To Investigate the Mechanism of Qinpi Tongfeng Formula in Treating Acute Gouty Arthritis by UHPLC-Q-Orbitrap-MS, Network Pharmacology and Experimental Validation.

Background: Acute gouty arthritis (AGA) is characterized by the accumulation of monosodium urate crystals within the joints, leading to inflammation and severe pain. Western medicine treatments have limitations in addressing this condition. Previous studies have shown the efficacy of Qinpi Tongfeng formula (QPTFF) in treating AGA, but further investigation is needed to understand its mechanism of action. Methods: We used ultra-high-performance liquid chromatography tandem Q-Exactive Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-MS) to identify compounds in QPTFF. Target proteins regulated by these compounds were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Chemistry Database, and Swiss Target Prediction Database. AGA-related targets were searched and screened from various databases, including Genecards, PharmGKB, Drugbank, etc. Intersection targets of QPTFF and AGA were analyzed for protein-protein interaction networks, GO function enrichment, and KEGG pathway enrichment. We then verified QPTFF's mechanism of action using an AGA rat model, assessing pathological changes via H&E staining and target expression via ELISA, RT-qPCR, and Western blot. Results: UHPLC-Q-Orbitrap-MS identified 207 compounds in QPTFF, with 55 selected through network pharmacology. Of 589 compound-regulated targets and 1204 AGA-related targets, 183 potential targets were implicated in QPTFF's treatment of AGA. Main target proteins included IL-1ß, NFKBIA, IL-6, TNF, CXCL8, and MMP9, with the IL-17 signaling pathway primarily regulated by QPTFF. Experimental results showed that medium and high doses of QPTFF significantly reduced serum inflammatory factors and MMP-9 expression, and inhibited IL-17A, IL-6, IKK-ß, and NF-κB p65 mRNA and protein expression in AGA rats compared to the model group. Conclusion: Key targets of QPTFF include IL-1ß, NFKBIA, IL-6, TNF-α, CXCL8, and MMP9. QPTFF effectively alleviates joint inflammation in AGA rats, with high doses demonstrating no liver or kidney toxicity. Its anti-inflammatory mechanism in treating AGA involves the IL-17A/NF-κB p65 signaling pathway.

An intent classification method for questions in "Treatise on Febrile diseases" based on TinyBERT-CNN fusion model.

"Treatise on Febrile Diseases" is an important classic book in the academic history of Chinese material medica. Based on the knowledge map of traditional Chinese medicine established by the study of "Treatise on Febrile Diseases", a question-answering system of traditional Chinese medicine was established to help people better understand and use traditional Chinese medicine. Intention classification is the basis of the question-answering system of traditional Chinese medicine, but as far as we know, there is no research on question intention classification based on "Treatise on Febrile Diseases". In this paper, the intent classification research is carried out based on the Chinese material medica-related content materials in "Treatise on Febrile Diseases" as data. Most of the existing models perform well on long text classification tasks, with high costs and a lot of memory requirements. However, the intent classification data of this paper has the characteristics of short text, a small amount of data, and unbalanced categories. In response to these problems, this paper proposes a knowledge distillation-based bidirectional Transformer encoder combined with a convolutional neural network model (TinyBERT-CNN), which is used for the task of question intent classification in "Treatise on Febrile Diseases". The model used TinyBERT as an embedding and encoding layer to obtain the global vector information of the text and then completed the intent classification by feeding the encoded feature information into the CNN. The experimental results indicated that the model outperformed other models in terms of accuracy, recall, and F1 values of 96.4%, 95.9%, and 96.2%, respectively. The experimental results prove that the model proposed in this paper can effectively classify the intent of the question sentences in "Treatise on Febrile Diseases", and provide technical support for the question-answering system of "Treatise on Febrile Diseases" later.

Efficacy and Safety of Qinpi Tongfeng Formula Combined with Bloodletting Therapy in the Treatment of Acute Gouty Arthritis: A Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Acute gouty arthritis (AGA) is a common arthritis disease, with the characteristics of acute onset, severe condition, and poor prognosis. The conventional treatments have shown certain curative effects but are accompanied with many adverse reactions. The combination of orally taken Qinpi Tongfeng Formula (QPTFF) and bloodletting therapy could effectively alleviate arthralgia and joint swelling in AGA patients. However, there is a lack of high-quality randomized controlled trials (RCTs) to evaluate the clinical efficacy and safety of the combined therapy against AGA. METHODS: This is a prospective, randomized, parallel controlled trial conducted in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine to explore the efficacy and safety of QPTFF combined with bloodletting therapy in the treatment of AGA. Eighty-six AGA patients meeting the inclusion and exclusion criteria will be randomly divided into the treatment group and control group in a 1 : 1 ratio using a randomization table. The investigators and the patients will not be blinded, while the outcome assessors and statisticians will be blinded to the allocation. Patients in the treatment group will take QPTFF and bloodletting therapy simultaneously, while patients in the control group will be instructed to orally take colchicine tablets. The primary outcome is the total effective rate, and the secondary outcomes are the pain changes after the first treatment, pain scores, complete pain relief time, joint symptom scores, TCM syndrome score, and laboratory test. SPSS22.0 will be used for statistical analysis. Discussion. This study will evaluate the clinical efficacy and safety of QPTFF combined with bloodletting therapy in the treatment of AGA, and the results of this study will provide reliable clinical evidence for the clinical use of QPTFF combined with bloodletting in the treatment of AGA. The trial is registered with ChiCTR2100048836.

Baicalin alleviates adriamycin-induced focal segmental glomerulosclerosis and proteinuria by inhibiting the Notch1-Snail axis mediated podocyte EMT.

Podocyte injury is an early event and core in the development of focal segmental glomerular sclerosis (FSGS) that induces poor prognosis. Epithelial-mesenchymal transition (EMT) as a response of podocyte to injury leads to podocyte depletion and proteinuria. The abnormally reactivated NOTCH pathway may be involved in podocyte EMT. Baicalin, as a natural flavonoid compound, had significant inhibitory activity on tissue fibrosis and tumor cell invasion. However, its potential role and molecular mechanisms to injured podocyte in FSGS are little known. Here we found that baicalin could inhibit podocyte EMT markers expression and cell migration induced by TGF-ß1, accompanied by the up-regulated expression of slit diaphragm (SD) proteins and cell-cell adhesion molecule. Further investigation revealed that EMT inhibition of baicalin on injured podocyte is mainly mediated by the reduction of notch1 activation and its downstream Snail expression. Using the adriamycin-induced FSGS model, we determined that baicalin suppresses the Notch1-Snail axis activation in podocytes, relieves glomerulus structural disruption and dysfunction, and reduces proteinuria. Altogether, these findings suggest that baicalin is a novel renoprotective agent against podocyte EMT in FSGS and indicate its underlying mechanism that involves in negative regulation of the Notch1-Snail axis.