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*

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

ObjectiveTo investigate the possible mechanism of Huatan Sanjie Formula （化痰散结方， HSF） in treating Graves' disease （GD） from the perspective of thyroid angiogenesis. MethodsThirty-six BALB/c female mice were randomly divided into a normal control group （n=9） and a modeling group （n=27）. Mice in the modeling group were injected with 2.0×10⁹ PFU/ml of Ad-TSHR289 adenovirus into the tibialis anterior muscle to build GD model. Nine weeks after immunization， the successfully modeled mice were randomly divided into model group， methimazole （MMI） group and HSF group， with 9 mice in each group. The MMI group was given 5.2 mg/（kg·d） of methimazole tablets by gavage， while the HSF group was given HSF at a relative crude drug dosage of 7.02 g/（kg·d） by gavage. The normal control group and the model group were given 0.1 ml/10 g of pure water by gavage. All groups were administered intragastrically once a day for a total of 4 weeks. The levels of thyroxine （T4） and thyrotropin receptor autoantibodies （TRAb） in serum were detected by radioimmunoassay， while the pathological changes of the thyroid gland were assessed by HE staining. The vascular morphology of thyroid tissue was observed by CD34 immunohistochemical staining， and the microvessel density （MVD） was counted. The protein expression of vascular endothelial growth factor A （VEGFA） and vascular endothelial growth factor receptor 2 （VEGFR2） in thyroid was detected by Western-blot. ResultsCompared to those in the normal control group， the thyroid volume of the mice in the model group significantly increased with excessive congestion， and the pathology showed significant thyroid follicular hyperplasia， columnar and proliferated epithelial cells， and enlarged follicle size； serum T4 and TRAb significantly increased， as well as the count of thyroid MVD， and the protein expressions of thyroid VEGFA and VEGFR2 （P＜0.01）. Compared to those in the model group， the thyroid glands of the mice in the MMI group and the HSF group were significantly reduced， and the congestion was improved； pathology showed that thyroid follicular hyperplasia and epithelial cell proliferation were reduced， with smooth edges of the follicles and the significantly reduced inward protrusion； serum T4 and TRAb significantly decreased， as well as the thyroid MVD， thyroid VEGFA and VEGFR2 protein expressions （P＜0.05 or P＜0.01）. There was no significant difference in all indicators between the MMI group and the HSF group （P＞0.05）. ConclusionHSF may inhibit thyroid angiogenesis by down-regulating thyroid VEGFA/VEGFR2 signaling pathway， thereby improving goitre and hyperfunction in GD mice.

Objective:To find benefit of adaptive challenges in age-related macular degeneration (AMD) patients of long-term treatment in the challenge of vision decline, and provide new ideas for improving the quality of life of patients.Methods:It was a phenomenological study from qualitative research, selected by purpose sampling method and semi-structured interview which involved 20 AMD patients who received intravitreal treatment of drug in the Ophthalmology Department of Affiliated Hospital of Nantong University from January to March 2023.Two interviewees comprehensively read and analyzed the transcript of the interview and its meaning, subsequently Colaizzi seven-step analysis method was used to classify and encode the transcribed data.Results:Among 20 patients, there were 9 males and 11 females, aged 56-81 years old. Patients with AMD experience a sense of benefit in their long-term management of the condition, adapting to the challenges posed by declining strength, which could be summarized into four main themes: moderate sense of decision control, satisfactory social support, active self-management of the disease, and an improvement in quality of life.Conclusions:Patients with AMD experience a sense of disease-related benefit during the long-term management of visual acuity challenges. Healthcare professionals should guide patients to seek this benefit from adverse events, identify the adaptive challenges patients face, and leverage their adaptive leadership skills. Furthermore, offering multi-channel low vision rehabilitation services can assist patients in enhancing their adaptive capabilities, ultimately contributing to further improving their quality of life.

