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*

Objective:To evaluate the effect of electroacupuncture (EA) on ionotropic purinergic receptor 4 (P2X4R)/nuclear factor-kappa B (NF-κB) signaling pathway during spinal cord injury (SCI) in rats.Methods:Thirty-six clean-grade healthy adult female Sprague-Dawley rats, weighing 210-250 g, were divided into 3 groups ( n=12 each) using a random number table method: sham surgery group (S group), SCI group, and SCI+ EA treatment group (SCI+ EA group). The SCI model was established by the Allen′s method in anesthetized animals. In group S, only the spinous processes and vertebral laminae were resected, but the spinal cord was not injured. On the 7th day after developing the model, EA of Jiaji, Dazhui, and Mingmen lasting 30 min was performed once a day for 7 consecutive days, with a depth of 2 mm, intensity of 12-15 mV, frequency of 2 Hz, in SCI+ EA group. The mechanical paw withdraw threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before developing the model and 3, 7, 14, 21 and 28 days after developing the model, and the motor function was assessed using the Basso-Beattie-Bresnahan (BBB) score. The recovery of motor function was assessed using footprint analysis at 28 days after developing the model. After the final behavioral testing, the rats were sacrificed, and spinal cord tissues were harvested to observe the pathological changes of the spinal cord tissues using hematoxylin-eosin staining, to detect the expression of P2X4R and phosphorylated NF-κB p65 (p-NF-κB p65) (by immunohistochemical analysis and Western blot) and to determine contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with the baseline measured at 1 day before developing the model, the MWT and BBB scores were significantly decreased and the TWL was shortened at each time point after developing the model in SCI group and SCI+ EA group ( P<0.05). Compared with S group, the MWT and BBB scores were significantly decreased and the TWL was shortened at each time point after developing the model, the expression of P2X4R and p-NF-κB p65 in spinal cord tissues was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI group ( P<0.05). Compared with SCI group, the MWT and BBB scores were significantly increased and the TWL was prolonged at 14, 21 and 28 days after developing the model, the expression of P2X4R and p-NF-κB p65 in spinal cord tissues was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased ( P<0.05), and the pathological damage of spinal cord tissues was alleviated and footprints were reduced in SCI+ EA group. Conclusions:The mechanism by which EA alleviates SCI may be related to the inhibition of the activation of the P2X4R/NF-κB signaling pathway and the reduction in the inflammatory response in rats.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Objective To analyze the influencing factors of death in the elderly with coronavirus disease 2019(COVID-19).Methods The case data of death caused by COVID-19 in West China Fourth Hospital from January 1 to July 8,2023 were collected,and surviving cases from the West China Elderly Health Cohort infected with COVID-19 during the same period were selected as the control.LASSO-Logistic regression was adopted to analyze the data after propensity score matching and the validity of the model was verified by drawing the receiver operating characteristic curve.Results A total of 3 239 COVID-19 survivors and 142 deaths with COVID-19 were included.The results of LASSO-Logistic regression showed that smoking(OR=3.33,95%CI=1.46-7.59,P=0.004),stroke(OR=3.55,95%CI=1.15-10.30,P=0.022),malignant tumors(OR=19.93, 95%CI=8.52-49.23, P<0.001),coronary heart disease(OR=7.68, 95%CI=3.52-17.07, P<0.001),fever(OR=0.51, 95%CI=0.26-0.96, P=0.042),difficulty breathing or asthma symptoms(OR=21.48, 95%CI=9.44-51.95, P<0.001),and vomiting(OR=8.19,95%CI=2.87-23.58, P<0.001)increased the risk of death with COVID-19.The prediction model constructed based on the influencing factors achieved an area under the curve of 0.889 in the test set.Conclusions Smoking,stroke,malignant tumors,coronary heart disease,fever,breathing difficulty or asthma symptoms,and vomiting were identified as key factors influencing the death risk in COVID-19.
Humans ; COVID-19/mortality* ; Aged ; Propensity Score ; China/epidemiology* ; Risk Factors ; Logistic Models ; Smoking ; SARS-CoV-2 ; Male ; Female ; Stroke ; Neoplasms

