ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Sleep deprivation (SD) has emerged as a significant modifiable risk factor for Alzheimer’s disease (AD), with mounting evidence demonstrating its multifaceted role in accelerating AD pathogenesis through diverse molecular, cellular, and systemic mechanisms. SD is refined within the broader spectrum of sleep-wake and circadian disruption, emphasizing that both acute total sleep loss and chronic sleep restriction destabilize the homeostatic and circadian processes governing glymphatic clearance of neurotoxic proteins. During normal sleep, concentrations of interstitial Aβ and tau fall as cerebrospinal fluid oscillations flush extracellular waste; SD abolishes this rhythm, causing overnight rises in soluble Aβ and tau species in rodent hippocampus and human CSF. Orexinergic neurons sustain arousal, and become hyperactive under SD, further delaying sleep onset and amplifying Aβ production. At the molecular level, SD disrupts Aβ homeostasis through multiple converging pathways, including enhanced production via beta-site APP cleaving enzyme 1 (BACE1) upregulation, coupled with impaired clearance mechanisms involving the glymphatic system dysfunction and reduced Aβ-degrading enzymes (neprilysin and insulin-degrading enzyme). Cellular and histological analyses revealed that these proteinopathies are significantly exacerbated by SD-induced neuroinflammatory cascades characterized by microglial overactivation, astrocyte reactivity, and sustained elevation of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) through NF‑κB signaling and NLRP3 inflammasome activation, creating a self-perpetuating cycle of neurotoxicity. The synaptic and neuronal consequences of chronic SD are particularly profound and potentially irreversible, featuring reduced expression of critical synaptic markers (PSD95, synaptophysin), impaired long-term potentiation (LTP), dendritic spine loss, and diminished neurotrophic support, especially brain-derived neurotrophic factor (BDNF) depletion, which collectively contribute to progressive cognitive decline and memory deficits. Mechanistic investigations identify three core pathways through which SD exerts its neurodegenerative effects: circadian rhythm disruption via BMAL1 suppression, orexin system hyperactivity leading to sustained wakefulness and metabolic stress, and oxidative stress accumulation through mitochondrial dysfunction and reactive oxygen species overproduction. The review critically evaluates promising therapeutic interventions including pharmacological approaches (melatonin, dual orexin receptor antagonists), metabolic strategies (ketogenic diets, and Mediterranean diets rich in omega-3 fatty acids), lifestyle modifications (targeted exercise regimens, cognitive behavioral therapy for insomnia), and emerging technologies (non-invasive photobiomodulation, transcranial magnetic stimulation). Current research limitations include insufficient understanding of dose-response relationships between SD duration/intensity and AD pathology progression, lack of long-term longitudinal clinical data in genetically vulnerable populations (particularly APOE ε4 carriers and those with familial AD mutations), the absence of standardized SD protocols across experimental models that accurately mimic human chronic sleep restriction patterns, and limited investigation of sex differences in SD-induced AD risk. The accumulated evidence underscores the importance of addressing sleep disturbances as part of multimodal AD prevention strategies and highlights the urgent need for clinical trials evaluating sleep-focused interventions in at-risk populations. The review proposes future directions focused on translating mechanistic insights into precision medicine approaches, emphasizing the need for biomarkers to identify SD-vulnerable individuals, chronotherapeutic strategies aligned with circadian biology, and multi-omics integration across sleep, proteostasis and immune profiles may delineate precision-medicine strategies for at-risk populations. By systematically examining these critical connections, this analysis positions sleep quality optimization as a viable strategy for AD prevention and early intervention while providing a comprehensive roadmap for future mechanistic and interventional research in this rapidly evolving field.

