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*

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective:To discuss the effect of long non-coding RNA(lncRNA)DUXAP8 in exosomes(Exo)derived from the lung cancer A549 cells on the growth and immune escape of the lung cancer cells,and to clarify the mechanism.Methods:The human lung cancer cell line A549 was cultured,and its exosomes were extracted and identified.The A549 cells were treated with PKH67-labeled Exo to observe the uptake of Exo by A549 cells.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression level of lncRNA DUXAP8 in A549 cells before and after Exo treatment.The A549 cells were divided into control group(no treatment),Exo group(A549 cells treated with Exo),Exo+sh-NC group(A549 cells treated with Exo and then transfected with sh-NC),and Exo+sh-DUXAP8 group(A549 cells treated with Exo and then transfected with sh-DUXAP8).RT-qPCR method was used to detect the expression level of lncRNA DUXAP8 in A549 cells in various groups;colony formation assay was used to detect the colony formation abilities of the A549 cells in various groups;5-ethynyl-2'-deoxyuridine(EdU)staining method was used to detect the proliferation abilities of the A549 cells in various groups.After co-culturing A549 cells in various groups with human peripheral blood lymphocytes,flow cytometry was used to detect the percentages of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in various groups;3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)method was used to detect the killing rates of human peripheral blood lymphocytes on the A549 cells in various groups.Results:The diameter of Exo vesicles was 50-150 nm,and the exosome-specific marker proteins cluster of differentiation 63(CD63),cluster of differentiation 9(CD9),tumor susceptibility gene 101(TSG101),and heat shock protein 70(HSP70)were positively expressed,indicating successful exosome extraction.A549 cells efficiently took up PKH67-labeled Exo.The RT-PCR results showed that compared with A549 cells cultured alone,the expression level of lncRNA DUXAP8 in the A549 cells was increased after treatment with Exo derived from A549 cells(P<0.05).compared with control group,the expression level of lncRNA DUXAP8 in the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the expression level of lncRNA DUXAP8 in the A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there were no significant difference in the expression level of IncRNA DUXAP8 in the cells in Exo+sh-NC group(P>0.05).The colony formation assay results showed that compared with control group,the number of colony formation of the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the number of colony formation of the A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there was no significant difference in the number of colony formation of the A549 cells in Exo+sh-NC group(P>0.05).The EdU staining results showed that compared with control group,the EdU-positive rate of the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the EdU-positive rate in A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there was no significant difference in the EDU-positive rate in the cells in Exo+sh-NC group(P>0.05).The flow cytometry results showed that compared with control group,the percentage of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in Exo group was decreased(P<0.05);compared with Exo group,the percentage of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in Exo+sh-DUXAP8 group was increased(P<0.05),while there was no significant difference in the percentage of activated CD8+T lymphaytes in Exo+sh-NC group(P>0.05).The MTT assay results showed that compared with control group,the killing rate of human peripheral blood lymphocytes on the A549 cells in Exo group was decreased(P<0.05);compared with Exo group,the killing rate of human peripheral blood lymphocytes on A549 cells in Exo+sh-DUXAP8 group was increased(P<0.05),while no significant difference was observed in Exo+sh-NC group(P>0.05).Conclusion:The lncRNA DUXAP8 in exosomes derived from the lung cancer A549 cells promotes the proliferation of lung cancer cells and tumor immune escape.

As a new generation of time-of-flight mass spectrometry,multiple-reflection time-of-flight mass spectrometry(MR-TOF-MS)has been increasingly applied in the fields such as nuclear physics,chemistry,and biology due to its ultra-high resolution and rapid analysis capabilities.However,the analytical performance of MR-TOF-MS largely depends on the ion bunch state entering the mass analyzer.In this study,a rectangular ion trap(RIT)was developed,designed and processed using printed circuit board technology,as an ion accumulating and focusing device for MR-TOF mass analyzer.Compared to traditional ion traps composed of two sets of planar electrodes,this RIT had higher voltage utilization efficiency,resulting in more efficient ion collection and focusing.The ions were cooled to a sufficiently small bunch for precise mass measurement with MR-TOF-MS mass spectrometry in only 1 ms of cooling time in the RIT,then orthogonally ejected to the MR-TOF mass spectrometer for mass analysis.Experimental results indicated that the working cycle,ion flux,and ion focusing state of the RIT fully met the requirements of the MR-TOF mass analyzer.When coupled with the MR-TOF mass analyzer,the RIT enabled MR-TOF-MS to achieve a mass resolution of 1.5×105.

