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*

Intrahepatic cholangiocarcinoma(ICC)is a malignant tumor originating from the epithelial cells of the intrahepatic bile ducts,with adenocarcinoma being its predominant pathological type.Due to its insidious onset and the difficulty of early diagnosis,ICC has a high mortality rate.Currently,complete resection of the tumor through surgery remains the only potential curative treatment for ICC,but only a small proportion of patients are eligible for surgery.In this context,a multidisciplinary comprehensive treatment model,centered around surgery and combined with systemic chemotherapy,targeted therapy,immunotherapy,supplemented by local interventional therapies and radiotherapy,has emerged as an effective strategy for improving the prognosis of ICC patients.This paper systematically reviews the latest research advances in chemotherapy,targeted therapy,immunotherapy,and local treatment for ICC,and summarizes the current clinical treatment strategies,aiming to provide a robust reference for the precise treatment of patients with advanced ICC.

Objective:To analyze the clinicopathological characteristics and prognostic factors in gastric cancer patients with bone metastasis,and to evaluate the impact of different treatment regimens on survival in patients with synchronous and metachronous bone metastasis.Methods:A total of 120 gastric cancer patients with bone metastasis treated at Nanjing Drum Tower Hospital between 2015 and 2023 were enrolled,including 36 with synchronous bone metastasis and 84 with metachronous bone metastasis.Clinicopathological features were compared between the two groups using the χ2 test.Cox proportional hazards regression model was employed to identify risk factors for overall survival after bone metastasis(OS-BM).The Kaplan-Meier method was used to analyze the effects of different treatments on OS-BM in both synchronous and metachronous groups.Results:Among the 120 patients,104(86.6%)had metastases to other organs.Comparative analysis revealed that synchronous bone metastasis patients exhibited elevated serum C-reactive protein and decreased serum albumin,whereas metachronous bone metastasis patients had reduced peripheral white blood cell and neutrophil counts(all P<0.05).Metachronous bone metastasis(HR=2.35,95%CI[1.47,3.74],P<0.01),serum CA125≥30.2 U/mL(HR=1.6,95%CI[1.03,2.48],P=0.036),white blood cell count≥9.5×10?/L(HR=2.15,95%CI[1.17,3.92],P=0.013),and absence of immunotherapy(HR=2.26,95%CI[1.5,3.39],P<0.01)were independent risk factors affecting patient prognosis.Combined immunotherapy significantly prolonged OS-BM in gastric cancer patients with bone metastasis compared to non-immunotherapy regimens(9.63 vs 4.53 months,P=0.002).Patients with metachronous bone metastasis demonstrated better response to immunotherapy compared to those with synchronous metastases(median OS-BM:10.8 vs 7.3 months,P=0.004).Conclusion:Immunotherapy is an independent protective factor for survival in gastric cancer patients with bone metastasis.Early combination therapy centered on immunotherapy alongside chemotherapy is recommended to prolong survival in such patients.

Intrahepatic cholangiocarcinoma(ICC)is a malignant tumor originating from the epithelial cells of the intrahepatic bile ducts,with adenocarcinoma being its predominant pathological type.Due to its insidious onset and the difficulty of early diagnosis,ICC has a high mortality rate.Currently,complete resection of the tumor through surgery remains the only potential curative treatment for ICC,but only a small proportion of patients are eligible for surgery.In this context,a multidisciplinary comprehensive treatment model,centered around surgery and combined with systemic chemotherapy,targeted therapy,immunotherapy,supplemented by local interventional therapies and radiotherapy,has emerged as an effective strategy for improving the prognosis of ICC patients.This paper systematically reviews the latest research advances in chemotherapy,targeted therapy,immunotherapy,and local treatment for ICC,and summarizes the current clinical treatment strategies,aiming to provide a robust reference for the precise treatment of patients with advanced ICC.

