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*

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.

ObjectiveTo explore the association between short-term exposure to atmospheric fine particulate matter （PM_2.5） and ozone （O₃） and systemic inflammatory indicators in patients with pneumonia， and to identify the susceptible populations. MethodsFrom September 2018 to April 2020， data of 1 480 patients admitted for pneumonia was collected from a tertiary hospital in Taiyuan City. Generalized additive models （GAMs） were used to explore the associations between PM_2.5 and O₃ exposure and inflammatory indicators of patients with pneumonia； and to explore the susceptibility factors and susceptible populations to PM_2.5 and O₃ exposures through stratified analyses. ResultsThe short-term exposure to PM_2.5 was associated with changes in peripheral blood C-reation protein （CRP）， erythrocyte sedimentation （ESR）， easinophil （EOS）， neutrophil （NEU） and neutrophil-lymphocyte ratio （NLR） in patients with pneumonia， and there were different degrees of hysteresis effects， with the effect values reaching a maximum at lag03， lag03， lag0， lag03， lag03， respectively， which were 4.13% （95%CI： 0.43%‒7.84%）， 3.10% （95%CI： 0.24%‒5.97%）， 5.27% （95%CI： 3.12%‒7.42%）， 1.85% （95%CI： 0.36%‒3.34%）， and 2.53% （95%CI： 0.53%‒4.74%） for every 10 μg·m^-3 of PM_2.5. The changes in O₃ concentration were associated with the elevation of peripheral blood PCT and ESR in patients with pneumonia， and their effect values all reached the maximum at lag01 d， every 1 μg·m^-3 of O₃ elevation increased by 0.38% （95%CI： 0.04%‒0.73%） and 0.47% （95%CI： 0.19%‒0.76%）， respectively. Stratified analyses showed that the associations of PM_2.5 with peripheral blood CRP， ESR， NEU， and NLR in pneumonia patients were more significant in males， the elderly， and those with onset in the cold season； the associations of O₃ with peripheral blood PCT and ESR in pneumonia patients were more significant in the elderly and those with onset in the warm season， and the peripheral blood CRP and PCT in female patients with pneumonia were more susceptible to the changes of O₃. ConclusionShort-term exposure to atmospheric PM_2.5 and O₃ are positively associated with changes in inflammatory indicators in patients with pneumonia， and the effects of PM_2.5 on patients with pneumonia are more extensive than those of O₃， with a longer lag effect. In addition， elderly patients with pneumonia are more sensitive to air pollution， male patients with pneumonia are more sensitive to PM_2.5， and female patients with pneumonia are more sensitive to O₃. Cold and warm seasons can exacerbate the effects of PM_2.5 and O₃ on inflammatory indicators in patients with pneumonia， respectively， and the patients must be protected well.

Obese patients may have abnormal metabolism of branched-chain amino acids(BCAA).Elevated levels of BCAA can lead to insulin resistance(IR)through various mechanisms,which may make it a sensitive indicator for predicting the occurrence of diabetes mellitus.This article reviews the research progress on the correlation between BCAA metabolism,obesity and IR.

