Sensorineural hearing loss is one of the most common sensory disorders. In recent years, auditory neuropathy spectrum disorders caused by mutations in the OTOF gene have garnered significant attention worldwide, marking it as the first deafness gene with breakthroughs in gene therapy. Most patients with OTOF gene mutations present with stable, congenital, or prelingual onset of hearing loss, which can range from severe to profound and even complete hearing loss. However, a minority of patients may exhibit mild to moderate progressive hearing loss or temperature-sensitive hearing loss. This review further explores the genotype-phenotype relationship of the OTOF gene based on reported cases in China and abroad. Additionally, we analyze the characteristics of the natural history of OTOF gene mutations within the Chinese population. This study aims to provide a reference for the clinical diagnosis, evaluation, and treatment of hearing loss associated with OTOF gene mutations.
Humans ; Mutation ; Phenotype ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Membrane Proteins/genetics*

Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

Objective:To explore the effects of bone mineral density (BMD) on postoperative cage subsidence in patients undergoing anterior cervical discectomy and fusion (ACDF) in different regions of the vertebrae.Methods:The study is a retrospective case-control analysis. The clinical and imaging data of 164 cervical spondylosis patients who underwent ACDF at Department of Spine Surgery, the Third Hospital of Hebei Medical University between January 2021 and June 2024 were retrospectively reviewed. Data from 147 patients (230 intervertebral spaces) constituted the analysis set, including 80 males and 67 females, with an age of (54.5±11.2) years (range: 32 to 81 years). Patients were grouped based on postoperative cage subsidence: 74 patients were included in the subsidence group, and 73 patients were included in the non-subsidence group (grouped by patients); 99 intervertebral spaces were included in the subsidence group, and 131 intervertebral spaces were included in the non-subsidence group (grouped by intervertebral space). Cage subsidence was defined as a≥3 mm loss of intervertebral height at the operated level on lateral radiographs during follow-up. Cervical BMD was assessed using Hounsfield Units (HU) values obtained from CT images. Independent sample t-test or Chi-squared test were used to compare baseline characteristics between groups. Multivariate Logistic regression analyzed the influence of HU values at different locations on cage subsidence. Receiver operating characteristic (ROC) curve analysis calculated the area under the curve (AUC) to evaluate the predictive value of HU values for cage subsidence and determine optimal thresholds. The Delong test compared the predictive differences for subsidence among HU values from different vertebral locations at the surgical fixation levels. A validation set comprising clinical data from 17 single-level surgery patients was used to further verify the accuracy of the established thresholds for predicting cage subsidence. Results:In the analysis set, there were no statistically significant differences in age, sex, body mass index, or underlying diseases between patients in the subsidence group and the non-subsidence group (all P>0.05). The HU values of subsided intervertebral spaces were lower than those of non-subsided intervertebral spaces (upper vertebra: 360.1±86.4 vs. 301.7±93.3, t=4.899, P<0.01; lower vertebra: 328.8±83.6 vs. 282.5±88.1, t=4.062, P<0.01; endplate of the upper vertebra: 604.7±150.9 vs. 521.6±125.3, t=4.446, P<0.01; endplate of the lower vertebra: 554.4±157.9 vs. 502.8±139.0, t=2.582, P=0.010). ROC curves showed that HU values at different locations of the surgical level all had predictive value for cage subsidence (upper vertebra: AUC=0.702, P<0.01; lower vertebra: AUC=0.667, P<0.01; endplate of the upper vertebra: AUC=0.657, P<0.01; endplate of the lower vertebra:AUC=0.610, P<0.01). The optimal thresholds for predicting cage subsidence for the upper vertebral body, lower vertebral body, endplate of the upper vertebra, and endplate of the lower vertebra were 325.0, 247.1, 533.1, and 547.4, respectively. However, the differences in predictive value among HU values from different vertebral locations were not statistically significant( P>0.05). In the validation set, the sensitivity and specificity of the HU value of upper vertebra for predicting cage subsidence were 6/7 and 9/10, respectively; for the lower vertebra, they were 5/7 and 9/10; for the endplate of the upper vertebra, they were 6/7 and 8/10; for the endplate of the lower vertebra, they were 5/7 and 8/10. Conclusion:The BMD of different parts of the vertebral body has potential predictive value for cage subsidence after ACDF surgery.