Objective:To explore the relationship between Epstein-Barr virus (EBV) infection, hepatitis B virus (HBV) reactivation and clinical features and prognosis in HBV-infected non-Hodgkin lymphoma (NHL) patients and influencing factors of HBV reactivation.Methods:A retrospective cohort study was conducted. A total of 80 NHL patients with hepatitis B surface antigen (HBsAg) positive (which was defined as HBV positive) who were admitted to the Second People's Hospital of Lianyungang and Jiangsu Province Hospital from December 2012 to October 2022 were selected. All patients were divided into EBV-positive group and EBV-negative group according to EBV DNA results, and further grouped into the HBV reactivation group and the non-reactivation group according to whether HBV were reactivated after chemotherapy. The clinical characteristics of patients among groups were compared. Multivariate logistic regression model was used to analyze the factors influencing HBV reactivation. The Kaplan-Meier method was used to evaluate the progression-free survival (PFS) and overall survival (OS) of patients, and the log-rank test was used for inter-group comparison.Results:Among NHL patients with HBV positive, 27 cases (33.8%) were EBV-positive and 29 cases (36.3%) were HBV reactivation. Compared with the EBV-negative group, the proportion of patients with Ann Arbor stage Ⅲ-Ⅳ [92.6% (25/27) vs. 66.0% (35/53)], elevated β 2-microglobulin level [88.9% (24/27) vs. 62.3% (33/53)], bone marrow involvement [40.7% (11/27) vs. 15.1% (8/53)], and HBV reactivation [51.9% (14/27) vs. 28.3% (15/53)] was higher in the EBV-positive group, and the differences were statistically significant (all P<0.05). There were no statistically significant differences in the composition of patients stratified by age, gender, pathological type, B symptom, lactate dehydrogenase level, international prognostic index score, number of extranodal involvements, liver involvement, hepatitis outbreak, prophylactic anti-HBV therapy, hepatitis B surface antibody (HBsAb), rituximab therapy, and the last chemotherapy effects between the 2 groups (all P > 0.05). Compared with the HBV non-reactivation group, the proportion of patients undergoing hepatitis outbreak [48.3% (14/29) vs. 17.6% (9/51)], not receiving prophylactic anti-HBV therapy [65.5% (19/29) vs. 39.2% (20/51)], HBsAb negative [79.3% (23/29) vs. 21.6% (11/51)], EBV positive [48.3% (14/29) vs. 25.5% (13/51)], receiving rituximab [82.8% (24/29) vs. 60.8% (31/51)] was higher in the HBV reactivation group, and the differenves were statistically significant (all P < 0.05); while there were no statistically significant differences in the composition of patients stratified by the other clinical characteristics between the 2 groups (all P > 0.05). Multivariate logistic regression analysis showed that EBV-positivity was an independent risk factor for HBV reactivation after chemotherapy in NHL patients with HBsAg positive ( OR = 7.073, 95% CI: 1.613-31.010, P = 0.009), while HBsAb positive ( OR = 0.038, 95% CI: 0.008-0.186, P < 0.001) and preventive anti-HBV therapy ( OR = 0.172, 95% CI: 0.039-0.756, P = 0.020) were independent protective factors. The last follow-up was in December 2023 and the median follow-up time was 36.5 months. There were no statistically significant differences in PFS and OS between the EBV-positive group and the EBV-negative group, HBV reactivation group and the non-reactivation group (all P > 0.05). Conclusions:Among HBV-infected NHL patients, those with concurrent EBV infection have a more advanced clinical stage and are very prone to bone marrow invasion, and they also show a higher probability of HBV reactivation; HBV reactivation may be related to whether receiving preventive anti-HBV therapy and rituximab therapy. EBV infection may increase the risk of HBV reactivation in NHL patients; EBV infection and HBV reactivation may not be relevant to the prognosis of patients.

Acute T-lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy, and in recent years, with the advancement of combined chemotherapy and hematopoietic stem cell transplantation, the prognosis of T-ALL has improved significantly, but for patients with primary drug resistance or relapsed/refractory disease the prognosis is still poor. The plant homeodomain finger 6 (PHF6) is a tumor suppressor protein, it plays a pivotal role in T cell differentiation, epigenetic regulation and oncogenic pathway synergy, and its mutations and deletions are commonly associated with the development of T-lymphocytic leukemia. However, the underlying mechanism of PHF6 in the pathogenesis of T-ALL remains unclear. This article reviews the structure, function and mechanism of action of PHF6 in T-ALL, the important coexisting genes associated with the progression of T-ALL, and the research progress in targeted therapy.

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Objective To assess the efficacy of a novel inguinal tourniquet in healthy individuals and to investigate the relationship between localized inguinal compression and femoral artery blood flow occlusion.Methods A self-controlled study was conducted.From November 9 to November 30,2024,11 volunteers were recruited at the Third Medical Center of Chinese PLA General Hospital.Three compression methods--finger pressure,a novel groin tourniquet,and a SAM junction tourniquet(SJT)—were applied bilaterally to the inguinal region until distal blood flow signals disappeared.Each compression method was tested in 22 trials with a 5-minute interval between operations.Differences in hemostatic efficacy between bilateral inguinal regions and across compression methods were compared.Subsequently,the novel tourniquet was incrementally pressurized in 120 mmHg multiples using an integrated pressure device to analyze trends in popliteal artery blood flow velocity.Observational indicators included the internal pressure of the tourniquet pressurization device,peak systolic velocity(PSV)of popliteal artery,inguinal surface pressure magnitude,inguinal surface pressure distribution,and pain scores(assessed using a single-dimensional numerical rating scale).Results No statistically significant difference was observed in the minimum pressure required to occlude femoral artery blood flow bilaterally(P>0.05).The success rates of femoral artery blood flow occlusion at the inguinal region were 100%for the novel inguinal tourniquet,SJT,and finger pressure.The novel inguinal tourniquet induced the highest pain scores,ranging from 5 to 8.A significant reduction in PSV of popliteal artery was noted when the intra-tourniquet pressure reached 360 mmHg and 480 mmHg(P<0.05),with a 95%hemostasis efficacy observed within the range of 360-600 mmHg.No significant association was observed between the recovery of popliteal artery blood flow after limb movement and inguinal pressure distribution(P>0.05).The PSV of popliteal artery exhibited the strongest negative correlation with the average pressure within the inguinal compression area(r=-0.79,P<0.001),with a linear regression fitting line of y=69.69-0.13x(P<0.001,R2=0.58).Conclusions The novel inguinal tourniquet effectively occludes femoral artery blood flow within a pressure range of 360-600 mmHg,accompanied by moderate-to-severe pain.Its hemostatic mechanism mainly relies on increasing the mean pressure within the inguinal compression area.

