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.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Objective To investigate the role of the pituitary tumor-transforming gene 3(PTTG3P)/microRNA-146a-3p(miR-146a-3p)/pituitary tumor-transforming gene 1(PTTG1)pathway in the castration-resistant transformation of prostate cancer(PCa).Methods Real-time quantitative PCR(qPCR)was used to detect the differences in PTTG3P mRNA expression between androgen-dependent PCa cells LNCaP and cas-tration-resistant PCa(CRPC)cells PC3 and DU145,as well as between primary PCa tissues and CRPC tis-sues.PTTG3P overexpression vectors and PTTG1 interference vectors(shPTTG1)were constructed and transfected into LNCaP cells.The cells were divided into the LNCaP group(control),LNCaP/PTTG3P group(transfected with PTTG3P overexpression vector),and LNCaP/PTTG3P/shPTTG group(transfected with PTTG3P overexpression vector and shPTTG).Under castrated conditions,qPCR was used to detect the ex-pression levels of PTTG3P mRNA and miR-146a-3p in each group of LNCaP cells.Cell viability assays in vitro were conducted to assess the growth status of each group of LNCaP cells,colony formation assays were performed to evaluate the tumorigenic ability of each group of LNCaP cells,and Western blotting was used to detect PTTG1 protein expression levels in each group of LNCaP cells.To investigate the role of miR-146a-3p in the PTTG3P/PTTG1 pathway,LNCaP cells were transfected with a miR-146a-3p mimic to establish a miR-146a-3p mimic cell line,and then transfected with the PTTG3P overexpression plasmid to create a miR-146a-3p mimic+PTTG3P cell line.A luciferase reporter assay was conducted to verify the relationship between miR-146a-3p and PTTG1.Results Compared with androgen-dependent PCa cells LNCaP and treatment-naive PCa tissues,PTTG3P mRNA expression was higher in CRPC cells PC3,DU145,and tissues(P<0.05).Un-der castration conditions,the cell viability and colony formation ability of the LNCaP/PTTG3P group were higher than those of the LNCaP group(P<0.05);cell viability and colony formation ability in the LNCaP/PTTG3P/shPTTG group were lower than those in the LNCaP/PTTG3P group(P<0.05);miR-146a-3p ex-pression was lower in CRPC than in treatment-naive PCa tissues(P<0.05).Overexpression of miR-146a-3p inhibited PTTG1 expression in LNCaP cells,and overexpression of PTTG3P reversed this effect(P<0.05).Conclusion Overexpression of PTTG3P promotes the progression of PCa to CRPC through the miR-146a-3p/PTTG1 pathway.The mechanism may involve PTTG3P competitively binding to miR-146a-3p,thereby upreg-ulating PTTG1 expression.

