ObjectiveTo investigate the differences in clinical features and outcomes between patients with hepatic Wilson's disease （WD） presenting with the syndrome of combined phlegm and stasis and the syndrome of dampness-heat internal accumulation. MethodsA retrospective cohort study was conducted by consecutively recruiting patients with hepatic WD from the Encephalopathy Center of the First Affiliated Hospital of Anhui University of Chinese Medicine between January 2022 and August 2025. According to traditional Chinese medicine （TCM） syndrome differentiation， the patients were assigned into a combined phlegm and stasis group and a dampness-heat internal accumulation group. All the patients received standard treatment. Baseline data， laboratory indicators， complications， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， and Chronic Liver Failure-Sequential Organ Failure Assessment （CLIF-SOFA） score were recorded. The clinical features and outcomes of the two groups of patients were compared by t-test， U-test and multivariate logistic regression. ResultsA total of 141 patients with hepatic WD were included. The combined phlegm and stasis group comprised 68 patients with an average age of （28.22±10.47） years， including 43 males and 25 females. The dampness-heat internal accumulation group comprised 73 patients with an average age of （30.22±8.79） years， including 44 males and 29 females. Univariate analysis showed no statistically significant differences in age or gender between the two groups. The combined phlegm and stasis group had lower platelet （PLT）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， creatine （CRE）， total cholesterol （TC）， and triglycerides （TG） levels （P<0.05 or P<0.01） and higher total bilirubin （TBIL） and prothrombin time （PT） （P<0.05） than the dampness-heat internal accumulation group. There were no statistically significant differences in the incidence of hepatic encephalopathy， infection， spontaneous bacterial peritonitis， ascites， or gastrointestinal bleeding between the two groups. The incidence of splenomegaly and the MELD score were higher in the combined phlegm and stasis group （P<0.05）. The CTP and CLIF-SOFA scores were also higher in the combined phlegm and stasis group， while these differences were not statistically significant. Eleven patients in the combined phlegm and stasis group and 9 patients in the dampness-heat internal accumulation group developed liver failure. Multivariate logistic regression analysis showed that PT （OR=1.794， 95%CI 1.249-2.576）， TBIL （OR=1.111， 95%CI 1.026-1.203）， ALT （OR=1.053， 95%CI 1.004-1.105）， and TCM syndrome （OR=5.420， 95%CI 1.384-21.227） were independent risk factors for the development of liver failure in hepatic WD. ConclusionCompared with the hepatic WD patients with the syndrome of dampness-heat internal accumulation， those with the syndrome of combined phlegm and stasis exhibit severe liver function impairment and disease conditions. Furthermore， TCM syndrome serves as an independent predictive factor for the occurrence of liver failure in patients with hepatic WD.

ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction （GDFMD） in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome， thereby providing evidence-based medical evidence for the treatment of Wilson's disease （WD）-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1， 2023， to October 1， 2024. Participants were divided into a control group and an observation group， with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate （DMPS）. On this basis， the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days， for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses， respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement （LSM）， liver serological markers ［alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， type Ⅳ collagen （C-Ⅳ）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢNP）， and hyaluronic acid （HA）］， fibrosis index based on 4 factors （FIB-4）， AST to platelet ratio index （APRI）， unified Wilson's disease rating scale part Ⅱ （UWDRS-Ⅱ）， traditional Chinese medicine （TCM） syndrome score， 24-hour urinary copper， and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment， LSM levels decreased in both groups after two and four treatment courses （P<0.05）. Compared with those after treatment， there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses， and the improvement of LSM levels in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， the levels of HA， LN， PⅢNP， and C-Ⅳ decreased in both groups after two and four treatment courses （P<0.05）. Compared with those after treatment， there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses， and the levels of HA， LN， and PⅢNP were more obvious （P<0.05）. After four treatment courses in the observation group， the levels of HA， LN， PⅢNP， and C-Ⅳ were improved more significantly （P<0.05）. Compared with those before treatment， ALT and AST levels decreased in both groups after two and four treatment courses （P<0.05）. Compared with the control group after treatment， there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses， and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， APRI score and FIB-4 index level decreased in both groups after two and four treatment courses （P<0.05）. Compared with those in control group after treatment， there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses， and the APRI score in the observation group was more obvious after four treatment courses （P<0.05）， with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment， the levels of TCM syndrome scores decreased in both groups after two and four treatment courses （P<0.05）. Compared with that of the control group after treatment， there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses， and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously， and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses （P<0.05）. Compared with those of the control group after treatment， there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses， and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious （P<0.05）. Compared with those before treatment， the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses （P<0.05）. Compared with those in the control group after treatment， the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses （P<0.01）. After two treatment courses， the 24-h urine copper level in the observation group showed a gradual decreasing trend， although it was higher than that before treatment. After four treatment courses， the control group had an improvement rate of 91.43%， an effective rate of 34.29%， and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%， an effective rate of 71.43%， and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group （P<0.05）. Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy， and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety， which is worthy of clinical popularization and application.

ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction （GDFMD） in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome， thereby providing evidence-based medical evidence for the treatment of Wilson's disease （WD）-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1， 2023， to October 1， 2024. Participants were divided into a control group and an observation group， with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate （DMPS）. On this basis， the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days， for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses， respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement （LSM）， liver serological markers ［alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， type Ⅳ collagen （C-Ⅳ）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢNP）， and hyaluronic acid （HA）］， fibrosis index based on 4 factors （FIB-4）， AST to platelet ratio index （APRI）， unified Wilson's disease rating scale part Ⅱ （UWDRS-Ⅱ）， traditional Chinese medicine （TCM） syndrome score， 24-hour urinary copper， and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment， LSM levels decreased in both groups after two and four treatment courses （P<0.05）. Compared with those after treatment， there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses， and the improvement of LSM levels in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， the levels of HA， LN， PⅢNP， and C-Ⅳ decreased in both groups after two and four treatment courses （P<0.05）. Compared with those after treatment， there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses， and the levels of HA， LN， and PⅢNP were more obvious （P<0.05）. After four treatment courses in the observation group， the levels of HA， LN， PⅢNP， and C-Ⅳ were improved more significantly （P<0.05）. Compared with those before treatment， ALT and AST levels decreased in both groups after two and four treatment courses （P<0.05）. Compared with the control group after treatment， there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses， and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， APRI score and FIB-4 index level decreased in both groups after two and four treatment courses （P<0.05）. Compared with those in control group after treatment， there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses， and the APRI score in the observation group was more obvious after four treatment courses （P<0.05）， with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment， the levels of TCM syndrome scores decreased in both groups after two and four treatment courses （P<0.05）. Compared with that of the control group after treatment， there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses， and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously， and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses （P<0.05）. Compared with those of the control group after treatment， there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses， and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious （P<0.05）. Compared with those before treatment， the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses （P<0.05）. Compared with those in the control group after treatment， the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses （P<0.01）. After two treatment courses， the 24-h urine copper level in the observation group showed a gradual decreasing trend， although it was higher than that before treatment. After four treatment courses， the control group had an improvement rate of 91.43%， an effective rate of 34.29%， and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%， an effective rate of 71.43%， and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group （P<0.05）. Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy， and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety， which is worthy of clinical popularization and application.

Wilson disease （WD） is an autosomal recessive disorder of copper metabolism， and decoppering therapy and symptomatic treatment are the main Western medicine therapies for WD. This article systematically reviews the understanding of the etiology and pathogenesis of WD in traditional Chinese medicine （TCM） and points out that abnormal natural endowment is the core etiology and pathogenesis of WD， with internal accumulation of copper toxicity as the manifestation， liver/spleen/kidney dysfunction as the root cause， and intermingled “toxin， stasis， phlegm， and deficiency” as the key pathogenesis. Literature research and clinical observation are conducted to summarize the common TCM syndromes of WD， including stagnation of liver Qi， internal retention of damp-heat， phlegm-stasis-heat accumulation syndrome， liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency， and syndrome of deficiency damage and phlegm stasis. This article proposes the corresponding therapies and representative prescriptions for each syndrome and discusses the advantages of treatment by stage and integrated traditional Chinese and Western medicine therapy. This article aims to provide a systematic reference for the syndrome differentiation-based treatment of WD in clinical practice of TCM， thereby giving full play to the advantages of TCM in the treatment of this disease.

