Advances in Clinical and Experimental Medicine最新文献

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic condition with relapsing-remitting course. Diarrhea and abdominal pain are the most common IBD symptoms. Fibroblast growth factor 19 (FGF19) is an endocrine factor that inhibits hepatic bile acid production and may be used as a diagnostic marker for bile acid malabsorption.

Objectives: To assess serum FGF19 levels in active and inactive phases of IBD and find a potential correlation between FGF19 and disease activity.

Material and methods: Fasting serum FGF19 levels were measured in 105 IBD patients (47 UC patients, 41 CD patients without previous ileocecal resection (NR-CD), 17 CD patients after ileocecal resection (IR-CD), and 17 control subjects). The disease activity was assessed using clinical, laboratory and endoscopic criteria.

Results: Inverse correlations were found between FGF19 level and intensity of diarrhea (in UC), abdominal pain intensity (in UC and IR-CD) and inflammatory markers (in UC and IR-CD). Moreover, FGF19 concentration was inversely correlated with clinical and endoscopic activity indices in UC and CD.

Conclusions: Fluctuations in FGF19 level related to clinical and endoscopic activity of UC and CD revealed a clear pattern of higher values in remission than in active disease phases. Fibroblast growth factor 19 may serve as a potential diagnostic biomarker and constitute a new therapeutic target in IBD.

Background: Lhermitte's sign (LS) is an important clinical marker for patients with multiple sclerosis (MS). Research on pediatric-onset MS (POMS) and LS is limited. To date, there has been no research conducted on the clinical and artificial intelligence (AI)-based radiological correlation of LS.

Objectives: This follow-up study aims to investigate the relationship between LS and clinical findings according to AI-based radiological characteristics of patients with POMS.

Material and methods: Basic descriptive statistics of patients with POMS according to sociodemographic, clinical and radiological findings were collected. Variables were evaluated at a 95% confidence level (95% CI), and a value of p < 0.05 was accepted as statistically significant. The LS in patients with MS was classified according to its presence in the past and at the time of the study screening: group A: absent; group B: positive in the past but absent at screening; group C: present both in the past and at the screening; group D: absent in the past but present at the screening. In addition, patients were grouped according to the duration of their MS, with the following classifications: <10 years and at least 10 years.

Results: A total of 1,298 records were identified in the database search. Ninety-two patients who met the inclusion criteria were included in the study. The frequency of upper cervical lesions (C1-4 vertebral segmental levels) was higher in group B and C than in group A (p = 0.017). Among patients with an MS duration of 10-years, C1-4 lesions were least frequent in group A.

Conclusions: Spinal imaging with AI-based programs can be used at least as much as brain magnetic resonance imaging (MRI) for early diagnosis, prognosis and treatment response. We have for the first time investigated LS in a large sample of patients with POMS. It is, however, recommended to conduct further multicenter studies to more specifically identify LS in patients with POMS.

Chronic pain is a common, long-standing and bitter experience affecting a huge percentage of the still increasing elderly population. Owing to the multifactorial etiopathology and complex clinical presentation with a lot of severe consequences, management of the permanent pain should be varied and tailored to the particular patient. This approach comprises multimodal pharmacotherapy, including all analgesics and adjuvants, likewise selected interventions, physical therapy and rehabilitation, as well psychological counselling.

Acute ischemic stroke (AIS) has a high rate of death and causes long-term disability, leading to a global economic burden annually. Therefore, discovering biomarkers to improve AIS patient prognosis is critical. Previous studies reported an association between serum cystatin C (CysC) levels and outcomes in AIS patients, but the results remain controversial. This systematic review and meta-analysis aimed to explore the relationship between serum CysC and AIS patient outcomes using currently available studies. The literature search included PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wan Fang databases. Outcomes included poor functional recovery, cognitive dysfunction and death. Weighted mean difference (WMD) with 95% confidence interval (95% CI) was used as an effect index for measurement data. Results demonstrated that serum CysC was significantly higher in AIS patients with poor functional recovery (WMD = 0.18, 95% CI: 0.08-0.28), cognitive dysfunction (WMD = 0.16, 95% CI: 0.09-0.23) and death (WMD = 0.32, 95% CI: 0.02-0.62) than in the control groups when follow-up time was <1 month. These findings show that high serum CysC levels were associated with poor AIS patient outcomes. Further studies are needed to examine whether reducing serum CysC can prevent poor outcomes in AIS patients.

Background: Current knowledge regarding synthetic magnetic resonance imaging in ischemic stroke (MAGiC) is inadequate.

Objectives: The study aimed to investigate the diagnostic and prognostic prediction value of MAGiC in acute ischemic stroke (AIS) patients.