Background Permethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. Objective To observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. Methods HMC3 were treated with 0, 10, 25, and 55 μmol·L⁻¹ permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L⁻¹ permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L⁻¹ permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. Results HMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L⁻¹ permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L⁻¹ permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L⁻¹ compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L⁻¹ permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L⁻¹ permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L⁻¹ permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L⁻¹ permethrin groups (P<0.05). Conclusion Permethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.

OBJECTIVE To evaluate the cost-effectiveness of clopidogrel versus aspirin monotherapy regimens for secondary prevention of ischemic stroke and to provide economic evidence and reference for clinical medication and decision-making. METHODS Based on the CAPRIE trial， a Markov model was constructed； the probabilities of risk events， health utility values， and costs of risk event management were obtained from relevant literature. The cycle length was 6 months， and the time horizon was 10 years. A discount rate of 5% per year was applied. The primary outcomes were total costs， quality-adjusted life-years （QALYs）， and incremental cost-effectiveness ratio （ICER）. Cost-utility analysis was performed for above 2 regimens by using TreeAge Pro software. The one-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were conducted to validate the robustness of the analyses. RESULTS Compared with the aspirin regimen （325 mg/d of CAPRIE trial dose）， the ICER values of clopidogrel regimen for secondary stroke prevention for 10 years， 20 years and 30 years were 4 284.06， 4 201.20 and 3 986.78 yuan/QALY， respectively， which were E-mail：liuxiaoyanrj@sjtu.edu.cn all less than the willing-to-pay （WTP） threshold of one time 。 China’s per capita gross domestic product （GDP） in 2021. E-mail：scilwsjtu-wb@yahoo.com Compared with the aspirin regimen （clinically recommended dose in China， 100 mg/d）， the ICER values of clopidogrel regimen for stroke secondary prevention for 10 years， 20 years and 30 years were 58 238.27， 42 164.72 and 36 164.77 yuan/QALY， respectively， which were all less than WTP threshold. When comparing with aspirin regimen of 325 mg/d， results of one-way sensitivity analysis showed that the cost of clopidogrel and aspirin， probability of the first recurrence of ischemic stroke were sensitive factors of model. Results of probabilistic sensitivity analysis showed that when WTP was set at one time GDP per capita in China in 2021， clopidogrel had a probability of being cost- effective of about 66.5%. Results of scenario analysis showed that neither changing the time horizon to 10， 20 or 30 years nor using different doses of aspirin （50， 100， 150， 200 or 250 mg/d） would not alter any conclusions. CONCLUSIONS Compared with aspirin monotherapy， clopidogrel monotherapy is more cost-effective for secondary prevention of ischemic stroke.

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

Objective:To investigate the teaching effect of flipped classroom combined with problem-based learning (PBL) in the teaching of the Diagnostic Audiology course.Methods:A total of 72 undergraduate students majoring in audiology and speech rehabilitation in the classes of 2019 and 2020 in Chongqing Medical University were enrolled as subjects, and three chapters of the Diagnostic Audiology course were selected for teaching reform. The 34 students in the class of 2019 were enrolled as control group and received lecture-based learning (LBL), and the 38 students in the class of 2020 were enrolled as experimental group and received flipped classroom combined with PBL. The teaching effect was evaluated by comparing the two groups in terms of classroom test scores, classroom participation scores, degree of satisfaction with teaching effect, and overall satisfaction with teaching. SPSS 23.0 software was used to perform the t-test, the chi-square test, and the Mann-Whitney U test. Results:The experimental group had a significantly higher classroom test score than the control group (25.95±1.21 vs. 23.21±1.55, P<0.001). In terms of classroom participation scores, the experimental group had significantly higher scores of participation in class discussion, cooperative and collaborative abilities, and questioning skills than the control group (all P<0.001). In terms of the degree of satisfaction with teaching, compared with the control group, the experimental group had significantly higher degrees of satisfaction in the dimensions such as interest in learning, mastery of theoretical knowledge, teamwork and collaboration abilities, self-learning ability, and self-presentation ( P=0.005, 0.009, 0.001, 0.016, and 0.005). In addition, the experimental group had a significantly higher degree of overall satisfaction with teaching than the control group ( P=0.006). Conclusion:Flipped classroom combined with PBL has a good teaching effect in the Diagnostic Audiology course and thus holds promise for further application.

