The Kaohsiung journal of medical sciences最新文献

Universal neonatal hepatitis B virus (HBV) vaccination and the advent of direct-acting antivirals (DAA) against hepatitis C virus (HCV) have reshaped the epidemiology of chronic liver diseases. However, some aspects of the management of chronic liver diseases remain unresolved. Nucleotide analogs can achieve sustained HBV DNA suppression but rarely lead to a functional cure. Despite the high efficacy of DAAs, successful antiviral therapy does not eliminate the risk of hepatocellular carcinoma (HCC), highlighted the need for cost-effective identification of high-risk populations for HCC surveillance and tailored HCC treatment strategies for these populations. The accessibility of high-throughput genomic data has accelerated the development of precision medicine, and the emergence of artificial intelligence (AI) has led to a new era of precision medicine. AI can learn from complex, non-linear data and identify hidden patterns within real-world datasets. The combination of AI and multi-omics approaches can facilitate disease diagnosis, biomarker discovery, and the prediction of treatment efficacy and prognosis. AI algorithms have been implemented in various aspects, including non-invasive tests, predictive models, image diagnosis, and the interpretation of histopathology findings. AI can support clinicians in decision-making, alleviate clinical burdens, and curtail healthcare expenses. In this review, we introduce the fundamental concepts of machine learning and review the role of AI in the management of chronic liver diseases.

Recurrent spontaneous abortion (RSA) has a complex pathogenesis with an increasing prevalence and is one of the most intractable clinical challenges in the field of reproductive medicine. Quercetin (QCT) is an effective active ingredient extracted from Semen Cuscutae and Herba Taxilli used in traditional Chinese medicine for tonifyng the kidneys and promoting fetal restoration. Although QCT helps improve adverse pregnancy outcomes, the specific mechanism remains unclear. The trophoblast cell line HTR-8/SVneo cultured in vitro was treated with different concentrations of QCT, and the cell counting kit-8 assay, wound healing assay, transwell assay, and western blotting were used to evaluate the effects and mechanisms of QCT on the proliferation, migration, and invasion of HTR-8/SVneo cells, respectively. To assess the expression levels of miR-149-3p and AKT serine/threonine kinase 1 (AKT1), quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were performed. A dual-luciferase reporter assay was used to investigate the potential regulatory relationship between miR-149-3p and AKT1. Our results showed that QCT promoted the proliferation, migration, and invasion of trophoblast cells, promoted the expression of MMP2, MMP9, and vimentin, and downregulated the expression of E-cadherin. Mechanistically, QCT downregulated the expression of miR-149-3p and upregulated the expression of AKT1, and miR-149-3p directly targets AKT1, negatively regulating its expression. Overexpression of miR-149-3p and silencing of AKT1 counteracted the promotional effects of QCT on trophoblast proliferation, migration, and invasion. Taken together, QCT regulates the migration and invasion abilities of HTR-8/SVneo cells through the miR-149-3p/AKT1 axis, which may provide a promising therapeutic approach for RSA.

Striated esophageal muscle contraction (SEC) is important for pharyngeal swallowing and deglutition augmentation against aspiration. Its clinical relevance is unclear in patients with ineffective esophageal motility (IEM). In this study, we aimed to characterize and compare SEC in consecutive patients with and without IEM. All eligible patients were evaluated for SEC, primary and secondary peristalsis using high-resolution manometry (HRM) with one mid-esophageal injection port. Primary peristalsis was assessed with 10 5-mL liquid swallows and multiple rapid swallows (MRS), while secondary peristalsis was performed with rapid air injections of 20 mL. All peristatic parameters of HRM were measured, and SEC and its contractile integral (SECI) were evaluated. One hundred and forty patients (59.3% women, mean age 46.1 ± 13.1 years) were included. There was no difference in SECI between patients with and without IEM (p = 0.91). SECI was also similar between patients with and without secondary peristalsis for IEM (p = 0.63) or normal motility (p = 0.80). No difference in SECI was seen between patients with and without MRS for IEM (p = 0.55) or normal motility (p = 0.88). SECI was significantly higher in male patients than female patients in IEM patients (p = 0.01). SECI significantly correlated with age in patients with normal motility (r = -0.31, p = 0.01). Aging may have a negative impact on SEC in patients with normal motility, while gender difference in SECI occurs in IEM patients. Neither secondary peristalsis nor MRS influences SECI.

This study aimed to investigate the role of cluster of differentiation 276 (CD276) in evaluating the prognosis of clear cell renal carcinoma (ccRCC) and to build a nomogram for predicting ccRCC progression post-surgery. Using data downloaded from The Cancer Genome Atlas (TCGA) database, we constructed a Kaplan-Meier (KM) curve depicting the relationship between CD276 expression levels and the progression-free interval (PFI) in 539 ccRCC cases. We further validated this by plotting a KM curve of the relationship between CD276 expression levels and PFI in 116 ccRCC patients from our hospital. Using clinical data collected from 116 patients, we identified independent risk factors affecting postoperative PFI in patients with ccRCC through univariate and multivariate COX analyses and created a nomogram for visual representation. Both TCGA and clinical data revealed a negative correlation between the expression levels of CD276 and PFI (p < 0.05). Univariate COX analysis revealed that the prognostic nutritional index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic inflammatory index, World Health Organization grading, tumor diameter, CD276 expression levels, T stage, and N stage were related to PFI (p < 0.05). Furthermore, multivariate COX analysis indicated that tumor diameter and CD276 expression levels were independent risk factors for postoperative PFI in patients with ccRCC (p < 0.05). The calibration curve of the established nomogram exhibited a slope close to 1, with a Hosmer-Lemeshow goodness-of-fit test result of 2.335 and a p-value of 0.311. In patients with ccRCC, a negative correlation was noted between tumor CD276 expression and PFI. The larger the tumor diameter and the higher the tumor CD276 expression level, the shorter is the PFI.

