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.

Objective: To investigate the emotional and behavioral problems among preschool children and the correlations with maternal parenting competence and family rearing environment, so as to provide a scientific basis and practical guidance for the physical and mental health development of preschool children. Methods: In June 2025, 660 preschool children aged 3-6 years old were selected from 10 kindergartens in Hefei, Anqing, and Tongling in Anhui Province by using a stratified cluster random sampling method. A questionnaire survey was conducted among all parents of preschool children using the Parent version of the Strengths and Difficulties Questionnaire, the Child Family Rearing Environment Scale, and the Chinese version of the Parenting Sense of Competence Scale. Pearson correlation analysis and multiple linear regression analysis were used to analyze the related factors of emotional and behavioral problems among preschool children. SPSS macro program Process 4.1 and Bootstrap method were used to test the mediating effect of family parenting environment between emotional and behavioral problems among preschool children and maternal parenting competence. Results: The detection rate of emotional and behavioral problems among preschool children was 20.15%. The total scores of family rearing environment and maternal parenting competence were negatively correlated with emotional and behavioral problems among preschool children ( r =-0.45,-0.79), and the total score of family rearing environment was positively correlated with the total score of maternal parenting competence ( r =0.43) (all P <0.01). Multiple linear regression showed that, after controlling whether being only child, parents educational level, registered residence location and other variables, family rearing environment, self efficacy and satisfaction were all negative predictors of emotional and behavioral problems among preschool children ( B =-0.07, -0.42, -0.42, all P <0.01). The mediation effect results showed that maternal parenting competence could positively predict the family rearing environment ( B =0.75), while maternal parenting competence and family rearing environment could both negatively predict emotional and behavioral problems among preschool children ( B =-0.49, -0.06 ) (all P <0.05). The Bootstrap sampling method test results showed that the effect value of the indirect effect of maternal parenting competence on emotional and behavioral problems through the family rearing environment was -0.04, and the effect proportion was 8.21 %. Conclusion Preschool children with a better family rearing environment and stronger maternal parenting competence are less likely to have emotional and behavioral problems, among which the family rearing environment has a mediating effect.

ObjectiveTo investigate the mechanisms by which Shangxia Liangji pills improve cognitive function in Alzheimer's disease （AD） mice based on the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway， aiming to provide experimental evidence for its clinical use in AD treatment. MethodsFifty APP/PS1 double-transgenic mice were randomly divided into a model group， Shangxia Liangji pills low-dose group， medium-dose group， high-dose group， and donepezil hydrochloride group， with 10 mice in each group. Additionally， 10 C57BL/6 mice of the same genetic background were assigned to the normal group. Cognitive function was assessed using the Morris water maze and novel object recognition tests. Hippocampal pathological changes were observed using transmission electron microscopy and Nissl staining. Neuroinflammation in hippocampal tissue was detected by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of PI3K/Akt pathway-related proteins， postsynaptic density protein 95 （PSD95）， and amyloid precursor protein （APP） in hippocampal tissue were measured by Western blot. ResultsCompared with the normal group， the model group exhibited significantly increased total swimming distance and escape latency， significantly reduced number of platform crossings （P<0.01）， and a decreased recognition index （P<0.01）. Marked neuronal apoptosis was observed in the hippocampal region， with a marked reduction in the number of neurons in the CA3 region （P<0.01）. Levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in hippocampal tissue were significantly elevated （P<0.01）. APP expression in hippocampal tissue was markedly upregulated （P<0.01）， while PSD95， p-PI3K/PI3K， and p-Akt/Akt protein expression were significantly downregulated （P<0.01）. Compared with the model group， the Shangxia Liangji pills high-dose group showed significantly reduced total swimming distance and escape latency， significantly increased number of platform crossings （P<0.01）， and an elevated recognition index （P<0.01）. Hippocampal neuronal apoptosis was alleviated， with a significant increase in the number of neurons in the CA3 region （P<0.01）. Levels of IL-6， IL-1β， and TNF-α were significantly decreased （P<0.01）. APP expression was downregulated （P<0.05）， while PSD95， p-PI3K/PI3K， and p-Akt/Akt protein expression were significantly upregulated （P<0.01）. ConclusionShangxia Liangji pills may improve cognitive function in AD mice by modulating the PI3K/Akt pathway， thereby reducing neuroinflammation and alleviating neuronal and synaptic injury.

