It is believed that gout is rooted in spleen-kidney depletion， and damp-heat， turbidity toxin， and phlegm stasis are the sources. The treatment principle should be fortifying the spleen and boosting the kidney to consolidate the root， while draining dampness and removing turbidity， clearing heat and resolving toxins， relieving stasis and dissolving phlegm to clear the source. Staged treatment based on the relationship and transition between healthy qi deficiency and excess pathogen is recommended. For intercritical gout when there is internal accumulation of damp turbidity mainly， the treatment method should be draining dampness and removing turbidity by Chushi Fuling Decoction （除湿茯苓汤） with modifications. During the acute stage of gout when damp-heat toxin accumulation is the most urgent， it is recommended to clear heat and resolve toxins with self-made Qingpi Tongfeng Formula （清皮痛风方） with modifications. During the chronic stage of gout， when spleen deficiency and damp-heat and phlegm-stasis obstruction are the predominant， the method of fortifying spleen， clearing heat and draining dampness， as well as dissolving phlegm and dissipating stasis should be implemented， by using self-made Qingre Shenshi Decoction （清热渗湿汤） with modifications and Erchen Decoction and Taohong Siwu Decoction （二陈汤合桃红四物汤） with modifications， respectively.For gouty nephropathy， when spleen-kidney depletion is the root， and phlegm， stasis and toxin are accompanied， it is recommended to fortify spleen and boost kidney， and dissolve phlegm， move stasis and resolve toxins using self-made Bupi Yishen Decoction （补脾益肾汤） with modifications.

Refractory rheumatoid arthritis belongs to the category of "stubborn bi （痹）" and "lame bi" in traditional Chinese medicine. It is believed that pathogenic toxin is an important pathogenic factor of refractory rheumatoid arthritis， and "healthy qi deficiency and toxins accumulation" is its core pathogenesis. Pathogenic toxin can be divided into latent and internal toxin， among which latent toxin includes congenital latent toxin and acquired exogenous and drug-induced latent toxin； and internal toxin is directly produced by the dysfunction of the body's zang-fu （脏腑） organs， or is transformed from dampness， turbidity， phlegm and stasis. Pathogenic toxin can flow into the meridians and collaterals， quickly corrode the bones and joints， harm the five zang organs， secretly consume the body's healthy qi， and accumulate and entrench. Based on this， the treatment principle of "reinforcing healthy qi and resolving toxins" has been established， emphasizing that the key is to strengthen the origin of the body's healthy qi and to attack the pathogenic toxin from its weakness. In clinical practice， it is suggested to trace the root cause， and treat the disease based on the cause. Besides reinforcing the body's healthy qi， the methods such as clearing heat to resolve toxins， draining dampness to resolve toxins， dispelling wind to remove toxins， dispersing cold to resolve toxins， dissolving phlegm to resolve toxins， and dispersing stasis to resolve toxins can be supplemented， so as to reinforce the healthy qi and dispel pathogens simultaneously and thereby improving the clinical efficacy.

ObjectiveTo combine metabolomics， proteomics， and transcriptomics to analyze the biological characteristics of damp-heat toxin accumulation syndrome and damp-heat accumulation syndrome in acute gout. MethodsBlood samples were collected from 15 patients with damp-heat toxin accumulation syndrome and 15 patients with damp-heat accumulation syndrome in acute gout in clinical practice. Metabolomics technology was applied to detect serum metabolites， and an orthogonal partial sample least squares discriminant analysis model was constructed to screen for metabolites with significant intergroup changes， and enrichment pathway analysis and receiver operating characteristic （ROC） curve analysis were performed. Astral data independence acquisition （DIA） was used to detect serum proteins， perform principal component analysis and screen differential proteins， demonstrate differential ploidy by radargram， apply subcellular localisation to analyse protein sources， and finally apply weighted gene co-expression network analysis （WGCNA） to find key proteins. Transcriptome sequencing technology was also applied to detect whole blood mRNA， screen differential genes and perform WGCNA， and construct machine learning models to screen key genes. ResultsMetabolome differential analysis revealed 62 differential metabolites in positive ion mode and 26 in negative ion mode. These differential metabolites were mainly enriched in the mTOR signaling pathway and FoxO signaling pathway， with trans-3,5-dimethoxy-4-hydroxycinnamaldehyde， guanabenz， 4-aminophenyl-1-thio-beta-d-galactopyranoside showing the highest diagnostic efficacy. The proteome differential analysis found that 55 proteins up-regulated and 20 proteins down-regulated in the samples of damp-heat toxin accumulation syndrome. Notably， myelin basic protein （MBP）， transferrin （TF）， DKFZp686N02209， and apolipoprotein B （APOB） showed the most significant differences in expression. Differential proteins were mainly enriched in pathways related to fat digestion and absorption， lipid and atherosclerosis， and cholesterol metabolism. WGCNA showed the highest correlation between damp-heat toxin accumulation syndrome and the brown module， with proteins in this module primarily enriched in the hypoxia-inducible factor 1 （HIF-1） signaling pathway and lipid and atherosclerosis. Transcriptomic differential analysis identified 252 differentially expressed genes， with WGCNA indicating the highest correlation between damp-heat toxin accumulation syndrome and the midnight blue module. The random forest （RF） model was identified as the optimal machine learning model， predicting apolipoprotein B receptor （APOBR）， far upstream element-binding protein 2 （KHSRP）， POU domain class 2 transcription factor 2 （POU2F2）， EH domain-containing protein 1 （EHD1）， and family with sequence similarity 110A （FAM110A） as key genes. Integrated multi-omics analysis suggested that damp-heat toxin accumulation syndrome in the acute phase of gout is closely associated with lipid metabolism， particularly APOB. ConclusionCompared to damp-heat accumulation syndrome in the acute phase of gout， damp-heat toxin accumulation syndrome is more closely associated with lipid metabolism， particularly APOB， and lipid metabolism disorders contribute to the development of damp-heat toxin accumulation syndrome in patients with acute gout.