Objective To investigate the therapeutic effects of copper-doped barium titanate(BaCuTiO4)piezoelectric materials combined with low-intensity pulsed ultrasound(LIPUS)to activate their piezoelectric-catalytic synergistic effect for treating implant-associated infections.Methods BaCuTiO4 coatings were synthesized on the surface of Ti-6Al-4V substrates using a hydrothermal method,and their surface morphology was characterized by scanning electron microscopy.The piezoelectric characteristics of the coatings were analyzed using a piezoresponse force microscope.An in vitro biofilm model of methicillin-resistant staphylococcus aureus(MRSA)was used,with barium titanate(BaTiO3)coatings serving as the control group.Under LIPUS intervention(1.0 W/cm2,1 MHz,10 min),the bacterial viability was assessed using colony counting to evaluate the antibacterial performance of the BaCuTiO4 coatings.Confocal microscopy was used to observe biofilm viability in different groups,assessing the biofilm removal capability of the coatings.Reactive oxygen species(ROS)generation in each group was detected using Rhodamine b as a probe to evaluate the catalytic efficiency of the coatings in generating ROS.Results Copper doping significantly reduced the piezoelectric coefficient of the coating(from 17.7 pm/V to 7.8 pm/V),bringing its piezoelectric performance closer to the requirements of natural bone tissues.Under LIPUS activation,the BaCuTiO4 coatings increased the generation efficiency of reactive oxygen species by 67.5％and effectively disrupted and removed biofilms formed by MRSA,achieving an antibacterial rate of 90.5％.Conclusions The BaCuTiO4 coatings achieve efficient antibacterial and biofilm-clearing functions through a piezoelectric-catalytic synergistic mechanism.Their piezoelectric properties are well-matched with natural bone tissues,promoting implant osseointegration.

Objective To investigate the therapeutic effects of copper-doped barium titanate(BaCuTiO4)piezoelectric materials combined with low-intensity pulsed ultrasound(LIPUS)to activate their piezoelectric-catalytic synergistic effect for treating implant-associated infections.Methods BaCuTiO4 coatings were synthesized on the surface of Ti-6Al-4V substrates using a hydrothermal method,and their surface morphology was characterized by scanning electron microscopy.The piezoelectric characteristics of the coatings were analyzed using a piezoresponse force microscope.An in vitro biofilm model of methicillin-resistant staphylococcus aureus(MRSA)was used,with barium titanate(BaTiO3)coatings serving as the control group.Under LIPUS intervention(1.0 W/cm2,1 MHz,10 min),the bacterial viability was assessed using colony counting to evaluate the antibacterial performance of the BaCuTiO4 coatings.Confocal microscopy was used to observe biofilm viability in different groups,assessing the biofilm removal capability of the coatings.Reactive oxygen species(ROS)generation in each group was detected using Rhodamine b as a probe to evaluate the catalytic efficiency of the coatings in generating ROS.Results Copper doping significantly reduced the piezoelectric coefficient of the coating(from 17.7 pm/V to 7.8 pm/V),bringing its piezoelectric performance closer to the requirements of natural bone tissues.Under LIPUS activation,the BaCuTiO4 coatings increased the generation efficiency of reactive oxygen species by 67.5％and effectively disrupted and removed biofilms formed by MRSA,achieving an antibacterial rate of 90.5％.Conclusions The BaCuTiO4 coatings achieve efficient antibacterial and biofilm-clearing functions through a piezoelectric-catalytic synergistic mechanism.Their piezoelectric properties are well-matched with natural bone tissues,promoting implant osseointegration.