This study aims to investigate the effects of the Galectin-3 (Gal-3) inhibitor TD139 on inflammation and the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 pathway in gestational diabetes mellitus (GDM). Human placental tissues were treated with TD139 and TNF-α, assessing Gal-3, ERK/JNK/p38 activation, and inflammatory cytokines. GDM was induced in mice via subcutaneous injections of streptozotocin (STZ). After confirming GDM, mice were treated with 15 mg/kg TD139 on GD 10.5 12.5, 14.5, 16.5, and 18.5. Serum inflammatory cytokines were measured on GD 20.5, and post-delivery placental tissues were analyzed. Data were analyzed using one-way or two-way repeated measures ANOVA with post hoc tests. TD139 suppressed TNF-α-induced increases in Gal-3, IL-1β, IL-6, MCP-1, and ERK/JNK/p38 activation in placental tissues. In STZ-induced GDM mice, TD139 reduced glucose levels, weight loss, and food and water intake. TD139 significantly lowered TNF-α, IL-1β, IL-6, and MCP-1 in serum and placental tissues and inhibited the ERK/JNK/p38 pathway. TD139 improved pup numbers in GDM mice compared to untreated ones. TD139 reduces inflammation and inhibits the ERK/JNK/p38 pathway in TNF-α stimulated placental tissues and STZ-induced GDM mice, suggesting its therapeutic potential for managing GDM-related placental inflammation and improving pregnancy outcomes. The study used TNF-α to mimic GDM in placental tissues and an STZ-induced GDM mouse model, which may not fully represent human GDM complexity. Future research should explore alternative models, and broader signaling pathways, and thoroughly evaluate TD139's safety in pregnancy.

Different human leukocyte antigen (HLA) genotypes have been known to be associated with the risk of development of Sjögren's syndrome in different populations, but this association has never been reported in Taiwan. We enrolled 1044 subjects (673 patients, 371 controls) and tested their HLA-DR genotypes. We found an increased risk of Sjögren's syndrome in patients carrying HLA-DR8. DR1 and DR14 were associated with increased risk of eye involvement (uveitis, scleritis or optic neuritis), while DR15 was associated with increased risk of interstitial lung disease. DR8 was associated with increased risk of formation of multiple antibodies: anti-Ro, rheumatoid factor and antinuclear antibodies (ANA) reaching titer 1:80 or above. DR9 was associated with decreased risk of formation of anti-La antibodies and increased risk of formation of antithyroglobulin antibodies. DR10 was associated with risk of formation of anticyclic citrullinated peptide (anti-CCP) antibodies, and DR11 was associated with increased risk of formation of anti-La antibodies. Oral ulcer was found to be negatively associated with anti-Ro antibodies and with anti-ENA antibodies. Skin lesions were associated with ANA antibody titer elevation to 1:80 or above. Malignancies of any kind were associated with the presence of cryoglobulin. Females were more likely to be diagnosed at a younger age than males. There was no statistically significant relationship between HLA-DR genotype and age at disease diagnosis. In patients with Sjögren's syndrome in Taiwan, the presence of HLA-DR8 appeared to be a risk factor. In addition, we found several associations between HLA-DR genotype, clinical presentation, and autoantibody status among them.

Previous studies have supported a tumor-suppressive role of semaphorin 3A (SEMA3A) in several tumors including oral squamous cell carcinoma (OSCC). However, in-depth characterization of the role of SEMA3A in OSCC and the underlying molecular mechanisms is lacking. Gene and protein expressions were detected using quantitative real-time PCR, western blot assay, and immunohistochemistry. OSCC cell metastasis was evaluated using Transwell and angiogenesis of human umbilical vein endothelial cells (HUVECs) was determined using tube formation assay. The interactions among molecules were predicted using bioinformatics analysis and validated using luciferase activity experiment and RNA immunoprecipitation assay. Pulmonary metastasis was evaluated using hematoxylin and eosin staining after constructing a lung metastasis tumor model in mice. SEMA3A expression was decreased in OSCC cells and its overexpression led to suppression of epithelial-mesenchymal transition (EMT), migration, and invasion of OSCC cells and angiogenesis of HUVECs. miR-32-5p was identified as an upstream molecule of SEMA3A and long non-coding RNA NR2F2 antisense RNA 1 (NR2F2-AS1) was validated as an upstream gene of miR-32-5p. Further experiments revealed that the inhibitory effects of NR2F2-AS1 overexpression on EMT, migration, invasion of OSCC cells, and angiogenesis of HUVECs as well as tumor growth and metastasis in mice were mediated via the miR-32-5p/SEMA3A axis. To conclude, NR2F2-AS1 may attenuate OSCC cell metastasis and angiogenesis of HUVECs and suppress tumor growth and metastasis in mice via the miR-32-5p/SEMA3A axis.