ObjectiveThis study aims to identify cuproptosis-related gene biomarkers in Alzheimer's disease（AD） using bioinformatics and machine learning methods， validate them at the clinical specimen level， and predict potential traditional Chinese medicine（TCM）. MethodsDifferentially expressed genes in the AD group and normal group were obtained using the Gene Expression Omnibus （GEO） database， and intersections were taken with reported cuproptosis-related genes to obtain differentially expressed cuproptosis-related genes. Machine learning methods were applied to identify core differential genes of cuproptosis in AD. Peripheral blood's single nucleated cells from clinical AD patients were collected， and the relative gene expression was clinically verified by real-time polymerase chain reaction（Real-time PCR）. Potential TCM regulating cuproptosis for AD were predicted by COREMINE database. ResultsA total of 12 cuproptosis-related genes were obtained， mainly involved in pathways of tricarboxylic acid cycle， 2-oxocarboxylic acid metabolism， and carbon metabolism. Five core cuproptosis-related genes， dihydrolipoamide dehydrogenase （DLD）， glutaminase （GLS）， pyruvate dehydrogenase E1 subunit beta （PDHB）， full name nuclear factor （erythroid-derived 2）-related factor 2 （NFE2L2）， and dihydrolipoamide branched-chain transacylase E2 （DBT） were finally screened using four machine methods. Thirty cases each of normal and AD patients were collected clinically. Compared with those in the normal group， minimum mental state examination （MMSE） and Montreal cognitive assessment （MoCA） were significantly decreased in the AD group （P<0.01）， Homocysteine（Hcy）， interleukin（IL）-6， C-reactive protein（CRP） ， and β amyloid protein（Aβ） indexes were significantly increased （P<0.01）， and malondialdehyde（MDA） indexes were decreased （P<0.05）. Superoxide dismutase（SOD） levels were significantly decreased （P<0.01）. The mRNA relative expressions of NFE2L2 and DBT were up-regulated （P<0.05）， and those of DLD， GLS， and PDHB were significantly down-regulated （P<0.01）. The TCM regulating cuproptosis-related genes for the treatment of AD were mainly based on the four Qi such as warmth， calmness， and cold， and the five flavors including bitterness， sweetness， and pungency， and it was attributed to the meridians of the liver， spleen， stomach， and kidney， with the efficacy of tonifying Qi， activating blood， eliminating phlegm， and resoling dampness. ConclusionDLD， GLS， NFE2L2， PDHB， and DBT can be used as novel diagnostic molecular markers for AD cuproptosis-related genes， and the corresponding potential therapeutic TCM can provide new ideas for the treatment of AD by TCM.

Wilson disease is a copper metabolism disorder caused by mutations in the ATP7B gene， which encodes a copper-transporting ATPase β， and can result in multisystem damage. The kidneys are the third most commonly affected organs after the liver and brain. In recent years， numerous diagnostic and treatment guidelines for Wilson disease have emerged. However， most of these focus primarily on hepatic and neurological manifestations and their management， with limited coverage of renal involvement. The high incidence， low awareness， and lack of clinical specificity of Wilson disease-related renal damage （WDRD） have made early detection and intervention particularly challenging in clinical practice. To further optimize the treatment of patients with WDRD， improve clinical diagnosis and management， and enhance patients' quality of life， the Neurology Committee of the Chinese Association of Integrative Medicine， in April 2024， initiated a revision of the first expert consensus on the integrated diagnosis， treatment， and management of WDRD. This effort brought together experts in hepatology， encephalopathy （neurology）， and nephrology from many tertiary-level grade A hospitals and research institutions across China. Through comprehensive literature review and integration of frontline clinical experience， the expert group jointly developed Chinese Expert Consensus on Integrated Chinese and Western Medicine Management of Wilson Disease-related Renal Damage （hereinafter referred to as the "Consensus"）. This article provides a detailed interpretation of the Consensus in terms of diagnostic criteria， traditional Chinese medicine （TCM） syndrome differentiation and treatment classification， and comprehensive disease management， aiming to better guide clinical application. Regarding diagnostic criteria， the Consensus integrates the latest standards in China and abroad， highlights the importance of biochemical diagnosis， and compensates for the limitations of genetic testing. In the area of TCM syndrome differentiation and treatment， the Consensus refines four major syndrome types， introduces a newly defined syndrome， i.e.， phlegm， blood stasis， and heat accumulation， and elaborates on treatment principles， prescriptions， and clinical modification rules for each syndrome. For comprehensive disease management， the Consensus emphasizes multi-dimensional intervention strategies， including diet， exercise， emotional regulation， medication， and medical care， with the goal of maximally controlling the progression of renal dysfunction and helping patients achieve a better quality of life.