Objective:To investigate the impact of abnormal patterns of 75 g oral glucose tolerance test (OGTT) in the second trimester on the risk of large for gestational age (LGA) newborn deliveries.Methods:General clinical data and OGTT results of 66 290 pregnant women who received regular prenatal care and delivered in Guangdong Maternal and Child Health Hospital from December 24, 2016 to July 26, 2022 were collected. According to the results of OGTT, the pregnant women were divided into 8 groups: normal blood glucose group (normal fasting blood glucose, 1-hour and 2-hour after oral glucose, 54 518 cases), gestational diabetes mellitus (GDM) 0 group (only abnormal fasting blood glucose, 1 430 cases), GDM 1 group (only abnormal blood glucose at 1-hour after oral glucose, 2 150 cases), GDM 2 group (only abnormal blood glucose at 2-hour after oral glucose, 3 736 cases), GDM 0+1 group (both fasting blood glucose and 1-hour after oral glucose were abnormal, 371 cases), GDM 0+2 group (both fasting blood glucose and 2-hour after oral glucose were abnormal, 280 cases), GDM 1+2 group (abnormal blood glucose at 1-hour and 2-hour after oral glucose, 2 981 cases) and GDM 0+1+2 group (abnormal fasting blood glucose, 1-hour and 2-hour after oral glucose, 824 cases). Multivariate logistic regression was used to analyze the effects of different abnormal OGTT patterns on LGA. In addition, the blood glucose measurements at the three time points of OGTT were combined and used as continuous variables in the receiver operating characteristic (ROC) curve to evaluate the predictive value of each blood glucose measurement mode for LGA and the area under the curve (AUC) was compared.Results:(1) Multivariate logistic regression analysis showed that the risks of LGA were significantly increased in GDM 0 group ( OR=1.76, 95% CI: 1.50-2.08; P<0.001), GDM 0+1 group ( OR=2.29, 95% CI: 1.72-3.04; P<0.001), and GDM 0+1+2 group ( OR=1.98, 95% CI: 1.61-2.43; P<0.001). (2) ROC curve analysis showed that fasting blood glucose, 1-hour after oral glucose, 2-hour after oral glucose, fasting+1-hour after oral glucose, fasting+2-hour after oral glucose, 1-hour+2-hour after oral glucose, and fasting+1-hour+2-hour after oral glucose had certain predictive value for LGA (all P<0.001). The AUC of fasting blood glucose measurement was higher than that of 2-hour blood glucose measurement in predicting LGA, and the difference was statistically significant ( P<0.05). There was no significant difference in the AUC between fasting blood glucose and other blood glucose measurement modes for predicting LGA (all P>0.05). Conclusions:In the abnormal OGTT patterns, pregnant women with abnormal fasting blood glucose, abnormal fasting+1-hour after oral glucose, and abnormal fasting+1-hour+2-hour after oral glucose have an increased risk of LGA. Fasting blood glucose measurement is of great significance for the prediction of LGA, and could be used as an optimal indicator to evaluate the risk of LGA in clinical practice.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Objective:To evaluate oncological and reproductive outcomes of women ≤40 years undergoing fertility-sparing surgery (FSS) for stage Ⅱ or Ⅲ borderline ovarian tumor (BOT).Methods:The patients with BOT and ≤40 years old with stage Ⅱ-Ⅲ BOT who underwent FSS enrolled from the First Affiliated Hospital of Zhengzhou University between January 2011 and March 2023 were analyzed retrospectively. The clinical data and follow-up results were obtained and analyzed. The univariate and multivariate Cox proportional hazard regression analysis were used to explore high-risk factors associated with prognosis. Additionally, pregnancy outcomes were also analyzed.Results:(1) A total of 79 patients with stage Ⅱ-Ⅲ BOT who have been treated with FSS were conducted, with an average age of (27.5±6.7) years old. The median tumor maximum diameter were 10.4 cm (range: 4.8-90.0 cm). The International Federation of Gynecology and Obstetrics (FIGO) stage was stage Ⅱ in 45 cases and stage Ⅲ in 34 cases. According to the pathological types, there were 48 cases of serous tumor, 21 cases of mucinous tumor, 1 case of endometrioid tumor, and 9 cases of mixed types. There were 41 cases of unilateral ovarian involvement, 38 cases of bilateral ovarian involvement. There were 5 cases of microinvasion, 17 cases of micropapillary subtype. Extra-ovarian invasive implants were found in 5 cases, and there were 31 cases of merged ascites. (2) Tumor outcomes: the median follow-up time from primary cytoreduction were 58 months (range: 8-146 months). At the end of the observation period, 24 cases (30%, 24/79) recurred, among them 5 cases had two recurrences and 2 cases had three recurrences. There were 2 cases (3%, 2/79) of death and 1 case (1%, 1/79) of survival with tumor. (3) Analysis of prognostic risk factors: the results of univariate analysis showed that mucinous tumor, tumor maximum diameter >13.15 cm, FIGO stage Ⅲ, merged ascites, micropapillary subtype, invasive implantation, and bilateral ovarian involvement were independent risk factors (all P<0.05) for disease-free survival (DFS). FIGO stage Ⅲ ( HR=4.555, 95% CI: 1.525-13.607; P=0.007) and micropapillary subtype ( HR=2.396, 95% CI: 1.003-5.725; P=0.049) were found to be related to DFS through the multivariable Cox proportional hazard regression analysis. (4) Pregnancy outcomes: among the patients with fertility intentions 36 cases (46%,36/79), 29 cases (81%, 29/36) had successful pregnancies, and 27 cases (75%, 27/36) had successful births. Conclusions:Patients with stage Ⅱ-Ⅲ BOT underwent FSS have favorable survival and pregnancy rates. Micropapillary subtypes and FIGO staging (stage Ⅲ) are the significant risk factors of DFS.