Objective To investigate the risk factors for pneumonia complicating infectious mononucleosis(IM)in adults and construct a nomogram prediction model.Methods A retrospective analysis was conducted on 198 IM patients admitted to the Second Affiliated Hospital of Air Force Medical University from January 2015 to December 2021.Patients were divided into pneumonia group(n=52)and non-pneumonia group(n=146)based on whether pulmonary infection occurred during hospitalization.The baseline data(age,gender,place of onset,etc.),clinical manifestations(maximum body temperature,lymph node enlargement,splenomegaly,etc.),and inflammatory indicators[white blood cell count(WBC),C-reactive protein(CRP),etc.]were compared between the two groups.Kaplan-Meier curves were plotted to analyze the key indicators affecting the hospital stay of IM patients.Multivariate logistic regression was used to analyze the independent risk factors for pneumonia complicating IM in adults and construct a nomogram prediction model based on the identified risk factors.The predictive efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve and the consistency of the model was assessed using the calibration curve.The fit of the model was evaluated using the Hosmer-Lemeshow test.Additionally,the sensitivity,specificity,and accuracy of the model were assessed using confusion matrix.Results Compared with non-pneumonia group,the pneumonia group had a significantly higher proportion of patients from rural areas,with body mass index(BMI)≥24 kg/m2,smoking history,hepatomegaly,fever duration of≥7 d,as well as increased total hospitalization costs and average daily hospitalization costs,and prolonged hospital stay(P<0.05).The proportion of patients with a history of antibiotic use was lower in the pneumonia group(P<0.05).Kaplan-Meier survival analysis showed that patients from rural areas,with BMI≥24 kg/m2,smoking history,no prophylactic use of antibiotics,fever duration≥7 d,and hepatomegaly had significantly prolonged hospital stays(P<0.05).Multivariate logistic regression analysis revealed that living in a rural area(OR=4.089,P<0.05),hepatomegaly(OR=4.082,P<0.05),and elevated WBC(OR=1.205,P<0.05)were independent risk factors for pneumonia complicating IM in adults,while the prophylactic use of antibiotics(OR=0.142,P<0.05)was an independent protective factor.The area under the ROC curve of the constructed nomogram prediction model was 0.827(95%CI 0.762-0.892),and the slope of the calibration curve was close to 1,and the Hosmer-Lemeshow test showed χ2=5.299,P=0.725,indicating good consistency and fit of the prediction model.The results of the confusion matrix assessment showed that the sensitivity of the model was 0.669(0.624-0.773),the specificity was 0.827(0.724-0.930),and the accuracy was 0.732(0.665-0.793).Conclusion The nomogram prediction model based on place of onset,hepatomegaly,the prophylactic use of antibiotics and WBC has excellent fit and discrimination,providing an effective quantitative tool for prognosis assessment of IM.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

OBJECTIVE To investigate the changes in high performance liquid chromatography （HPLC） fingerprint spectra and nucleoside components between Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and its processed product Succus bambusae pinella preparata， providing a reference for the quality evaluation of the latter. METHODS HPLC fingerprint was established for 10 batches of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and its processed product Succus bambusae pinella preparata following the Similarity Evaluation System of TCM Chromatographic Fingerprints （2012 Edition）. Hierarchical cluster analysis （HCA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS- DA） were conducted on their common peaks. The contents of four nucleoside components， hypoxanthine， uridine， adenine， and guanosine， in both Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata were determined. RESULTS The similarity between the fingerprints of the 10 batches of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine， Succus bambusae pinella preparata， and their corresponding reference fingerprints ranged from 0.851 to 0.990. A total of 10 common peaks were obtained for both samples， and 4 components were identified as hypoxanthine， uridine， adenine， and guanosine. The results of HCA， PCA and OPLS-DA showed that the samples of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata were clustered into separate categories， with OPLS-DA selecting 4 differential components between them， ranked by variable importance projection values as peak 8， peak 1， peak 6 （adenine） and peak 10. The content determination results showed that the average contents of hypoxanthine， uridine， adenine and guanosine in Succus bambusae pinella preparata declined by 15.90%， 12.00%， 26.04% and 22.18% compared to Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine， respectively， with statistically significant differences in the contents of hypoxanthine， adenine and guanosine （P＜0.05 or P＜0.01）. CONCLUSIONS The established fingerprint and content determination methods are simple to operate and have good repeatability， which are suitable for qualitative and quantitative analysis of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata. The average contents of the four nucleoside components decreased after the processing of Succus bambusae pinella preparata.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective:To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province.Methods:Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden.Results:From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women.Conclusions:The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.