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 analyze the clinical characteristics of mycoplasma pneumoniae pneumonia(MPP)in children with atopic constitution and exploring the predictors of disease conditions.Methods A total of 250 children diagnosed with MPP in the Department of Pediatric Respiratory Medicine,Xinhua Hospital,Shanghai Jiaotong University School of Medicine from September 2019 to September 2022 were selected and divided into atopic group(n=149)and non-atopic group(n=101)according to whether they were atopic,to explore the clinical characteristics of MPP in children with atopic constitution and the risk factors of severe mycoplasma pneumoniae pneu-monia(SMPP).The efficacy of the combined test of lactate dehydrogenase(LDH),immunoglobulin E(IgE)and serum amyloid A(SAA)in predicting the development of SMPP in MPP children with atopic constitution was evaluated by the receiver operating character-istic(ROC)curve.Results Children in the atopic group had more pronounced symptoms of cough,wheezing,nasal congestion,croup,combined pleural effusion with severe pneumonia and the proportion requiring hormone therapy than those in the non-atopic group,and the differences were statistically significant(P＜0.05).Logistic regression analysis showed that serum IgE,SAA and LDH levels were in-dependent risk factors for the development of SMPP in MPP children with atopic constitution(P＜0.05);ROC curve analysis showed that the combined test of IgE,LDH and SAA could be used to predict the development of SMPP in MPP children with atopic constitution,with an area under the curve(AUC)of 0.881,sensitivity of 81.0％,and specificity of 85.0％.Conclusion MPP children with atopic con-stitution are more likely to develop SMPP and require hormone therapy.The combined detection of serum IgE,SAA and LDH can effec-tively predict the occurrence of SMPP in MPP children with atopic constitution.

Objective:To investigate the effects of bisphenol A(BPA)on the proliferation activity and stemness characteristics of endometrial mesenchymal stem/stromal cells(eMSCs),and to elucidate the improvement effect of human umbilical cord mesenchymal stem cell-derived supernatant(hUCMSC-Sup)on the cell injury.Methods:The eMSCs were cultured in vitro and treated with different concentrations of BPA(0,200,250,300,350,and 400 μmol·L-1).The eMSCs were divided into control group(only cultured with culture solution),BPA group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA),BPA+hUCMSC-Sup group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA and 50%volumetric ratio of hUCMSC-Sup),and BPA+CHIR-99021 group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA and 10 μmol·L-1 CHIR-99021).The survival rates of eMSCs in various groups were detected by methyl thiazolyl tetrazolium(MTT)assay.The numbers and diameters of the spheroids in various groups were detected by spheroids formation assay,the proliferation activities of the cells in eMSCs stem cell spheroids in various groups were detected by CCK-8 assay;the percentage of CD73+cells in eMSCs in various groups were detected by flow cytometry;the expression levels of sex determining region Y-box 2(Sox2),octamer-binding transcription factor 4(Oct4),and Nanog mRNA in the eMSCs in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method,the expression levels of β-catenin protein in the eMSCs in various groups were detected by Western blotting method.Results:The MTT results showed that after treated with BPA for 24 and 48 h,compared with 0 μmol·L-1 BPA group,the survival rates of eMSCs in 200,250,300,350,and 400 μmol·L-1 BPA groups were significantly decreased(P<0.01).At 24 and 48 h after treatment,compared with control group,the survival rate of the eMSCs in BPA group was significantly decreased(P<0.01);at 48 h after treatment,compared with BPA group,the survival rate of the eMSCs in BPA+hUCMSC-Sup group was significantly inereased(P<0.05).The spheroids formation assay results showed that compared with culture 3 d group,the numbers and diameters of stem cell spheroids of the eMSCs in culture 4 d group and culture 5 d group were significantly increased(P<0.05 or P<0.01);compared with control group,after 48 h of culture,the number and diameter of the cells in eMSCs stem cell spheroids in BPA group were significantly decreased(P<0.05 or P<0.01).The CCK-8 results showed that after 24 and 48 h of treatment,compared with control group,the proliferation activity of the cells in eMSCs stem cell spheroids in BPA group was significantly decreased(P<0.01);compared with BPA group,the proliferation activity of the cells in eMSCs stem cell spheroids in BPA+hUCMSC-Sup group was significantly increased(P<0.01).The flow cytometry results showed that compared with control group,the percentage of the CD73+cells in the eMSCs in BPA group was significantly decreased(P<0.01);compared with BPA group,the percentage of the CD73+cells in eMSCs in BPA+hUCMSC-Sup group was significantly increased(P<0.01).The RT-qPCR results showed that compared with control group,the expression levels of Sox2,Oct4,and Nanog mRNA in the cells in BPA group were significantly decreased(P<0.01);compared with BPA group,the expression levels of Sox2,Oct4,and Nanog mRNA in the cells in BPA+hUCMSC-Sup group and BPA+CHIR-99021 group were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression level of β-catenin protein in the eMSCs in BPA group was significantly decreased(P<0.01);compared with BPA group,the expression levels of β-catenin protein in the eMSCs in BPA+hUCMSC-Sup group and BPA+CHIR-99021 group were signifrcantly inereased(P<0.01).Conclusion:BPA can inhibit the stemness characteristics of the eMSCs,and injury the self-renewal and repair of endometrium;its mechanism may be related to down-regulating the activity of Wnt/β-catenin signal pathway in the cells.hUCMSC-Sup can promote the proliferation of injured eMSCs,and has improvement effect on the stemness injury induced by BPA.

