BACKGROUND:Vascular endothelial growth factor receptor tyrosine-kinase inhibitors (VEGFR-TKIs) are widely used for solid tumors but frequently cause hand-foot skin reaction (HFSR), which compromises quality of life and dosage tolerance. Tao-Hong-Si-Wu Decoction (THSWD), a classical Chinese medicine formula, has been approved to alleviate TKI-associated HFSR and called for further mechanism research. METHODS:Sorafenib, one of the VEGFR-TKIs, was used for establishing an HFSR rat model. Sprague-Dawley rats were randomized to control, model, urea cream, or low/medium/high-concentration THSWD groups. THSWD and urea cream were externally used for paws. Mass spectrography was employed to identify the ingredients of THSWD. RNA-seq, network pharmacology, and molecular docking were performed to predict the potential mechanism. Then plantar mechanical withdrawal threshold (PWT), clinical skin scoring, hematoxylin-eosin and Masson's trichrome staining, transmission electron microscopy, Western blotting, and TUNEL assays to evaluate apoptosis, autophagy, and RAGE/PI3K/AKT signaling molecules were compared between groups. Furthermore, local (plantar) AAV2/9-mediated RAGE overexpression or knockdown to validate the effect target of THSWD. RESULTS:THSWD improved lesion of paws and increased PWT, better than urea cream. Histology revealed correction of hyperkeratosis and collagen disarray. Ultrastructurally, mitochondrial swelling decreased and autophagosomes increased. Relative to the model group, THSWD downregulated Bax and cleaved caspase-3, upregulated Bcl-2, increased the LC3B-II/LC3B-I ratio, and restored PI3K expression and the p-AKT/AKT ratio, indicating inhibition of excessive apoptosis and promotion of protective autophagy via the RAGE/PI3K/AKT axis. TUNEL-positive cells were markedly reduced. Network pharmacology and docking supported a multi-component, multi-target mode of action converging on AGE-RAGE and PI3K-AKT pathways. RNA-seq showed that THSWD significantly remodeled HFSR-related transcriptomic profiles, enriching pathways linked to lipid-metabolic regulation and attenuation of excessive inflammation. RT-qPCR further supported these transcriptomic findings at the transcriptional level. Similarly, in experiments investigating AAV-mediated regulation of RAGE, RAGE immunofluorescence in plantar skin confirmed successful AAV2/9-mediated overexpression and knockdown, RAGE overexpression enhanced, whereas RAGE knockdown diminished, the protective effects of THSWD on macroscopic appearance, histology, ultrastructure, and paw-withdrawal threshold (PWT), establishing RAGE as a critical mediator. CONCLUSIONS:THSWD soaking effectively mitigates sorafenib-induced HFSR, in rat model. By regulating RAGE/PI3K/AKT signaling to coordinate keratinocyte apoptosis and autophagy, THSWD promotes holistic restoration of skin barrier structure and function. These findings revealled the potential mechanism of THSWD topically treating VEGFR-TKI-induced HFSR.
Objective: To observe the effect of Health Qigong and exercise on anxiety, depression, and relapse tendency among drug addicts under compulsory isolation through a randomized controlled experiment. Methods: We selected a total of 90 participants from 420 male drug addicts who were in compulsory isolation due to drug use, and randomly divided them into three groups, namely the Health Qigong exercise group, the aerobic exercise group, and the control group. Exercise interventions were administered for 12 weeks. The Health Qigong group did the prescribed Health Qigong exercise workout while the aerobic exercise group performed the eighth set of broadcast gymnastics. The participants of the control group maintained their routine lifestyle, with no exercise. We used SAS, SDS, and the relapse tendency scale for assessments before and after the exercise intervention. Results: Only the Health Qigong group showed significant improvement in depression after the exercise intervention (p < 0.05), while relapse tendency did not improve in the Health Qigong and aerobic groups. However, the relapse tendency in the dimensions of drug rehabilitation confidence and objective environmental impact increased significantly in the control group (p < 0.05). Conclusion: Health Qigong can improve depression and exercise can prevent the increase of relapse tendency in compulsory drug rehabilitees.
