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.Phosphatidylethanolamine promotes macrophage senescence and liver injury by activating endoplasmic reticulum stress
Longchuan HAN ; Yue LI ; Zhihui ZOU ; Jing LUO ; Ruoyi LI ; Yingting ZHANG ; Xinxin TANG ; Lihong TIAN ; Yuheng LU ; Ying HUANG ; Ming HE ; Yinkun FU
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(6):693-704
Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.
3.Study on ICD-10 coding of sepsis related diseases in the context of DRG payment
Bingjue XIE ; Lu TANG ; Ying SHE ; Tingting TANG ; Ping SONG
Modern Hospital 2025;25(3):375-378
Objective To enhance the accuracy of sepsis related disease coding and primary diagnosis selection,thereby ensuring the quality of medical record home page and DRG data.Methods Sepsis related disease concepts and coding rules have been reviewed by combining clinical and International Classification of Diseases(ICD-10)expertise.The main diagnostic selection principles of sepsis were summarized based on the filling criteria of the medical record home page and the medical insur-ance settlement list,and sepsis coding ideas were analyzed through clinical cases.Results Negative or unidentified pathogens are classified as A41.9,while sepsis with identified pathogens is mainly classified as A40-A41.8;sepsis of newborn is classified as P36;sepsis during pregnancy,childbirth and puerperium is respectively classified as O03-O08,O75.3,and O85;sepsis follow-ing surgery or operations is classified as T80.2,T81.4,or T88.0;sepsis with organ dysfunction or septic shock should be separate-ly coded as R65.1 or R57.2.The main diagnostic selection of sepsis follows the principle of etiology priority,and the cause and pathogen of sepsis should be confirmed when coding.Conclusion Coders need to master the clinical knowledge and coding rules related to sepsis,read the medical records carefully and strengthen communication with doctors to enhance the accuracy of coding and improve the main diagnosis,thereby ensuring the quality of medical record home page and the accuracy of DRG grouping re-sults.
4.Study on ICD-10 coding of sepsis related diseases in the context of DRG payment
Bingjue XIE ; Lu TANG ; Ying SHE ; Tingting TANG ; Ping SONG
Modern Hospital 2025;25(3):375-378
Objective To enhance the accuracy of sepsis related disease coding and primary diagnosis selection,thereby ensuring the quality of medical record home page and DRG data.Methods Sepsis related disease concepts and coding rules have been reviewed by combining clinical and International Classification of Diseases(ICD-10)expertise.The main diagnostic selection principles of sepsis were summarized based on the filling criteria of the medical record home page and the medical insur-ance settlement list,and sepsis coding ideas were analyzed through clinical cases.Results Negative or unidentified pathogens are classified as A41.9,while sepsis with identified pathogens is mainly classified as A40-A41.8;sepsis of newborn is classified as P36;sepsis during pregnancy,childbirth and puerperium is respectively classified as O03-O08,O75.3,and O85;sepsis follow-ing surgery or operations is classified as T80.2,T81.4,or T88.0;sepsis with organ dysfunction or septic shock should be separate-ly coded as R65.1 or R57.2.The main diagnostic selection of sepsis follows the principle of etiology priority,and the cause and pathogen of sepsis should be confirmed when coding.Conclusion Coders need to master the clinical knowledge and coding rules related to sepsis,read the medical records carefully and strengthen communication with doctors to enhance the accuracy of coding and improve the main diagnosis,thereby ensuring the quality of medical record home page and the accuracy of DRG grouping re-sults.
5.Analysis on the disease burden trend and attributable risk factors of common gynecological cancers in China from 1990 to 2021
Xiao-hui ZHOU ; Yi-xin ZOU ; Zhuo-ying LI ; Yu-xuan XIAO ; Dan-dan TANG ; Yu-xin ZHOU ; Pei-wen LU ; Qun XU ; Yong-bing XIANG
Fudan University Journal of Medical Sciences 2025;52(6):783-793
Objective To describe and analyze the current status,changing trend and influencing factors of the disease burden of cervical,endometrial and ovarian cancer in China from 1990 to 2021.Methods Data on incidence,mortality,disability-adjusted life year(DALY),and other indicators for cervical,endometrial and ovarian cancer were collected from the 2021 Global Burden of Disease database.Joinpoint regression models were used to analyze time trends,and age-period-cohort(APC)models assessed their impact on incidence and mortality.Spearman correlation analysis was performed to evaluate the relationship between the sociodemographic index(SDI)and the cancer indicators.Finally,the attributable risk factors for the disease burden were analyzed.Results From 1990 to 2021,age-standardized incidence rates of cervical and endometrial cancers in China significantly increased,while ovarian cancer showed no significant change.Age-standardized mortality,DALY,and years of life lost due to premature death(YLL)decreased significantly.The disease burden was heavier in middle-aged and older groups.APC model indicated an increase in cervical cancer incidence and a decrease in mortality over time.Furthermore,the incidence risks of cervical and endometrial cancers were elevated in successive birth cohorts,whereas a lower risk was observed for ovarian cancer.Correlation analysis showed significant associations between cancer incidence and mortality with SDI.Obesity has significantly contributed to the disease burden of common gynecologic cancers in China.Conclusion Mortality rates of cervical,endometrial and ovarian cancer have declined,while the incidence of cervical and endometrial cancers has significantly increased.The trends in incidence and mortality are influenced by age,period and cohort effects.Future efforts should focus on controlling risk factors like obesity to reduce the disease burden.
