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*

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective To develop a rehabilitation nursing model for knee osteoarthritis(KOA)of external treatment in traditional Chinese medicine(TCM).Methods Between February and June 2023,a preliminary KOA rehabilitation nursing model was developed through literature search and semi-structured interview method.Two rounds of Delphi consultations were conducted with the selected experts,to establish a rehabilitation nursing model for KOA of TCM external treatment.Results A total of 24 experts from different regions participated in the consultation.The final rehabilitation nursing model of TCM external treatment for KOA included 3 primary indicators,16 secondary indicators and 91 tertiary indicators.The response rates from the two rounds of expert consultation were 96.00%and 100.00%,respectively,and the rates of expert opinion proposal were 58.33%and 8.33%,respectively.The expert authority coefficient were 0.906 and 0.923.The two rounds of expert consultation were 0.137 and 0.236 in Kendall's coefficient of concordance(W),with statistically significant differences(both P<0.001).The importance scores of each item in the second inquiry ranged from 3.75 to 4.88,and the coefficient of variation ranged from 0.07 to 0.30,and the full score ratio ranged from 20.83%to 87.50%.Conclusion The rehabilitation nursing model for KOA of TCM external treatment developed in this study is significant,scientific and feasible.It provides a guidance for medical professionals.

Objective To investigate the correlation between PPARγ and female interstitial cystitis/bladder pain syndrome (IC/BPS) and to establish a predictive model. Methods Clinical data were collected from 89 female IC/BPS patients (observational group) admitted to the hospital from June 2022 to December 2023,and 90 healthy female volunteers undergoing physical examinations during the same period (control group). Plasma levels of inflammatory factors,total antioxidant capacity (TAC),total glutathione (GSH),malondialdehyde (MDA),and PPARγ levels were measured. Significant clinical features were identified using LASSO regression and fitted into a multivariate logistic regression model. The diagnostic efficacy was assessed through receiver operat-ing characteristic (ROC) curves. Results Compared to the control group,the observation group exhibited signifi-cantly elevated age,BMI,NLR,absolute neutrophil count,IFN-α,IL-1β,IL-6,IL-8,TNF-α and CD3+CD4+T expression levels,while absolute lymphocyte count,IL-10,TAC,GSH and plasma PPARγ expression levels were significantly decreased (all P<0.05). LASSO regression identified 8 variables,including NLR,IFN-α,absolute neutrophil count,IL-1β,IL-6,TNF-α,CD3+CD4+T and PPARγ,which were incorporated into the predictive model. Multivariate binary logistic regression analysis revealed that elevated levels of IL-1β,TNF-α and CD3+CD4+T cells,along with reduced PPARγ levels,were independent risk factors for IC/BPS. ROC curve analy-sis indicated that the diagnostic efficacy of the combined PPARγ and clinical parameters (age,IL-1β,TNF-α and CD3+CD4+T) (AUC=0.901) was superior to PPARγ alone (AUC=0.839). Conclusion Plasma PPARγ levels are significantly reduced in female IC/BPS patients and serve as a potential diagnostic marker,with combined clinical parameters enhancing diagnostic accuracy.

