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.

Objective: To investigate the effects of RING 1 and YY1 binding protein (RYBP), a member of the polycomb group (PcG), on bladder cancer cell proliferation and invasion, as well as the underlying mechanisms involved, so as to provide reference for the prevention and treatment of bladder cancer. Methods: Overexpressing and knocking down of RYBP were achieved in bladder cancer cell lines (T24, UM-UC-3, and 5637) via plasmids or siRNAs.Cell proliferation was assessed via thiazolyl blue (MTT) and colony formation assays, whereas migration was evaluated via scratch and Transwell assays.Changes in epithelial-mesenchymal transition (EMT) markers and other related proteins were examined with Western blotting. Results: RYBP overexpression significantly inhibited bladder cancer cell proliferation, invasion, and migration, whereas RYBP knockdown promoted these behaviors.Western blotting results revealed that RYBP overexpression downregulated the expressions of EMT markers N-cadherin, Vimentin, and Slug, but upregulated the expression of E-cadherin.Conversely, RYBP knockdown upregulated the expressions of N-cadherin, Vimentin, and Slug, while reducing the expression of E-cadherin. Conclusion: RYBP appears to inhibit the proliferation and migration of bladder cancer cells via the EMT pathway, indicating its potential application in bladder cancer therapies.

ObjectiveTo analyze the epidemiological trends and characteristics of brucellosis in humans (hereinafter referred to as brucellosis) in Tangshan City, Hebei Province from 2016 to 2023, and to provide a scientific basis for formulating brucellosis prevention and control strategies in the region. MethodsThe incidence data of human brucellosis in Tangshan City from 2016 to 2023 were collected from the China Disease Prevention and Control Information System. The diagnosis time, infection route, and clinical characteristics of the cases were obtained from the case investigation reports. Descriptive epidemiological methods were used to analyze the temporal, spatial, demographic distributions, and clinical characteristics of human brucellosis. Brucella species were identified using agglutination tests with bacterial suspension and A/M antigen-positive serum. ResultsA total of 2 193 cases of human brucellosis were confirmed and clinically diagnosed in Tangshan City from 2016 to 2023, with the peak incidence occured from March to August, and which exhibited distinct geographic distribution patterns. The highest incidence rate was found in people aged 60‒<70 years. The occupation of cases were primarily farmers. The incidence rate in males (528/100 000) was higher than that in females (184/100 000). All cases had confirmed exposure to infected animals or contaminated animal products. ConclusionThe epidemic of human brucellosis in Tangshan exhibited an overall steady downward trend from 2016 to 2023, except for a slight increase in 2016 and 2021, with the incidence rate controlled at 289/100 000‒335/100 000. The prevention and control situation of human brucellosis still remains severe, with the highest incidence rate in the eastern region of Tangshan, which are characterized by the breeding, slaughtering, and processing of cattle and sheep. Therefore, it it is necessary to enhance the prevention and control of human brucellosis among the personnel engaged in these industries in the eastern areas.

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

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

Cervical cancer is one of the most common gynecological malignant tumors,the five-year survival rate decreased significantly in the case of lymph node metastasis and distant metasta-sis,so the development of new anti-cervical cancer drugs is of great significance for the treatment of cervical cancer.Molecular docking technology is one of the most commonly used research methods in computer aided drug design,which is widely used in screening the effective components of drugs,finding the targets of drugs acting on tumors and exploring the mechanism of antineoplastic drugs.This paper reviews the molecular docking technology in the screening of anti-cervical cancer drugs,the determination of anti-tumor targets and the mechanism of anti-cervical cancer,in order to provide more sufficient theoretical basis for the screening of anti-cervical cancer drugs and new drug research and development.

