The ability to localize sound sources rapidly allows human beings to efficiently understand the surrounding environment. Previous studies have suggested that there is an auditory "where" pathway in the cortex for processing sound locations. The neural activation in regions along this pathway encodes sound locations by opponent hemifield coding, in which each unilateral region is activated by sounds coming from the contralateral hemifield. However, it is still unclear how these regions interact with each other to form a unified representation of the auditory space. In the present study, we investigated whether functional connectivity in the auditory "where" pathway encoded sound locations during passive listening. Participants underwent functional magnetic resonance imaging while passively listening to sounds from five distinct horizontal locations (-90°, -45°, 0°, 45°, 90°). We were able to decode sound locations from the functional connectivity patterns of the "where" pathway. Furthermore, we found that such neural representation of sound locations was primarily based on the coding of sound lateralization angles to the frontal midline. In addition, whole-brain analysis indicated that functional connectivity between occipital regions and the primary auditory cortex also encoded sound locations by lateralization angles. Overall, our results reveal a lateralization-angle-based representation of sound locations encoded by functional connectivity patterns, which could add on the activation-based opponent hemifield coding to provide a more precise representation of the auditory space.
Humans ; Sound Localization/physiology* ; Male ; Female ; Magnetic Resonance Imaging ; Young Adult ; Functional Laterality/physiology* ; Adult ; Brain Mapping ; Auditory Cortex/physiology* ; Acoustic Stimulation ; Auditory Pathways/physiology* ; Brain/physiology*

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

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*

OBJECTIVES: To investigate the impact of high expression of transmembrane and coiled helix structural domain 1 (TMCO1) on prognosis of gastric cancer and the possible mechanisms. METHODS: TMCO1 expression in gastric cancer and its effect on gastric cancer progression and prognosis were analyzed using publicly available databases and clinical data of patients undergoing radical surgery in our hospital, and its possible biological functions were explored using KEGG and GO analyses. In gastric cancer HGC-27 cells, the effects of lentivirus-mediated TMCO1 overexpression and TMCO1 silencing on cell apoptosis, proliferation, invasion and migration were examined. RESULTS: TMCO1 expression was significantly elevated in gastric cancer tissues (P<0.05), and its high expression was positively correlated with cancer progression (P<0.001) and a lowered postoperative 5-year survival rate of the patients (P<0.05). Bioinformatic analyses suggested that TMCO1 may affect gastric cancer cell apoptosis via Wnt signaling. In HGC-27 cells, TMCO1 overexpression significantly promoted tumor cell proliferation, inhibited cell apoptosis, and enhanced cell migration and invasion, whereas TMCO1 silencing produced the opposite effects. Western blotting showed that β-catenin levels were significantly upregulated in TMCO1-overexpressing cells and downregulated in cells with TMCO1 silencing. CONCLUSIONS TMCO1 is overexpressed in gastric cancer tissues, and its high expression promotes gastric cancer progression and affects long-term prognosis of the patients possibly by activating the Wnt/ β-catenin signaling pathway to inhibit apoptosis of gastric cancer cells.
Humans ; Stomach Neoplasms/metabolism* ; Apoptosis ; Prognosis ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Wnt Signaling Pathway ; beta Catenin/metabolism* ; Gene Expression Regulation, Neoplastic

