Wilson disease （WD） is one of the few treatable neurogenetic disorders. Currently， Western medicine remains the main treatment method for WD， while since the 1990s， multiple studies conducted by Professor Yang Renmin and his team have shown that traditional Chinese medicine （TCM） also has a favorable therapeutic effect. Based on the principle of low-copper diet for WD， this article systematically elaborates on the advantages， limitations， and key considerations of current Western medicine therapies （pharmacotherapy， liver transplantation， and splenectomy） and reviews the research findings of TCM in China， especially the wide application of Gandou Decoction in clinical practice. Studies have shown that Gandou Decoction can effectively improve neurological symptoms， protect hepatic and renal function， and avoid the adverse drug reactions associated with metal chelating agents， and therefore， it can be used an effective long-term adjuvant therapy for WD. It should be noted that symptoms and signs should be considered in integrated traditional Chinese and Western medicine therapy for WD， and high-copper TCM drugs should be avoided to prevent deterioration.

Objective: To explore the barriers to physical activity behavior among overweight and obese children and adolescents, so as to provide evidence for developing physical activity intervention programs. Methods: From March to April 2025, 13 overweight or obese children and adolescents from one primary school and one secondary school in Nanjing were selected by purposive sampling for semi structured interviews. Guided by the capability, opportunity and motivation-behavior model, data were coded, categorized and analyzed using content analysis. Results: A total of 13 interviews were completed, with a cumulative duration of 358 minutes. Three themes and eight subthemes were identified:capability factors, including physical discomfort and limited physical fitness, weak exercise skills and insufficient behavioral regulation ability, and insufficient psychological capability; opportunity factors, including insufficient family support and negative influence, pressure from school and peer environments, and limited time resources and exercise conditions; and motivation factors, including low self efficacy and situations prone to giving up, and insufficient positive feedback and lack of attractiveness of exercise forms. Conclusions Barriers to physical activity among overweight and obese children and adolescents result from the combined effects of capability, opportunity and motivation. It is necessary to lower the threshold for initiating exercise, strengthen positive experiences and feedback, and build integrate family-school support environments to promote the initiation and maintenance of physical activity behaviors in children and adolescents.

The ethical review exemption system was introduced to meet the needs of modernized ethical governance， implement hierarchical management for ethical review projects involving human subjects， and explore an ethical management model that reduces procedural supervision for specific types of research involving no greater than minimal risk. Through a comparative study， this paper seeks to elaborate on the differences between China and the United States （US） in the ethical review exemption system from multiple aspects， such as ethical regulations， risk definition， preconditions， applicable scenarios， and operational procedures. The aim is to provide references for ethical review committees to better implement the ethical review exemption system， enhance policy research， and ensure the fairness and objectivity of ethical review. Through the comparative study of the ethics review exemption system in China and the US， the following recommendations are proposed for institutions implementing the ethical review exemption system for reference. First， the system should clearly define the meaning of ethical review exemption to prevent researchers or even committee members from misunderstanding it as falling outside the scope of ethical review， thereby exposing research participants’ rights and interests to unnecessary risks. Second， the system should specifically explain the preconditions， including the requirements for research types and research risks. Among them， risks should be considered from multiple dimensions such as physiology， psychology， society， and economy. Clear explanations should be provided for involving commercial interests and sensitive personal information. Finally， the system should establish basic principles and judgment criteria for applicable scenarios， including specifying exactly what the public data refers to and legal requirements that need to be met， providing a concept of anonymization to distinguish it from deidentified information data， and clarifying the relevant regulations and ethical principles to be followed， as well as the clear requirements for informed consent.