Objective:To quantitatively evaluate the level of the three medical linkage in China from 2009 to 2022,explore the influencing factors and driving paths of the three medical linkage in China,and provide a new perspective for promoting the development of the three medical linkage.Methods:An optimized coupling coordination degree model was used to calculate the coupling coordination degree between the trinity healthcare systems and different binary systems within the systems in 31 provinces of China(excluding Hong Kong,Macao and Taiwan),and the Fuzzy-set Qualitative Comparative Analysis method was used to explore the condition configurations of multi-factor-driven three medical linkage.Results:From 2009 to 2022,the coupling coordination degree between the trinity healthcare systems in each province of China generally showed an increasing trend year by year.Among the binary systems,the overall coordinated development situation between the medical and medical insurance systems was the best and the regional development was the most balanced.The coupling coordination degree gap between the trinity healthcare system and the internal binary systems among provinces gradually widened,and the multi-polarization trend intensified.The paths to promote high-level three medical linkage can be summarized into two types:internal and external balanced development type(H1)and government-led type(H2,H3),among which the H1 path with per capita GDP and health expenditure as core conditions was the most common.Conclusion:It is suggested to enhance institutional and technological innovation,and integrate resources through a cross-departmental collaboration mechanism and digital technology.Provinces should select high-level optimization paths by leveraging regional endowments to narrow the regional development gap.Meanwhile,under the impetus of high-level policies,the protection and supervision system continues to improve,thereby promoting the three medical linkage.

Objective:To explore the mediating effect of psychological resilience between family function and post-traumatic growth in young and middle-aged stroke patients,and to provide a theoretical basis for formulating targeted intervention strategies.Methods:This study was a prospective study,a total of 80 young and middle-aged stroke patients admitted in our hospital from February 2023 to August 2024 were selected by the convenient sampling method.The general information of the patients was collected by using a self-made questionnaire,the Connor-Davidson resilience scale(CD-RISC),family care index questionnaire(APGAR)and post-traumatic growth inventory(PTGI)were used to measure psychological resilience,family function and post-traumatic growth levels respectively.The correlations among family function,post-traumatic growth and psychological resilience were analyzed through Person correlation analysis.Construct models of family function and post-traumatic growth to exam ine the mediating effect of psychological resilience,and the scatter plots of correlations and the mediating effect model diagrams were drawn.Results:There were significant differences in the scores of family function,psychological resilience and post-traumatic growth among patients with different characteristics(P＜0.05).The scores of family function,psychological resilience and post-traumatic growth of patients with characteristics such as being married,having a higher educational level,being slightly dependent on daily living skills and having their spouses as the main caregivers were significantly higher(P＜0.05).Pearson correlation analysis showed that family function was significantly positively correlated with psychological resilience(r=0.951,P＜0.05),family function was significantly positively correlated with post-traumatic growth(r=0.939,P＜0.05)and post-traumatic growth was significantly positively correlated with post-traumatic growth(r=0.959,P＜0.05).The structural equation model indicates that psychological resilience plays a partial mediating role between family function and post-traumatic growth,with the mediating effect accounting for 28.42％(95％CI:0.12-0.30)of the total effect.Conclusion:Family function can play an indirect role through psychological resilience to promote post-traumatic growth in young and middle-aged stroke patients,clinically,the collaborative intervention of family function and psychological resilience should be emphasized.

