markers(aspartate aminotransferase-to-platelet ratio index and fibrosis-4)(all P＜0.05),as well as significantly lower total cholesterol,high-density lipoprotein,albumin,alpha-fetoprotein,and lymphocytes(all P＜0.05).As for the elderly patients with HBV-ACLF,there were significant differences between the survival group and the death/transplantation group in total cholesterol,total bilirubin,international normalized ratio(INR),alpha-fetoprotein,platelet,creatinine,serum sodium,monocytes,and the incidence rate and grade of hepatic encephalopathy(all P＜0.05).In addition,the multivariate logistic regression analysis showed that INR(odds ratio[OR]=11.351,95%confidence interval[CI]:1.942-66.362,P＜0.05),monocyte count(OR=23.636,95%CI:1.388-402.529,P＜0.05),total bilirubin(OR=1.007,95%CI:1.001-1.013,P＜0.05),and platelet count(OR=0.968,95%CI:0.945-0.993,P＜0.05)were independent influencing factors for the 90-day prognosis of elderly patients with HBV-ACLF,and the nomogram model constructed based on these factors had a relatively high predictive value,with an area under the ROC curve of 0.915,a sensitivity of 88.0%,and a specificity of 86.7%.The nomogram model showed relatively high efficiency and degree of fitness in the verification set,and the decision curve suggested that the model had good benefits,with a higher prediction efficiency compared with the commonly used prediction models such as MELD score and COSSH-ACLF Ⅱ score.Conclusion Elderly HBV-ACLF patients may have a high short-term mortality rate due to the reductions in liver synthesis,reserve function,and regenerative ability and immune dysfunction.INR,monocyte count,total bilirubin,and platelet count have a relatively high value in predicting the risk of death in elderly HBV-ACLF patients,and the nomogram model constructed based on these factors has a relatively high prediction efficiency.

Objective: To investigate the effect and mechanism of polysaccharide of atractylodes macrocephala (PAM) on the growth of colon cancer cells in mice bearing in-situ colon cancer transplantation tumor. Methods: 1×107 colon cancer HT-29 cells labeled with luciferase were injected into colon serosa of the mice to establish the in-situ colon cancer transplantation tumor model. When the tumor volume reached 230 mm3, the mice were given 30 mg/kg PAM (PAM group) or equal volume of normal saline (Control group) by gavage for 10 consecutive days. The effect of PAM on the growth of colon cancer cells in mice was tested by in vivo tumor imaging technology. The expressions of MHCII and IL-12 in granulocytes, dendritic cells and macrophages, the activation of lymphocytes, and IFN-γ expression in CD4+ and CD8+ cells of tumor tissues were detected by Flow cytometry. Results: PAM significantly inhibited the growth of colon cancer cells in mice bearing in-situ colon cancer transplantation tumor (P<0.01). PAM activated immune cells though increasing the expression levels of MHCII and IL-12 in dendritic cells and macrophages (both P<0.01). PAM significantly increased the frequency of CD8+ cells, NK cells, CD44+/NK cells and CD44+/CD4+ cells in tumor tissues and the number of CD8+ cells and NK cells per unit volume (all P<0.01). PAM significantly increased the IFN-γ secretion of CD4+ and CD8+ cells (both P<0.01), too. Conclusion: PAM inhibits the growth of colon cancer by activating immune cells in tumor tissues of mice bearing in-situ colon cancer transplantation tumor.

Objective To investigate the effects of acyl-CoA synthetase 5 (ACS5) silencing by siRNA on expression and proliferation of colon carcinoma cell lines.Methods The expression of ACS5 in 30 case colon carcinoma and adjacent tissues were analyzed by immunohistochemical staining.The siRNA of ACS5 with Lipofectamine2000TM was transfected into colon carcinoma cell lines (HT-29 and SW480).The expression of ACS5 in colon carcinoma cell lines (HT-29 and SW480) was detected by real-time reverse transcription polymerase chain reaction.Proliferation of colon carcinoma cell lines was analyzed by 3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS).Results The expression of ACS5 in colon cancer was significantly higher than in adjacent tissues by immunohistochemical staining.The mRNA of ACS5 in siRNA-ACS5 group (0.18 ± 0.03) was significantly lower than in NC siRNA group (2.55 ± 0.31) and blank control group (2.48 ± 0.12) in HT-29 colon cancer lines,and the inhibition ratio was 92.96％ (F =146.9,P ＜0.01).The mRNA of ACS5 in siRNA-ACS5 group (0.14 ± 0.01) was significantly lower than in NC siRNA group (1.21 ± 0.05) and blank control group (1 ± 0.03) in SW480 colon cancer lines,and the inhibition ratio was 88.5％ (F =826.5.9,P ＜ 0.01).Proliferation of HT-29 and SW480 colon cancer line in siRNA-ACS5 group was slower on 72 h and 96 h than in NC siRNA group and blank control group (P ＜ 0.05).Conclusions Expression of ACS5 is elevated in colon cancer tissues.siRNA interference of colon cancer line downregulated ACS5 expression and inhibited the proliferation of the colon cancer cells.