BACKGROUND:As a multifunctional histone acetyltransferase,E1A binding protein P300(EP300)is widely involved in biological processes such as gene expression regulation,cell growth and differentiation,and has been associated with a variety of inflammatory and immune-related diseases.However,its specific role in the pathogenesis of allergic rhinitis is unclear.OBJECTIVE:To explore the changes in gene expression related to allergic rhinitis,analyze its association with programmed cell death,and search for potential biomarkers and therapeutic targets.METHODS:(1)Gene expression data of patients with allergic rhinitis and the control group were collected from the GSE51392,GSE43523 and GSE206149 datasets.Differentially expressed genes were screened and weighted gene co-expression network analysis was performed.(2)From March 2022 to May 2024,10 patients with allergic rhinitis who underwent vidian neurectomy and 10 healthy controls were recruited from the Fifth Affiliated Hospital of Xinjiang Medical University.Blood and nasal mucosal tissue samples were collected from the patients before and after surgery.(3)A rat model of allergic rhinitis was established and EP300 was knocked down.The rats were divided into control group,model group,model+shEP300-NC group,and model+shEP300 group.ELISA,hematoxylin-eosin staining,RT-qPCR and western blot assay were used to detect the levels of inflammatory factors,pathological changes in nasal mucosal tissues,and the expression of related genes and proteins.RESULTS AND CONCLUSION:(1)A total of 43 intersection genes were identified between allergic rhinitis and the control group.Weighted gene co-expression network analysis revealed that the Green module was strongly correlated with allergic rhinitis.Through intersection analysis with genes related to programmed cell death and common differentially expressed genes,the key gene EP300 was obtained.(2)Compared with the preoperative status of patients with allergic rhinitis,the levels of interleukin-4,interleukin-5,interleukin-13,EP300,LC3B,Beclin1,cleaved-Caspase were significantly decreased,while the expressions of p62 and Bcl2 in nasal mucous tissue were significantly increased after surgery.(3)Compared with the control group,the levels of interleukin-4,interleukin-5,interleukin-13,EP300,LC3B,Beclin1,and cleaved-Caspase were significantly increased,while the expressions of p62 and Bcl2 in nasal mucous tissue were significantly decreased in the model group.Compared with the model group,the above indicators had opposite changes.To conclude,EP300 can participate in allergic rhinitis by regulating inflammation,autophagy and apoptosis.

BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.

BACKGROUND:As a multifunctional histone acetyltransferase,E1A binding protein P300(EP300)is widely involved in biological processes such as gene expression regulation,cell growth and differentiation,and has been associated with a variety of inflammatory and immune-related diseases.However,its specific role in the pathogenesis of allergic rhinitis is unclear.OBJECTIVE:To explore the changes in gene expression related to allergic rhinitis,analyze its association with programmed cell death,and search for potential biomarkers and therapeutic targets.METHODS:(1)Gene expression data of patients with allergic rhinitis and the control group were collected from the GSE51392,GSE43523 and GSE206149 datasets.Differentially expressed genes were screened and weighted gene co-expression network analysis was performed.(2)From March 2022 to May 2024,10 patients with allergic rhinitis who underwent vidian neurectomy and 10 healthy controls were recruited from the Fifth Affiliated Hospital of Xinjiang Medical University.Blood and nasal mucosal tissue samples were collected from the patients before and after surgery.(3)A rat model of allergic rhinitis was established and EP300 was knocked down.The rats were divided into control group,model group,model+shEP300-NC group,and model+shEP300 group.ELISA,hematoxylin-eosin staining,RT-qPCR and western blot assay were used to detect the levels of inflammatory factors,pathological changes in nasal mucosal tissues,and the expression of related genes and proteins.RESULTS AND CONCLUSION:(1)A total of 43 intersection genes were identified between allergic rhinitis and the control group.Weighted gene co-expression network analysis revealed that the Green module was strongly correlated with allergic rhinitis.Through intersection analysis with genes related to programmed cell death and common differentially expressed genes,the key gene EP300 was obtained.(2)Compared with the preoperative status of patients with allergic rhinitis,the levels of interleukin-4,interleukin-5,interleukin-13,EP300,LC3B,Beclin1,cleaved-Caspase were significantly decreased,while the expressions of p62 and Bcl2 in nasal mucous tissue were significantly increased after surgery.(3)Compared with the control group,the levels of interleukin-4,interleukin-5,interleukin-13,EP300,LC3B,Beclin1,and cleaved-Caspase were significantly increased,while the expressions of p62 and Bcl2 in nasal mucous tissue were significantly decreased in the model group.Compared with the model group,the above indicators had opposite changes.To conclude,EP300 can participate in allergic rhinitis by regulating inflammation,autophagy and apoptosis.