Objective:To reassess the pathogenicity of copy number variants (CNVs) involving chromosomal microdeletions and microduplications classified as variants of uncertain significance (VUS).Methods:This retrospective study analyzed 1 882 pregnant women who underwent invasive prenatal diagnosis for chromosomal microarray analysis (CMA) at the First Medical Center, Chinese PLA General Hospital between January 1, 2018, and December 31, 2022. The results were classified according to the American College of Medical Genetics and Genomics guidelines, with 82 fetuses rated as VUS selected for the study. We analyzed invasive prenatal diagnostic indications, followed up on fetal ultrasound findings, parental origin identification results, and pregnancy outcomes, and reclassified VUS CNVs based on the latest evidence. Descriptive statistical analysis was applied to the data.Results:(1) Among the 82 fetuses with VUS CNVs, prenatal diagnostic indications included fetal structural abnormalities detected by ultrasound (21 cases, 25.6%), abnormal non-invasive prenatal testing (NIPT) results (12 cases, 14.6%), high-risk serum screening (seven cases, 8.5%), advanced maternal age (≥35 years at expected delivery, 28 cases, 34.1%), and other indications (14 cases, 17.1%). Sixteen cases (19.5%) exhibited abnormal phenotypes, with seven pregnancies terminated due to severe structural abnormalities detected by prenatal ultrasound. Seventy-five live births were followed up for 25 (13-66) months. (2) Among the 82 cases, five fetuses had two VUS CNVs detected by CMA, while the remaining 77 had only one, totaling 87 VUS CNVs. Of these, 63 (72.4%) were chromosomal microduplications and 24 (27.6%) were chromosomal microdeletions. The size of the CNV segments ranged from 0.85 (0.05-5.61) Mb, with 82 segments less than 2 Mb. Parental origin identification was refused by 44 cases (53.7%), while 38 (46.3%) underwent the test, revealing eight (21.0%) de novo variants and 30 (78.9%) inherited from either parent (12 maternal and 18 paternal). (3) Among the 87 VUS CNVs, the ratings of 11 CNVs (12.6%) changed after re-evaluation. This included one 4p16.2 microdeletion and two 15q11.2 microdeletions being upgraded to pathogenic, one 16p13.11 microduplication being upgraded to likely pathogenic, one Xp22.31 microduplication and two 2q13 microdeletions being downgraded to likely benign, and four Xp22.31 microduplications being downgraded to benign. (4) Among the 16 fetuses with abnormal phenotypes, seven with prenatal abnormalities terminated pregnancies, including six with structural abnormalities and one with severe fetal growth restriction. After re-evaluation, one case was upgraded to pathogenic, while six remained VUS. Nine live births with postnatal abnormal phenotypes showed no change in classification after re-evaluation. Among the 66 cases (80.5%) without abnormal phenotypes, 10 had their classifications changed after re-evaluation. Conclusions:Fetuses with VUS CNVs often exhibit no significant abnormal phenotypes and have a relatively favorable prognosis, however, further floow-up is still needed. Parental origin identification can provide valuable insights for genetic counseling.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Traditionally, type 2 diabetes was regarded as a chronic, progressive metabolic disorder, with its pathogenesis considered a continuous and irreversible process. However, with advancements in diabetes research, treatment options have become more diverse, offering the potential for " diabetes remission". Achieving remission holds substantial significance for patients, their families, and society as a whole. This article provides an overview of the latest research progress on the remission of type 2 diabetes mellitus.

Objective To investigate the correlation between PPARγ and female interstitial cystitis/bladder pain syndrome (IC/BPS) and to establish a predictive model. Methods Clinical data were collected from 89 female IC/BPS patients (observational group) admitted to the hospital from June 2022 to December 2023,and 90 healthy female volunteers undergoing physical examinations during the same period (control group). Plasma levels of inflammatory factors,total antioxidant capacity (TAC),total glutathione (GSH),malondialdehyde (MDA),and PPARγ levels were measured. Significant clinical features were identified using LASSO regression and fitted into a multivariate logistic regression model. The diagnostic efficacy was assessed through receiver operat-ing characteristic (ROC) curves. Results Compared to the control group,the observation group exhibited signifi-cantly elevated age,BMI,NLR,absolute neutrophil count,IFN-α,IL-1β,IL-6,IL-8,TNF-α and CD3+CD4+T expression levels,while absolute lymphocyte count,IL-10,TAC,GSH and plasma PPARγ expression levels were significantly decreased (all P<0.05). LASSO regression identified 8 variables,including NLR,IFN-α,absolute neutrophil count,IL-1β,IL-6,TNF-α,CD3+CD4+T and PPARγ,which were incorporated into the predictive model. Multivariate binary logistic regression analysis revealed that elevated levels of IL-1β,TNF-α and CD3+CD4+T cells,along with reduced PPARγ levels,were independent risk factors for IC/BPS. ROC curve analy-sis indicated that the diagnostic efficacy of the combined PPARγ and clinical parameters (age,IL-1β,TNF-α and CD3+CD4+T) (AUC=0.901) was superior to PPARγ alone (AUC=0.839). Conclusion Plasma PPARγ levels are significantly reduced in female IC/BPS patients and serve as a potential diagnostic marker,with combined clinical parameters enhancing diagnostic accuracy.

Objective To develop a rehabilitation nursing model for knee osteoarthritis(KOA)of external treatment in traditional Chinese medicine(TCM).Methods Between February and June 2023,a preliminary KOA rehabilitation nursing model was developed through literature search and semi-structured interview method.Two rounds of Delphi consultations were conducted with the selected experts,to establish a rehabilitation nursing model for KOA of TCM external treatment.Results A total of 24 experts from different regions participated in the consultation.The final rehabilitation nursing model of TCM external treatment for KOA included 3 primary indicators,16 secondary indicators and 91 tertiary indicators.The response rates from the two rounds of expert consultation were 96.00%and 100.00%,respectively,and the rates of expert opinion proposal were 58.33%and 8.33%,respectively.The expert authority coefficient were 0.906 and 0.923.The two rounds of expert consultation were 0.137 and 0.236 in Kendall's coefficient of concordance(W),with statistically significant differences(both P<0.001).The importance scores of each item in the second inquiry ranged from 3.75 to 4.88,and the coefficient of variation ranged from 0.07 to 0.30,and the full score ratio ranged from 20.83%to 87.50%.Conclusion The rehabilitation nursing model for KOA of TCM external treatment developed in this study is significant,scientific and feasible.It provides a guidance for medical professionals.