【Objective】 To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). 【Methods】 A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). 【Results】 Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P<0.05) and history of infection within 30 days before transplantation (OR 3.37, 95% CI 1.59-7.17, P<0.05) may be independent risk factors for CRE intestinal colonization. Of the 95 CRE strains, the top five species were carbapenem-resistant Klebsiella pneumoniae (38/95, 40.0%), carbapenem-resistant Escherichia coli (29/95, 30.5%), carbapenem-resistant Enterobacter cloacae (13/95, 13.6%), carbapenem-resistant Klebsiella acidophilus (6/95, 6.3%) and carbapenem-resistant Proteus mirabilis (3/95, 3.1%). The incidence of post-transplant BSI was 12.0% (29/241) in the CRE-colonized group and 3.3% (8/241) in the non-colonized group. In the colonization group, 100% of the pathogens of BSI were identical with those of CRE colonization. 【Conclusion】 Bacterial culture of anal swab during haplo-HSCT is helpful for detection of CRE colonization in intestinal tract, which provides some clinical basis for active monitoring of key flora, prevention and control of infection.

Activity-based protein profiling(ABPP)and affinity-based protein profiling(AfBPP)are reliable chemical proteomics techniques that exhibit significant advantages in identifying the direct acting targets of small molecule drugs and toxicants,which can help researchers understand the pharmaco-logical and toxicological mechanisms of active small molecules.This paper introduces ABPP and AfBPP technologies and summarizes the applications of this technique in drug off-target effect and target iden-tification of toxicants in recent years,such as drug off-target effect of crenolanib,BIA 10-2474,orlistat and target identification of VX,fenitrothion,acrolein.It is hoped that this review will give readers a better idea of ABPP/AfBPP and offer a line of thinking for researchers in the fields of pharmacology,toxicology and chemical biology.

Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention, which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6 (Ce6), hydrophilic chemotherapeutic drug berberrubine (BBR) and matrix metalloproteinase-2 (MMP-2) response peptide (PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6 (BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine (PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively, we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect.

Objective:To evaluate the effect of general anesthesia on microelectrode recording (MER) during deep brain stimulation (DBS) of subthalamic nucleus (STN) in the patients with primary Parkinson′s disease (PD).Methods:Forty-four patients of both sexes with primary PD (duration of disease ≥ 5 yr and/or obvious symptom fluctuation), undergoing bilateral STN DBS from March 2008 to March 2018, aged<80 yr, were selected and divided into 2 groups by a random number table method: awake group ( n=26) and general anesthesia group ( n=18). In awake group, 0.5% ropivacaine was used for incision infiltration at skin incision.Patients in GA group received propofol and remifentanil by target-controlled infusion with Narcotrend to monitor the depth of anesthesia, and 0.5% ropivacaine was used for incision infiltration at skin incision.The total number of trajectories and length of STN were recorded during MER.Movement disorders were evaluated at 1 week before surgery and 6 months after surgery, and the improvement rate of dyskinesia was calculated.The postoperative anesthesia-, hardware- and stimulation-related complications were recorded. Results:There were no significant differences between the two groups in the total number of trajectories, length of STN and improvement rate of postoperative movement disorders ( P>0.05). Conclusion:General anesthesia does not affect the MER during STN DBS in the patients with primary PD.

Objective    To investigate the feature of the angulation between left pulmonary artery (LPA) and main pulmonary artery (MPA) and its relationship to pulmonary artery development in patients with tetralogy of Fallot (TOF). Methods    A total of 101 TOF patients in West China Hospital from 2014 to 2018 were enrolled in a TOF group, including 62 males and 39 females, aged 6.8 (0.3-45.8) years, and another 20 patients without basic cardiac diseases at the same stage were enrolled in a control group, including 10 males and 10 females, aged 6.9 (0.3-54.0) years. Diameters of LPA, right pulmonary artery (RPA) and MPA, the angulation between LPA and MPA (MPA-LPA), McGoon ratio, and Nakata index were measured and compared between the two groups. The relationship between the above data and MPA-LPA angulation was also analyzed. Results    The average MPA-LPA angulation was smaller in the TOF group than that in the control group (113.63° vs. 128.45°, P=0.001 8). The MPA Z score was also smaller in the TOF group than that in the control group (0.46 vs. 2.75, P=0.000 4). No relationship was found by correlation analysis between the MPA-LPA angulation and MPA Z score or LPA Z score in the control group (P=0.239 6, 0.114 7) and the TOF group (P=0.759 3, 0.242 7). The McGoon ratios (2.22±0.72, 2.43±0.94, P=0.340 0) and Nakata index (359.3±294.24, 395.52±329.31, P=0.650 0) were not significantly different between the two groups. Conclusion    The angulation of LPA-MPA and MPA Z score are smaller in the TOF group than those in the control group. There is no relationship between MPA-LPA angulation and pulmonary artery diameters. The LPA-MPA angulation should not be considered as an influence factor for LPA development and trans-annular patch surgery.

Schizophrenia is a common severe mental illness with unknown etiology, 1/7-1/3 of which onset in children and adolescents. The treatment of childhood schizophrenia is more difficult,and the prognosis is even worse,so the early identification and timely intervention has great significance. Event-relat-ed potentials ( ERPs) are bioelectrical activities that occur in the brain during external or internal stimuli. They reflect the electrophysiological changes in the brain during cognitive activity. In recent years,scholars at home and abroad have tried to find biomarkers of early identification of childhood schizophrenia through ERPs. The main contents include:error related negativity (ERN),mismatched negativity (MMN),N100, P300 and so on.It was found that children and adolescents with schizophrenia prodromal symptoms and high-risk children and adolescents have decreased ERN,MMN,N100,P300 amplitudes,and prolonged P300 laten-cy. However,some of these results are still lack of consistency and need further research. And combined with brain imaging and molecular biology for clinical validation,it will be more helpful to the early identification of childhood schizophrenia.