ETHNOPHARMACOLOGICAL RELEVANCE:Exocarpium Citri Grandis (Huajuhong) is an authentic Chinese materia medica with excellent curative effects on relieving cough and reducing phlegm, which has been reputed as "Southern Ginseng" in China for a long history. AIM OF THE STUDY:To establish a sequential grade evaluation method with strong operability and controllable quality for Huajuhong decoction pieces. MATERIALS AND METHODS:(1) Indicators of ingredients and bio-effects were predicted by network pharmacology, and the potential pharmacodynamic ingredients and key targets were analyzed integrating screening results and literatures. (2) 45 batches of Huajuhong decoction pieces from different producing areas were collected and graded by original plant, planting place, and harvesting time. The chemical indicators determination of Huajuhong decoction pieces was conducted by Ultra Performance Liquid Chromatography (UPLC). (3) 112 rats with idiopathic pulmonary fibrosis (IPF) model were used to evaluated the efficacy within graded groups. RESULTS:(1) There are 22 key targets corresponding to 20 potential ingredients related to immunity and inflammation pathways for Huajuhong. Naringin and rhoifolin were chosen as the chemical indicators, and IL-6, IL-8, MCP-1, MIP-1α, TNF-α, TGF-β1 were selected as bio-indicators for different grades of Huajuhong decoction pieces. (2) The contents of the naringin and rhoifolin can reflect the quality of different grades of Huajuhong decoction pieces. (3) The efficacy of different grades of Huajuhong decoction pieces can delay the progression of IPF in varying degrees via the selected bio-indicators' pathways. CONCLUSIONS:This sequential grading evaluation method is an attempt to apply systems pharmacology which integrates network pharmacology, quantitative chemical and experiments on animals to the classification of TCM decoction pieces. Combining the concepts of traditional theory and modern technology to explain the complex grading mechanism of TCM decoction pieces is worth popularizing and applying.
中美贸易摩擦升级,我国中药产品对美出口深受影响.通过文献调查和政策分析,提出促进中药产品出口美国的合理建议.文献研究:以"中药对外出口""美国中药"为主题词,搜索Medlab、CNKI数据库,分析中药产品对美贸易现状;政策研究:以商务部、外交部、国家中医药管理局等发布的我国中药对美国贸易报告为依据,分析中药产品出口策略,总结我国中药产品出口的现状特点和成功经验,并提出有效促进中药产品对美贸易的新思路.我国中药产品对美出口额稳定增长,存在增速缓慢、市场份额小和结构不合理的现象.分析中药在美准入方式和我国中药出口政策,从提高中药产品质量、按需设计上市方案和制定相应国际标准及法规3方面,提出"保质促销,立规促贸"的对美贸易新方案.
Qingfei Paidu Decoction is a traditional Chinese medicine compound recommended by National Health Commission of the People's Republic of China and National Administration of Traditional Chinese Medicine for clinical therapies of coronavirus disease 2019(COVID-19). Qingfei Paidu Decoction consists of 21 traditional Chinese medicines, such as Asari Radix et Rhizoma. However, the dosage of Asari Radix et Rhizoma has been questioned by some people, because of one ancient proverb. To explore the rationality of the dosage of Asari Radix et Rhizoma in Qingfei Paidu Decoction, this study systematically examined the ancient and modern physicians' understanding of the toxicity of Asari Radix et Rhizoma, and collated the application and dosage of Asari Radix et Rhizoma in ancient prescriptions and modern clinics based on literature analysis. As a result, we found that ancient and modern physicians have different understanding on the toxicity of Asari Radix et Rhizoma and that the theory about the dosage of Asari Radix et Rhizoma is flawed. We also found that the dose of Asari Radix et Rhizoma in ancient and modern clinical applications was not constrained by ancient experience. Physicians usually increase the dosage of Asari Radix et Rhizoma in clinical therapy according to the actual conditions, and there were no adverse reactions. Additionally, according to laws and regulations concerning medical affairs, physician could increase or decrease the dosage of the drug under special circumstances. Based on the analysis of safety and effectiveness of Asari Radix et Rhizoma in Qingfei Paidu Decoction, we conclude that the dose of Asari Radix et Rhizoma in Qingfei Paidu Decoction is safe, effective and reasonable.