Objective To investigate the relationship of C-reactive protein-albumin-lymphocyte(CALLY)index,serum autotaxin and serine protease 2(PRSS2)with postoperative recurrence and metastasis in gastric cancer patients.Methods A total of 188 patients who underwent radical gastrectomy for gastric cancer from December 2019 to December 2021 were selected as the research subjects.According to the postoperative situation,they were divided into the recurrence and metastasis group(n=72)and the non-recurrence and metastasis group(n=116).C reactive protein(CRP)was detected by immunoturbidimetry,albumin was detected by bromocresol green method,lymphocyte count was detected by blood routine analyzer,and CALLY index was calculated.Enzyme-linked immunosorbent assay was used to detect serum levels of autotaxin and PRSS2,and Spearman/Pearson correlation analysis was used to analyze the correlation between CALLY index,serum autotaxin,PRSS2 levels and clinical data.Multivariate logistic regression was used to analyze the influencing factors of recurrence and metastasis in patients with gastric cancer after radical resection,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of CALLY index,serum autotaxin and PRSS2 levels for recurrence and metastasis in patients with gastric cancer after radical resection.Kaplan-Meier method was used to analyze the relationship between CALLY index,serum autotaxin,PRSS2 levels and postoperative recurrence and metastasis.Results Compared with the non-recurrence and metastasis group,the recurrence and metastasis group had a higher proportion of patients with TNM stage Ⅲ,Borrmann type Ⅲ-Ⅳ,lymphovascular invasion,neoadjuvant therapy and postoperative chemotherapy,higher serum levels of autotaxin and PRSS2,and lower CALLY index(P<0.01).TNM stage,Borrmann type,lymphovascular invasion,neoadjuvant therapy and postoperative chemotherapy were negatively correlated with CALLY index,and positively correlated with serum autotaxin and PRSS2 levels,while serum autotaxin and PRSS2 levels were negatively correlated with CALLY index(P<0.01).TNM stage,Borrmann type,lymphovascular invasion,CALLY index,autotaxin and PRSS2 were the influencing factors of recurrence and metastasis in patients with gastric cancer after radical resection(P<0.05,P<0.01).The area under the curve(AUC)of CALLY index,autotaxin and PRSS2 for predicting recurrence and metastasis was 0.962,which was significantly larger than that of CALLY index,autotaxin and PRSS alone(P<0.01).The 3-year recurrence and metastasis rate of patients with low CALLY index expression[56.52%(52/92)]was higher than that of patients with high CALLY index expression[20.83%(20/96)](P<0.01).The 3-year recurrence and metastasis rate of patients with high expression of autotaxin[49.47%(47/95)]was higher than that of patients with low expression[26.88%(25/93)](P<0.01).The 3-year recurrence and metastasis rate of patients with high PRSS2 expression[47.87%(45/94)]was higher than that of patients with low PRSS2 expression[28.72%(27/94)](P<0.01).Conclusion The CALLY index decreases,and serum autotaxin and PRSS2 increase in patients with postoperative recurrence and metastasis of gastric cancer.The combined prediction of the three factors demonstrates higher predictive performance for postoperative recurrence and metastasis.

Objective:To generate a rabbit polyclonal antibody specific for human acetylated KHSRP and to evaluate its poten-tial value and clinical significance in detecting colorectal cancer samples.Methods:An acetylated peptide Lys205(K205)of KHSRP protein was designed and synthesized,which was coupled to KLH at its carboxyl terminus to form an antigen-carrier conjugate.After five times immunization in New Zealand rabbits,blood serum was separated to determine antibody titer by indirect ELISA.Polyclonal antibody by affinity chromatography method was purified,and specificity of antibody was determined by Western blot and immunohis-tochemistry(IHC).Results:Final rabbit serum antibody ELISA titer was>5.12×105,which could be used for specific detection of K205-acetylated KHSRP protein by Western blot and IHC.Conclusion:Role of KHSRP in tumor may be closely related to its surface acetylation modification.A rabbit polyclonal antibody against human acetylated KHSRP has been successfully generated,and an excel-lent foundation for assessing relationship between acetylated KHSRP and tumor processes in cancer diseases has been made.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Objective:To generate a rabbit polyclonal antibody specific for human acetylated KHSRP and to evaluate its poten-tial value and clinical significance in detecting colorectal cancer samples.Methods:An acetylated peptide Lys205(K205)of KHSRP protein was designed and synthesized,which was coupled to KLH at its carboxyl terminus to form an antigen-carrier conjugate.After five times immunization in New Zealand rabbits,blood serum was separated to determine antibody titer by indirect ELISA.Polyclonal antibody by affinity chromatography method was purified,and specificity of antibody was determined by Western blot and immunohis-tochemistry(IHC).Results:Final rabbit serum antibody ELISA titer was>5.12×105,which could be used for specific detection of K205-acetylated KHSRP protein by Western blot and IHC.Conclusion:Role of KHSRP in tumor may be closely related to its surface acetylation modification.A rabbit polyclonal antibody against human acetylated KHSRP has been successfully generated,and an excel-lent foundation for assessing relationship between acetylated KHSRP and tumor processes in cancer diseases has been made.