Objective:To investigate the relationships among coping styles,negative life events,meaning in life,and psychological resilience in adolescents.Methods:A total of 1 434 adolescents aged 13 to 17 years comple-ted online questionnaire survey.The Simplified Coping Style Questionnaire(SCSQ),Adolescent Self-Rating Life E-vents Checklist(ASLEC),Chinese Meaning in Life Questionnaire(C-MLQ),and Connor-Davidson resilience scale(CD-RISC)were used to assess coping styles,perceived impact of negative life events,experience and pursuit of meaning in life,and ability to cope with and adapt to adversity,respectively.Logistic regression was used to explore the associations among these variables.Results:A total of 723 students(50.4％)tended to adopt negative coping styles when facing adverse events.Positive coping styles were negatively associated with being in senior high school(OR=0.62,P＜0.05)and impact of life events(OR=0.97,P＜0.001),while positively associated with sense of meaning in life(OR=1.04,P＜0.001)and psychological resilience(OR=1.04,P＜0.001).Conclusion:Among adolescents,positive coping styles are inversely associated with impact of negative life events,and positively associ-ated with both the sense of life meaning and psychological resilience.

Objective:To investigate the relationships among coping styles,negative life events,meaning in life,and psychological resilience in adolescents.Methods:A total of 1 434 adolescents aged 13 to 17 years comple-ted online questionnaire survey.The Simplified Coping Style Questionnaire(SCSQ),Adolescent Self-Rating Life E-vents Checklist(ASLEC),Chinese Meaning in Life Questionnaire(C-MLQ),and Connor-Davidson resilience scale(CD-RISC)were used to assess coping styles,perceived impact of negative life events,experience and pursuit of meaning in life,and ability to cope with and adapt to adversity,respectively.Logistic regression was used to explore the associations among these variables.Results:A total of 723 students(50.4％)tended to adopt negative coping styles when facing adverse events.Positive coping styles were negatively associated with being in senior high school(OR=0.62,P＜0.05)and impact of life events(OR=0.97,P＜0.001),while positively associated with sense of meaning in life(OR=1.04,P＜0.001)and psychological resilience(OR=1.04,P＜0.001).Conclusion:Among adolescents,positive coping styles are inversely associated with impact of negative life events,and positively associ-ated with both the sense of life meaning and psychological resilience.

Hungary, as the first European country to legislate TCM, its legislation experience has significant implications for the international development of TCM. This article reviewed the historical process of TCM legislation in Hungary, summarized its legislative achievements, and analyzed the problems encountered during the implementation process. It was found that the current challenges faced by TCM legislation in Hungary mainly include constraints from the dominance of modern medicine, restrictions from strict qualification requirements, insufficient public awareness, difficulties in TCM registration, and challenges in policy coordination and cooperation. Based on these findings, the article proposed countermeasures such as improving the legal framework, strengthening educational cooperation, enhancing public awareness, promoting the mutual recognition of standards between China and Europe, and deepening China-Hungary collaboration. These measures aim to further improve the legislation and implementation of TCM in Hungary, thereby promoting the healthy development of TCM in Hungary and the global service trade of TCM.

Objective To investigate the effect of PIAS3 on glucose fluctuation-induced oxidative stress and mito-chondrial dysfunction in rat cardiomyocytes.Methods H9c2 were cultured in vitro,and divided into normal glucose control group(Control),mannitol-induced osmotic pressure control group(MG),constant high glucose group(HG),intermittent hyperglycemia group(IHG),IHG+siRNA NC group,and IHG+PIAS3 siRNA group.Cell proliferation was assessed using CCK-8 assay.LDH release,MDA and GSH levels,as well as SOD activity,were detected using corresponding kits.Mitochondrial membrane potential was evaluated via JC-1 staining combined with flow cytometry.ROS levels in cells and mitochondria were determined using DCFH-DA and MitoSOX staining,re-spectively.Protein expression of PI3K,p-PI3K,AKT,and p-AKT was analyzed by Western blot.Results Com-pared with the control group,intermittent hyperglycemia promoted oxidative stress and mitochondrial dysfunction,significantly upregulated PIAS3 expression(P＜0.001)and downregulated p-PI3K and p-AKT protein levels(P＜0.001).Knockdown of PIAS3 significantly alleviated oxidative stress and mitochondrial dysfunction induced by glucose fluctuations,and increased p-PI3K and p-AKT protein levels(P＜0.001).Conclusions Knockdown of PIAS3 may alleviate glucose fluctuation-induced oxidative stress and mitochondrial dysfunction in ratcardiomyocytes by activating the PI3K/AKT signaling pathway.

Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders (NDDs) in the offspring, especially in the case of drug exposure. However, little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors. We collected and manually curated sub-pathways and pathways (sub-/pathways) and drug information to propose an analytical framework for predicting drug candidates. This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs. Further, specific and pleiotropic sub-/pathways/drugs were identified using entropy, and sex bias was analyzed in conjunction with logistic regression and random forest models. We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs, showing temporal or spatial changes across fetal development. Moreover, 5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels. A user-friendly NDDP visualization website ( https://ndd-lab.shinyapps.io/NDDP ) was developed to allow researchers and clinicians to access and retrieve data easily. Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories. This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/metabolism* ; Male ; Prenatal Exposure Delayed Effects ; Fetal Development/drug effects* ; Drug Discovery/methods* ; Brain/metabolism*

ObjectiveTo explore the efficacy-driving mechanism of Danhong injection （DHI） in the treatment of stable angina pectoris （SAP） based on the composition-activity relationship of target modules and clarify the pharmacological effects of DHI. MethodAccording to the angina frequency （AF） in the Seattle Angina Questionnaire （SAQ） that was obtained in the previous clinical trial， the patients before and after DHI treatment were grouped based on efficacy. The transcriptomic data of the patients before treatment and in the best efficacy group 30 days post-treatment were selected as the data source， and then weighted gene co-expression network analysis （WGCNA） was employed to construct the co-expression network. Relevant modules in the network were identified and associated with clinical features. In addition， the On-modules （Z value below 0） were identified by Zsummary. The topological indicators such as density， centrality， and clustering coefficient were adopted to explore the dynamics of DHI efficacy at the network level and module level， respectively. In addition， the driver genes were screened by the personalized network control （PNC） algorithm. Finally， rat H9C2 cells were used to establish the model of hypoxia/reoxygenation （H/R）， which was used to confirm the potential therapeutic target of DHI for SAP and provide a scientific basis for revealing the therapeutic mechanism of DHI. ResultWe identified 19 modules in the best efficacy group of DHI for SAP， and the comparison between day 0 and day 30 revealed 12 On-modules. The changes of network topological indicators at the network and module levels confirmed the correlation between the best efficacy of DHI treatment and topological dynamics. Finally， the driver genes， Klotho and fibroblast growth factor 22 （FGF22）， in DHI treatment of SAP were verified by the H9C2 cell model of H/R. ConclusionBased on clinical transcriptome data， this study determined the composition-activity relationship of target modules of DHI for SAP， which provided a scientific basis for deciphering the efficacy-driven mechanism of DHI for SAP.

In order to provide a reference basis for the development of relevant compound preparations， this article takes a comprehensive analysis of the usage and dosage of famous classical formulas in Han dynasty from various perspectives， and gives corresponding countermeasures on this basis. Through the comprehensive analysis of the classification and statistics of Zhongjing's medication characteristics， decoction methods， administration and dosage， and combining conversion methods of weights and measures by ancient medical practitioners， along with the dosage and administration of the listed Han dynasty famous classical formulas， it was found that the "Jiangxi method" served as a general guideline for administration according to Zhongjing's original text. This method allowed for flexible dosing based on the conversion of the ancient measurements to modern equivalents［13.8 g per Liang（两）］， ensuring the safe and effective medication of these formulas. After combing， it is found that although the dosage of single medicine is large in famous classical formulas from Han dynasty， the administration is flexible. The crude drug amount per administration serves as the foundational dose， with the frequency of administration adjusted flexibly according to the condition. This dosing approach becomes the key for the rational development of compound formulations of famous classical formulas. Based on the conclusions of the study， it is recommended that when developing compound formulations of famous classical formulas in Han dynasty， the original administration method and dosage should be respected. The original crude drug amount per administration should be considered as the daily foundational dose， with the frequency of administration described within a range（1 to N times per day， where N is the maximum number of administrations as per the original text）. The specific frequency of administration can be adjusted flexibly by clinical practitioners based on the individual condition. This approach should also be adopted in toxicological studies， where the dosage per administration serves as the basis for toxicity research， and the toxicity profile at the maximum administration frequency should be observed， providing guidance on the clinical safety range. Corresponding drug labels should provide information within a range to indicate toxicological risk intervals.

