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.

To evaluate the reliability of flash continuous glucose monitoring(CGM) and itsaccuracy in supporting clinical decision-making after pancreatic surgery.

ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

OBJECTIVES: Osteoarthritis (OA) and sarcopenia are significant health concerns in the elderly, substantially impacting their daily activities and quality of life. However, the relationship between them remains poorly understood. This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia. METHODS: Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between disease and control groups were identified using R software. Common DEGs were extracted via Venn diagram analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs. Protein-protein interaction (PPI) networks were constructed, and candidate hub genes were ranked using the maximal clique centrality (MCC) algorithm. Further validation of hub gene expression was performed using 2 independent datasets. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia. Mouse models of OA and sarcopenia were established. Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model. The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement. Real-time reverse transcription PCR (real-time RT-PCR) was employed to assess the mRNA expression levels of candidate key genes in both models. Gene set enrichment analysis (GSEA) was conducted to identify pathways associated with the selected shared key genes in both diseases. RESULTS: A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia, including 76 upregulated and 13 downregulated genes. These 89 DEGs were significantly enriched in protein digestion and absorption, the PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction. PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes. Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets, AEBP1 and COL8A2 were ultimately selected as the common key genes for both diseases, both of which showed a significant upregulation trend in the disease groups (all P<0.05). The value of area under the curve (AUC) for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7, indicating that both genes have potential value in predicting OA and sarcopenia. Real-time RT-PCR results showed that the mRNA expression levels of AEBP1 and COL8A2 were significantly upregulated in the disease groups (all P<0.05), consistent with the results observed in the bioinformatics analysis. GSEA revealed that AEBP1 and COL8A2 were closely related to extracellular matrix-receptor interaction, ribosome, and oxidative phosphorylation in OA and sarcopenia. CONCLUSIONS AEBP1 and COL8A2 have the potential to serve as common biomarkers for OA and sarcopenia. The extracellular matrix-receptor interaction pathway may represent a potential target for the prevention and treatment of both OA and sarcopenia.
Sarcopenia/genetics* ; Osteoarthritis/genetics* ; Computational Biology/methods* ; Humans ; Protein Interaction Maps/genetics* ; Animals ; Mice ; Gene Expression Profiling ; Gene Ontology ; Transcriptome ; Male ; Signal Transduction/genetics* ; Gene Regulatory Networks

OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression. METHODS: In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88^flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis. RESULTS: In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression. CONCLUSIONS Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals ; Chondrocytes/cytology* ; Apoptosis/physiology* ; Mice ; Cilia/metabolism* ; Osteoarthritis/pathology* ; Extracellular Matrix/metabolism* ; Mice, Knockout ; Disease Progression ; Interleukin-1beta ; Male ; Cells, Cultured

Objective:This article explores the diagnosis and treatment of a special type of laryngeal foreign body with granuloma in children, providing a clinical reference for standardized diagnosis and treatment. Methods:This article retrospectively analyzes one case admitted to our department and five other cases reported in relevant literature involving a special type of laryngeal foreign body with granuloma in children. It summarizes the clinical characteristics of this disease and explores its diagnosis and treatment. Results:①A total of 6 cases were misdiagnosed and had a long course of illness. Five cases had no clear history of foreign body at the first visit. One case had foreign body history but no foreign body was found. ②The clinical symptoms were diverse, which could be hoarseness, cough, wheezing, dyspnea, or no symptoms. ③A total of 3 cases were diagnosed by laryngoscopy, and 3 cases were diagnosed by laryngoscopy and imaging examination. ④Foreign bodies that were not wrapped in granulomas, were removed first and then the granulomas were treated; foreign bodies wrapped in granulomas were removed after the removal of granulomas. Conclusion:A special type of laryngeal foreign body with granuloma may lack of accurate foreign body history, resulting in long-term retention of foreign bodies, leading to granuloma formation and misdiagnosis. Electronic laryngoscopy combined with CT examination contribute to early diagnosis. Low temperature plasma under endoscope and anesthetic laryngoscope is conducive to the exposure and precise removal of foreign bodies and avoids tracheotomy to a certain extent.
Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Foreign Bodies/surgery* ; Granuloma, Foreign-Body/therapy* ; Larynx/pathology* ; Retrospective Studies

Objective:To explore the efficacy of using drug combination and sublingual immunotherapy（SLIT） for pediatric obstructive sleep apnea（OSA） and allergic rhinitis（AR） after adenotonsillectomy, in order to provide a more optimized treatment plan after the surgery. Methods:A total of 95 pediatric OSA combined with AR were selected. According to the treatment plan, they were divided into the SLIT group（postoperative medication combined with SLIT） and the control group（postoperative medication treatment only）. The comparisons were made between the two groups regarding the scores of the 18-item Quality of Life Questionnaire for Obstructive Sleep Apnea（OSA-18） and the Visual Analogue Scale（VAS） before and at 1 month, 3 months, 6 months, 1 year, and 2 years after treatment; the monthly total medication scores（TMS） from 1 month to 3 months, 4 months to 6 months, 7 months to 1 year, and 1 year to 2 years after treatment, as well as the number of acute attacks of AR in the 1st year and 2nd year after treatment; and the Lund-Kennedy scores and nasal resistance grading of nasal endoscopy before and at 1 month, 3 months, 6 months, 1 year, and 2 years after treatment. The effectiveness and safety were also analyzed. Results:After one year of treatment, the OSA-18 score, VAS score, TMS and Lund-Kennedy score in the SLIT group were significantly better than those in the control group. The nasal resistance was significantly reduced（P<0.05）, and the frequency of AR attacks was significantly lower than that in the control group（P<0.05）. After 2 years of treatment, the VAS score, Lund-Kennedy score and nasal resistance classification in the SLIT group tended to stabilize, while the OSA-18 score continued to decline. Conclusion:After surgery for pediatric OSA combined with AR, the use of drugs combined with SLIT can effectively alleviate AR symptoms, further improve OSA-related symptoms and quality of life, reduce drug dependence, decrease the frequency of AR attacks, and enhance the long-term efficacy of the surgery.
Humans ; Sleep Apnea, Obstructive/surgery* ; Rhinitis, Allergic/therapy* ; Quality of Life ; Child ; Tonsillectomy ; Treatment Outcome ; Adenoidectomy ; Sublingual Immunotherapy ; Drug Therapy, Combination ; Male ; Female