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 evaluate the effects of the alpha-lipoic acid on hepatic ischemia/reperfusion (I/R) injury and the role of (ALDH2).Methods:This experiment was performed in two parts in vivo and in vitro experiments. In vivo experiment Twenty-four male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 4 groups ( n=6 each) by the random number table method: sham operation group (Sham group), hepatic I/R group (IR group), and hepatic I/R plus α-lipoic acid group (IR+ ALA group) and hepatic I/R+ α-lipoic acid+ daidzin group (IR+ ALA+ D group). Hepatic I/R was induced by occlusion of the left and middle hepatic lobes for 60 min, followed by 6 h of reperfusion in anesthetized rats.In IR+ ALA+ D group, ALDH2 inhibitor daidzin 50 mg/kg was intraperitoneally injected at 45 min before ischemia.Alpha-lipoic acid 100 mg/kg was intraperitoneally injected at 30 min before ischemia in IR+ ALA group and IR+ ALA+ D group.Blood samples from the inferior vena cava were collected at the end of reperfusion to determine serum AST and ALT activities.Then the rats were sacrificed, and livers were removed for microscopic examination of pathological changes of the lung tissues which were scored and for determination of ALDH2 activity, level of reactive oxygen species (ROS) and expression of 4-hydroxy-trans-2-nonenal (4-HNE) and malondialdehyde (MDA) (by immuno-histochemistry). In vitro experiment Rat BRL-3A hepatocytes cultured in vitro were divided into 4 groups ( n=15 each) by the random number table method: control group (C group), hypoxia-reoxygenation group (HR group), hypoxia-reoxygenation+ α-lipoic acid group (HR+ ALA group) and hypoxia-reoxygenation+ α-lipoic acid+ daidzin group (HR+ ALA+ D group). BRL-3A hepatocytes were exposed to 95% N 2-5% CO 2 in an incubator at 37 ℃ for 6 h followed by reoxygenation with 95% O 2-5% CO 2 for 24 h. At 60 min before hypoxia, alpha-lipoic acid 100 μmol/L was addded in HR+ ALA group, and alpha-lipoic acid 100 μmol/L and daidzin 60 μmol/L were added in HR+ ALA+ D group.At 24 h of reoxygenation, cell viability was measured by CCK-8 method, ALDH2 activity was determined by spectrophotometry, ROS level was detected by DCFH-DA fluorescent probe method, and mitochondrial membrane potential (MMP) was measured by JC-1 method. Results:In vivo experiment Compared with Sham group, the serum AST and ALT activities, liver injury score, level of ROS in liver tissues and expression of 4-HNE and MDA were significantly increased ( P<0.05), and no significant change was found in ALDH2 activity in IR group ( P>0.05). Compared with IR group, the serum AST and ALT activities, liver injury score, level of ROS in liver tissues and expression of 4-HNE and MDA were significantly decreased, and the ALDH2 activity was increased in IR+ ALA group ( P<0.05). Compared with IR+ ALA group, the serum AST and ALT activities, liver injury score, level of ROS in liver tissues and expression of 4-HNE and MDA were significantly increased, and the ALDH2 activity was decreased in HR+ ALA+ D group ( P<0.05). In vitro experiment Compared with C group, the cell viability and MMP were significantly decreased, and the level of ROS was increased ( P<0.05), and no significant change was found in the activity of ALDH2 in HR group ( P>0.05). Compared with HR group, the cell viability, ALDH2 activity and MMP were significantly increased, and the level of ROS was decreased in HR+ ALA group ( P<0.05). Compared with HR+ ALA group, the cell viability, ALDH2 activity and MMP were significantly decreased, and the level of ROS was increased in HR+ ALA+ D group ( P<0.05). Conclusions:Alpha-lipoic acid can reduce hepatic I/R injury in rats, and the mechanism is related to activation of ALDH2, reduction of accumulation of toxic aldehyde and restoration of MMP.

Objective:To investigate the characteristics of distribution and drug resistance of urinary bacteria in the mid-stream urine of patients with infectious stones.Methods:The retrospective study analyzed the clinical data of 254 patients with infectious stones in the First Affiliated Hospital of Guangzhou Medical University from September 2016 to September 2018. All patients were treated with PCNL. Overall, there were 101 male and 153 female patients, with the mean age of(51.5±12.3) years, and the mean stone burden of 1443.5(660.8, 2837.5) mm2. There were 58 (22.8%) patients with hypertension, 17(6.7%) patients with diabetes and 195(76.8%)with hydronephrosis. The mid-stream urine samples were obtained for bacterial culture and susceptibility test, and the results of urine culture and antimicrobial susceptibility were recorded and analyzed.Results:Of 254 patients involved in this study, 89(35.0%) were positive and 165 (65.0%) were negative for urinary bacterial culture of the mid-stream. The proportion of patients with positive urine bacterial culture of the mid-stream who had positive urine leucocytes, positive urine nitrite and postoperative pyrexia were 86.5%(77/89), 64.0%(57/89), 25.8%(23/89), respectively, which was higher than that of patients with negative urine bacterial culture of the mid-stream [50.3%(83/165), 14.5%(24/165), 14.5%(24/165), P<0.05]. Four teen kinds of bacteria were detected from the mid-stream urine, and the three bacteria with the highest detection rate in turn were Escherichia coli of 38.2%(34/89), Proteus mirabilis of 15.7%(14/89), and Pseudomonas aeruginosa of 11.2%(10/89). The results of this study showed that three common bacteria had high resistance to drug including Cefazolin, Cefuroxime, Cefuroxime ester, Ampicillin and Co-trimoxazole (all resistance rate>40%). The resistance rates of Escherichia coli and Pseudomonas aeruginosa to Ciprofloxacin and Levofloxacin were higher than or equal to 40%. The resistance rates of Escherichia coli and Proteus mirabilis to meropenem, imipenem, ertapenem, piperacillin/tazobactam and amikacin were all lower than 10%. In addition, the resistance rates of Escherichia coli to nitrofurantoin and tigecycline and Proteus mirabilis to tobramycin, aztreonam and cefoxitin were all less than 10%. The resistance rates of Pseudomonas aeruginosa to ceftazidime, cefepime, gentamicin and aztreonam were less than 10%. Conclusions:The highest detection rate of urinary bacteria in culture of the mid-stream with infectious stones are Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa, all of which showed high resistance to Ampicillin, Cotrimoxazole, and some cephalosporins. Escherichia coli and Pseudomonas aeruginosa showe high resistance to Ciprofloxacin and Levofloxacin, and all of the three bacteria have low resistance rates to some β-Lactamase inhibitor complex and carbapenems, suggesting a reference for clinical empirical medical treatment.