Objective To investigate the potential mechanisms by which the natural herbal monomer scutellarin alleviates ischemic stroke(IS)using network pharmacology and in vivo experimental validation.Methods Potential targets of scutellarin were predicted using SwissTargetPrediction and PharmMapper,and standardized via UniProt.IS-related differentially expressed genes(DEGs)were obtained from the GSE22255 dataset in the GEO database,with screening criteria of|log10FC|≥1 and P＜0.05.Venny 2.1.0 analysis was used to identify overlapping targets.Protein-protein interaction(PPI)networks were constructed using STRING and visualized in cytoscape.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed.Molecular docking was conducted using AutoDock Vina 1.5.6 to assess the binding affinity between scutellarin and hub targets.Middle cerebral artery occlusion(MCAO)mouse model was established and divided into sham,MCAO,and MCAO+scutellarin groups.Real-time PCR was used to detect mRNA expression of hub genes and phosphatidylinositol 3-kinase(PI3K)/Akt pathway components in the ischemic cortex.Results A total of 325 scutellarin targets and 2168 IS-related DEGs were identified,with 29 overlapping targets.GO analysis yielded 51 biological processes,5 cellular components,and 8 molecular functions.KEGG enrichment highlighted PI3K/Akt and metabolic pathways.PPI analysis identified Caspase-3,epidermal growth factor receptor(EGFR),prostaglandin-endoperoxide synthase 2(PTGS2),peroxisome proliferator activated receptor alpha(PPARA),and interleukin-2(IL-2)as key hub proteins.Molecular docking showed strong binding affinities between scutellarin and these proteins.Real-time PCR result confirmed that scutellarin modulated the expression of hub genes and activated the PI3K/Akt pathway.Conclusion In the MCAO mouse model,scutellarin exerts neuroprotective effects by modulating targets such as CASP3,EGFR,PTGS2,PPARA,and IL-2,and activating the PI3K/Akt signaling pathway,exhibiting multi-target and multi-pathway characteristics.

Objective To investigate the effects of different anesthesia depths on stress states and inflammatory mediators in patients undergoing video-assisted thoracoscopic lobectomy.Methods A total of 89 lung cancer patients who underwent video-assisted thoracoscopic lobectomy were selected as study subjects.Based on intraoperative bispectral index(BIS)range,the patients were divided into deep anesthesia group(BIS of 40 to＜50,n=45)and shallow anesthesia group(BIS of 50 to＜60,n=44).Vital signs(mean arterial pressure,heart rate and blood oxygen saturation),anesthesia re-covery time,extubation time,dosage of vasoactive drugs,postoperative pain intensity[Visual Ana-logue Scale(VAS)],postoperative analgesic dosage,perioperative stress state[prostaglandin E2(PGE2),nerve growth factor(NGF)and substance P(SP)],levels of inflammatory mediators[neuron-specific enolase(NSE),tumor necrosis factor-α(TNF-α)and S100β protein]at different time points(before anesthesia induction,immediately after intubation,before lesion resection and at the end of surgery)and the incidence of anesthesia-related adverse reactions were compared between the two groups.Results Before lesion resection and at the end of surgery,the mean arterial pressure and heart rate in the deep anesthesia group were significantly lower than those in the shallow anesthe-sia group(P＜0.05).The anesthesia recovery time and extubation time in the deep anesthesia group were significantly longer than those in the shallow anesthesia group(P＜0.05).At the end of surgery and on postoperative day one,the levels of PGE2,NGF and SP in the deep anesthesia group were significantly lower than those in the shallow anesthesia group,while the levels f NSE,TNF-α and S100β protein were significantly higher than those in the shallow anesthesia group(P＜0.05).There were no significant differences in the dosage of vasoactive drugs,VAS scores,sufentanil dos-age and the incidence of anesthesia-related adverse reactions between thetwo groups(P＞0.05).Conclusion During one-lung ventilation in patients undergoing video-assisted thoracoscopic surgery lobectomy,deep anesthesia can effectively control surgical stress and maintain stability of intraopera-tive hemodynamics,but it is associated with delayed postoperative awakening and more pronounced inflammatory response.Shallow anesthesia results in faster postoperative awakening and lower levels of inflammatory mediators,but it is associated with more significant intraoperative stress response and unstable hemodynamics.