BackgroundThe global prevalence of depressive disorders is high， with a significant treatment gap remaining. Escitalopram oxalate， as a commonly used antidepressant in clinical practice， has a single target and is prone to cause adverse reactions such as gastrointestinal discomfort. The traditional Mongolian medicine Zadi-5 pills has a multi-target anti-depression mechanism and unique advantages such as improving the intestinal flora. However， there is currently a lack of randomized controlled trial evidence for the combined treatment of first-episode depression， along with insufficient research on its metabolic safety and potential drug interactions. ObjectiveTo explore the efficacy and safety of Zadi-5 pills combined with escitalopram oxalate in the treatment of the first-episode depression， so as to provide references for Mongolian medicine in depression management. MethodsA randomized controlled trial was conducted. A total of 103 patients with first-episode depression who were treated in the outpatient or inpatient departments of the Inner Mongolia Autonomous Region Mental Health Center from January 2023 to December 2024 and met the diagnostic criteria for depressive episode as defined in International Classification of Diseases， tenth edition （ICD-10） were included. Random numbers were generated using the RAND function in Excel software， and the patients were divided into the study group （n=52） and the control group （n=51）. Both groups received escitalopram oxalate treatment， starting from 5 mg/d and gradually increasing to 20 mg/d. The study group additionally received Zadi-5 pills， 13 pills per day. The treatment duration for both groups was 6 weeks. Before treatment and at the 2^nd， 4^th， and 6^th weeks of treatment， the severity of depressive symptoms was evaluated using the Hamilton Depression Scale-24 item （HAMD-24）. At these time points， blood was collected on an empty stomach at 7∶00 for the detection of liver function （aspartate aminotransferase， alanine aminotransferase）， triglycerides， and the blood concentration of escitalopram oxalate. ResultsA total of 100 patients completed the study， with 50 cases in the study group and the control group. The results of the repeated measures ANOVA showed that the interaction effect between group and time in the HAMD-24 score was statistically significant （F _interaction= 18.070， P<0.01）. At the end of the 4^th and 6^th weeks of treatment， the HAMD-24 score of the study group was lower than those of the control group （P<0.05）. At each time point after treatment， the reduction rate of the HAMD-24 score in the study group was higher than those of the control group， and the differences were all statistically significant （P<0.05）. The interaction effect between the triglyceride level groups and time was statistically significant （F_interaction=3.381， P<0.05）.After treatment， the triglyceride levels in the study group showed a downward trend， while those in the control group showed an upward trend. There was no statistically significant interaction effect between the groups and time for liver function （aspartate aminotransferase and alanine aminotransferase） and the blood concentration of escitalopram oxalate （P>0.05）. ConclusionCompared with escitalopram oxalate treatment alone， the combination of Zadi-5 pills and escitalopram oxalate is more effective in treating the first-episode depression， without increasing the risk of liver damage. The combined medication may have a potential beneficial effect on lipid metabolism. ［Funded by Inner Mongolia Autonomous Region Health Science and Technology Planning Project （number， 202202107）］

ObjectiveTo observe the clinical effectiveness of horticultural therapy involving the planting of Chinese medicinal herbs （mint and lily potted plants） combined with intradermal needling therapy for generalized anxiety disorder （GAD） of liver depression transforming into fire syndrome under transcranial magnetic stimulation and basic psychological therapy， and to explore the possible mechanisms of action. MethodsA total of 180 patients with GAD of liver depression transforming into fire syndrome were randomly divided into three groups， horticultural therapy group， intradermal needling group， and horticultural therapy+intradermal needling group， with 60 patients in each. All groups received basic treatment including basic psychological therapy and transcranial magnetic stimulation. The horticultural therapy group received horticultural therapy in addition to the basic treatment； the intradermal needling group received intradermal needling therapy once a week for 8 weeks in addition to the basic treatment； the horticultural therapy+intradermal needling group received both horticultural therapy and intradermal needling therapy， following the same procedures and duration. Hamilton Anxiety Rating Scale （HAMA）， Self-Rating Anxiety Scale （SAS）， and Pittsburgh Sleep Quality Index （PSQI） scores were assessed at baseline and after 2， 4， 6， and 8 weeks of treatment. Serum levels of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） were measured before treatment and after 8 weeks of treatment. Motor-evoked potential （MEP） baseline levels were recorded before treatment， and MEP amplitude ratios were compared after 1 week and 8 weeks of treatment. Clinical effectiveness and safety were evaluated after 8 weeks of treatment. Pearson correlation analysis was used to examine the relationships between serum ACTH and CORT levels， MEP amplitude， and anxiety. ResultsIn the horticultural therapy group and intradermal needling group， HAMA， SAS and PSQI scores after 4， 6， and 8 weeks treatment were lower than baseline scores （P＜0.05）. In the horticultural therapy+intradermal needling group， these scores showed a significant decline starting after 2 weeks treatment and continuing through 8 weeks after treatment （P＜0.05）. The HAMA， SAS， and PSQI scores in the horticultural therapy+intradermal needling group were significantly lower than those in the other two groups after 2， 4， 6， and 8 weeks treatment （P＜0.05）. After 8 weeks of treatment， serum CORT and ACTH levels in the horticultural therapy+intradermal needling group were significantly lower than baseline levels （P＜0.05） and were also lower than those in the horticultural therapy group and intradermal needling group at the same time point （P＜0.01）. When comparing the level after 8 weeks treatment to that after 1 week treatment， under PAS10 stimulation， the MEP amplitude ratio in the intradermal needling group decreased at 30 minutes， while in the horticultural therapy+intradermal needling group， the MEP amplitude ratio decreased at all time points （P＜0.05 or P＜0.001）； under PAS25 stimulation， the MEP amplitude ratio in the horticultural therapy group increased at 20 minutes， and in the intradermal needle group at 10 minutes （P＜0.05）. In the horticultural therapy+intradermal needling group， the MEP amplitude ratio increased significantly at all time points after treatment （P＜0.001）. The cure rate in the horticultural therapy+intradermal needling group （74.14%， 43/58） was significantly higher than that in the horticultural therapy group （30.00%， 18/60） and the intradermal needling group （48.28%， 28/58， P＜0.05）. Correlation analysis revealed that serum ACTH and CORT levels were positively correlated with HAMA scores （r = 0.488， P＜0.01； r = 0.428， P＜0.01）. Following PAS10 intervention， the MEP amplitude ratio was positively correlated with HAMA scores （r = 0.458， P＜0.01）， whereas after PAS25 intervention， the MEP amplitude ratio was negatively correlated with HAMA scores （r = -0.562， P＜0.01）. ConclusionHorticultural therapy combined with intradermal needling treatment， under transcranial magnetic stimulation and basic psychological therapy， demonstrates significant clinical effectiveness in patients with GAD of liver depression transforming into fire syndrome. Its mechanism of action may be related to the regulation of hyperactivation of the hypothalamic-pituitary-adrenal （HPA） axis and the reduction of cortical excitability.

