This paper summarizes Professor LIU Fengbin's clinical experience in treating autoimmune liver disease （AILD） using the method of nourishing yin and removing stasis based on stage differentiation. He believes that the pathogenesis of AILD generally involves both deficiency in essence and excess in manifestation， with essence deficiency often presenting as liver and kidney yin deficiency， which may progress to spleen deficiency and yang deficiency over time. The excess manifestation commonly includes qi stagnation， blood stasis， damp-heat， and phlegm toxicity. Clinically， he advocates for the treatment principle of nourishing yin and removing stasis. On the foundation of nourishing liver and kidney yin， different pathological factors causing stasis are eliminated according to their nature. Treatment is also tailored to different stages of AILD. In the early and asymptomatic stages， liver qi stagnation and spleen deficiency are prominent， warranting a therapeutic approach of soothing the liver， regulating qi and strengthening the spleen. The modified Chaishao Qizhi Decoction （柴芍气滞汤） is used. During the symptomatic stage， pathogenic factors become more pronounced， often accompanied by a significant deficiency of vital qi， with damp-heat， water retention， and phlegm toxicity as key pathological features. The treatment should focus on strengthening the spleen and dispelling dampness， using modified Sijunzi Decoction （四君子汤） combined with Yinchen Wuling Powder （茵陈五苓散）. In the liver function decompensation stage， vital qi is severely deficient while pathogenic factors persist， with damp-heat， phlegm toxicity， and blood stasis obstructing the liver collaterals. Treatment should focus on nourishing blood， softening the liver， strengthening the spleen， and resolving stasis， using the modified Ruangan Yangxue Decoction （软肝养血汤）. Throughout the treatment process， emphasis is placed on tonifying the liver and kidneys while protecting yin fluids.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Therapeutic cancer vaccines have experienced a resurgence over the past ten years. Cancer vaccines are typically designed to enhance specific stages of the cancer-immunity cycle, primarily by activating the immune system to promote tumor regression and overcome immune resistance. In this review, we summarize the significant recent advancements in cancer immunotherapy based on the cancer-immunity cycle, including the effector cell function, infiltration, initiation, and exhaustion. We summarize the identification of tumor antigens and their delivery through cancer vaccines. We discuss how specific stages of the cancer-immunity cycle have been leveraged to augment anti-tumor immune responses and improve vaccine efficacy. Additionally, the impact of aging and myelosuppression, two prevalent forms of immunological stress, on the effectiveness of therapeutic cancer vaccines is deliberated. Finally, we summarize the current status of various therapeutic cancer vaccines at different clinical trial phases.
Humans ; Cancer Vaccines/therapeutic use* ; Neoplasms/therapy* ; Immunotherapy/methods* ; Antigens, Neoplasm/immunology* ; Animals

Chinese medicine therapy for removing gallstones is one of the methods for the treatment of cholelithiasis.In the view of Professor Liu Fengbin,attacking of external pathogens,improper diet and emotional disorders contribute to the main causes of cholelithiasis,and the pathogenesis of cholelithiasis is due to qi stagnation of both liver and gallbladder,and internal obstruction of damp-heat.The occurrence of cholelithiasis is closely related to deficiency of spleen and stomach,and is correlated with the pathological factors of turbid phlegm and blood stasis.For the Chinese medicine treatment of cholelithiasis,Professor Liu follows the principle of"treatment in accordance with three categories of etiological factors"(i.e,seasons,environment and body constitution).He advocates the integration of traditional Chinese medicine and western medicine,and is good at utilizing Lingnan herbs and distinctive herbs that can dissolve stones and remove stones.The treatment for cholelithiasis is mainly through the therapies of soothing liver and alleviating depression,clearing heat and removing dampness,and normalizing gallbladder function to remove stones,and is also supplemented by the therapies of invigorating spleen and replenishing qi,regulating qi to resolve phlegm,and activiting qi movement and blood circulation.Modified Da Chaihu Decoction plus Sijin Decoction is often used as a basic formula for treating cholelithiasis,which is mainly composed of Desmodii Styracifolii Herba,Galli Gigerii Endothelium Corneum,Bupleuri Radix,Curcumae Radix,Scutellariae Radix,Aucklandiae Radix,Aurantii Fructus Immaturus stir-fried with bran,Paeoniae Radix Rubra,Linderae Radix,and Rhei Radix et Rhizoma.

