Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

Aconitum (Ranunculaceae) has a long-standing history in traditional Chinese medicine (TCM), where it has been widely used to treat conditions such as rheumatoid arthritis (RA), myocardial infarction, and heart failure. However, the potency of Aconitum alkaloids, the primary active components of Aconitum, also confers substantial toxicity. Therefore, assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety. Metabolomics, a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways, provides a comprehensive view of the metabolic state across multiple systems in vivo. This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity, identifying potential sensitive biomarkers, and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM. This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing, aiming to identify more viable methods for characterizing toxic medicinal plants.
Aconitum/metabolism* ; Metabolomics/methods* ; Alkaloids/metabolism* ; Humans ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

A method was developed for determination of dilauryl thiodipropionate(DLTDP)in fried foods by coupling solid-phase extraction(SPE)pretreatment with reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS/MS)detection.Samples were extracted with n-hexane as the solvent,purified using a neutral alumina SPE cartridge,and finally analyzed by RPLC-MS/MS.Quantitative analysis was performed using matrix-matched calibration curves combined with an external standard method under optimal experimental conditions.The results showed that DLTDP exhibited good linearity in the range of 2.0-50.0 μg/L,with a correlation coefficient(R2)≥0.999.The limit of detection(LOD)and the limit of quantification(LOQ)of the method were 0.15 mg/kg and 0.5 mg/kg,respectively.The mean recoveries at three fortification levels(0.5,1.0,and 200 mg/kg)in different samples ranged from 84.8%to 96.8%,with the relative standard deviations(RSDs)all less than 8.0%.The developed method was highly sensitive,accurate and reliable,and easy to operate,making it well suited for the routine quantitative analysis of DLTDP in fried foods.

Objective To investigate the longitudinal relationship between sleep duration(SD)and positive youth development(PYD)among primary and secondary school students in Chengdu city using a cross-lagged model,and to provide scientific evidence for enhancing sleep management practices for students.Methods A total of 4061 students of grades 3 through 9 from the Chengdu Child Positive Development Cohort were included in this three-wave longitudinal study.There was a one-year interval between one survey and the following round of survey,and the time points for the baseline,12-month follow-up,and 24-month follow-up surveys were designated T0,T1,and T2.The PYD of the participants was assessed using the Chinese version of the Positive Youth Development Scale.The demographic data and the average daily SD over the past month were collected.Spearman correlation analysis was performed to examine the associations between SD and PYD,and a cross-lagged model was used to investigate the longitudinal relationship between them.Results The average daily SD for the 3 rounds of surveys conducted at T0,T1,and T2 was 9.00(8.04,10.00)hours,10.44(9.67,11.11)hours,and 10.39(9.83,11.00)hours,respectively,while the PYD scores were 5.30(4.73,5.71),5.27(4.73,5.73),and 5.39(4.89,5.77),respectively.Statistical significance was found in the differences of SD and PYD scores across the 3 rounds(P＜0.05).Spearman correlation analysis revealed synchronous correlations between SD and PYD at all three time points(r=0.10 at T0,r=0.18 at T1,and r=0.21 at T2,P＜0.05)and significant lagged correlations(e.g.,r=0.10 for T1-PYD and T2-SD,and likewise,significant correlation was found for the 3 other cross-lagged paths).The cross-lagged model demonstrated that PYD at T0 and T1 positively predicted SD at T1 and T2,respectively(β0-1=0.116[95％CI,0.083-0.150],β1-2=0.097(95％CI,0.067-0.127),P＜0.05),and that SD at T0 and T1 also positively predicted PYD at T1 and T2(β0-1=0.028[95％CI,0-0.056],β1-2=0.042[95％CI,0.010-0.074],P＜0.05).According to these findings,a bidirectional predictive relationship between SD and PYD across different time points was observed in primary and secondary school students.Furthermore,PYD demonstrated better performance for predicting SD than SD did for PYD.Subgroup analysis by sex confirmed the robustness of the predictive power of PYD for SD.Conclusion This study reveals a positive bidirectional predictive relationship between SD and PYD among primary and secondary school students,suggesting that higher levels of PYD may contribute to adequate sleep.These findings provide critical scientific evidence for schools and families to strengthen sleep management and promote the holistic development and well-being of adolescents.