Objective To investigate the risk factors for abnormal cardiac function in patients with hepatolenticular degeneration （also known as Wilson disease ，WD） using cardiac magnetic resonance imaging （CMR）， and to identify indicators with a value for early diagnosis. Methods Patients diagnosed with WD were randomly selected to undergo CMR examination， and based on CMR findings， they were divided into abnormal group and normal group. A univariate analysis was used to obtain potential risk factors， then a multivariate logistic regression analysis was performed for variables with a significant difference， and finally the receiver operating characteristic （ROC） curve analysis was performed for the independent risk factors identified. Results A total of 42 WD patients were enrolled， with 21 in the abnormal CMR group and 21 in the normal CMR group. Compared with the normal CMR group， the abnormal CMR group had a significantly higher age and significantly higher levels of total bilirubin， serum copper， and peak 24-hour urinary copper during treatment. The multivariate Logistic regression analysis showed that white blood cell count （WBC） （OR=2.927， 95%CI 1.127‒7.839， P=0.028）， serum copper（OR=3.822， 95%CI 1.108‒13.178， P=0.034）， and type Ⅳ collagen （OR=1.097， 95%CI 1.011‒1.191，P=0.027） were independent risk factors for CMR abnormalities in WD patients. The ROC curve analysis showed that among the above three indicators used alone， serum copper had the highest diagnostic value with an area under the ROC curve （AUC） of 0.713， followed by WBC（AUC=0.651） and type Ⅳ collagen （AUC=0.644）， and the combination of these three indicators had significantly higher diagnostic efficacy （AUC=0.869）. Conclusion Serum copper is the single indicator with the highest diagnostic efficacy for CMR abnormalities in WD patients， but the combination of serum copper， WBC， and type Ⅳ collagen has a significantly better diagnostic value in identifying abnormal cardiac function in WD patients.

Objective: To explore the developmental trajectories of depression in children and adolescents and their association with family types, and to analyze the role of being an only child in the context, so as to provide a basis for early identification of mental health issues in children and adolescents. Methods: The study was a secondary analysis based on the existing database of the Jiangsu Provincial Student Common Diseases and Health Influencing Factors Monitoring and Intervention Project. A total of 11 502 students who had completed at least two measurements using the Chinese version of the Center for Epidemiologic Studies Depression Scale (CES-D) between 2022 and 2024, and had complete information on family type, gender, and age, were selected as the study subjects. Latent class trajectory modeling was used to identify depression developmental trajectories. Multinomial Logistic regression was applied to analyze the association between family type and depression developmental trajectories, and the interaction effect of family type and being an only child was tested. Results: Three types of depression developmental trajectories were identified among children and adolescents: low stable type (91.3%, 10 504 students), moderate rising type (4.3%, 500 students), and high declining type (4.3%, 498 students). Significant differences were observed among the different trajectory groups in terms of gender, age, parental education level, family type, baseline CES-D score, and baseline school type ( χ 2/H=17.48, 139.97, 19.72 , 30.77, 1 081.35, 220.81, all P <0.05). Multinomial Logistic regression analysis showed that, using the low stable type as the reference trajectory group and the nuclear family as the reference family type, after adjusting for confounding factors such as gender, age, and parental education level, single parent families ( OR=1.87, 95%CI= 1.16-3.03) and grandparent headed families ( OR=1.83, 95%CI =1.04-3.21) were significantly associated with the high declining type trajectory (both P <0.05). No significant association was found between family type and the moderate rising type trajectory (all P >0.05). The interaction effect between family type and being an only child was not statistically significant ( LRT=7.71, df=8, P =0.46). Conclusions Depressive symptoms in children and adolescents show heterogeneous developmental patterns during school age. Children and adolescents from single parent and intergenerational families are more likely to follow the high decreasing trajectory.