Mild cognitive impairment due to Alzheimer′s disease is an inevitable pathological stage in the early development of Alzheimer′s disease, which can be classified as "microlumps in the brain collaterals" in traditional Chinese medicine. Based on the theory of latent toxin blocking collaterals, this article discusses the etiology and pathogenesis, clinical sequelae, and traditional Chinese medicine intervention strategies for mild cognitive impairment due to Alzheimer′s disease. The onset of mild cognitive impairment due to Alzheimer′s disease is very similar to the latent pathogen theory, which states that "the latent pathogen is latent and then develops, the poison is deep and difficult to cure, and the development can be recognized but the latent pathogen cannot be detected." Combining clinical experience, our team believes that the basic nature of the disease is a slight deficiency and a slight excess of symptoms. A slight deficiency of the five zang viscera and six fu viscera as root and a latent toxin colling collaterals of qi, fire, phlegm, and blood stasis as manifestaion. These usually start from the qi depression and develop into phlegm coagulation and blood stasis, then end up in latent toxin and gradually become the healthy qi deficiency. Therefore, the deficiency of vital qi and incubation of evil, latent toxin blocking collaterals the pathogenesis of early intervention of this disease should be carried out, upholding the idea that "the upper workman treats the disease before it is diagnosed." The principle of strengthening vital qi to eliminate pathogenic factors, slowing down and promoting pathogenic factors elimination, establishing the method of supporting correctness and wisdom, simultaneously detoxifying and clearing the blood stasis, pattern differentiation as the main and the disease differentiation as the first, combining the disease and pattern, and adjusting the macroscopic and microscopic, focusing simultaneously on eliminating and replenishing, dispel phlegm and remove blood stasis, achieve a strong vital qi and the elimination of evil, and enhance intelligence, delay or even block the progression of mild cognitive impairment due to Alzheimer′s disease, improve patients′ quality of life, and provide a theoretical basis for the early clinical prevention and treatment of Alzheimer′s disease.

ObjectiveTo explore the role of cuproptosis and identify cuproptosis-related genes in Wilson disease （WD） through bioinformatics analysis and clinical validation，providing implications and directions for the diagnosis and treatment of WD. Methods（1） Screening of target genes： The differentially expressed genes （DEGs） between WD and healthy control were obtained from GeneCards，and the cuproptosis-related genes were obtained from Gene Expression Omnibus （GEO） and published literature.The cuproptosis-related genes in WD were obtained by intersection.Through gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses，the specific biological process，functions or metabolic pathways of cuproptosis-related genes in WD were predicted.Molecular docking and PyMOL visualization were then performed to analyze and verify the potential regulatory mechanism of Gandou Fumu Decoction for cuproptosis.（2）Validation of target genes： The blood samples of 15 WD patients treated in the department of encephalopathy and 15 healthy volunteers undergoing physical examinations in the health management center were randomly collected from the First Affiliated Hospital of Anhui University of Chinese Medicine.The expression levels of target genes were determined by Western blot and real-time PCR. Results（1） A total of 3 607 DEGs in WD were obtained from GSE107323 in GEO，and 68 cuproptosis-related genes were obtained from GeneCards and published literature.Twelve common target genes were obtained by intersection，including three up-related genes（SQSTM1，MIF1，and TAX1BP1） and nine down-regulated genes（CP，SERPINE1，AOC3，GPX4，SLC27A5，VEGF-A，PDHB，PDK1，and ATP7B）.The common target genes were mainly enriched in monocarboxylic acid metabolism，oxidoreductase activity，negative regulation of molecular functions，which mainly involved HIF-1，ferroptosis and other signaling pathways.Molecular docking and PyMOL visualization results showed Gandou Fumu Decoction had good binding ability with the cuproptosis-related genes PDK1，SERPINE1，VEGFA，and AOC3 in WD.（2）A total of 30 blood samples were collected，including 15 WD patients and 15 health volunteers.Western blot results showed that expression levels of target genes were consistent with the results obtained by bioinformatics analysis.RT-qPCR results showed that compared with healthy volunteers，WD patients had down-regulated mRNA levels of SERPINE1，GPX4，SLC27A5，and VEGF-A and up-regulated mRNA levels of SQSTM1 and MIF1（P<0.05）. ConclusionThe expression levels of cuproptosis-related genes in WD patients are consistent with the results predicted by bioinformatics analysis.The characteristic preparation Gandou Fumu Decoction of Xin'an Medicine showed good binding abilities with the cuproptosis-related genes in WD.Cuproptosis may play a key role in the pathophysiological mechanism of WD，which can provide a new target for the diagnosis and treatment of WD.

Hepatolenticular degeneration， also known as Wilson disease （WD）， is a hereditary disease caused by mutations in the ATP7B gene， leading to copper metabolism disorders. Gene mutations result in impaired synthesis of copper-binding protein， and abnormal excretion of copper through bile leads to pathological deposition of copper in various organs， ultimately causing multi-organ damage. The insidious onset and low specificity of symptoms make it difficult to diagnose this disease. On the basis of existing studies and the theory of latent toxin， this paper proposes that latent toxin in kidney collaterals is the main pathogenesis of renal injury in WD. It is pointed out that health Qi deficiency and latent pathogen are the premises for the occurrence of this disease， and the transformation of latent pathogen into toxin is the ley pathological process. Toxin damaging kidney collaterals is the ultimate result. According to the pathogenesis， this paper proposes the treatment principle of reinforcing healthy Qi and resolving toxin and treatment based on syndrome differentiation. This review provides new ideas for the diagnosis and treatment of renal injury in WD with traditional Chinese medicine.