Objective To explore the application value of musculoskeletal ultrasound(MSUS)in grading acute gastrocnemius muscle injuries.Methods A retrospective analysis was conducted on ultrasound images of 291 patients who presented with sudden calf pain and suspected acute gastrocnemius muscle injury in the General Hospital of Central Theater Command from March 2019 to July 2024.The images were independently reviewed and assessed by three ultrasound doctors with different qualifications to determine the presence and grade of gastrocnemius muscle injury.The consistency of grading results among three doctors was compared.The diagnostic results of three doctors were summarized.Then,the diagnostic results of 29 patients who underwent routine MRI scans were compared with those of MSUS,and the agreement between the two imaging modalities was assessed using the Kappa test.Results Among the 291 patients,171 cases(58.8%)were diagnosed with gastrocnemius muscle injury,including 55 cases(32.2%)with grade Ⅰ,109 cases(63.7%)with grade Ⅱ,and 7 cases(4.1%)with grade Ⅲ.There were 159 cases(93.0%)of unilateral medial head injury,10 cases(5.8%)of unilateral lateral head injury,and 2 cases(1.2%)of bilateral medial and lateral head injury.Compared with patients without gastrocnemius muscle injury,patients with gastrocnemius muscle injury were older(P<0.05),with no significant difference in gender and laterality(P>0.05).No significant differences in baseline characteristics were found among patients with different grades of injury(P>0.05).The three doctors diagnosed 173(59.5%),171(58.8%),and 171(58.8%)cases of injury,respectively,with an inter-class correlation coefficient(ICC)of 0.947(P<0.001).Among 29 patients who underwent MRI,the diagnostic agreement between MRI and ultrasound for grade Ⅰ,Ⅱ and Ⅲ injury was 8(27.6%),18(62.1%)and 3(10.3%)for MRI;and 9(31.0%),17(58.6%)and 3(10.3%)for MSUS,respectively,with a Kappa value of 0.808(P<0.001).Conclusions MSUS is effective for assessing the grade of acute gastrocnemius muscle injury,and shows high diagnostic consistency among doctors with different qualifications.It is recommended as the preferred method for diagnosing gastrocnemius muscle injury.

Objective To explore the value of shear wave elastography(SWE)combined with cervical length(CL)measurement in predicting spontaneous preterm birth(SPB)at 20 to 27 weeks of gestation.Methods A total of 161 pregnant women with antenatal care and examination in the hospi-tal from January 2020 to June 2022 were selected as research objects.All pregnant women underwent CL measurement and SWE detection by ultrasound during 20 to 27 weeks of gestation to obtain CL and SWE parameters.The occurrence of SPB was followed up,and the correlations of CL and SWE param-eters with the occurrence of SPB were analyzed.Results Among the 161 pregnant women,34 pa-tients experienced SPB.There were significant differences in the external os strain(EOS),elastic contrast index(ECI),internal os strain(IOS),and hardness ratio(HR)of SWE parameters between pregnant women with and without preterm birth(P＜0.05).Similarly,there was a significant differ-ence in CL between the two groups(P＜0.05).Spearman correlation analysis showed that ECI,IOS and EOS were positively correlated with the occurrence of preterm birth(P＜0.05),while HR and CL were negatively correlated with the occurrence of preterm birth(P＜0.05).The receiver operating characteristic(ROC)curve showed that the area under the curve(AUC)for CL in predicting preterm birth was 0.800,with a cut-off value of 2.710 cm.Among the SWE parameters,the AUCs for ECI,HR,IOS and EOS in predicting preterm birth were 0.651,0.642,0.705 and 0.653 respectively,with cut-off values of 5.140,53.650％,0.320 and 0.330 respectively.The ROC curve showed that the AUC for predicting preterm birth by SWE parameters combined with CL was 0.813,which was significantly higher than the AUC for prediction by the combination of the four SWE parameters(P＜0.05).The sensitivity and specificity at the maximum Youden index were 0.794 and 0.732 respectively.Conclusion CL,as well as ECI,HR,IOS and EOS among SWE parameters,have certain value in predicting SPB in pregnant women at 20 to 27 weeks of gestation,especially when the five indicators are combined for prediction.The critical values for prediction are 2.710 cm,5.140,53.650％,0.320 and 0.330 respectively.