OBJECTIVE To evaluate the efficacy and safety of sacituzumab tirumotecan combined with bevacizumab for the treatment of human epidermal growth factor receptor 2-negative （HER2－） breast cancer with brain metastases.METHODS Clinical data of 90 patients with HER2－ breast cancer with brain metastases treated at the First Affiliated Hospital of Nanyang Medical College from December 2024 to November 2025 were retrospectively collected. According to the treatment regimens， the patients were divided into a control group （ n ＝55） and an experimental group （ n ＝35）. Patients in the experimental group received sacituzumab tirumotecan combined with bevacizumab， whereas those in the control group received conventional systemic therapy， including albumin-bound paclitaxel-based regimens， capecitabine-based regimens， or gemcitabine/vinorelbine combined with platinum-based regimens. Short-term efficacy， progression-free survival （PFS）， brain metastasis-related efficacy， adverse events， treatment discontinuation due to adverse events， and treatment-related deaths were compared between the two groups.RESULTS The objective response rate （ORR）， disease control rate， median PFS， intracranial disease control rate， and proportion of patients with improvement in neurological symptoms in the experimental group were significantly higher than in the control group （ P ＜0.05）. Stratified analysis showed that PFS of the experimental group was significantly longer than the control group among patients with Breast-Graded Prognostic Assessment scores ≥2.0 and ＜2.0 （ P ＜0.05）. There were no statistically significant differences in the proportion of patients with glucocorticoid dose reduction/discontinuation， the incidence of adverse events of different grades， or the rate of treatment discontinuation due to adverse events between the two groups （ P ＞0.05）. No treatment-related deaths occurred in either group.CONCLUSIONS Compared with conventional systemic therapy， sacituzumab tirumotecan combined with bevacizumab can improve the ORR and prolong PFS in patients with HER2－ breast cancer with brain metastases， with an overall manageable safety profile.

Urinary control in females is a complex physiological process.From an anatomical perspective,this article explores the role of static urethral anatomical changes and dynamic functional anatomical changes in the occurrence of female stress urinary incontinence (SUI).In SUI patients,the changes in the urethra include mucosal atrophy,reduced elasticity,sphincter dysfunction,and shortening of the functional urethral length.The surrounding supportive structures involved in the development of SUI include weakened bladder neck support,damage to the hammock structure,weakened pubic urethral ligament and dysfunction of the levator ani muscle.Additionally,damage to the pelvic floor nerve plays an important role in the pathophysiology of SUI.In terms of dynamic functional anatomy,this article analyzes three dynamic interlocking mechanisms,including the interlock between the bladder neck and pelvic diaphragm,the external urethral sphincter and levator ani muscle,the posterior urethra and perineal body.Through these dynamic mechanisms,the static structure is coordinated and supported,helping to maintain normal urinary control function.These analyses aid in understanding the mechanisms underlying urinary control problems in SUI patients.In summary,this article attempts to construct a clear theoretical framework for the clinical diagnosis and treatment of female SUI by systematically analyzing the static and dynamic factors of female urinary control mechanisms.

Diabetic cognitive impairment （DCI） has an insidious onset and progressive and irreversible development. There is currently no first-line treatment for DCI. Early intervention of diabetes with traditional Chinese medicine （TCM） can effectively control blood sugar and improve cognitive impairment， which has significant advantages. As a representative of bitter and cold heat-clearing medicines， Coptidis Rhizoma， known for its abilities to clear heat and dampness and remove turbidity and toxins， has been widely used in the clinical prevention and treatment of diabetes， Alzheimer's disease， vascular dementia， and other cognitive impairments. This article systematically summarized relevant literature and observed that Coptidis Rhizoma has shown good potential in the prevention and treatment of DCI with its active ingredients such as berberine and quercetin， drug pairs such as Coptidis Rhizoma-Scutellariae Radix， Coptidis Rhizoma-Acorus Tatarinowii Rhizoma， Coptidis Rhizoma-Pinelliae Rhizoma， Coptidis Rhizoma-Zingiberis Rhizoma， and prescriptions such as Gegen Qinliantang， Huanglian Jiedutang， Banxia Xiexintang， Huanglian Wendantang， Jiaotai Wan， Danggui liuhuangtang， and related Chinese patent medicines. Its mechanism may be related to regulating glucose metabolism， improving insulin resistance， improving amyloid β-protein （Aβ） deposition and tau protein phosphorylation， inhibiting neuroinflammation and oxidative stress， and regulating the "microbe-gut-brain axis". The article systematically reviewed the research progress of Coptidis Rhizoma and its prescriptions in the prevention and treatment of DCI， aiming to preliminarily explain the scientific connotation of Coptidis Rhizoma and provide a basis for its clinical application in the prevention and treatment of DCI.