Objective:To investigate the effect of puerarin on myocardial inflammation in rats with heart failure from the Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB)inflammatory pathway.Methods:The rat model of heart failure was established by subcutaneous injection of isoproterenol(5 mg/kg for 7 days),and was divided into model group,puerarin group,TLR4 activator group(RS09,25 μg/kg),TLR4 inhibitor group(TAK-242,0.5 mg/kg),puerarin+TLR4 activator group,with 20 rats in each group.Another 20 rats were selected as normal control group.Echocardiography was used to detect heart function;HE staining was used to observe pathological damage of myocardial tissue;TUNEL method was used to detect apoptosis of myocardial tissue cells;ELISA method was used to detect the levels of inflammatory factors IL-6,IL-1β and tumor necrosis factor-α(TNF-α)in myocardial tissue;immunohistochemical method was used to detect the expression of TLR4 and macrophage activation marker-F4/80;Western blot was used to detect the protein expressions of TLR4/NF-κB pathway,MyD88,IL-1 receptor-associated kinase(IRAK)and Galec-tin-3.Results:Compared with the normal control group,the necrosis,inflammatory infiltration and apoptosis of rat myocardial cells were severe in the model group,the heart function was decreased,the inflammatory factor release,macrophage activation,and TLR4/NF-κB pathway protein expression were increased(P<0.05).Puerarin and TLR4 inhibitors could improve the pathological damage of heart failure rats such as myocardial cell necrosis,inflammatory infiltration and apoptosis to the same extent,improve heart function,reduce inflammatory response,inhibit macrophage activation and reduce TLR4/NF-κB pathway activation(P<0.05).TLR4 activator could promote the activation of TLR4/NF-κB pathway,aggravate myocardial cell damage,apoptosis and cardiac function damage in rats with heart failure,and weaken the above-mentioned effects of puerarin(P<0.05).Conclusion:Puerarin may inhibit the activation of TLR4/NF-κB pathway,reduce myocardial inflammation,and play an anti-heart failure effect.

Objective:To explore the influence of deviation of the bolt in femoral neck system (FNS) on the short-term outcomes in young and middle-aged patients with displaced femoral neck fracture.Methods:A retrospective analysis was conducted of the 114 young and middle-aged patients with displaced femoral neck fracture who had been treated with FNS at Department of Orthopaedics, Suzhou Municipal Hospital from December 2019 to January 2023. Based on the postoperative measurements of the deviation of the bolt tip to the central axis of the femoral head and neck (W), the patients were divided into a central group (W≤20%) and a deviation group (W>20%). In the central group of 63 cases, there were 27 males and 36 females with a mean age of (46.4±8.0) years. In the deviation group of 51 cases, there were 20 males and 31 females with a mean age of (45.1±9.8) years. The 2 groups were compared in terms of weight-bearing time, fracture healing time, tip-apex distance, degree of femoral neck shortening, Harris Hip Score and EuroQol five-dimensional questionnaire-5L (EQ-5D-5L) utility value at the last follow-up, as well as complications and revision surgeries.Results:There was no statistically significant difference in the preoperative general information, auxiliary reduction or quality of fracture reduction between the 2 groups, showing comparability between groups ( P>0.05). There was no significant difference in the partial weight-bearing time between the 2 groups ( P>0.05). In the central group, the full weight-bearing time [15.0 (14.0, 16.0) weeks] and fracture healing time [14.0 (12.0, 15.0) weeks] were significantly shorter than those in the deviation group [16.0 (15.0, 19.0) weeks; 15.0 (13.0, 17.0) weeks], the tip-apex distance [(21.4±3.4) mm] was significantly shorter than that in the deviation group [(23.5±2.7) mm], the Harris Hip Score [(90.6±6.1) points] and EQ-5D-5L utility value [0.9 (0.8, 0.9)] at the last follow-up were significantly higher than those in the deviation group [(87.7±6.2) points; 0.9 (0.8, 0.9)], and the incidences of moderate and severe femoral neck shortening [25.4% (16/63)], avascular necrosis of the femoral head [0 (0/63)] and revision surgery [0 (0/63)] were significantly lower than those in the deviation group [66.7% (34/51), 7.8% (4/51), 9.8% (5/51)] (all P< 0.05). Conclusion:A closer positioning of the FNS bolt to the central axis of the femoral head and neck favors satisfactory short-term outcomes and a lower revision surgery rate in young and middle-aged patients with displaced femoral neck fracture.