The core pathogenesis of membranous nephropathy is spleen-kidney depletion and dampness-stasis blocking collaterals， in which spleen-kidney depletion runs through the whole process of membranous nephropathy. Spleen and kidney depletion often occurs in the early stage of membranous nephropathy， accompanied by the progression of the disease and the stagnation of deficiency and qi， which leads to the obstruction of kidney collaterals by patho-logical products such as phlegm， blood stasis and water-dampness， and then the formation of stasis obstruction in kidney collaterals over time. Huangqi （Radix Astragali） as an important herb for supplementing spleen and boosting kidney can be used to fortify spleen， consolidate kidney and generate essence， and to boost qi， expel blood and unblock collaterals when treating membranous nephropathy. With combined medicinals， it can dispel and remove wind， astringe， store and consolidate essence， unblock stagnation and remove excess， strengthen efficiency and supplement deficiency， raise yang and lift the sunken. Besides， it is emphasized that caution should be taken against the drawbacks that excessive sweet may constrain the stomach， and the sweet and the warm may assist heat in the treatment of membranous nephropathy. The degree at which the spleen is supplemented and the kidney boosted should be chosen properly， and the medication contraindications should be cautioned.

We summarize our clinical experience with the use of wind herbs for membranous nephropathy treatment.The pathology of membranous nephropathy is mainly based on the spleen and kidney,with wind pathogen,dampness-heat,and blood stasis as the main pathological factors.The imbalance of the spleen ascending clear and kidney-transforming qi is the fundamental pathogenesis of membranous nephropathy.Wind herbs are light and gentle in nature,and they can dispel wind,assist in raising the spleen yang,aid in kidney qi transformation,and promote the unblocking of qi and blood stasis.This corresponds to the pathogenesis of membranous nephropathy,which involves wind invasion,deficiency of the spleen and kidney,failure to ascend clear yang,and stagnation of qi and blood.In the clinical treatment of membranous nephropathy,the use of wind herbs such as ephedra,cassia twig,mulberry leaf,chrysanthemum flower,and other herbs,along with blood-activating and collateral-opening herbs such as incised notopterygium rhizome and root,rhizome ligustici,zedoray rhizome,and pangolin scales,is proposed.Chinese thorowax root,largetrifoliolious bugbane rhizome,divaricate saposhnikovia,incised notopterygium rhizome and root,and other pungent herbs combined with ginseng,membranous milkvetch root,and other sweet-tonifying herbs can tonify yang and benefit the spleen,enhancing the tonifying effect.Ephedra,cassia twig,fresh ginger,prepared common monkshood branched root,manchurian wildginger,and other pungent-warm herbs can warm the kidney,support yang,and promote qi transformation and water metabolism.In clinical treatment of membranous nephropathy,satisfactory result have been achieved by making use of the characteristics of wind herbs.

Targeted protein degradation(TPD)has rapidly emerged as a therapeutic modality to eliminate previously undruggable proteins by repurposing the cell's endogenous protein degrada-tion machinery.However,the susceptibility of proteins for targeting by TPD approaches,termed"degradability",is largely unknown.Here,we developed a machine learning model,model-free anal-ysis of protein degradability(MAPD),to predict degradability from features intrinsic to protein tar-gets.MAPD shows accurate performance in predicting kinases that are degradable by TPD compounds[with an area under the precision-recall curve(AUPRC)of 0.759 and an area under the receiver operating characteristic curve(AUROC)of 0.775]and is likely generalizable to inde-pendent non-kinase proteins.We found five features with statistical significance to achieve optimal prediction,with ubiquitination potential being the most predictive.By structural modeling,we found that E2-accessible ubiquitination sites,but not lysine residues in general,are particularly associated with kinase degradability.Finally,we extended MAPD predictions to the entire proteome to find 964 disease-causing proteins(including proteins encoded by 278 cancer genes)that may be tractable to TPD drug development.

Immunoglobulin A (IgA) nephropathy is a globally prevalent type of primary glomerulonephritis, characterized by complex symptoms and diverse clinical manifestations. The internationally recognized " multiple hit hypothesis" explains the systemic immune disease features of IgA nephropathy. However, current treatment strategies primarily focus on local pathological changes, inadequately addressing its complex systemic mechanisms. The " qi cycle in round" theory, an integral concept of the academic thought of HUANG Yuanyu, a prominent medical expert from the Qing Dynasty, offers a concise and insightful framework for understanding complex pathologies. For example, this theory provides valuable insights for elucidating the pathogenesis of IgA nephropathy and guiding its clinical management by simplifying intricate systemic processes. This study applies the " qi cycle in round" theory to postulate that patients with IgA nephropathy experience disrupted qi flow owing to spleen-stomach qi deficiency and dampness-heat accumulation. These imbalances manifest as internal symptoms, such as diarrhea; external vulnerability to illness; upper body symptoms, like sore throat; and lower body symptoms, such as hematuria and proteinuria. Pathologically, the condition is characterized by immune complex deposition. This article also emphasizes strategies that prioritize tonifying spleen-stomach qi to enhance the pivotal functions of transportation and transformation. Regulating qi and relieving stagnation are emphasized to harmonize ascending and descending dynamics. Additionally, eliminating turbidity and unblocking collaterals are highlighted to promote qi transformation. These approaches aim to restore the harmonious operation of organ qi dynamics and harmonious qi transformation functions. This study aims to provide a reference for syndrome differentiation and IgA nephropathy treatment using traditional Chinese medicine based on the " qi cycle in round" theory.