This study explored the comorbidity mechanisms of coronary heart disease and depression from the perspectives of "constraint causing disease" and "disease causing constraint"， for which "constraint" is the link， and the key lies in the stagnation of qi. The heart storing manifestations in traditional Chinese medicine （TCM） encompasses most physiological processes of the circulatory system， the mental nervous system， and some functions of the endocrine system， and cardiovascular diseases and psychological disorders are closely related to it. In TCM， it is proposed that the stagnation of heart yang leading to "yang deficiency" is the pathogenesis of chest tightness， and emotional disturbance leading to the stagnation of yang qi aggravates the chest tightness， reflecting the process of "disease causing constraint". As the disease progresses， the appearance of phlegm and stasis further worsens the condition， reflecting the process of "constraint causing disease". Based on modern medical understanding， the abnormal accumulation of lipids， platelets， oxidative products， cytokines， and other substances constitute a form of "constraint"， which is also the material basis for the comorbidity of coronary heart disease and depression. These substances promote neuronal damage or apoptosis in the emotional and cognitive regions， inducing the onset of depression， reflecting the process of "disease causing constraint". Meanwhile， adverse emotions lead to sympathetic nerve excitement， resulting in the production of catecholamines， promoting platelet aggregation， elevating levels of inflammatory markers， and increasing the risk of coronary heart disease， reflecting the process of "disease causing constraint".

Danggui Sinitang is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Han dynasty. It is composed of Angelicae Sinensis Radix， Cinnamomi Ramulus， Paeoniae Radix Alba， Asari Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Tetrapanacis Medulla， and Jujubae Fructus and serves as a classic formula for treating the syndrome of blood deficiency and cold reversal. This study systematically reviews the records of Danggui Sinitang in ancient Chinese medicine books of various dynasties and the modern clinical applications to probe into the composition， plant species， processing， dosage， decocting method， and indications of Danggui Sinitang， aiming to provide a reference for the development and clinical application of this classic formula. The review of the records showed that there were a variety of records of Danggui Sinitang with different composition， and the composition of this formula listed in the Treatise on Cold Damage has a significant impact on later generations and has been used by medical practitioners throughout history. Although the dosage of some drugs decreased during the Ming and Qing dynasties， the medical practitioners continued to use the original formula. In terms of processing， although there were slight changes in the processing of Angelicae Sinensis Radix， Paeoniae Radix Alba， Glycyrrhizae Radix et Rhizoma， and Tetrapanacis Medulla， the original processing method was inherited. In terms of indications， Danggui Sinitang was designed to treat cold reversal due to blood deficiency and dysentery. Furthermore， it was used to treat headache， convulsive disease， infantile convulsion， and private part adduction in the Ming and Qing dynasties. Nowadays， this formula is mostly used to treat diabetes peripheral neuropathy， rheumatoid arthritis， dysmenorrhea， Raynaud's disease and other diseases. In terms of precautions， ancient physicians believed that Danggui Sinitang should not be taken by pregnant women and should only be used for limb chills caused by blood deficiency and cold coagulation. For limb chills caused by other reasons， this formula should not be used indiscriminately. Modern research has not reported any serious adverse reactions related to this formula. Danggui Sinitang has a definite therapeutic effect. In subsequent research and development， quality control standards of Danggui Sinitang should be established while its safety is ensured， and the related preparations should be developed and applied.