Objective Data mining technology was used to mine the medication rules of the prescriptions used in the treatment of pediatric atopic dermatitis by Chinese medical master XUAN Guo-Wei.Methods The medical records of effective cases of pediatric atopic dermatitis treated by Professor XUAN Guo-Wei at outpatient clinic were collected,and then the medical data were statistically analyzed using frequency statistics,association rule analysis and cluster analysis.Results A total of 242 prescriptions were included,involving 101 Chinese medicinals.There were 23 commonly-used herbs,and the 16 high-frequency herbs(frequency＞100 times)were Glycyrrhizae Radix et Rhizoma,Saposhnikoviae Radix,Glehniae Radix,Perillae Folium,Ophiopogonis Radix,Cynanchi Paniculati Radix et Rhizoma,Microctis Folium,Dictamni Cortex,Scrophulariae Radix,Coicis Semen,Cicadae Periostracum,Lilii Bulbus,Rehmanniae Radix,Kochiae Fructus,Sclerotium Poriae Pararadicis,and Euryales Semen.The analysis of the medicinal properties showed that most of the herbs were sweet and cold,and mainly had the meridian tropism of the spleen,stomach and liver meridians.The association rule analysis yielded 24 commonly-used drug combinations and 20 association rules.Cluster analysis yielded 2 core drug combinations.Conclusion For the treatment of pediatric atopic dermatitis,Professor XUAN Guo-Wei focuses on the clearing,supplementing and harmonizing therapies,and the medication principle of"supporting the healthy-qi to eliminate the pathogen,and balancing the yin and yang"is applied throughout the treatment.

Objective To explore the role and possible molecular mechanism of Isocitrate dehydrogenase 1(IDH1)gene in proliferation and migration of intrahepatic cholangiocarcinoma(iCCA)cell HuCCT1.Methods HuCCT1 cells with IDH1 gene knockout(HuCCT1IDH1-/-)were constructed by CRISPR/Cas9 gene editing technology.To investigate the capacities of proliferation,migration and invasion of HuCCT1WT(HuCCT1 cells with wild-type IDH1 gene)and HuCCT1IDH1-/-cells,assays of CCK-8,clone formation,scratch and transwell were performed.Western blotting was used to detect the expression levels of epithelial-mesenchymal transition(EMT)associated proteins E-cadherin,N-cadherin,Vimentin,MMP-9,Wnt3a and β-catenin in two groups of cells.The transcriptome sequencing data of HuCCT1WT and HuCCT1IDH1-/-cells were analyzed by bioinformatics methods,Western blotting was used to verify the expression of signaling pathway-related proteins.Results Compared with HuCCT1WT cells,HuCCT1IDH1-/-cells showed the number of proliferation and clone formation significantly reduced(P<0.05),the proportion of cells blocked in G2/M phase was significantly increased(P<0.01),the rate of scratch healing was significantly decreased(P<0.01),and the number of migrated cells(P<0.001)and invaded cells(P<0.05)was significantly reduced.qRT-PCR assay showed that the expression levels of IDH1,Vimentin,MMP-9 and genes related to the regulation of G2/M cycle proliferation,Cyclin A2,Cyclin B1 and CDK1 mRNA were down-regulated in HuCCT1IDH1-/-cells(P<0.05),and the expression of CDH1 mRNA encoding E-cadherin was up-regulated(P<0.01);Western blotting assay showed that the expression level of E-cadherin in HuCCT1IDH1-/-cells was significantly increased(P<0.05),and the expression level of N-cadherin,Vimentin and MMP-9 protein was significantly decreased(P<0.05)than that in HuCCT1WT cells.Data of transcriptome sequencing revealed 1476 differentially expressed genes(DEGs)between two groups of HuCCT1 cells.Go enrichment analysis showed the DEGs were significantly enriched in cell biological processes associated with inflammatory response,cell signaling and cell metabolism.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis suggested that the DEGs may be involved in some signaling pathways such as Wnt,MAPK,Rap1,Hippo and TNF,which are closely related to the regulation of proliferation and invasion of tumor cells.Western blotting verification results showed that compared with HuCCT1WT cells,the relative expression of Wnt3a and β-catenin proteins of HuCCT1IDH1-/-cells was significantly decreased(P<0.05).Conclusions IDH1 gene may participate in the control of biological functions of HuCCT1 cells,including cell proliferation,migration,invasion and epithelial mesenchymal transition.The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.