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*

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Objective To investigate the characteristics of thickness changes in peripapillary retinal nerve fiber layer(pRNFL)and identify related risk factors in patients with Moyamoya disease(MMD).Methods A retrospective study was conducted on 150 MMD patients(150 eyes)aged 6-65 years admitted to the Neurosurgery Department of the Fifth Medical Center,Chinese PLA General Hospital from May 2016 to December 2023(observation group),and 150 age-matched healthy volunteers(150 eyes)from the hospital's ophthalmology outpatient department(control group).Both groups were subdivided into pediatric(≤18 years),young adult(18-40 years),and middle-aged(40-65 years)subgroups.The pRNFL thickness in four quadrants was measured by optical coherence tomography(OCT):superior(pRNFL-Sup),inferior(pRNFL-Inf),nasal(pRNFL-Nas),temporal(pRNFL-Tmp),and average thickness(pRNFL-Avg).General clinical data and pRNFL thickness were compared between two groups.Univariate and multivariate logistic regression analyses were performed to identify risk factors for pRNFL thinning in MMD patients.The cohort was randomly divided into training(n=210)and validation(n=90)sets at a 7:3 ratio.A predictive model for pRNFL thinning in MMD patients was constructed based on logistic regression results.Model performance was evaluated using the area under the receiver operating characteristic curve(AUC),and clinical utility was assessed via decision curve analysis.Results Compared with control group,MMD patients exhibited significantly reduced pRNFL-Avg,pRNFL-Sup,pRNFL-Tmp,and pRNFL-Inf thickness(P<0.05 or P<0.001),while pRNFL-Nas showed no significant difference(P>0.05).In the pediatric subgroup,pRNFL-Avg and pRNFL-Inf were thinner(P<0.05).In the young adult subgroup,pRNFL-Avg and pRNFL-Sup were reduced(P<0.001 or P<0.05).In the middle-aged subgroup,pRNFL-Avg,pRNFL-Sup,pRNFL-Inf,and pRNFL-Tmp were all thinner(P<0.05 or P<0.001).Multivariate logistic regression identified visual field defects(OR=15.28,95%CI 2.95-79.10),disease duration(OR=1.11,95%CI 1.05-1.18),and the number of involved cerebral vessels(OR=1.49,95%CI 1.01-2.22)as independent risk factors for pRNFL thinning.The predictive model achieved AUC of 0.94(95%CI 0.91-0.97)and 0.95(95%CI 0.91-0.99)in the training and validation sets,respectively.Decision curve analysis confirmed the model's favorable clinical net benefit.Conclusion Thinning of pRNFL was observed in Moyamoya disease patients with visual field defects,disease duration,and cerebral vascular involvement identified as independent risk factors for pRNFL atrophy.

Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

Objective To establish a stable liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for detecting gamma-aminobutyric acid(GABA)in plasma,and to evaluate the value of GABA detection in the diagnosis of sleep disorders.Methods GABA was detected using a UPLC Xevo TQs system.The method was pre-validated and its performance was verified to establish a reference range for healthy individuals.The difference in plasma GABA levels between apparently healthy individuals and patients with sleep disorders was compared.Results We employed deuterated compounds as isotopic internal standards and utilized an Amide chromatographic column for separation.The mobile phase was 0.050%formic acid in water and 90%acetonitrile in water containing 0.175%formic acid and 5 mmol/L ammonium acetate with gradient elution in the column temperature of 35℃.The linear range for the detection of GABA by LC-MS/MS was 0.05-10.00 μmol/L,with a lower limit of quantification of 0.02 μmol/L,the inter-day CV<3.00%and intra assay CV<4.00%,respectively,and the recovery rate was 101.06%-109.02%.The reference ranges for plasma GABA were established by analyzing 300 healthy controls stratified by age:18-34 years(0.08-0.15 μmol/L),35-49 years(0.10-0.20 μmol/L),and≥50 years(0.12-0.23 μmol/L).Then plasma GABA was used as a biomarker for auxiliary diagnosis of sleep disorders in analyzing 221 patients and 300 healthy controls,which revealed that AUC values were 0.510(P=0.850),0.686(P=0.002),and 0.890(P<0.001)in the groups of 18-34 years,35-49 years,and≥50 years,respectively,with optimal cut-off values of 0.09,0.10 and 0.11 μmol/L.Conclusion A reliable LC-MS/MS method for detecting GABA has been established,which can detect plasma GABA levels sensitively and accurately and can be used in assisting the clinical diagnosis of sleep disorders.

Objective To establish a stable liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for detecting gamma-aminobutyric acid(GABA)in plasma,and to evaluate the value of GABA detection in the diagnosis of sleep disorders.Methods GABA was detected using a UPLC Xevo TQs system.The method was pre-validated and its performance was verified to establish a reference range for healthy individuals.The difference in plasma GABA levels between apparently healthy individuals and patients with sleep disorders was compared.Results We employed deuterated compounds as isotopic internal standards and utilized an Amide chromatographic column for separation.The mobile phase was 0.050%formic acid in water and 90%acetonitrile in water containing 0.175%formic acid and 5 mmol/L ammonium acetate with gradient elution in the column temperature of 35℃.The linear range for the detection of GABA by LC-MS/MS was 0.05-10.00 μmol/L,with a lower limit of quantification of 0.02 μmol/L,the inter-day CV<3.00%and intra assay CV<4.00%,respectively,and the recovery rate was 101.06%-109.02%.The reference ranges for plasma GABA were established by analyzing 300 healthy controls stratified by age:18-34 years(0.08-0.15 μmol/L),35-49 years(0.10-0.20 μmol/L),and≥50 years(0.12-0.23 μmol/L).Then plasma GABA was used as a biomarker for auxiliary diagnosis of sleep disorders in analyzing 221 patients and 300 healthy controls,which revealed that AUC values were 0.510(P=0.850),0.686(P=0.002),and 0.890(P<0.001)in the groups of 18-34 years,35-49 years,and≥50 years,respectively,with optimal cut-off values of 0.09,0.10 and 0.11 μmol/L.Conclusion A reliable LC-MS/MS method for detecting GABA has been established,which can detect plasma GABA levels sensitively and accurately and can be used in assisting the clinical diagnosis of sleep disorders.

ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.

Schizophrenia is a serious mental disorder that is often associated with profound impairment in patients′ daily functioning, and its etiology and pathophysiology are still to be fully elucidated. There is a pathological correlation between inflammation, brain injuries, and the pathogenesis of schizophrenia, with microglia actively participating in these processes. This review provides a comprehensive overview of the impact of microglial cells on neurodevelopment and neuroplasticity, and microglia abnormalities mediating the onset of schizophrenia by contributing to damage in different brain regions.