Driven by multiple factors such as policy incentives,enhanced economic capacity of residents,aging popula-tion,and medical system reform,China's rehabilitation industry has been in a rapid development stage where opportunities and challenges coexist.Various rehabilitation hospitals urgently need new development thinking on how to seize the new opportunities for the development of rehabilitation medicine,give full play to the benefits of high-quality rehabilitation medical resources,and deal with the development of rehabilitation institutions under the new situation.Taking the tertiary rehabilitation hospital where the authors work as an example,this paper deeply analyzes the practical difficulties and challenges faced by the development of reha-bilitation hospital under the new circumstance,further explores the construction of a new working mode based on people-oriented and medical-rehabilitation integration.It also briefly summarizes the beneficial experiences and practices in the reform of rehabili-tation service models,and elaborates on the periodic achievement,so as to provide a meaningful reference for the majority of re-habilitation hospitals to plan and practice high-quality development and reform.

Objective To observe the effects of Daizong Prescription on glycogen metabolism in adipose tissue of obese mice;To explore its regulatory mechanism in activating browning in the white adipose tissue.Methods A obesity model was established by feeding high-fat diet to C57BL/6J mice.The obese mice were divided into model group,metformin group(0.15 g/kg),and Daizong Prescription low-(0.20 g/kg)and high-dosage(0.40 g/kg)groups.Mice fed a standard diet were set as the normal group,with 12 mice in each group.Each medication group was given corresponding drugs by gavage for 6 consecutive weeks.Body mass and fasting blood glucose were monitored,serum triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)contents were measured.Brown adipose tissue from the interscapular region and white adipose tissue from the inguinal,perirenal and epididymal region were collected,the adipose tissue mass was measured,and the body fat coefficient was calculated.HE staining was performed to observe morphological changes in adipose tissue,PAS staining was used to observe glycogen distribution in adipose tissue,immunohistochemistry staining was performed to detect the expressions of Gys2,Ppp1r3c,and GSK-3β in inguinal white adipose tissue.Results Compared with the normal group,the body mass and fasting blood glucose in different time points of the model group significant increase(P<0.05,P<0.01),and serum TC and HDL-C contents significantly increased(P<0.01);the mass and body fat coefficient of white adipose tissue in inguinal,perirenal,and epididymis significantly increased(P<0.01),the cells in white adipose tissue in inguinal were hypertrophic and appeared as large vacuoles,with less glycogen accumulation,the expressions of Gys2 and Ppp1r3c significantly decreased(P<0.01).Compared with the model group,the mice in Daizong Prescription high-dosage group showed a significant decrease in body mass and fasting blood glucose at 4 and 6 weeks of administration(P<0.05,P<0.01),and the contents of serum TG,TC,HDL-C,and LDL-C were significantly decreased(P<0.01);the mass and body fat coefficient in white adipose tissue of perirenal and epididymal significantly decreased(P<0.05,P<0.01),and the mass of inguinal white adipose tissue significantly decreased(P<0.05),multiple irregularly shaped small vacuoles could be seen in inguinal white adipose tissue,accompanied by nuclear aggregation and increased glycogen accumulation,the expressions of Gys2 and Ppp1r3c significantly increased(P<0.01).There was no significant difference in the expression of GSK-3β inguinal white adipose tissue of mice among the groups.Conclusion Daizong Prescription can increase the activity of Gys2 by upregulating the expression of Ppp1r3c,promote glycogen synthesis,induce browning of adipose tissue,increase fat heat production,and improve obesity and related disorders of glycolipid metabolism.