Objective:To explore the effects of bone mineral density (BMD) on postoperative cage subsidence in patients undergoing anterior cervical discectomy and fusion (ACDF) in different regions of the vertebrae.Methods:The study is a retrospective case-control analysis. The clinical and imaging data of 164 cervical spondylosis patients who underwent ACDF at Department of Spine Surgery, the Third Hospital of Hebei Medical University between January 2021 and June 2024 were retrospectively reviewed. Data from 147 patients (230 intervertebral spaces) constituted the analysis set, including 80 males and 67 females, with an age of (54.5±11.2) years (range: 32 to 81 years). Patients were grouped based on postoperative cage subsidence: 74 patients were included in the subsidence group, and 73 patients were included in the non-subsidence group (grouped by patients); 99 intervertebral spaces were included in the subsidence group, and 131 intervertebral spaces were included in the non-subsidence group (grouped by intervertebral space). Cage subsidence was defined as a≥3 mm loss of intervertebral height at the operated level on lateral radiographs during follow-up. Cervical BMD was assessed using Hounsfield Units (HU) values obtained from CT images. Independent sample t-test or Chi-squared test were used to compare baseline characteristics between groups. Multivariate Logistic regression analyzed the influence of HU values at different locations on cage subsidence. Receiver operating characteristic (ROC) curve analysis calculated the area under the curve (AUC) to evaluate the predictive value of HU values for cage subsidence and determine optimal thresholds. The Delong test compared the predictive differences for subsidence among HU values from different vertebral locations at the surgical fixation levels. A validation set comprising clinical data from 17 single-level surgery patients was used to further verify the accuracy of the established thresholds for predicting cage subsidence. Results:In the analysis set, there were no statistically significant differences in age, sex, body mass index, or underlying diseases between patients in the subsidence group and the non-subsidence group (all P>0.05). The HU values of subsided intervertebral spaces were lower than those of non-subsided intervertebral spaces (upper vertebra: 360.1±86.4 vs. 301.7±93.3, t=4.899, P<0.01; lower vertebra: 328.8±83.6 vs. 282.5±88.1, t=4.062, P<0.01; endplate of the upper vertebra: 604.7±150.9 vs. 521.6±125.3, t=4.446, P<0.01; endplate of the lower vertebra: 554.4±157.9 vs. 502.8±139.0, t=2.582, P=0.010). ROC curves showed that HU values at different locations of the surgical level all had predictive value for cage subsidence (upper vertebra: AUC=0.702, P<0.01; lower vertebra: AUC=0.667, P<0.01; endplate of the upper vertebra: AUC=0.657, P<0.01; endplate of the lower vertebra:AUC=0.610, P<0.01). The optimal thresholds for predicting cage subsidence for the upper vertebral body, lower vertebral body, endplate of the upper vertebra, and endplate of the lower vertebra were 325.0, 247.1, 533.1, and 547.4, respectively. However, the differences in predictive value among HU values from different vertebral locations were not statistically significant( P>0.05). In the validation set, the sensitivity and specificity of the HU value of upper vertebra for predicting cage subsidence were 6/7 and 9/10, respectively; for the lower vertebra, they were 5/7 and 9/10; for the endplate of the upper vertebra, they were 6/7 and 8/10; for the endplate of the lower vertebra, they were 5/7 and 8/10. Conclusion:The BMD of different parts of the vertebral body has potential predictive value for cage subsidence after ACDF surgery.

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.
Mice ; Animals ; Otoacoustic Emissions, Spontaneous/physiology* ; Hearing/physiology* ; Ear, Inner ; Hearing Loss/therapy* ; Genetic Therapy ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Membrane Proteins

OBJECTIVE To estimate the cost-utility of sacituzumab govitecan （SG） versus single-agent chemotherapy in the treatment of hormone receptor-positive （HR+）/human epidermal growth factor receptor 2-negative （HER2－） advanced metastatic breast cancer. METHODS From the perspective of the Chinese medical system， a three-state partitioned survival model was constructed to examine the cost-utility of SG versus single-agent chemotherapy based on TROPiCS-02 trial. The cycle length was set to 1 month， and the time horizon was 10 years. The annual discount was 5%. The model output included total costs and quality adjusted life month （QALM）， and incremental cost-effectiveness ratio （ICER） was calculated for cost-utility analysis， by setting willingness-to-pay （WTP） threshold at 3 times gross domestic product （GDP） per capita of China in 2023 （22 340 yuan/QALM）. Univariate sensitivity analyses， probability sensitivity analyses， and scenario analyses were performed to evaluate the robustness of the results and calculate the price threshold when SG had economic advantages. RESULTS SG group gained incremental 4.25 QALM and 561 570 yuan compared with single-agent chemotherapy， which resulted in an ICER of 132 102/QALM that was higher than WTP. The results of the univariate sensitivity analysis showed that the monthly average cost of SG had the greatest impact on the results； the results of probability sensitivity analysis showed that the probability of SG scheme being cost-effective at the WTP threshold was 0. The results of scenario analysis showed that the conclusions of this study were robust under different time horizons （5， 10， 15 years）. The price threshold for SG being cost-effective was 1 344 yuan per 180 mg. CONCLUSIONS Based on the perspective of Chinese medical system， SG appears to be not cost-effective compared with single-agent chemotherapy for HR+/ HER2－ advanced metastatic breast cancer at the price of 8 400 yuan per 180 mg. A substantial price cut should be taken to be cost- effective.

With the economic development of China and transformation of medical model, people pay more attention to their spiritual world and psychological health, and medical psychology has become a major in urgent need of construction. Foreign medical/clinical psychology education was established earlier and has become relatively mature, thus making its experience valuable for reference. This paper compares and analyzes the current situation of undergraduate medical psychology education, and puts forward optimization strategies from the aspects of college planning, curriculum training scheme and teachers’ teaching philosophy, hoping to provide some ideas for the construction of undergraduate medical psychology education in China.

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; ≥80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.