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 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 value of REG3α,sST2 and TNFR1 in peripheral blood for risk stratification and prognostic evaluation of acute graft-versus-host disease(aGVHD)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children.Methods:From January 2020 to March 2022,70 children with aGVHD after allo-HSCT in the First Affiliated Hospital of Zhengzhou University were selected as the research objects,of which 50 cases were mild aGVHD(grade Ⅰ-Ⅱ)and 20 cases were severe aGVHD(grade Ⅲ-Ⅳ).30 healthy children who underwent physical examinations in our hospital during the same period were selected as the control group.Luminex platform was used to detect the protein expression levels of REG3α,sST2 and TNFR1 during aGVHD occurrence,and the differences between the three groups were analyzed by one-way ANOVA.According to the outcome of aGVHD treatment within 28 days,the patients were divided into a good prognosis group of 58 cases and a poor prognosis group of 12 cases.The ROC curve was used to analyze the value of REG3α,sST2 and TNFR1 in predicting the prognosis of children with aGVHD.Results:The peripheral blood levels of REG3α,sST2 and TNFR1 in the mild aGVHD and severe aGVHD groups were significantly higher than those in the control group(P＜0.05),and those in the severe aGVHD group were significantly higher than those in the mild aGVHD group(P＜0.05).Compared with the good prognosis group,the peripheral blood levels of REG3α,sST2 and TNFR1 in the poor prognosis group were significantly higher(t=9.27,3.33,2.97;P＜0.01).ROC curve analysis showed that the area under the curve(AUC),sensitivity and specificity of the combined detection of REG3α,sST2 and TNFR1 in predicting the prognosis of children with aGVHD were higher than those of the above indicators detected alone or in pairs.Conclusion:The expression levels of REG3α,sST2 and TNFR1 were related to the severity of aGVHD.The combination of REG3α,sST2 and TNFR1 has a high clinical value in predicting the prognosis of children with aGVHD,which is expected to provide a reliable reference for clinical evaluation of the prognosis of children with aGVHD.

Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.

Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9％NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P＜0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.

Objective To observe the effects of Wuzi Yanzong Pill(WYP)on motor function in a mouse model of Parkinson's disease(PD)and to explore its potential mechanisms.Methods Twenty-four male C57BL/6 mice were randomly divided into control group,model group and WYP group,with 8 mice in each group.Mice in model and WYP group were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 7 consecutive days to establish a PD model.From the 1st day of model preparation,mice in WYP group were gavaged with WYP solution[16 g/(kg·d)]twice daily for 14 consecutive days.At the same time,mice in control group and model group were gavaged with 0.9%NaCl solution[50 ml/(kg·d)]twice a day.Gait experiment was utilized to assess the behavioral performance of mice in each group.Immunofluorescence staining was conducted to detect the number of tyrosine hydroxylase(TH)-positive cells in the substantia nigra region,the fluorescence intensity of nuclear factor E2-related factor 2(Nrf2),and the number of NeuN neurons co-labeled with Nrf2 in each group.Western blotting was employed to determine the expression levels of TH,Kelch-like ECH-associated protein 1(Keap-1),Nrf2,and heme oxygenase-1(HO-1)in the brain tissue of mice in each group.Results The gait experiment results showed that,compared with control group,standing time of the left front paw,right front paw,left hind paw,and right hind paw of the mice in model group was significantly shortened(P<0.01),while swinging time of the left front paw,right front paw,left hind paw,and right hind paw was significantly prolonged(P<0.05).Compared with model group,standing time of the left front paw and right hind paw of the mice in WYP group was significantly prolonged(P<0.05),while swing time of the left front paw and right front paw was significantly shortened(P<0.05).Immunofluorescence staining and Western blotting results showed that,compared with control group,in model group the number of TH-positive cells,average fluorescence intensity of Nrf2,and HO-1 levels decreased(P<0.01),while the Keap-1 protein level increased(P<0.01),and the number of Nrf2 expression on NeuN neurons decreased(P<0.001).Compared with model group,the number of TH-positive cells,average fluorescence intensity of Nrf2,HO-1 level,and the number of Nrf2 expression on NeuN neurons in the brain tissue of mice in WYP group increased(P<0.05),while Keap-1 protein level decreased(P<0.05).Conclusions WYP could alleviate the motor dysfunction and protect dopaminergic neurons in PD mice.The underlying mechanism may be related to the regulation of Keap-1/Nrf2/HO-1 pathway to inhibit oxidative stress response.