摘要 目的 探讨血浆神经胶质细胞原纤维酸性蛋白（GFAP）及同型半胱氨酸（Hcy）水平对肝豆状核变性（又称肝豆状核变性，WD）的诊断及肝脑型鉴别诊断价值。方法 招募安徽中医药大学第一附属医院脑病中心2023年1月—2025年1月收治的WD患者共120例，其中WD脑型63例，WD肝型57例，以及同期在体检中心筛查的30名健康志愿者。采用ELISA法测定纳入对象血浆GFAP、Hcy水平，进行组间差异性比较和ROC曲线分析。并运用Spearman相关分析探讨血浆GFAP、Hcy水平与统一肝豆状核变性评定量表评分（UWDRS）、24 h尿铜及血清铜蓝蛋白（CER）水平的相关性。结果 WD肝型及脑型患者的血浆GFAP水平均显著高于对照组（P<0.05），且WD脑型较WD肝型升高更为显著（P<0.05）。血浆Hcy水平也在WD肝型及脑型患者中明显升高（P<0.05），但在WD肝型、脑型间未表现出显著差异。血浆GFAP诊断WD脑型的曲线下面积（AUC）为0.861，截断值为135.71 pg/ml，敏感度68.3％，特异度82.3％；该指标诊断WD肝型的AUC为0.695，截断值为129.84 pg/ml，敏感度64.7％，特异度83.3％；其在WD肝型及脑型鉴别诊断中的AUC为0.75，截断值为151.12 pg/ml，敏感度73.9％，特异度87.8％。血浆Hcy诊断WD的AUC为0.788，截断值为15.59 μmol/L，敏感性77.9％，特异性66.7％。Spearman相关性分析结果显示，WD肝型及脑型患者血浆GFAP、Hcy水平与UWDRS评分及24 h尿铜水平均呈正相关（P<0.05），与CER水平无显著相关性（P>0.05）。结论 血浆GFAP、Hcy水平与WD神经及肝脏功能受损程度密切相关，且为早期诊断WD以及血浆GFAP对WD各分型的鉴别诊断提供了一定的临床价值。 Abstract Objective To investigate the value of plasma glial fibrillary acidic protein （GFAP） and homocysteine （Hcy） in the diagnosis of hepatolenticular degeneration （also know as Wilson disease， WD） and the differential diagnosis of the hepatic and neurological forms of WD. Methods A total of 120 WD patients who were admitted to Encephalopathy Center of our hospital from January 2023 to January 2025 were enrolled， among whom there were 63 patients with neurological WD and 57 patients with hepatic WD， and 30 healthy volunteers who underwent physical examination during the same period of time were enrolled as control group. ELISA was used to measure the plasma levels of GFAP and Hcy， and the differences between groups were analyzed. The receiver operating characteristic（ROC） curve analysis was performed， and the Spearman correlation analysis was used to investigate the correlation of the plasma levels of GFAP and Hcy with Unified Wilson Disease Rating Scale （UWDRS） score， 24-hour urinary copper， and the serum level of ceruloplasmin （CER）. Results The patients with hepatic or neurological WD had a significantly higher plasma level of GFAP than the control group（P<0.05）， and the patients with neurological WD had a significantly greater increase than those with hepatic WD（P<0.05）. The patients with hepatic or neurological WD also had a significant increase in the plasma level of Hcy（P<0.05）， but with no significant difference between the patients with hepatic WD and those with neurological WD.Plasma GFAP had an area under the ROC curve（AUC） of 0.861 in the diagnosis of neurological WD， with a cut-off value of 135.71 pg/ml， a sensitivity of 68.3%，and a specificity of 82.3%；plasma GFAP had an AUC of 0.695 in the diagnosis of hepatic WD， with a cut-off value of 129.84 pg/ml， a sensitivity of 64.7%， and a specificity of 83.3%； in the differential diagnosis of hepatic and neurological WD， plasma GFAP had an AUC of 0.75， with a cut-off value of 151.12 pg/ml，a sensitivity of 73.9%， and a specificity of 87.8%. Plasma Hcy had an AUC of 0.788 in the diagnosis of WD， with a cut-off value of 15.59 μmol/L， sensitivity of 77.9%， and specificity of 66.7%. The Spearman correlation analysis showed that in the patients with hepatic or neurological WD， the plasma levels of GFAP and Hcy were positively correlated with UWDRS score and 24-hour urinary copper （P<0.05）， but they were not significantly correlated with the level of CER （P>0.05）. Conclusion The plasma levels of GFAP and Hcy are closely associated with the degree of neurological and hepatic impairment in WD， which provides a certain clinical value for the early diagnosis of WD and the differential diagnosis of hepatic and neurological WD.
Homocysteine

Objective To investigate the influencing factors for hemorrhagic transformation （HT） after intravenous thrombolysis （IVT） in patients with acute ischemic stroke （AIS） in plateau areas. Methods A retrospective analysis was performed for AIS patients who were admitted to our hospital from February 2019 to April 2024 and received IVT with urokinase or recombinant tissue plasminogen activator， and according to the presence or absence of HT after IVT， they were divided into HT group and non-HT group. The multivariate Logistic regression analysis was used to investigate the independent risk factors for HT after IVT in AIS patients. Results A total of 437 AIS patients who underwent IVT were included in this study， among whom 45 （10.3%） experienced HT. There were significant differences between the HT group and the non-HT group in the proportion of patients with a past history of atrial fibrillation， systolic blood pressure on admission， NIHSS score before thrombolysis， neutrophil-to-lymphocyte ratio （NLR）， and blood glucose before thrombolysis （all P<0.05）. The above factors were included in a multivariate logistic regression model， and the results showed that blood glucose on admission（OR=1.122，95%CI 1.007~1.251，P<0.05） and history of atrial fibrillation （OR=3.896，95%CI 1.632~9.303，P<0.05）were independent risk factors for HT after IVT. Conclusion History of atrial fibrillation， systolic blood pressure on admission， NIHSS score before thrombolysis， blood glucose level on admission， and NLR level before treatment are influencing factors for HT after IVT in AIS patients in plateau areas， among which history of atrial fibrillation and blood glucose level before thrombolysis are independent risk factors.