6.Investigation and analysis of factors influencing employee satisfaction in a children's hospital in the context of national examination
Lu TANG ; Ying SHE ; Bingjue XIE
Modern Hospital 2025;25(9):1381-1385
Objective To understand the current status of employee satisfaction in a certain tertiary public children's hospital under the background of the national performance assessment,explore its influencing factors,and provide data support for improving employee satisfaction.Methods A satisfaction survey was conducted throughout the hospital in July 2024 using the employee questionnaire of the national performance assessment for tertiary public hospitals.The survey covered basic information,salary and benefits,career development and promotion,work content and environment,superior-subordinate relationships,peer relationships,intention to leave,and overall satisfaction.Multiple ordered logistic regression was used to explore the influencing factors of satisfaction.Results A total of 1 675 valid questionnaires were collected.The overall satisfaction score of employees was(78.18±20.63)points,and the intention to leave score was(75.10±24.86)points.The score for peer relationships was relatively high(79.47±14.82)points,while the scores for work content and environment,superior-subordinate relationships,salary and benefits,and career development and promotion were relatively low,at(63.05±17.78)points,(63.54±20.04)points,(63.87±24.37)points,and(69.26±23.43)points,respectively.The results of multiple ordered logistic regression analysis showed that employee job satisfaction was influenced by factors such as gender,years of service,and job position.The degree of influence of each dimension of satisfaction on overall satisfaction was salary and benefits,work content and environ-ment,peer relationships,superior-subordinate relationships,and career development and promotion,in that order.Conclusion The overall satisfaction of employees is on par with that of general hospitals,but there is still considerable room for improve-ment in the dimensions of work content and environment and superior-subordinate relationships.In the future,the hospital should attach great importance to the dimensions with lower satisfaction scores,continuously improve the work environment,deepen the salary distribution system,and ensure that employee satisfaction is effectively enhanced,laying a solid foundation for the high-quality development of the hospital.
7.RICH1 regulates myocardial fibrosis through TGF-β/SMAD signaling pathway
Lu-xuan WAN ; Ying-qing HU ; Yuan-yuan LIU ; Yong-song TANG ; Jun-yi HUANG ; Zi-xuan ZHANG ; Xiao-xiao MAO ; Xin-wen NIE ; Zhan-hong REN
Chinese Pharmacological Bulletin 2025;41(11):2089-2096
Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.
8.RICH1 regulates myocardial fibrosis through TGF-β/SMAD signaling pathway
Lu-xuan WAN ; Ying-qing HU ; Yuan-yuan LIU ; Yong-song TANG ; Jun-yi HUANG ; Zi-xuan ZHANG ; Xiao-xiao MAO ; Xin-wen NIE ; Zhan-hong REN
Chinese Pharmacological Bulletin 2025;41(11):2089-2096
Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.
9.Association between psychological resilience and internet addiction among senior primary school students in Jiading District,Shanghai
Yan LU ; Tuersunniyazi MAIHELIYAKEZI ; Li WANG ; Jin-jin TANG ; Zhe LIANG ; Ying-zhu WANG ; Hui-jing SHI
Fudan University Journal of Medical Sciences 2025;52(4):519-524
Objective To explore the association between psychological resilience and internet addiction among senior primary school students,so as to provide a scientific basis for formulating strategies for preventing internet addiction and enhancing psychological resilience in this group.Methods A stratified cluster sampling method was employed.In May 2021,a total of 1 618 fourth-and fifth-grade students from 5 primary schools in Jiading District,Shanghai were surveyed on psychological resilience and internet addiction through questionnaires.Independent sample t-tests,chi-square tests,and Logistic regression models were used for data analysis.Results Among the 1 618 students,the prevalence rate of internet addiction was 8.8%(142 students).The total score of psychological resilience(t=6.215,P<0.001)and the scores of three dimensions,namely family support(t=3.509,P<0.001),goal focus(t=6.965,P<0.001),and positive perception(t=5.887,P<0.001),of those reported with internet addiction were all significantly lower than those without internet addiction.Multivariate logistic regression analysis showed that compared with individuals with low psychological resilience,those with moderate(aOR=0.395,95%CI:0.267-0.584,P<0.001)and high psychological resilience(aOR=0.167,95%CI:0.077-0.365,P<0.001)had a lower probability of internet addiction.The three sub-dimensions of psychological resilience,namely goal focus,positive perception and family support,also showed a statistically significant negative association with internet addiction in these students.Conclusion Nearly one-tenth senior primary school students in Jiading District self-reported internet addiction.Higher levels of psychological resilience were associated with a lower probability of internet addiction among senior primary school students.Focusing on enhancing the goal focus,positive perception and family support dimensions in psychological resilience may be of great significance for preventing internet addiction among senior primary school students.
10.Proficiency testing for 11 clinical biobanks in Beijing City: simulation study and result analysis
Qian ZHANG ; Yun ZHANG ; Lu HAN ; Min LIU ; Yongbo YU ; Yan WANG ; Ying HU ; Hui ZHONG ; Dan GUO ; Shipeng SUN ; Jinxi LIN ; Siyuan XU ; Xiaokun TANG ; Gaoyuan SUN ; Chuanbao ZHANG ; Hexin LI
Chinese Journal of Preventive Medicine 2025;59(9):1590-1596
Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.

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