Neuroblastoma(NB),the most common type of extracranial solid tumor in children,is char-acterized by high malignancy and poor prognosis,warranting in-depth investigation.In recent years,mi-croRNAs(miRNAs)have emerged as crucial post-transcriptional regulators playing pivotal roles in tu-morigenesis and progression.Building upon this background,the present study specifically focuses on in-vestigating miR-3910's biological functions and underlying molecular regulatory mechanisms in the NB SH-SY5Y cell line.Through bioinformatics analysis and transcriptome sequencing,we identified potential key target molecules of miR-3910,thereby providing genetic targets for the precise diagnosis and effective treatment of NB.In this study,qRT-PCR was employed to measure miR-3910 expression levels in SH-SY5Y cells transfected with mimic negative control and miR-3910 mimic.Compared to the nc group,miR-3910 expression was significantly upregulated in the mimic group(P＜0.01).The CCK-8 assay and scratch wound healing assay were used to quantitatively assess the impact of miR-3910 on cell prolif-eration and migration.Results showed that cell proliferation significantly increased at 48 h(P＜0.05),and migration ability was markedly enhanced at 48 h(P＜0.01).Flow cytometry was applied to deter-mine the effect of miR-3910 on cell cycle progression,revealing accelerated cell cycle progression,a re-duced proportion of G0/G,phase cells(P＜0.01),and a significant increase in S-phase cells(P＜0.05).Integrated bioinformatics analysis and high-throughput transcriptome sequencing predicted key molecular changes in SH-SY5Y cells following miR-3910 overexpression.Transcriptome sequencing and bioinformatics analysis identified six NB-related genes:EIF3CL(EIF3C),RNF103-CHMP3(VPS24),SULT1A4(SULT1A4),CORO7-PAM16(CORO7),H4C12(Histone H4),and TBC1D3(TBC1D3A/B/C)(aliases sourced from the GeneCards database).qRT-PCR and Western blotting(WB)results are consistency with sequencing results(P＜0.01).In conclusion,miR-3910 overexpression significantly promotes SH-SY5Y cell proliferation,migration,and cell cycle progression,while uncovering a series of potential key target molecules.These findings provide new insights into the pathogenesis of NB and offer a theoretical foundation and potential intervention targets for molecular-targeted therapy in NB.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective To observe the changes in the serum level of tumor necrosis factor-α(TNF-α)during pegylated interferon-alpha(PEG-IFN-α)treatment in inactive HBsAg carriers(IHCs),to investigate the association between the dynamic changes of TNF-α and HBsAg clearance,and to assess the value of TNF-α as a potential biomarker for predicting the therapeutic efficacy of PEG-IFN-α.Methods A prospective study was conducted among 455 IHCs who attended our hospital from January 2018 to March 2023,and they were divided into treatment group and IHC control group.The 210 IHCs in the treatment group voluntarily received PEG-IFNα-2b treatment for 48 weeks,followed by follow-up for 24 weeks,and the 245 IHCs in the IHC control group were followed up for 72 weeks without treatment.The serum level of TNF-α was measured at baseline(week 0)and at weeks 12,24,48,and 72,and at week 72,the treatment group was further divided into HBsAg clearance group and non-clearance group.The serum level of TNF-α at different time points was compared between groups.The logistic regression analysis was used to assess the value of TNF-α in predicting HBsAg clearance.The t-test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance used for comparison between multiple groups;the repeated measures analysis of variance was used for comparison of normally distributed repeated measurement data within each group and between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Univariate and multivariate logistic regression analyses were used to investigate the predictive factors for HBsAg clearance,and the receiver operating characteristic(ROC)curve was used to determine the cut-off value of TNF-α in predicting HBsAg clearance.Results At week 72,compared with the IHC control group,the treatment group had significantly higher HBsAg clearance rate(46.2%vs 1.2%,χ2=133.333,P<0.001)and seroconversion rate(34.8%vs 0.8%,χ2=94.650,P<0.001).The HBsAg clearance group and the non-clearance group had a significant increase in the serum level of TNF-α during treatment,which gradually returned to the baseline level after drug withdrawal(F=351.733 and 76.434,both P<0.001).Comparisons between groups showed that the HBsAg clearance group had the highest serum level of TNF-α at weeks 12,24,and 48,followed by the non-clearance group and the IHC control group(all P<0.001).The multivariate logistic regression analysis showed that baseline HBsAg level(odds ratio[OR]=0.329,95%confidence interval[CI]:0.189-0.571,P<0.001),baseline HBV DNA<20 IU/mL(OR=1.414,95%CI:1.057-1.787,P=0.045),ALT≥2×upper limit of normal at week 12(OR=1.127,95%CI:1.028-1.722,P=0.043),TNF-α level at week 12(OR=1.336,95%CI:1.018-1.754,P=0.037),and TNF-α level at week 24(OR=1.879,95%CI:1.477-2.391,P<0.001)were independent predictive factors for HBsAg clearance.The ROC analysis showed that TNF-α level at week 12 had an area under the ROC curve(AUC)of 0.846(95%CI:0.814-0.889)in predicting HBsAg clearance at week 72,with a sensitivity of 76.3%and a specificity of 81.0%,while TNF-α level at week 24 had an AUC of 0.912(95%CI:0.758-0.972),with a sensitivity of 81.4%and a specificity of 96.2%.Conclusion PEG-IFN-α can increase the serum level of TNF-α in IHCs,and the serum level of TNF-α at weeks 12 and 24 can effectively predict HBsAg clearance induced by PEG-IFN-α.

Objective:To explore the mediating effect of psychological resilience between family function and post-traumatic growth in young and middle-aged stroke patients,and to provide a theoretical basis for formulating targeted intervention strategies.Methods:This study was a prospective study,a total of 80 young and middle-aged stroke patients admitted in our hospital from February 2023 to August 2024 were selected by the convenient sampling method.The general information of the patients was collected by using a self-made questionnaire,the Connor-Davidson resilience scale(CD-RISC),family care index questionnaire(APGAR)and post-traumatic growth inventory(PTGI)were used to measure psychological resilience,family function and post-traumatic growth levels respectively.The correlations among family function,post-traumatic growth and psychological resilience were analyzed through Person correlation analysis.Construct models of family function and post-traumatic growth to exam ine the mediating effect of psychological resilience,and the scatter plots of correlations and the mediating effect model diagrams were drawn.Results:There were significant differences in the scores of family function,psychological resilience and post-traumatic growth among patients with different characteristics(P＜0.05).The scores of family function,psychological resilience and post-traumatic growth of patients with characteristics such as being married,having a higher educational level,being slightly dependent on daily living skills and having their spouses as the main caregivers were significantly higher(P＜0.05).Pearson correlation analysis showed that family function was significantly positively correlated with psychological resilience(r=0.951,P＜0.05),family function was significantly positively correlated with post-traumatic growth(r=0.939,P＜0.05)and post-traumatic growth was significantly positively correlated with post-traumatic growth(r=0.959,P＜0.05).The structural equation model indicates that psychological resilience plays a partial mediating role between family function and post-traumatic growth,with the mediating effect accounting for 28.42％(95％CI:0.12-0.30)of the total effect.Conclusion:Family function can play an indirect role through psychological resilience to promote post-traumatic growth in young and middle-aged stroke patients,clinically,the collaborative intervention of family function and psychological resilience should be emphasized.

The objective of this study was to evaluate the toxicity and safety of novel Mycobacterium tuberculosis fusion strain protein derivatives,referred to as B/R strain active proteins.In cellular experiments,RAW264.7 cells were treated with each vaccine preparation,and apoptosis rates were measured.In subsequent animal experiments,C57BL/6 mice were immunized via subcutaneous injection,and their survival and body weight changes were monitored and recorded at 2,4,8,12,and 16 weeks.The lungs and spleens were harvested to calculate organ coefficients,and pathological examinations were conducted.At the eighth week of immunization,the mice were infected with high concentrations of BCG,and pathological changes in the lungs and spleens were observed 4 weeks post-infection.The apoptosis rate at 6 hours was significantly higher in the experimental group than the PBS group(P<0.05).At 12 and 24 hours,the apoptosis rate in the experimental group remained higher than that in the PBS group,although this difference was not statistically significant.After immunization,mice in all four groups exhibited normal growth patterns,as indicated by stable body weight changes.At 4 and 12 weeks post-immunization,the lung coefficients in the protein group were significantly higher than those in the PBS group at the same time points.Additionally,the lung coefficients in the BCG group were significantly elevated across all time periods(P<0.05).The spleen coefficients in the protein and BCG groups were significantly higher than those in the PBS group at 2,4,8,12,and 16 weeks,whereas the ICD B/R group showed higher spleen coefficients than the PBS group only at week 8(P<0.05).Pathological examination revealed normal lung and spleen tissues in the PBS group.However,during the 2-8 weeks immunization period,lung and spleen tissues in all experimental groups exhibited varying degrees of damage,which gradually diminished by 12-16 weeks.Notably,no tuberculosis nodules were observed in any experimental group.After infection with high concentrations of BCG,no overt pathological changes were observed on the surfaces of the lungs and spleens in any group.Microscopic examination revealed less severe pathological changes in the lungs and spleens of mice in the experimental groups than the PBS group.Furthermore,no statistically significant differences were observed between the protein group and the BCG group.Our findings suggested that the B/R strain active proteins'toxicity and safety profiles were comparable to those of BCG,and showed immunoprotective effects.This study provides an experimental foundation for the development of a novel tuberculosis vaccine.

The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
Animals ; Ventricular Remodeling/drug effects* ; Heart Failure/physiopathology* ; Signal Transduction/drug effects* ; Mice ; Male ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Adenosine/analogs & derivatives* ; Myocytes, Cardiac/metabolism* ; Disease Models, Animal