Objective To investigate the role of Insulin like growth factor 2 mRNA binding protein 1(IGF2BP1)and long non-coding RNA LINC00160(LINC00160)in gastric cancer,and its potential mechanism of regulating the proliferation and invasion of gastric cancer cells.Methods Quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the expression level of LINC00160 in gastric cancer tissues and cells.Bioinformatics prediction,RNA-binding protein immunoprecipitation(RIP)and methylated RNA immunoprecipitation(MeRIP)were used to verify the binding effect of LINC00160 and IGF2BP1.The correlation between the expression of LINC00160 and IGF2BP1 in gastric cancer tissues was analyzed by Pearson assay.CCK-8 assay and Transwell assay were used to detect cell proliferation and invasion.The changes of aerobic glycolysis index[glucose intake,lactate production,and Adenosine-triphosphate(ATP),extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)]were detected and analyzed.Results Compared with normal tissues,the expression of LINC00160 in gastric cancer tissues(5.13±0.62 vs 1.02±0.03)was significantly up-regulated,and the difference was statistically significant(t=-36.266,P<0.001).The expression level of LINC00160 in gastric cancer cells was higher than that of human normal gastric epithelial cell line GES-1,and the difference was statistically significant(F=24.595,P<0.001).Compared with the control group,silenting LINC00160 significantly inhibited the proliferation(0.42±0.03 vs 1.03±0.04)and invasion(22.13%±1.97%vs 42.15%±2.67%)of AGS cells,decreased glucose uptake(2.11±0.26mmol/L vs 4.22±0.37mmol/L)and lactate production(6.84±1.25mmol/L vs 11.68±1.55mmol/L),decreased ECAR,and increased ATP(3.34±0.29mmol/L vs 1.87±0.24mmol/L)levels and OCR,and the differences were statistically significant(t=4.188～24.423,all P<0.01).The expression of IGF2BP1 protein in gastric cancer tissues(4.07±0.36)was significantly higher than that in adjacent tissues(1.01±0.03),and the difference was statistically significant(t=-46.396,P<0.01),and was positively correlated with the expression of LINC00160(r2=0.774 5,P<0.01).Mechanistic studies revealed that IGF2BP1 upregulated LINC00160 expression by binding m6A modified LINC00160 to promote its stability.Silencing IGF2BP1 significantly inhibited the expression of LINC00160 and the proliferation,invasion and aerobic glycolysis of gastric cancer cells,and the differences were statistically significant(t=4.386～11.989,all P<0.01).Overexpression of LINC00160 reversed the effect of IGF2BP1 silencing on AGS cells.Conclusion LINC00160 is significantly up-regulated in gastric cancer,and IGF2BP1 may stably regulate the expression of LINC00160 through m6A modification,promote the aerobic glycolysis of tumor cells,and participate in the occurrence and development of gastric cancer.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To investigate the levels of C reactive protein(CRP)and interleukin(IL)-6 in patients with myocardial infarction(MI)and their association with cardiac function.Methods:We enrolled 140 MI patients ad-mitted to Sanya Harbin Medical University Hongsen Hospital Co.,Ltd between January 2020 and December 2022,as MI group.According to coronary stenotic severity,they were divided into mild group(n=62),moderate group(n=41)and severe group(n=37),and 75 healthy individuals who underwent physical examination simultaneously were selected as control group.Serum CRP,IL-6,cardiac troponin Ⅰ(cTnⅠ)and creatine kinase isoenzyme MB(CK-MB)levels were measured by automatic biochemical analyzer,and left ventricular ejection fraction(LVEF)was assessed by echocardiography.Above-mentioned indexes were compared between MI group and control group,and among groups of different coronary disease severity.Pearson/Spearman correlation was used to analyze the asso-ciation of serum CRP and IL-6 levels with Gensini score,cTnⅠ,CK-MB levels,and LVEF in MI patients.Diag-nostic value of serum CRP and IL-6 levels for MI was analyzed by receiver operating characteristic(ROC)curve.Results:Compared with participants in control group,those in MI group had significant higher serum CRP,IL-6,cTnⅠ and CK-MB,and significant lower LVEF(P＜0.001 all).Serum CRP,IL-6,cTnⅠ and CK-MB levels sig-nificantly increased,and LVEF significant decreased in the order of mild group,moderate group and severe group(P＜0.01 all).Pearson/Spearman correlation analysis showed that serum CRP and IL-6 levels were positively cor-related with Gensini score,cTnⅠ,and CK-MB levels(r=0.496～0.646,P＜0.001all),and negatively correlated with LVEF(r=-0.530,-0.572,P＜0.001 all)in MI patients.ROC curve showed that the area under the curve(AUC)of CRP combined IL-6 diagnosing MI was 0.856(95％CI 0.802～0.900),which was significantly higher than those of CRP(AUC=0.770,95％CI 0.708～0.824)and IL-6(AUC=0.793,95％CI 0.733～0.845)alone(Z=3.295,2.877,P＜0.01 all).Conclusion:Serum CRP and IL-6 levels rise in MI patients,and they are closely associated with increased severity of coronary artery disease and reduced cardiac function.

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.

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:To investigate the effects of wheat-grain moxibustion at the Guanyuan point on testosterone(T)synthe-sis and the hypothalamic-pituitary-gonadal(HPG)axis in naturally aged mice.Methods:We fed 40 twelve-month-old SPF male C57BL/6J mice with a normal diet for 3 months,randomized them into a moxibustion and an aged group of an equal number,and se-lected 7 four-month-old ones as young controls.We treated the animals of the moxibustion group by wheat-grain moxibustion at the Guanyuan point,once 5 moxibustion sticks,qd,5 times a week,and fed those of the aged group normally,all for 12 weeks.After treatment,we obtained the testicular index of the mice,observed the histomorphology of the testis tissue by HE staining,measured the contents of T in the testis,gonadotropin-releasing hormone(GnRH)in the hypothalamus and total T(tT),free T(fT),luteinizing hormone(LH)and follicle-stimulating hormone(FSH)in the serum by ELISA,and determined the expressions of silence information regulator-1(SIRT1),P53,glutathione peroxidase(GPX4)and cholesterol side-chain?cleavage enzym e(CYP11A1)in the testis by Western blot.Results:Compared with the young controls,the mice in the aged group showed obviously losing and dull hair,energy declination,loose structure of the spermatogenic tubule with different degrees of cell loss and rupture,reduced testicular index,and ev-ident aging phenotype.In comparison with the aged mice,the animals of the moxibustion group were fairly energetic and exhibited dis-tinct structure of the spermatogenic tubules,orderly arranged and highly differentiated cells at all levels,significantly increased T lev-el,up-regulated expressions of SIRT1,GPX4 and CYP11 A1,and down-regulated expression of P53 in testis tissue,and elevated levels of GnRH,FSH,LH,tT and fT in the HPG axis.Conclusion:Wheat-grain moxibustion at the Guanyuan point protects testosterone synthesis in the testis tissue of naturally aged mice,promotes negative feedback regulation of the HPG axis,and improves low testoster-one.

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.