Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Objective:To understand the information needs and experiences of primary caregivers of patients in the emergency resuscitation room of the emergency department, and to provide a reference for clinical staff to meet caregivers′ information needs as well as to develop targeted and effective health information support for doctors and patients.Methods:A descriptive phenomenological research method was used to conduct semi-structured interviews with primary caregivers of 14 patients in the emergency resuscitation room of the First Affiliated Hospital of Nanjing Medical University from November 2023 to February 2024 through purposive sampling, and the Colaizzi 7-step analysis method was applied to summarize and analyze the interview data and refine the themes.Results:Totally 14 respondents aged 28-66, including 6 males and 8 females. Four themes were refined including diverse information needs, information access dilemma, integration of doctor-patient information for joint decision-making and communication, and desire for information and emotional support.Conclusions:The information needs of primary caregivers of patients in the emergency department were diverse, and caregivers were eager to seek patient-related information and crave emotional support and communication when faced with the onset of a patient's illness. Healthcare professionals should strengthen the assistance of caregivers′ information needs to improve the experience of patients and caregivers in medical consultation services and realize the sustainable development of the doctor-patient relationship.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Objective This study aimed to investigate the relationship between multiple inflammatory markers and poor outcome in patients with intracerebral hemorrhage,and to compare their predictive abilities.Methods We retrospectively analyzed the patients with intracerebral hemorrhage admitted to the Department of Neurology of the First Affiliated Hospital of Nanchang University from January 1,2015 to March 31,2023.According to the Modified Rankin Scale at 90 days after onset,the patients were divided into good outcome(mRS≤2 points)and poor outcome(mRS score≥3 points).Clinical information,laboratory examinations and follow-up data were compared between the two groups.Inflammatory markers include neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),monocyte to high-density lipoprotein ratio(MHR),systemic inflammatory response index(SIRI),systemic immune-inflammation index(SII),white blood cell count to mean platelet volume ratio(WMR),lymphocyte to monocyte ratio(LMR),and systemic coagulation-inflammation index(SCI).Univariate and multivariate logistic regression analysis were used to analyze the predictors of poor prognosis after intracerebral hemorrhage,and receiver operating characteristic curve(ROC)was constructed to compare their predictive ability.Results A total of 510 patients with intracerebral hemorrhage were included.Of those,297(58.2%)had good outcome,and 213(41.8%)had poor outcome.Comparison of baseline characteristics demonstrated that patients with poor prognosis had higher levels of white blood cells,neutrophils,high-density lipoprotein,fibrinogen,NLR,PLR,SIRI,SII,WMR at admission,larger baseline hematoma volume and baseline perihematomal edema volume,a higher proportion of lobar hemorrhage,older age,and lower levels of platelets,lymphocytes,LMR,and SCI(P<0.05).Multivariate regression analysis showed that NLR(OR:1.081,95%CI:1.032～1.1131,P=0.001),SIRI(OR:1.089,95%CI:1.014～1.169,P=0.019),SII(OR:1.000,95%CI:1.000～1.001,P=0.011),WMR(OR:2.627,95%CI:1.267～5.445,P=0.009)were independently associated with poor prognosis in patients with ICH.In ROC analysis,the area under the curve of NLR(0.729,95%CI:0.685～0.774)was higher than SIRI(0.692,95%CI:0.645～0.738),SII(0.688,95%CI:0.641～0.735)and WMR(0.65,95%CI:0.602～0.698)for predicting poor outcomes.Conclusion NLR,SIRI,SII and WMR at admission are independently associated with poor outcomes in patients with intracerebral hemorrhage,and NLR has the strongest predictive ability.

