OBJECTIVE To observe the clinical efficacy of Gandou Fumu Decoction(GDFMD)combined with swallowing func-tion training on Wilson's disease with dysphagia of phlegm stasis type.METHODS Sixty-eight WD patients in The First Affiliated Hospital of Anhui University of Chinese Medicine were randomly equally divided into a control group(34 cases)and a treatment group(34 cases)during October 2021 to October 2024.Control group patients were treated with basic therapy such as copper drainage and swallowing training,while patients in the treatment group received additional GDFMD.The scores of traditional Chinese medicine(TCM)syndrome scores,Water Swallow Test(WST),Standardized Swallowing Assessment(SSA),Functional Oral Intake Scale(FOIS),Barthel Scale were observed before and after the treatment.24-hour urinary copper,superoxide dismutase(SOD)and malon-dialdehyde(MDA)levels were measured in both groups.RESULTS After treatment,the TCM syndrome scores,SSA,WST scale scores and blood MDA levels of the two groups of patients were significantly reduced(P<0.05,P<0.01),and the treatment group was better than the control group(P<0.05);FOIS,Barthel scale scores,24-hour urine copper content and serum SOD level in both groups were significantly increased(P<0.05,P<0.01),and the treatment group was better than the control group(P<0.05).CON-CLUSION The combined therapy of Gandou Fumu Decoction with swallowing training can improve the swallowing function on Wil-son's disease with dysphagia of phlegm stasis type and enhance the copper removing.The mechanism may be related to improving the level of antioxidant stress.

OBJECTIVE To observe the clinical efficacy of Gandou Fumu Decoction(GDFMD)combined with swallowing func-tion training on Wilson's disease with dysphagia of phlegm stasis type.METHODS Sixty-eight WD patients in The First Affiliated Hospital of Anhui University of Chinese Medicine were randomly equally divided into a control group(34 cases)and a treatment group(34 cases)during October 2021 to October 2024.Control group patients were treated with basic therapy such as copper drainage and swallowing training,while patients in the treatment group received additional GDFMD.The scores of traditional Chinese medicine(TCM)syndrome scores,Water Swallow Test(WST),Standardized Swallowing Assessment(SSA),Functional Oral Intake Scale(FOIS),Barthel Scale were observed before and after the treatment.24-hour urinary copper,superoxide dismutase(SOD)and malon-dialdehyde(MDA)levels were measured in both groups.RESULTS After treatment,the TCM syndrome scores,SSA,WST scale scores and blood MDA levels of the two groups of patients were significantly reduced(P<0.05,P<0.01),and the treatment group was better than the control group(P<0.05);FOIS,Barthel scale scores,24-hour urine copper content and serum SOD level in both groups were significantly increased(P<0.05,P<0.01),and the treatment group was better than the control group(P<0.05).CON-CLUSION The combined therapy of Gandou Fumu Decoction with swallowing training can improve the swallowing function on Wil-son's disease with dysphagia of phlegm stasis type and enhance the copper removing.The mechanism may be related to improving the level of antioxidant stress.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

The recent discovery of activator compounds binding to an allosteric site on the NAD