Objective:To explore the genetic etiology for a child with Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 (PEOA6).Methods:A child who had attended the Women and Children′s Hospital Affiliated to Ningbo University on 7 August, 2023 was selected as the study subject. Clinical data of the child were analyzed retrospectively. The child and her parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study was approved by Medical Ethics Committee of the Women and Children′s Hospital Affiliated to Ningbo University (Ethics No. EC2020-048).Results:The child, a 7-year-old female, had presented with limb muscle pain, amyosthenia, significantly increased creatine kinase, congenital diaphragmatic hernia and recurrent respiratory tract infections. WES revealed that she has harbored a heterozygous c. 1590G>C (p.L530F) variant of the DNA2 gene, which was verified to have a de novo origin by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1590G>C was rated as a likely pathogenic variant (PS2+ PM2_Supporting+ PP3). Conclusion:The c.1590G>C (p.L530F) variant of the DNA2 gene probably underlay the PEOA6 in this child.

Objective To investigate the effect and mechanism of emodin on focal cerebral ischemia in rats based on myeloid differentiation factor 88(MyD88)/extracellular signal-regulated kinase(ERK)pathway and nuclear factor-κB(NF-κB)nuclear translocation.Methods SD rats were randomly divided into sham operation group,model group and emodin group,with six rats in each group.The rat model of transient middle cerebral artery occlusion(tMCAO)was established by middle cerebral artery embolization.Rats in the emodin group were given 40 mg·kg-1 emodin by gavage for three times at 72,48 and 24 hours before modeling.At 24 hours after modeling,the neurological function of rats was scored.TTC staining was used to detect the area of cerebral infarction.HE staining was used to observe the morphological changes of brain tissue.The mRNA expression levels of MyD88 and tumor necrosis factor-α(TNF-α)in brain tissue were detected by RT-qPCR.The expression levels of MyD88,ERK,p-ERK and TNF-α in brain tissue were detected by Western Blot.The protein expression of NF-κB in brain tissue was detected by immunofluorescence.Results Compared with the sham operation group,the neurological function score of the model group was significantly increased(P＜0.01),and the cerebral infarction area was significantly increased(P＜0.01).In the cortical area of the ischemic penumbra,cell necrosis,abnormal cell morphology,nuclear fragmentation and atrophy,and the number of cells decreased significantly;the mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly increased(P＜0.01,P＜0.001),the protein levels of MyD88,p-ERK/ERK and TNF-α were significantly increased(P＜0.05,P＜0.01,P＜0.001),and the proportion of NF-κB into nuclear cells was significantly increased(P＜0.001).Compared with the model group,the neurological function score of rats in the emodin group was significantly decreased(P＜0.05),and the area of cerebral infarction was significantly reduced(P＜0.05).The number and morphology of neurons in the ischemic penumbra cortex were restored to a certain extent.The mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly decreased(P＜0.05,P＜0.01),the protein levels of MyD88,p-ERK/ERK and TNF-α were significantly decreased(P＜0.05),and the proportion of NF-κB into nuclear cells was significantly decreased(P＜0.001).Conclusion Emodin has a preventive and protective effect on rats with focal cerebral ischemia,which may be related to its inhibition of MyD88 activation,ERK phosphorylation and NF-κB nuclear translocation,and then down-regulation of inflammatory cascades and secretion of pro-inflammatory factors such as TNF-α,thereby exerting anti-inflammatory effects.