Objective:Exploring the effect of Pinocembrin(Pino)regulating the Ras homolog gene family member A/Rho associated with curly helix binding protein kinase(RhoA/ROCK)signaling pathway of Ras homologous gene family members on the malignant biological behavior of gastric cancer cells.Methods:Cultivate human gastric cancer cells MGC803 with different concentrations of Pino(0～240μmol/L),detect cell survival rate using CCK-8 method,and screen for the optimal drug concentration.MGC803 cells were rseparated into MGC803 group(Control group),Pino-L group,Pino-M group,Pino-H group,and Pino-H+RhoA agonist CN03 group.The clone formation experiment was applied to detect the number of clones formed of cells in each group.Assessment of cell apoptosis using flow cytometry.Tran-swell invasion and migration experiments were used to detect the number of cells undergoing migration and invasion in each group;Detection of RhoA/ROCK signaling pathway and expression of epithelial mesenchymal transition related proteins in MGC803 cells using Western blot method.Results:Compared with the MGC803 group,the cell survival rate,clone formation number,migration cell number,and invasion cell number were all reduced in the Pino-L group,Pino-M group,and Pino-H group,and RhoA was also present in the cells,ROCK2,The expression levels of vimentin and N-cadherin gradually decreased(P<0.05),while the apoptosis rate and E-cadherin expression level gradually in-creased(P<0.05).The Pino-H+CN03 group reversed the trend of changes in the above indicators).Conclusion:Pino can prevent malignant biological behavior of gastric cancer cells,which may be related to the inhibition of the RhoA/ROCK signaling pathway.

Aim To examine the pathogenesis of disul-fide death gene in vascular dementia(VD)by bioin-formatics analysis of disulfide death differentially ex-pressed genes(DEGs)combined with experimental verification.Methods The death DEGs of disulfide were screened and their correlation was analyzed.The VD patients data in the data set were analyzed by clus-tering and typing and gene set variation.The clustering risk of DEGs was tested with a nomogram model,and the optimal learning model was predicted.After the es-tablishment of VD rat model,water maze test,HE stai-ning and RT-qPCR detection were performed to verify the results of health information.Results Four DEGs including SLC7A11 were obtained,which had antago-nistic or synergistic interaction with each other.The genetic data could be divided into two subtypes with significant differences.After typing,VD disulfide DEGs were mainly concentrated in GnRH signaling pathways.The accuracy of the nomogram prediction model was high.Generalized linear was the best ma-chine learning model.Compared with the sham opera-tion group,the escape latency of rats in the model group was prolonged,the number of crossing platforms decreased,the relative mRNA expression levels of Slc3a2 and Slc7a11 decreased,and LRPPRC in-creased.Conclusions SLC7A11 and other disulfide death DEGs and its related GnRH signaling pathway may be an important part of the pathogenesis of VD di-sulfide death.SLC3A2,LRPPRC and SLC7A11 can be used as characteristic genes in the regulation of VD by disulfide death,which may affect VD progression through the regulation of disulfide death.

Objective:To evaluate the clinical efficacy of Tianma Xionglin Zhixuan Tablets in treating hypertension patients with liver yang hyperactivity or comorbid phlegm-stasis syndrome and explore its therapeutic mechanisms through plasma metabolomics.Methods:Thirty-six hypertension patients(4 dropouts)diagnosed with liver yang hyperactivity or phlegm-stasis syndrome were enrolled as the treatment group from June 2022 to September 2023 at the First Affiliated Hospital of Hunan University of Chinese Medicine,while 30 healthy volunteers with balanced constitutions were recruited as the blank group.Plasma samples were collected from patients pre-and post-treatment and from healthy volunteers.Clinical outcomes,including syndrome scores,office blood pressure(BP),and 24-hour ambulatory BP,were recorded.Plasma metabolomic profiling was performed using liquid chromatography-mass spectrometry(LC-MS).Results:Compared with baseline,Tianma Xionglin Zhixuan Tablets significantly reduced traditional Chinese medicine syndrome scores(P＜0.01),office systolic/diastolic BP(P＜0.01),and 24-hour ambulatory BP parameters(24-hour mean BP,daytime/nighttime mean BP;all P＜0.01).Metabolomic analysis identified 45 differential metabolites between the blank group and pretreatment patients,and 64 metabolites altered post-treatment(VIP＞1,P＜0.05).Enrichment analysis of 16 overlapping endogenous metabolites revealed that Tianma Xionglin Zhixuan Tablets primarily modulated arachidonic acid metabolism and sphingolipid metabolism pathways.Conclusion:Tianma Xionglin Zhixuan Tablets demonstrates significant clinical efficacy in hypertension patients with liver yang hyperactivity or phlegm-stasis syndrome,potentially mediated through regulation of arachidonic acid and sphingolipid metabolism.