Material and methods: This prospective observational study enrolled 197 AIS patients between January 2022 and May 2023. All patients underwent routine magnetic resonance imaging (MRI), computed tomography (CT) scans, doppler ultrasound, MAGiC, and dynamic contrast-enhanced (DCE)-MRI. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-ch), low-density lipoprotein cholesterol (LDL-ch), C-reactive protein (CRP), and procalcitonin (PCT) were also measured, and the National Institutes of Health Stroke Scale (NIHSS) was used to evaluate stroke severity.

Results: T2 and proton density (PD) values were markedly lower in severe patients than in mild-to-moderate patients, and the DCE-MRI Ktrans value was substantially higher in severe patients compared to mild-to-moderate patients. Furthermore, T2 and PD correlated negatively, while Ktrans correlated positively with CRP. Receiver operating characteristic (ROC) showed T2 and Ktrans to have the best diagnostic potential as MAGiC and DCE-MRI parameters, respectively. As such, combining T2 and Ktrans could improve severe stroke diagnosis accuracy. Moreover, TG, LDL-ch, CRP, T2, and Ktrans were independent risk factors for severe stroke.

Conclusions: T2 and PD MAGiC parameters and the DCE-MRI Ktrans parameter could be used as indices to predict severe stroke, while combining T2 and Ktrans might provide better diagnostic accuracy.

Background: Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) are characterized by severe pulmonary fibrosis and immune dysregulation. Heat shock protein 90 (HSP90) is involved in the progression of pulmonary fibrosis and the immune response.

Objectives: This study aimed to explore whether HSP90 regulates the development of RA-ILD and its underlying mechanism.

Material and methods: In vivo, collagen-induced arthritis (CIA)-mice were treated with bleomycin (BLM) to establish an arthritic mouse model of pulmonary fibrosis. In vitro, human lung fibroblast 1 (HLF1) was exposed to transforming growth factor beta 1 (TGF-β1) to simulate an RA-ILD model. The RA-ILD models were treated with the HSP90 inhibitor ethoxyquin (EQ) to explore the potential mechanism of HSP90 in RA-ILD. Histopathological analysis was performed, and pulmonary fibrosis was evaluated. The differentiation of M1/M2 macrophages and Th1/Th17/Treg cells was assessed. The role of the TGF-β/Smad2/3 pathway in EQ-mediated RA-ILD progression was also explored.

Results: HSP90α and HSP90β were upregulated in the RA-ILD models. Ethoxyquin mitigated arthritis in BLM-CIA mice, and reduced the expression of alpha-smooth muscle actin (α-SMA), collagen I (Col-1) and fibronectin (FN), as well as hydroxyproline content, thereby relieving pulmonary fibrosis. In addition, EQ increased M1 macrophages and inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-α) levels; conversely, EQ decreased M2 macrophages and vascular endothelial growth factor (VEGF)-A and TGF-β1 contents. It also decreased Th17 (interleukin (IL)-17) while increasing Th1 (interferon gamma (IFN-γ)) and Treg (Foxp3), and restricted the expression of transforming growth factor beta type receptor I and II (TGF-βRI and TGF-βRII) and the phosphorylation of Smad2 and Smad3.

Conclusions: This study revealed that EQ regulated pulmonary fibrosis and cellular immunity by inhibiting HSP90, appearing to act through the TGF-β/Smad2/3 pathway. These findings suggest that EQ holds potential as a therapeutic agent for treating RA-ILD.

Background: Colorectal cancer (CRC) is one of the most common cancers, and its progression is regulated by several factors, including circular RNA (circRNA).

Objectives: The objective of this study was to determine the role, or roles, of circ_0000673 in CRC.

Material and methods: We used quantitative real-time polymerase chain reaction (qPCR) to detect the expression of circ_0000673, miR-548b-3p and cleavage and polyadenylation specific factor 6 (CPSF6) in DLD-1 and RKO cells. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to determine circ_0000673 roles in proliferation. Wound healing and transwell assays were used to detect cell migration and invasion abilities. Expression of CPSF6 protein and stem cell-associated proteins were examined using western blot. The putative relationship between miR-548b-3p and circ_0000673 or CPSF6 was verified with dual-luciferase reporter assay. The role of circ_0000673 in CRC was also investigated in a tumor xenograft assay in nude mice.

Results: Circ_0000673 expression was increased in CRC tissues and cancer cells. Silencing circ_0000673 reduced tumor cell proliferation, migration and invasion, while also decreasing cell stemness. MiR-548b-3p was found to be a target of circ_0000673, while CPSF6 was a downstream target of miR-548b-3p. The tumor-regulatory effects of si-circ_0000673, anti-miR-548b-3p and oe-CPSF6 were partially reversed by anti-miR-548b-3p, si-CPSF6 and si-circ_0000673, respectively, in rescue assays. Downregulation of circ_0000673 reduced solid tumor growth in vivo.