ObjectiveTo investigate the preventive effect and mechanism of Dendrobium officinale （DO） on non-alcoholic fatty liver disease （NAFLD） by network pharmacology and animal experiments. MethodsDO components in blood after administration were identified and analyzed using ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-QE-HF-MS/MS）. Network pharmacology and molecular docking methods were employed to obtain active ingredients and potential targets of DO for NAFLD control. High-fat feeds were used to replicate the NAFLD rat model. Biochemical kits were used for detecting the expression levels of blood lipids， hepatic lipids， and liver functions of rats. Hematoxylin-eosin （HE） staining and oil red O staining were employed to observe pathological changes in rat liver， and real-time fluorescence quantitative PCR （Real-time PCR） assay was performed to validate potential targets obtained from the network pharmacology analysis. ResultsA total of 13 DO components were identified in blood， including berberine， dihydrosanguinarine， and oxypeucedanin. A total of 14 potential targets were screened through network pharmacology， including Forkhead box protein O1 （FoxO1）， epidermal growth factor receptor （EGFR）， and insulin-like growth factor 1 （IGF-1R）， involving pathways such as the advanced glycation end product （AGE）/receptor for AGE （RAGE） signaling pathway， blood lipids and atherosclerosis， insulin resistance， and FoxO signaling. The results of animal experiments showed that the NAFLD rat model was successfully replicated. After the preventive treatment with DO for NAFLD rats， the indexes of blood lipids， hepatic lipids， and liver function were normalized； lipid deposition and lesions in the liver were significantly improved； the expression level of FoxO1 mRNA in the liver was significantly reduced （P<0.05）， and the mRNA expression levels of phosphatidylinositide 3-kinases （PI3K）， protein kinase B （Akt）， EGFR， and IGF-1R were significantly increased （P<0.05）. ConclusionDO has a preventive effect on NAFLD rats， and the mechanism of action may be related to the modulation of IGF1R and EGFR targets and activation of the PI3K/Akt/FoxO1 signaling pathway.

ObjectiveTo study the relationship between qi stagnation constitution and suboptimal health status (SHS) or lifestyle.MethodsFrom 2012 to 2013, we conducted a cross-sectional survey of 24 159 Chinese individuals aged 12–80 years. The qi stagnation constitution was assessed using the Constitution in Chinese Medicine Questionnaire. Health status was evaluated through medical records and the Subhealth Measurement Scale V1.0 (SHMS V1.0). Health-promoting lifestyles were measured using the Health-Promoting Lifestyle Profile II (HPLP-II).ResultsOf the 24 159 participants, 16.1% and 15.2% were classified as “always” and “sometimes” having the qi stagnation constitution, respectively. Those classified as “rarely” having the qi stagnation constitution scored higher on both the HPLP-II and SHMS V1.0. The participants classified as “always” having the qi stagnation constitution showed a significant association with SHS or disease compared to other imbalanced constitutions. Those in the “always” category were approximately 21 times more likely to be classified as having SHS (odds ratio [OR]: 21.17, 95% confidence interval [CI]: 15.74–28.45), whereas those in the “sometimes” category were approximately six times more likely (OR: 5.89, 95% CI: 5.04–6.90). Accordingly, the qi stagnation constitution score was significantly associated with the diagnosis of SHS, with an area under the curve of 0.77 (P .001). A score of 18.75 yielded the highest Youden Index (0.407), with a sensitivity of 60.5% and a specificity of 80.3%. Significant associations were observed between health-promoting lifestyles and qi stagnation constitution severity in an ordinal regression analysis (P .001). Protective factors included stress management (OR: 1.59), self-actualization (OR: 1.57), and exercise (OR: 1.36). In contrast, poorer interpersonal relationships (OR: 0.79), greater health responsibilities (OR: 0.86), and poorer nutrition (OR: 0.91) were associated with increased severity.ConclusionModulating the qi stagnation constitution through lifestyle interventions may help prevent the progression of SHS to disease, which aligns with core preventive principles in traditional Chinese medicine.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps