👤 Haji Akber Aisa

Compound Nujia honey paste (Nujia), a classic formulation from Traditional Uyghur Medicine, has been historically used for depression treatment and is listed in the Catalog of Ancient Classical Famous Formulas issued by the National Administration of Traditional Chinese Medicine and the National Medical Products Administration. Clarifying its pharmacodynamic material basis is essential for understanding its efficacy, yet this remains incompletely characterized. This study aimed to systematically elucidate Nujia's antidepressant efficacy and mechanisms by combining chemical analysis, computational prediction, and experimental validation in a CUMS rat model, providing a comprehensive approach to understanding its action. This study employed LC/MS to analyze the chemical constituents and blood-absorbed compounds of Nujia. This was combined with network pharmacology and molecular docking to predict and verify its potential antidepressant targets and signaling pathways. Using behavioral tests, ELISA, histopathology, Western blot, and qRT-PCR in a CUMS rat model, the research thoroughly evaluated Nujia's therapeutic effects and mechanisms, fostering trust in the findings. In this study, LC/MS analysis identified 124 chemical constituents from Nujia, and further analysis determined 26 blood-absorbed compounds (including 10 prototype compounds). Network pharmacology analysis revealed that its potential antidepressant effects are closely associated with core targets such as AKT1 and TNF, a prediction subsequently verified by molecular docking results. In the CUMS-induced rat model of depression, intervention with Nujia significantly ameliorated depression-like behaviors in the animals and alleviated neuropathological damage in the hippocampus and prefrontal cortex. Mechanistic investigations revealed that Nujia upregulated the levels of monoamine neurotransmitters (5-HT, DA, NE) and neurotrophic factors (BDNF, NGF) in serum, while downregulating the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-18). Further molecular experiments confirmed that Nujia likely mitigates neuroinflammation by inhibiting the TNF-α/NF-κB signaling pathway, and inhibits neuronal apoptosis by activating the PI3K/AKT signaling pathway and its downstream anti-apoptotic proteins. Furthermore, Nujia significantly upregulated the expression of key synaptic plasticity proteins (SYP, GAP43, and PSD95) in hippocampal tissue, thereby enhancing synaptic structure and function. These findings underscore the complex, multi-target mechanisms underlying Nujia's antidepressant effects, encouraging further exploration of its therapeutic potential. This study systematically elucidates that Nujia achieves its antidepressant therapeutic effects by mediating multi-pathway synergistic actions, including but not limited to the TNF-α/NF-κB and PI3K/AKT signaling pathways, to ameliorate neuroinflammation, attenuate apoptosis, and enhance synaptic plasticity. Show less

This article aims to analyze the safety and efficacy of Erdafitinib in the treatment of patients with advanced solid tumors harboring FGFR1-4 mutations. Search for relevant articles in databases such as PubMed, Embase, The Cochrane Library, Web of Science, and CNKI, covering the period from their establishment to October 25, 2024. Summarize the adverse drug reaction (AE) data, overall survival (OS), median progression-free survival (PFS), objective response rate (ORR), and other relevant data for patients with advanced solid tumors treated with Erdafitinib for FGFR1-4 mutations. Conduct a meta-analysis on the corresponding summarized data using the software Stata 18.0. Through our search, we identified a total of 10 articles involving 1019 patients. In urothelial carcinoma, the most prevalent adverse reactions are hyperphosphatemia (78.5%), diarrhea (56.5%), and stomatitis (51.1%). The most frequently reported adverse reactions in other solid tumors are hyperphosphatemia (66.5%), dry mouth (48.5%), and diarrhea (44.9%). Patients with urothelial carcinoma treated with Erdafitinib exhibit higher median progression-free survival (PFS) and objective response rate (ORR) compared to those treated with other solid tumor therapies. Current evidence indicates that Erdafitinib exhibits certain therapeutic efficacy in the treatment of advanced solid tumors harboring FGFR1-4 mutations, with the most pronounced therapeutic effect observed in urothelial carcinoma. The efficacy of Erdafitinib in treating other solid tumors requires further confirmation through larger-scale studies involving a broader range of FGFR1-4 mutant tumors. Show less