Conclusions: Circ_0000673 inhibition reduced CPSF6 expression by targeting miR-548b-3p, thereby blocking proliferation, migration and invasion of CRC tumor cells.

Background: Gecko has been widely documented in Chinese scientific literature as an anti-tumor agent for various illnesses for thousands of years, and more recently, it has been examined for its anti-tumor effects on several cancers. The effect of Gecko microRNAs (miRNAs) on hepatocellular carcinoma (HCC) has not yet been reported.

Objectives: This study was designed to identify miRNAs in Gecko through small RNA sequencing and utilize bioinformatics techniques to construct a potential regulatory network and explore the possible mechanisms of exogenous miRNAs involved in HCC.

Material and methods: RNA was extracted from Gecko tablets, and we screened the Gecko miRNA expression dataset after high-throughput sequencing. Bioinformatics analysis was used to identify novel Gecko and HCC survival-related miRNA-mRNA cross-species regulation networks.

Results: miR-100-5p, miR-99a-5p and miR-101-3p were identified as critical for the role of Geckos in HCC. Nine downstream mRNAs (EZH2, KPNA2, LMNB1, LRRC1, MRGBP, SMARCD1, STMN1, SUB1, and UBE2A) were identified as target genes for critical miRNAs. A miRNA-mRNA regulatory network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed these key mRNAs might be associated with both the suppression and progression of HCC. The novel network significantly correlated with the abundance of multiple immune cells, as determined with immune infiltration analysis.

Conclusions: These findings suggest that Gecko may inhibit progression and exert a therapeutic effect on HCC by targeting critical miRNA-mRNA networks for cross-species regulation. It also provides a reference for future research and development of traditional Chinese medicine (TCM).

Background: Oxidative damage plays an important role in the progression of rheumatoid arthritis (RA). Emerging research evidence suggests that natural antioxidants may effectively ameliorate this disease.

Objectives: To investigate the therapeutic effect of echinacoside (ECH) in a collagen-induced arthritis (CIA) mouse model and thus elucidate the underlying molecular mechanism in RA.

Material and methods: Collagen-induced arthritis mice were intraperitoneally administered 1% dimethyl sulfoxide (DMSO) (control) or 0.6 mg of ECH every other day for 1 month. Arthritis scores and the number of affected paws were assessed. On day 60, mice were euthanized, synovial tissue specimens were obtained, and serum interleukin (IL)-6 and IL-1â expression levels were measured. Mitochondrial morphologies, reactive oxygen species (ROS) content, expression of dynamin-related protein 1 (Drp1), IL-6, nod-like receptor protein 3 (NLRP3), kelch-like ECH-associated protein 1 (Keap1), and nuclear factor-erythroid-2-related factor 2 (Nrf2) contents in synovium were analyzed and compared between DMSOand ECH-treated CIA mice.

Results: Following ECH treatment, mitochondria of CIA-induced mice were found to be elongated, while their arthritis scores, inflammation and the number of affected paws, and the expression levels of Drp1, NLRP3, IL-6, ROS, and Keap1 were all found to be significantly reduced. Conversely, the level of antioxidant factor Nrf2 was found to be elevated. Further, mitochondrial fission was found to be inhibited in synovial tissues.

Conclusions: Our findings validate the therapeutic efficacy of ECH in the CIA mouse model. Echinacoside may suppress oxidative stress and inhibit inflammation by regulating the Nrf2/Drp1 pathway, thus supporting its utility in the treatment of RA.

Psychotic-like experiences (PLEs) refer to sub-threshold hallucinations and delusions observed in both clinical samples and the general population. Psychotic-like experiences have far-reaching implications for an individual's coping strategies and daily functioning. They are associated with both psychotic and non-psychotic disorders. This article presents a comprehensive review of the current literature on PLEs, incorporating a detailed exploration of the definition, prevalence, risk factors, functional impairments, and comorbid psychiatric disorders. Medline/PubMed and Embase were searched to establish and identify the literature. A total of 108 studies met our inclusion criteria. The genetic and biochemical backgrounds of PLEs are discussed, focusing on gene polymorphisms, changes in brain gyrification and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Psychological factors, such as trauma exposure, emotion regulation difficulties, cognitive biases, and attachment issues, were thoroughly examined, especially in terms of their impact on the emergence of PLEs. Here, we show how important the clinical aspects of developmental PLEs are, underlining the significance of an increased risk of self-harm and suicidal behaviors in those individuals and the comorbidity of psychiatric disorders in enabling clinicians to discern specific areas to observe. Although there is limited evidence on effective protocols for PLE management, various treatment approaches are explained. Despite increased research on PLEs in recent years, further investigation is needed to fully understand the nature of PLEs and to optimize therapeutic strategies. This article consolidates the current knowledge by synthesizing information on PLEs, including risk factors, comorbidities, treatments, and their impact on individual's lives.