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.

BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

OBJECTIVE: Prunella vulgaris L. has long been used for liver protection according to traditional Chinese medicine theory and has been proven by modern pharmacological research to have multiple potential liver-protective effects. However, its effects on non-alcoholic steatohepatitis (NASH) are currently uncertain. Our study explores the effects of P. vulgaris polysaccharides on NASH and intestinal homeostasis. METHODS: An aqueous extract of the dried fruit spikes of P. vulgaris was precipitated in an 85% ethanol solution (PVE85) to extract crude polysaccharides from the herb. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) was administrated to male C57BL/6 mice to establish a NASH animal model. After 4 weeks, the PVE85 group was orally administered PVE85 (200 mg/[kg·d]), while the control group and CDAHFD group were orally administered vehicle for 6 weeks. Quantitative real-time polymerase chain reaction analysis, Western blotting, immunohistochemistry and other methods were used to assess the impact of PVE85 on the liver in mice with NASH. 16S rRNA gene amplicon analysis was employed to evaluate the gut microbiota abundance and diversity in each group to examine alterations at various taxonomic levels. RESULTS: PVE85 significantly reversed the course of NASH in mice. mRNA levels of inflammatory mediators associated with NASH and protein expression of hepatic nucleotide-binding leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) were significantly reduced after PVE85 treatment. Moreover, PVE85 attenuated the thickening and cross-linking of collagen fibres and inhibited the expression of fibrosis-related mRNAs in the livers of NASH mice. Intriguingly, PVE85 restored changes in the gut microbiota and improved intestinal barrier dysfunction induced by NASH by increasing the abundance of Actinobacteria and reducing the abundance of Proteobacteria at the phylum level. PVE85 had significant activity in reducing the relative abundance of Clostridiaceae at the family levels. PVE85 markedly enhanced the abundance of some beneficial micro-organisms at various taxonomic levels as well. Additionally, the physicochemical environment of the intestine was effectively improved, involving an increase in the density of intestinal villi, normalization of the intestinal pH, and improvement of intestinal permeability. CONCLUSION PVE85 can reduce hepatic lipid overaccumulation, inflammation, and fibrosis in an animal model of CDAHFD-induced NASH and improve the intestinal microbial composition and intestinal structure. Please cite this article as: Zhu MJ, Song YJ, Rao PL, Gu WY, Xu Y, Xu HX. Therapeutic role of Prunella vulgaris L. polysaccharides in non-alcoholic steatohepatitis and gut dysbiosis. J Integr Med. 2025; 2025; 23(3): 297-308.
Animals ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Male ; Dysbiosis/drug therapy* ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/drug effects* ; Polysaccharides/therapeutic use* ; Prunella/chemistry* ; Mice ; Liver/metabolism* ; Plant Extracts/therapeutic use* ; Disease Models, Animal ; Diet, High-Fat

Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

Lymphomas are a highly heterogeneous group of tumors that are classified into several subtypes. The gold standard method for the molecular profiling of lymphoma is based on invasive lymph node or tissue biopsy. However, this method cannot accurately capture spatial tumor heterogeneity in each patient as well as systemic tumor invasion and tumor burden. Circulating tumor DNA (ctDNA) is an emerging and highly versatile biomarker that overcomes the basic limitations of imaging scanning and tissue biopsy; has the characteristics of being simple, rapid, and non-invasive; and has good specificity and high sensitivity. ctDNA testing has been applied to a variety of subtypes of lymphoma and has been used for somatic mutation genotyping, efficacy monitoring during treatment, detection of minimal residual disease, and the prediction of survival, which may help clinicians make better clinical decisions in the diagnosis and treatment of lymphoma patients. Furthermore, this study also aims to review the different methods of ctDNA analysis and describe the specific applications of ctDNA in different lymphoma subtypes.

Objective To design an anti-inversion performance evaluation system for ankle braces and validate its performance.Methods The system was composed of a simulation system,an inversion angle acquisition system,a lateral tension acquisition system for ankle joint and a data collection and procession system.The simulation platform made of aluminum alloy consisted of a standing platform and a landing pad,and the landing pad was made up of a platform and a slope for landing;the inversion angle acquisition system included markers,an image acquisition device and a fill light.The lateral tension acquisition system involved in a tension sensor,a detection sensor and an elastic cloth for fixation.The data collection and procession system comprised of a computer or smartphone,iXControl software,iXViewer software and a cell phone App that received real-time data from the lateral ankle tension acquisition device.The system developed underwent performance validation when applied to evaluating anti-inversion performance of volunteers without or with flexible or new braces.The traditional EMG testing method was used for EMG data acquisition for volunteers without or with flexible or new braces,and the consistency was explored between the testing results by the traditional method and the system.Results The system developed could evaluate the anti-inversion performance of ankle braces by simulating the process of ankle inversion during human high-altitude landing,and the results had high consistency with those by traditional EMG testing methods.Conclusion The system developed with simple structure and easy operation evaluates the anti-inversion performance of ankle braces.[Chinese Medical Equipment Journal,2024,45(11):21-26]

Traditional Chinese Medicine (TCM) shows unique advantages in the field of adjuvant treatment of gastric cancer. The main mechanism of TCM in improving gastric cancer includes regulating cell proliferation and apoptosis, reversing cell resistance, reducing the ability of invasion and metastasis and epithelial-mesenchymal transformation, regulating immune function, inhibiting neovascularization, regulating autophagy exosome, and ferroptosis.

BACKGROUND: Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown. METHODS: Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca 2+ -related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance. RESULTS: Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca 2+ is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments. CONCLUSIONS Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.
Animals ; Humans ; Mice ; Apoptosis ; Bone Marrow Cells ; Cell Communication ; Connexin 43/genetics* ; Gap Junctions/metabolism* ; Imatinib Mesylate/therapeutic use* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology* ; Mesenchymal Stem Cells/metabolism* ; Tumor Microenvironment ; Calcium/metabolism*

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins