Some patients with drug-induced liver injury （DILI） may present with similar features to patients with autoimmune hepatitis （AIH）， and such cases are defined as drug-induced autoimmune-like hepatitis （DI-ALH）. In 2022， the European Association for the Study of the Liver discussed the nomenclature， diagnosis， and treatment of DI-ALH and put forward expert opinions to establish the criteria for clinical diagnosis. However， the clinical diagnosis of DI-ALH remains complex and difficult， and there is no direct evidence for the link between drug intake and the body’s immune progression. Therefore， this article reviews the research advances in the diagnosis of DI-ALH from the four aspects of clinical phenotype， pathological diagnosis， diagnostic score， and clinical prognosis.

Background A diverse cohort of patients and susceptible individuals congregate in healthcare facilities, where exposure to pathogenic microorganisms associated with respiratory infectious diseases constitutes a significant risk factor for cross-infection. Central air-conditioning ventilation systems improve some indoor environment indicators while exacerbating the risk of transmission of respiratory infectious diseases. Objective To investigate the distribution characteristics of microbial communities in the central air-conditioning ventilation systems of hospitals, providing a scientific basis for the selection of microbial indicators in hygiene standards for hospital central air-conditioning ventilation systems and for hospital risk early warning systems. Methods In October 2023, two central air-conditioning ventilation systems were selected from a Grade 3A hospital in Shanghai: one was an all-air air-conditioning system serving the waiting area on the ground floor, and the other was a fan coil plus fresh air system serving the outpatient area on the third floor. Samples from four different components of the ventilation systems—air outlets, filters, surface coolers, and condensate trays—were collected for high-throughput sequencing of the 16S rRNA gene to analyze bacterial communities. Alpha-diversity and beta-diversity analyses were performed to investigate the microbial community composition and diversity characteristics of the hospital central air-conditioning ventilation systems. Functional analysis was conducted to determine the relative abundance of bacterial functions in these systems.Results A total of 528 operational taxonomic units (OTUs) were identified, encompassing 20 bacterial phyla, 37 classes, 79 orders, 123 families, and 240 genera. The analysis revealed that the bacterial community was predominantly composed of Proteobacteria, Gemmatimonadates, Bacteroidetes, and Actinobacteria. The diversity analysis indicated that bacterial community richness and diversity were highest in the condensate trays, while no statistically significant differences (P > 0.05) were observed in the bacterial community composition among the air outlets, filters, and surface coolers. The functional analysis showed that the bacterial communities in the central air-conditioning ventilation systems primarily exhibited chemoheterotrophic, oxidative energy-dependent heterotrophic, and ureolytic functional characteristics. Conclusion The dominance of Proteobacteria suggests that this phylum exhibits strong adaptability in the central air-conditioning ventilation systems, possibly related to its ability to survive and reproduce under varying environmental conditions. The diversity analysis indicates that the condensate tray is a critical area for bacterial proliferation in the central air-conditioning ventilation systems. The similarity in environmental conditions among the air outlets, filters, and surface coolers result in similar bacterial community structures. The functional analysis reveals that the bacterial communities possess robust energy conversion and metabolic capabilities, potentially contributing to processes such as organic matter decomposition and nitrogen cycling within the central air-conditioning ventilation systems.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal-epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound β-catenin mRNA, and recruited YTHDF2 to identify the m6A modified β-catenin in the 3'-UTR region to degrade β-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of β-catenin mRNA. ENO1/β-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of β-catenin mRNA by promoting the binding of ENO1 and β-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing β-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVES: To investigate the active components and possible mechanisms of n-butanol fraction of Periploca forrestii Schltr. ethanol extract for treating Alzheimer's disease (AD). METHODS: The active components of n-butanol fraction of Periploca forrestii Schltr. ethanol extract were analyzed using UPLC-QE-MS technique. In a SD rat model of AD induced by treatment with AlCl₃ and D-gal, the therapeutic effects of low, moderate and high doses of the n-butanol fraction, saline, and donepezil hydrochloride were evaluated using ELISA, HE and Nissl staining, immunohistochemistry and Western blotting. The therapeutic mechanisms of the n-butanol fraction were explored using network pharmacology and molecular docking. RESULTS: Seventeen active components were identified from the n-butanol fraction of Periploca forrestii Schltr. ethanol extract, including phenylpropanoids, flavonoids, anthraquinones, triterpenoids, steroids, and volatile oils. In the rat models of AD, treatment with the n-butanol fraction significantly lowed AChE content in the hippocampus, increased the contents of ACh, SOD, CAT, and GSH-Px, enhanced the expressions of neuronal apoptotic factors Bcl-2, PI3K, Akt, p-PI3K, and p-Akt, and reduced the expressions of Bax and caspase-3 proteins. The treatment also dose-dependently up-regulated hippocampal expressions of Nrf-2, HO-1 and BDNF and down-regulated Keap-1, Aβ and Tau expressions. Bioinformatics analysis identified 14 key intersected targets (including TNF, AKT1 and ESR1) between the n-butanol fraction and AD. CONCLUSIONS The therapeutic effect of n-butanol fraction of Periploca forrestii Schltr. ethanol extract in AD mice is mediated by its multiple active components that regulate multiple targets and pathways.
Animals ; Rats, Sprague-Dawley ; Rats ; 1-Butanol/chemistry* ; Plant Extracts/pharmacology* ; Periploca/chemistry* ; Ethanol/chemistry* ; Alzheimer Disease/drug therapy* ; Male ; Molecular Docking Simulation ; Apoptosis/drug effects*

The pain-evoked potential electroencephalogram (EEG) is an effective electrophysiological indicator for pain assessment, yet its extraction is challenging due to interference from background activity and involuntary blinks. Although existing blink artifact-removal methods show efficacy, they face limitations such as the need for reference signals, neglect of individual differences, and reliance on user input, hindering their practical application in clinical pain assessments. In this paper, we propose a novel framework applying adaptive quadrature mirror filter banks (AQMFB) with discrete wavelet transform (DWT) to remove blink artifacts in pain EEG. Unlike traditional DWT methods that apply fixed wavelets across subjects, our method adapts wavelet construction based on the characteristics of EEG. Experimental results demonstrate that AQMFB-DWT outperforms four leading methods in removing blink artifacts with minimal distortion of pain information, all within an acceptable processing time. This technique is a valuable preprocessing step for enhancing the extraction of pain-evoked potentials.
Humans ; Artifacts ; Blinking/physiology* ; Electroencephalography/methods* ; Pain/diagnosis* ; Male ; Wavelet Analysis ; Adult ; Female ; Evoked Potentials/physiology* ; Young Adult ; Brain/physiopathology* ; Pain Measurement/methods* ; Signal Processing, Computer-Assisted

Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal

Objective To investigate the effect and mechanism of Yiguan Decoction(YGJD)on the efficacy of M1 bone marrow-derived macrophages(M1-BMDMs)in the treatment of rats with liver cirrhosis induced by 2-AAF/CCl4.Methods BMDMs were isolated and induced into M1-BMDMs by lipopolysaccharide.A total of 50 male Wistar rats were randomly divided into normal group with 5 rats and model group with 45 rats.The rats for modeling were given subcutaneous injection of 50%CCl4 twice a week.Since week 7,the rats for modeling were randomly divided into model group(M group),YGJD group,M1-BMDM group,M1-BMDM+YGJD group,and sorafenib(SORA)group,and they were given subcutaneous injection of 30%CCl4 to maintain the progression of liver cirrhosis and intragastric administration of 2-AAF.CCR2 inhibitors were added to the drinking water,and each group was given the corresponding intervention.Related samples were collected at week 9.The rats were observed in terms of serum liver function parameters,liver pathology,hydroxyproline(Hyp)content in liver tissue,hepatic stellate cell activation,hepatic fibrosis and inflammation factors,and the expression levels of molecules associated with the Wnt signaling pathway.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the M group,the M1-BMDM+YGJD group had significant reductions in the serum levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin(TBil)(all P<0.05)and a significant increase in the content of albumin(Alb)(P<0.05),and compared with the M1-BMDM group,the M1-BMDM+YGJD group had a significant reduction in the serum level of TBil(P<0.05)and a significant increase in the serum level of Alb(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in the expression levels of CD68 and TNF-α(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in Hyp content and Sirius red positive area(P<0.05).As for the non-canonical Wnt signaling pathway molecules,compared with the M1-BMDM group,the M1-BMDM+YGJD group had significantly lower mRNA and protein expression levels of Wnt5a(P<0.05)and mRNA expression level of Fzd2(P<0.05),as well as significant reductions in the mRNA expression levels of Wnt4,Wnt5b,and Fzd3(P<0.05),while there were no significant changes in the mRNA expression levels of the canonical Wnt signaling pathway molecules β-catenin,LRP5,LRP6,Fzd5,and TCF.Conclusion YGJD can enhance the therapeutic effect of M1-BMDMs on rats with liver cirrhosis induced by 2-AAF/CCl4,possibly by inhibiting the non-canonical Wnt5a/Fzd2 signaling pathway,which provides new ideas for the synergistic effect of traditional Chinese medicine on M1-BMDMs in the treatment of liver cirrhosis.

Objective:To describe functional disability rate of anxiety disorders in Chinese community adults and explore related risk factors of functional disability.Methods:To conduct in-depth data analysis on China Mental Health Survey(CMHS).The diagnostic tool for anxiety disorders was the Composite International Diagnostic Inter-view-3.0,according to the Diagnostic and Statistical Manual for Mental Disorders,Fourth Edition(DSM-Ⅳ).The World Health Organization Disability Assessment Schedule,2nd edition,was the functional disability assessment standard for anxiety disorders.Weighted 12-month functional disability rate of DSM-Ⅳ anxiety disorder with co-morbidities and only anxiety disorder in population and those in patients,as well as days of partial disability were calculated.The effects of anxiety disorders comorbid other mental disorders and physical diseases and demographic factors on the severity and occurrence of functional disability were analyzed by multiple linear regression and logis-tic regression.Results:The functional disability rate of anxiety disorder with comorbidities in population was 1.7％,and 42.2％in patients,in which constituent rate of grade-four disability was the highest as 84.1％.The functional disability rate of only anxiety disorder in population was 0.3％,and 17.8％in patients.The medians of days of partial disability days in the past 30 days were from 0 to 14.42.Multiple linear regression showed a positive association between comorbid anxiety disorder with other mental disorders and physical diseases(β=0.24),comor-bid other mental disorders and physical diseases(β=0.21),physical diseases(β=0.18),comorbid anxiety disor-der and physical diseases(β=0.15),comorbid anxiety disorder with other mental disorders(β=0.08),other men-tal disorders(β=0.07),only anxiety disorder(β=0.06),lower education level(β=0.12),lower economic status(β=0.08),older age(β=0.06),non-marital status(β=0.06),male(β=0.02)and the severity of functional dis-ability.Logistic regression showed that comorbid anxiety with other mental disorders and physical diseases(OR=64.07),comorbid anxiety disorders with other mental disorders(OR=36.75),comorbid other mental disorders with physical diseases(OR=20.60),comorbid anxiety with physical diseases(OR=18.88),anxiety disorder(OR=9.20),other mental disorders(OR=6.65),physical diseases(OR=4.00),65 years old and over(OR=4.40),50 to 64 years old(OR=2.33),low economic status(OR=2.10),illiterate and below primary school educational level(OR=1.89),middle economic status(OR=1.70),elementary school educational level(OR=1.59),non-marital status(OR=1.47),male(OR=1.16)were the risk factors of the occurrence of functional disability.Conclusion:Comorbidity of anxiety disorders and other mental disorders,and physical diseases increases severity and occurrence of functional disability.Comorbidity,male,gender,older age,lower economic and educa-tional level and non-marital are risk factors of anxiety disorder functional disability.