This paper compares the philosophical structures of doctrine of five evolutive phases and six climate factors and The Book of Changes （《周易》） from three dimensions of "time， position， and virtue"， aiming to reveal the penetration of The Book of Changes thought in the formation of the doctrine of five evolutive phases and six climate factors and its own theoretical transformation. Both the "doctrine" and the "book" centered on "time"， recognizing temporal order through observation of celestial phenomena and calendar formulation. The Book of Changes emphasizes "seizing the timely moment" to master the principles of change in all things， while doctrine of five evolutive phases and six climate factors focuses on "understanding time" to clarify how qi relates to temporal phases. Regarding position， both treat it as time-derived and philosophically significant within a six-tier structure. The The Book of Changes uses yao （爻） positions for judging auspiciousness， inauspiciousness， regret and distress， with such judgement permeating the overall structure of the hexagram； the doctrine of five evolutive phases and six climate factors uses qi positions， where "dangwei （当位）" denotes normative qi transformation governing the overall pattern. Both hold that "virtue" arises from time‑position harmony， representing conformity to time and suitability to position. In The Book of Changes， "virtue" serves to encapsulate the attributes of things and the principles of heaven and earth， whereas the doctrine of five evolutive phases and six climate factors furhter extends "virtue" to denote the normative state of qi transformation. Thus， the intellectural structure of time， position and virtue in the doctrine of five evolutive phases and six climate factors was influenced by Yijing scholarship， within which it completed its theoretical evolution distinctly.

Childhood adversity is a risk factor for developing depressive symptoms or suffering from depressive disorders across the life course. However， existing evidence has focused on the analysis of the association between childhood adversity and depression from a single theoretical perspective， and there is a lack of comprehensive understanding of its multiple action pathways. By systematically summarizing the cumulative risk model， sensitive-period model， recency model， risk chain model， and the stress sensitization， stress amplification， and stress inoculation hypotheses， as well as the emerging pubertal stress recalibration hypothesis， this article attempts to construct an integrated theoretical framework to elucidate the internal logical synergy among these models. Furthermore， by reviewing relevant empirical evidence， this article analyzes the applicability and limitations of different theoretical models in illustrating the underlying psychopathological mechanisms of depression. The current evidence suggests that the impact of childhood adversity on the risk of psychopathology may be driven by a complex dynamic process involving the interaction of exposure timing， cumulative load， response boundaries of biological systems， and modification by later environments. Future research should utilize longitudinal cohorts and multimodal data within a unified analytical framework to comprehensively examine the multiple pathways through which childhood adversity affects the risk of depression. This will provide a reference for precisely identifying high-risk populations， targeting "recalibration windows" represented by adolescence， developing focused intervention strategies， and ultimately blocking the cascading effects of early life adversity as early as possible. ［Funded by the "Pioneer" and "Leading Goose" R&D program of Zhejiang Province （number， 2024C03006）］

Objective To prepare Zanthoxylum alkaloid thermosensitive hydrogel, optimize the preparation process and conduct related performance studies. Methods Zanthoxylum alkaloids were obtained by reflux extraction, followed by enrichment and purification using macroporous adsorption resin. Poloxamer 407 and Poloxamer 188 were used as substrates to prepare the thermosensitive hydrogel of Zanthoxylum alkaloids, and the preparation process was optimized by orthogonal design. The quality of the hydrogel was systematically evaluated based on its gelation temperature, gelation time, Fourier transform infrared （FTIR） spectroscopy, scanning electron microscopy （SEM） images, mechanical properties, and in vitro release profile. Results The optimal preparation conditions for the Zanthoxylum alkaloid thermosensitive hydrogel were: 20% （g/ml） poloxamer 407, 2% （g/ml） poloxamer 188 and 100 μg/ml Zanthoxylum alkaloid. The gelation temperature was 32.6℃, and the average gelling time was 143.3 s. The hydrogel appeared as a transparent liquid at room temperature and was transformed into a semi-solid gel state when the temperature exceeded 33℃. Experimental results confirmed the successful preparation of poloxamer 407 and poloxamer 188 thermosensitive hydrogel loaded with Zanthoxylum alkaloids, which exhibited good bio adhesion, self-healing properties, and tensile strength. Conclusion The Zanthoxylum alkaloid thermosensitive hydrogel demonstrated favorable mechanical properties and a sustained-release effect, showing promising potential for further development and application.