Objective:To discuss the effect of Aspergillus fumigatus(Af)on DNA damage and interleukin(IL)-33 expression in the human bronchial epithelial cells,and to clarify its related mechanism.Methods:Different concentrations(1,5,and 10 mg·L-1)of Af were used to stimulate the bronchial epithelial BEAS-2B cells to select the appropriate stimulation concentration.When the BEAS-2B cells were treated with N-acetylcysteine(NAC)and Af,the cells were divided into control group,Af group,NAC group,and Af+NAC group.When the BEAS-2B cells were treated with DNA double-strand break repair inhibitor NU7441 and Af,the cells were divided into control group,Af group,NU7441 group,and Af+NU7441 group.The comet assay was used to detect the percentages of comet tail DNA of cells in various groups;immunofluorescence method was used to detect the expression levels of DNA damage-related protein phosphorylated H2AX(yH2AX)in the cells in various groups;2,7-dichlorofluorescein diacetate(DCFH-DA)fluorescence probe was used to detect the levels of reactive oxygen species(ROS)in the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of interleukih-33(IL-33),thymic stromal lymphopoietin(TSLP),and interleukih-25(IL-25)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of phosphorylated nuclear factor κB(p-NF-κB),phosphorylated ataxia telangiectasia mutated(p-ATM),and γH2AX proteins in the cells in various groups.Results:Compared with control group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 1 mg·L-1 Af group showed no significant difference(P＞0.05),while the percentage of comet tail DNA and the expression level of γH2AX in the cells in 5 mg·L-1 Af group were significantly increased(P＜0.01);compared with 5 mg·L-1 Af group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 10 mg·L-1 Af group were significantly increased(P＜0.01).Compared with control group,the ROS levels in the bronchial epithelial cells in 1 mg·L-1 Af group was significantly increased(P＜0.05);compared with 1 mg·L-1 Af group,the ROS level in the cells in 5 mg·L-1 Af group was significantly increased(P＜0.01);compared with 5 mg·L-1 Af group,the ROS level in the cells in 10 mg·L-1 Af group was significantly increased(P＜0.05).After treatment of NAC,compared with Af group,the percentage of comet tail DNA(P＜0.01),the expression level of γH2AX(P＜0.05),and the ROS level(P＜0.01)in the cells in Af+NAC group were significantly decreased;after treatment of NU7441,compared with Af group,the percentage of comet tail DNA and the expression level of yH2AX in the cells in Af+NU7441 group were significantly increased(P＜0.01).The RT-qPCR results showed that after treatment of NAC,compared with control group,the expression level of IL-33 mRNA in the cells in Af group was significantly increased(P＜0.05);compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NAC group was significantly decreased(P＜0.05);after treatment of NU7441,compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NU7441 group was significantly increased(P＜0.05).The Western blotting results showed that after treatment of NAC,compared with control group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af group were significantly increased(P＜0.05);after treatment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NAC group were significantly decreased(P＜0.05);After treat ment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NU7441 group were significantly increased(P＜0.05).Conclusion:Af promotes the IL-33 expression in the human bronchial epithelial cells by causing DNA damage,and its mechanism may be related to the activation of ATM/NF-κB signaling pathway.

Objective:To evaluate inflammation early in the infarct zone and its dynamic changes after acute myocardial infarction (AMI) using 18F-FDG PET imaging, and analyze its relationship with left ventricular remodeling progression (LVRP). Methods:Sixteen Bama miniature pigs (4-6 months old, 8 females) were selected. AMI models were established by balloon occlusion of the left anterior descending artery. 18F-FDG PET imaging was performed before AMI and at days 1, 5, 8, and 14 post-AMI to evaluate the regional inflammation response. 18F-FDG SUV ratio (SUVR) and the percentage of uptake area of left ventricle (F-extent) in the infarct zone, and the SUVRs of the spleen and bone marrow, were measured. Echocardiography and 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT myocardial perfusion imaging (MPI) were performed at the above time points and on day 28 post-AMI to assess left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and myocardial perfusion defect extent. The degree of LVRP at day 28 post-AMI was defined as ΔLVESV(%)=(LVESV AMI 28 d-LVESV AMI 1 d)/LVESV AMI 1 d×100%. Data were analyzed using repeated measures analysis of variance, Kruskal-Wallis rank sum test and Pearson correlation analysis. Results:Twelve pigs were successfully modeled and completed the study. Inflammation in the infarct zone persisted until day 14 post-AMI. The SUVR of the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 1.03±0.08, 3.49±1.06, 2.93±0.90, 2.38±0.76, and 1.63±0.62, respectively ( F=49.31, P<0.001). The F-extent values in the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 0, (40.08±12.46)%, (40.00±12.76)%, (31.08±12.82)%, and 16.50%(7.25%, 22.00%), respectively ( H=37.61, P=0.001). There were no significant differences in the SUVRs of bone marrow and spleen before and after AMI ( F values: 0.69 and 0.77, both P>0.05). At day 1 post-AMI, both SUVR and F-extent in the infarct zone were significantly correlated with LVRP ( r values: 0.82 and 0.70, P values: 0.001 and 0.035). Conclusions:18F-FDG PET imaging can be used to evaluate inflammation in the infarct area and its dynamic changes after AMI. Inflammation in the infarct area is severe at day 1, and then gradually decreases. The extent and severity of inflammation visible on 18F-FDG PET imaging 1 d after AMI are closely related to LVRP.