Objective: To investigate the relationship between pubertal timing and depressive symptoms among high school students in Suzhou, so as to provide scientific evidence for promoting adolescents mental health. Methods: From October 2023 to January 2024, 3 369 students were selected from 20 high schools in Suzhou using stratified cluster random sampling method. Physical examinations and questionnaire surveys were conducted. The Preece & Baines growth Model 1 was used to calculate the age at take off of height velocity (ATO) and age at peak height velocity (APHV), categorizing students into three groups: early pubertal timing group (< P 15 ), ontime group ( P 15 - P 85 ), and delayed group (> P 85 ). Binary Logistic regression was used to analyze its association with depressive symptoms. Results: The ATO for male and female high school students in Suzhou was (9.35±1.23) and ( 8.12 ±1.52) years old, respectively. The mean APHV was (12.35±0.74) years old for boys and (10.91±0.82) years old for girls. The overall prevalence of depressive symptoms was 34.22%, with no statistically significant gender difference ( χ 2=0.42, P =0.52). Significant differences in depressive symptom prevalence were observed across grade levels, breakfast frequency, weekly days of moderate to vigorous physical activity, daily sleep duration, history of school bullying, and the presence of Internet addiction ( χ 2=5.03-69.21, all P < 0.05 ). After adjusting for age, body mass index, region, boarding status, breakfast frequency, weekly moderate to vigorous physical activity days, sleep duration, campus bullying, and presence of Internet addiction, Logistic regression analysis revealed that when ATO was used to evaluate pubertal timing, the risk of depressive symptoms in the delayed group of boys was 1.65 times that of the on time group (95% CI =1.24-2.19); when APHV was used to evaluate pubertal timing, the risks of depressive symptoms in the early pubertal timing group and delayed group of boys were 1.43 times (95% CI =1.07-1.91) and 1.41 times (95% CI =1.05-1.88) of that of the on time group, respectively (all P <0.05). No statistically significant associations were found among females (all P > 0.05 ). Conclusion The prevalence of depressive symptoms among high school students in Suzhou is relatively high, and both early and delayed puberty timing in boys are associated with depressive symptoms.

Objective To investigate the potential mechanism of action of polygonatum odoratum in treating Alzheimer's disease through the utilization of network pharmacology and molecular docking techniques.Methods The methods employed include target screening,Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and molecular docking simulations to assess the binding interactions between the active compounds in polygonatum odoratum(POD)and the key target proteins associated with Alzheimer's disease.Subsequently,lipopolysaccharide(LPS)was used to induce an inflammatory cell model in BV2 microglial cells.After treating the cell model with POD extract for 24 hours,the cells were collected,and the expression of the target genes were detected by Real-time PCR.Results Eight active ingredients and 172 targets of POD were screened.The biological processes such as protein phosphorylation and signal transduction,protein binding and ATP binding were obtained by GO functional analysis.KEGG enrichment yielded PI3K/Akt,cAMP and other signaling pathways.The molecular docking result showed that the active ingredient of POD had well binding activity with epidermal growth factor receptor(EGFR),proto-oncogene tyrosine-protein kinase Src(SRC),tumor necrosis factor(TNF),STAT3.Through Real-time PCR experiments,the gene expressions of inducible nitric oxide synthase(iNOS),prostaglandin G/H synthase 2(PTGS2),interleukin(IL)-6,and IL-1β in the LPS-induced inflammatory cell model were significantly upregulated.After treating the inflammatory model with POD extract for 24 hours,the expression of TNF-α was significantly reduced,the expression of STAT3 was upregulated,there were no significant changes in the expressions of SRC and EGFR.Conclusion Network pharmacology suggests polygonatum odoratum's potential anti-Alzheimer's effects may be mediated through its interaction with targets such as EGFR,TNF,SRC,and STAT3.The experimental results suggest that polygonatum odoratum exerts an anti-inflammatory effect by acting on TNF-α,which may further alleviate the symptoms of Alzheimer's disease.

Objective To analyze the publication condition and development trends of global post-stroke fatigue(PSF)research from 2004 to 2024.Methods Relevant literature on PSF pub-lished between January 1,2004,and August 1,2024,were systematically searched and screened from WoSCC database.Visual analysis of publication volume,contributing countries,institutions,authors,and keywords in PSF research was conducted using CiteSpace software.Results A total of 373 articles were included in this study.The overall publication volume related to PSF exhibited an upward trend.The country,institution,and author with the highest number of publications were the United Kingdom,the University of Oslo,and LERDAL A,respectively.High-frequency keywords in-cluded quality of life,depression,fatigue severity scale,follow up,epidemiology,symptoms,associ-ations,and rehabilitation,while the emerging keywords were health care professionals,risk factors,and participation.Conclusion PSF-related research has demonstrated an overall upward trend.As-sessment and measurement protocols,rehabilitation treatment approaches,impacts on quality of life,and the intrinsic relationship with depression have emerged as research hotspots.Further exploration of precise and systematic assessment methods,along with the construction of scientific rehabilitation management programs and risk prediction models,will become the focal points of future research.

Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.