Professor Liu Fengbin,a renowned traditional Chinese medicine(TCM)expert in Guangdong Province,specializes in treating digestive system disorders of hepatobiliary and splenic diseases with Chinese herbal medicine,and has accumulated extensive experience in intervening viral hepatitis type B and hepatitis B-related liver fibrosis.Professor Liu proposes that dampness,heat,stasis,toxin,and deficiency are the primary pathogenic factors of hepatitis B-related liver fibrosis.The disease is rooted in the liver,and is also closely related to the spleen and kidney and involves the gallbladder,stomach,and triple energizer.Based on TCM dialectical thinking and years of clinical practice,Professor Liu summarized the"eight methods for treating liver diseases"for intervening hepatitis B-related liver fibrosis with Chinese medicine,i.e.,method of activating the spleen and stomach,method of clearing heat and dispelling dampness,method of dispelling dampness and resolving turbidity,method of enriching yin and subduing fire,method of warming yang and tonifying the kidney,method of softening the liver and nourishing blood,method of activating blood circulation and softening hardness,and method of calming the mind and improving sleep.In clinical practice,these methods are flexibly combined based on patients'syndrome types and manifestations.Moreover,Professor Liu is skilled in using herbal groups having Lingnan medicinal characteristics,such as herbal group for clearing heat and removing toxin,and draining dampness to relieve jaundice which is composed of Mallotus Apelta Radix et Rhizoma,Abri Herba and Phyllanthi Urinariae Herba,herbal group for promoting digestion to remove food retention which is composed of Fermentum Rubrum,Crataegi Fructus and Hordei Fructus Germinatus,herbal group for removing blood and eliminating mass group which is composed of vinegar-processed Curcumae Rhizoma,vinegar-processed Trionycis Carapax and Eupolyphaga Steleophaga,and herbal group for protecting liver and lowering enzyme which is composed of Hoveniae Semen and Schisandrae Chinensis Fructus.Professor Liu's medication experience for intervening hepatitis B-related liver fibrosis will provide valuable references for TCM clinical practice in the management of liver diseases.

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD. Methods: Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. Results: In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression. Conclusions Ursolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*

OBJECTIVE: To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO). METHODS: Peripheral blood samples were collected from the proband and members of his pedigree with informed consent. Following extraction of genomic DNA, all coding exons and flanking intronic sequences (-10 bp) of the EXT1 and EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing. RESULTS: A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of the EXT1 gene in the proband and his affected father but not in a healthy sister and normal controls. The variant was classified as a pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (PVS1+PM2+PP1). Bioinformatic analysis predicted that the c.1911C>A variant may be disease-causing via nonsense-mediated mRNA decay and anomalous splicing. CONCLUSION The c.1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.
Codon, Nonsense ; Exons/genetics* ; Exostoses, Multiple Hereditary/genetics* ; Heterozygote ; Humans ; Pedigree

Objective: To analyze the relationship between fatigue and self- efficacy and empowerment in patients with rheumatoid arthritis. Methods: A total of 219 cases of rheumatoid arthritis were investigated by general data questionnaire, Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire, Chinese Version of Patient Perception of Empowerment Scale and Chinese Version of Arthritis Self-efficacy Scale-8. SPSS 20.0 software was used for correlation analysis and AMOS software was used to construct structural equation model to test the mediating effect of self-efficacy between empowerment level and fatigue in patients with rheumatoid arthritis. Results: There was a significant negative correlation between fatigue and empowerment level (r=-0.62, P <0.05), and a significant correlation between fatigue and self-efficacy (r=-0.81, P <0.05). Self-efficacy had a mediating effect on empowerment level and fatigue in patients with rheumatoid arthritis, and the mediating effect accounted for 96.41% of the total effect. Conclusions Self-efficacy has mediating effect between powerment level and fatigue in patients with rheumatoid arthritis.