This article summarizes current research and real-world evidence on the combined use of 5-aminosalicylates acid (5-ASA) with biologic agents in ulcerative colitis (UC) patients undergoing step-up therapy. Furthermore, it explores the potential value of whether combination therapy or not in different clinical scenarios. The findings provide insights for personalized UC treatment strategies and suggest directions for future research.

The scaphoid bone is one of the important bone of hand,which is frequently injured and difficult to treat in clinical practice.Therefore,it is very important to deeply study the microstructure and biomechanical characteristics of the scaphoid bone for understanding its injury mechanism and optimizing treatment scheme.Microcomputed tomography(micro-CT)provides high-resolution imaging of bone tissue,while finite element analysis can help to simulate the stress distribution and behavioral patterns of the scaphoid bone under various physiological and pathological states.The high-resolution three-dimensional image of the scaphoid bone obtained by micro-CT technology can be used to construct finite element models of real anatomical structure of the scaphoid bone,thus achieving accurate simulation of the mechanical properties of the scaphoid bone.The fusion of these two advanced technologies provides a new perspective for revealing the structural and functional relationships and injury mechanism of the scaphoid bone.Therefore,this paper reviews the anatomical characteristics of the scaphoid bone and its biomechanical behavior in different states,emphasizing the specific applications and advantages of micro-CT and finite element analysis techniques in the study of the scaphoid bone.By summarizing the research findings in recent years,this paper provides novel scientific basis and methods for the diagnosis,treatment,and prevention of scaphoid bone-related disorders.

Objective:The study aimed to validate the Neuroception of Psychological Safety Scale (NPSS) in terms of reliability and validity among individuals with mental disorders in China.Methods:The Study followed Brislin′s translation principles to adapt the scale into Chinese. From February to June 2023, a total of 638 hospitalized patients with mental disorders (477 with schizophrenia and 161 with mood disorders) were selected through gender-stratified simple random sampling from the Shanghai Pudong New Area Mental Health Center and the Shanghai Baoshan Mental Health Center. The Chinese version of the NPSS and the Security Questionnaire (SQ) were administered. The reliability of the scale was measured using split-half reliability and test-retest reliability. Validity was assessed through content validity, structural validity, convergent validity, and discriminative validity analyses. In addition, SQ was used as a criterion tool to test the validity of the criterion through Pearson correlation analysis.Results:The Chinese version of the NPSS contained 29 items, with total scores ranging from 29 to 145. Higher total scores indicated greater psychological safety. Item analysis showed a decider value of 10.58 to 20.80 (>3), and the correlation between items and total scores ranged from 0.579 to 0.749 (all P<0.05). The item-level content validity index (I-CVI) for the items ranged from 0.86 to 1.00, while the average scale-level content validity index (S-CVI/Ave) was 0.99. Exploratory factor analysis extracted three common factors: social participation, empathy, and bodily sensations, which is consistent with the structure of the original scale, explaining a cumulative variance contribution rate of 62.551%. Confirmatory analysis revealed a satisfactory model fit, with average variance extracted (AVE) values for the three dimensions ranging from 0.523 to 0.645, and composite reliability(CR) ranging from 0.905 to 0.938. The standard loading coefficients for the items ranged from 0.608 to 0.859, and inter-factor correlation coefficients were all smaller than the square roots of their respective AVE values. Pearson correlation analysis indicated significant positive relationships between the Chinese NPSS and SQ ( r=0.822-0.846, P<0.01). Reliability analysis showed Cronbach′s alpha coefficients of 0.903-0.959 for the total scale and subscales. After a 3-week interval, test-retest reliability (70 patients) ranged from 0.874 to 0.983, and split-half reliability was 0.869-0.969. All model fit indices met established criteria. Conclusions:The Chinese version of the NPSS demonstrates good reliability and validity, making it suitable for both research and clinical applications in assessing psychological security among individuals with schizophrenia and mood disorders.