Objective:To investigate the correlation between cognitive function and living ability of older adult patients living in a mining community.Methods:A total of 180 older adult patients living in a mining community who received treatment during July-October 2019 were included in this study. They were randomly divided into the low-age group (< 68 years old, n = 94) and the high-age group (≥ 68 years old, n = 86). Cognitive function and living ability were evaluated using the Mini-Mental State Examination (MMSE), The Montreal Cognitive Assessment (MoCA), and the Activity of Daily Living Scale (ADL). The relationship between cognitive function and living ability was investigated using hierarchical analysis and Pearson correlation analysis. Results:The proportions of older adult patients with abnormal cognitive function identified by the MMSE and MoCA were 39.4% and 66.0%, respectively in the low-age group, and they were 32.6% and 61.6%, respectively in the high-age group. The MoCA had a greater performance in identifying abnormal cognitive function in each group than the MMSE ( χ2 = 26.69, 10.18, both P < 0.001). There were no significant differences in proportions of older adult patients with abnormal cognitive function identified by the MMSE and MoCA between low-age and high-age groups ( χ2 = 0.90, 0.36, both P > 0.05). The proportion of older adult patients with abnormal living ability was not significantly different between low-age and high-age groups (4.3% vs. 10.5%, χ2 = 2.58, P > 0.05). Compared with patients negative for MMSE items, living ability and instrumental activity of daily living increased by 7.0% and 9.4% in low-age patients positive for MMSE items (both P < 0.05). Compared with patients negative for MoCA items, living ability increased by 3.5% in low-age patients positive for MoCA items ( P < 0.05). Correlation analysis revealed that total scores of MMSE and MoCA were significantly negatively correlated with ADL score ( r = -0.26, -0.27, both P < 0.001) and instrumental activity of daily living score ( r = -0.27, -0.27, P < 0.001). Conclusion:Cognitive function and living ability are correlated in older adult patients living in a mining community. We should pay attention to the screening results of cognitive disorder in older adult patients and improve their living ability by improving their cognitive function.

Objective:To investigate the characteristic of mild cognitive impairment (MCI) in the adults aged 48 years and over in a coal mine community, and to analyze its associated risk factors.Methods:From July to October 2019, a questionnaire survey for basic information was conducted among 180 middle-aged and elderly adults who met the inclusion criteria in the Datong coal mine community. The cognitive function was evaluated by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The effects of gender, age, years of education, sleep, living alone, physical exercise, social activities, smoking and drinking status, body mass index and chronic diseases on cognitive level were analyzed by single factor stratification and multiple linear regression.Results:There was no significant difference in the positive rate of MCI screened by MMSE and MoCA in the age groups of 48-<64, 64-<72 and 72-90 (original and corrected P>0.05); The positive rate of MCI in MoCA screening (64.4%, 66.7%, 60.9%) was significantly higher than that in MMSE (35.6%, 45.6%, 28.1%) (all P<0.05); MMSE was positively correlated with MoCA score ( r=0.762, P<0.001). With the increase of age, the scores of memory, execution and visual space detected by MoCA decreased significantly (all P<0.05), while the scores of attention, language and orientation did not change significantly (all P>0.05). Univariate stratification showed that the significant influencing factors of MMSE or MoCA scores were gender, age, years of education and sleep status (all P<0.05). Multiple linear regression analysis showed that gender ( βMMSE=-0.192; βMoCA=-0.140), years of education ( βMMSE=0.209; βMoCA=0.328) and sleep status( βMMSE=-0.162; βMoCA=-0.136) were risk factors affecting MMSE and MoCA scores ( P<0.05). Conclusions:More middle-aged and elderly adults with MCI might be observed in a coal mine community, and the main characteristics of MCI are impaired memory, executive function and visual space. To prevent and reduce the occurrence of dementia, early interventions of MCI should be carried out among the adults with female, old age, low years of education and poor sleep quality.