Objective To investigate the effects of astragaloside Ⅳ(AS-Ⅳ)on axon growth inhibitory factor A(Nogo-A)and its downstream pathway protein RHO-associated coiled spiral kinase 2(ROCK2)in experimental autoimmune encephalomyelitis(EAE)mice,and to explore the mechanism by which it promotes axon repair and regeneration.Methods EAE model was induced in C57BL/6 female mice by subcutaneous injection of myelin oligodendrocyte glycoprotein 35-55(MOG35-55).Mice were randomly divided into EAE group and AS-Ⅳ group(n=8 per group).EAE group received intraperitoneal injection of PBS on the 3rd day post-immunization,while AS-Ⅳ group was administered AS-Ⅳ at a dosage of 30mg/(kg.d)once daily,0.2 ml per injection,for 25 consecutive days.On the 28th day post-immunization,the expression levels of growth-associated protein 43(GAP-43),neuronal core antigen(NeuN),microtubule associated protein 2(MAP-2),glial fibroacidic protein(GFAP),and Iba1 in the spinal cord were detected using immunofluorescence assay.Real-time fluorescence quantitative PCR(qRT-PCR)was conducted to detect mRNA expression levels of GAP-43,Nogo-A,and Nogo receptor(NgR)genes.Western blotting was utilized to determine the expression levels of GAP-43,Nogo-A,ROCK2,phosphorylated myosin phosphatase(p-MYPT1),B-lymphoblastoma-2(Bcl-2),and Bcl-2 associated X protein(Bax).Results Compared with EAE group,AS-Ⅳ treatment significantly reduced the positive cell expression rates of Iba1 microglia and GFAP astrocyte in spinal cord(P<0.01 and P<0.001,respectively),while it also increased the positive expression rates of NeuN and MAP-2(P<0.001 and P<0.05,respectively).The treatment also upregulated the expression level of anti-apoptotic factor Bcl-2(P<0.001)and downregulated the expression level of pro-apoptotic factor Bax(P<0.05),leading to an increase in Bcl-2/Bax ratio(P<0.05).Furthermore,AS-Ⅳ enhanced the expression of GAP-43 protein(P<0.05)and decreased the mRNA expression levels of neuroregeneration inhibitor Nogo receptor(NgR)and ROCK2 gene(P<0.001,P<0.05,respectively);as well as decreased the expression levels of Nogo-A,ROCK2 and p-MYPT1 proteins(P<0.05,P<0.001).Conclusion AS-Ⅳ may inhibit the activation of microglia and astrocytes and neuronal apoptosis in EAE mice by inhibiting Nogo-A and downstream pathway ROCK 2,thereby promoting the expression of GAP-43,NeuN and MAP-2,alleviating neuronal damage,and facilitating axon repair and regeneration.

Aim To explore the role and mechanism of the effective ingredients of Scutellariae Radix in improving the fibrosis of diabetes cardiomyopathy(DCM).Methods The technology platform of Chinese medicine system pharmacology(TCMSP)and the small molecule drug target prediction(Swiss Target Prediction)platform were used to excavate the active components of Scutellariae Radix and the target of its response.DCM related disease gene targets were screened using GeneCards,Disgene,UniPort and OMIM databases,and intersecting genes were imported into the String 11.5 database to construct a drug-disease-protein interaction network diagram.Cytoscape 3.9.1 software was a-dopted to visualize the key target network.Metascape platform was used to explore the molecular targets of Scutellariae Radix effective ingredients against DCM,and draw pathway maps through the KEGG database.H9c2 and AC16 cardio-myocytes were stimulated with 5.5 mmol/L D-glucose as the normal glucose control group,35 mmol/L D-glucose as the high glucose group,and 10 μmol/L Baicalin was used for intervention.The levels of TGF-β1,collagen Ⅰ(COL Ⅰ)and collagen Ⅲ(CO LⅢ)mRNA were detected by RT-qPCR,and the expression of Smad2/3,p-Smad2/3,COL Ⅰ and COL Ⅲprotein were detected by Western blot,TGF-β1 level in supernatant was assessed by ELISA.Results Through the a-bove platform,a total of 33 effective ingredients including Baicalin,441 core targets,and 1 884 DCM disease genes were retrieved,150 core genes for treating DCM with Scutellariae Radix were obtained.The drug-disease interacted genes such as TGF-β1,TP53,MMP-9 and IL-6 were obtained through String PPI,KEGG signaling pathways such as MAPK and PI3K/Akt were enriched.In vitro experiments showed high glucose stimulation of H9c2 and AC16 cardiomyocytes led to upregulation of TGF-β1,COL Ⅰ and COL Ⅲ mRNA levels,p-Smad2/3,COL Ⅰ and COL Ⅲ protein levels,and signifi-cantly increased the content of TGF-β1 in the supernatant,while Baicalin weakened its expression.Conclusion The active ingredients of Scutellariae Radix exert anti DCM effects through multiple targets,among which Baicalin inhibits TGF-β1/Smad signaling to improve high glucose induced cardiomyocyte fibrosis and plays a protective role in DCM.

Atherosclerosis(As)is a chronic inflammatory disease caused by lipid deposition.Panvascular disea-ses,which are mainly caused by As,have gradually attracted the attention of many scholars,and their main pathological features are vascular lesions.Vitamin D plays an important role in anti-As in panvascular diseases.It is involved in the regulation of renin-angiotensin system(RAS),endothelial cell injury,immune response,neutrophil extracellular traps(NET)regulation,apoptosis and autophagy,and is a new target in panvascular diseases research.Traditional Chinese Medicine(TCM)has certain advantages in the prevention and treatment of panvascular diseases.Among them,single herbs,active ingredients and compound prescriptions can regulate vitamin D-related metabolism,and have unique scientific value for the prevention and treatment of As.This article mainly discusses the role of vitamin D in multiple pathological links of panvascular diseases and related Chinese medicine interventions,aiming to provide effective ideas for the prevention and treatment of panvascular diseases from the perspective of vitamin D.

Venous thromboembolism is a common comorbidity in neurosurgery department that can lead to life-threatening pulmonary embolism, endangering patient health. The unique characteristics of neurosurgical conditions often present a high risk of bleeding, which complicates the treatment of venous thrombosis. Although numerous observational studies and meta-analyses support the feasibility of initiating early anticoagulation prevention or treatment after hemorrhage stabilization in intracranial hemorrhagic conditions such as traumatic brain injury and cerebral hemorrhage, there is a lack of high-quality clinical research. As a result, neurosurgeons tend to adopt a conservative approach regarding pharmacological prophylaxis and anticoagulant treatment for venous thromboembolism. Key aspects such as the timing of prevention, monitoring, and discontinuation of treatment still require high-quality research to establish definitive guidelines.