International Journal of Medical Sciences最新文献

Background: Based on previous studies showing that frailty is associated with postoperative adverse events in older patients undergoing various surgical procedures, older patients with frailty may be more vulnerable to POCD. This study was designed to evaluate the effect of frailty on postoperative cognitive dysfunction (POCD) in aged rats undergoing general anaesthesia.

Methods: Male Sprague-Dawley rats aged 18 months were allocated to Control and Frailty groups according to hind limb immobilisation using aluminium splints. Before and after general anaesthesia, Y-maze test for cognitive function and frailty status were evaluated. Frailty, including muscle atrophy, assessed by quadriceps weight, was further evaluated by measuring glutathione peroxidase 4 (GPX4) and threonine.

Results: Twenty rats were enrolled and evenly allocated between the two groups, with no dropouts. There was no significant difference in the alternation ratio in the Y maze test between the groups before general anaesthesia; however, a significant difference was observed two days after general anaesthesia (65% ± 37% in the Control group vs 29% ± 28% in the Frailty group, p = 0.01). Body weight was similar between the groups throughout the study. By contrast, quadriceps weight was significantly lower in the Frailty group [2.4 (2.3-2.6) g vs 2.0 (1.7-2.3) g, p = 0.0001]. GPX4 and threonine levels in the quadriceps were also significantly lower in the Frailty group.

Conclusion: Frailty was significantly associated with POCD. Prevention of frailty may be important for reducing the risk of POCD.

Evidence suggests that the degree of insulin resistance in pregnancy (IRiP) seems to affect pregnancy outcomes regardless of the presence of gestational diabetes. A physiological moderate increase in IRiP is a protective factor for fetal development, but excessive enhancement can lead to maternal metabolic disorders and placental dysfunction, increasing the risk of gestational diabetes and adverse pregnancy outcomes, as well as having adverse effects on the long-term health of the offspring. This review briefly explores the key factors influencing IRiP, including pregnancy-specific and non-pregnancy-specific factors. It also discusses the assessment methods for insulin resistance that can be implemented during pregnancy and the increased probabilities of adverse effects on both the mother and the offspring, such as preeclampsia or eclampsia, neonatal hypoglycemia, and the risk of obesity and metabolic diseases in the offspring in the future. Finally, the intervention strategies were briefly described, such as in terms of diet, exercise, and medication, etc. This provides a basis and insights for the management and research of IRiP.

Background: Gastroesophageal reflux disease (GERD) is a common gastrointestinal condition associated with significantly impaired quality of life. While tea consumption has been associated with various health benefits, its relationship with GERD remains controversial. The aim of this study was to evaluate the relationship between the prevalence of GERD and tea consumption, including the type, drinking frequency and daily intake of tea, in a large Taiwanese cohort.

Methods: The type of tea was categorized as fully fermented, semi-fermented, and non-fermented; frequency and daily intake were recorded. Standardized self-reported questionnaires were used to record GERD status. Multivariable logistic regression was used to examine the association between tea consumption and GERD.

Results: Of the 27,119 participants, 4706 (17.4%) had GERD and 22,413 did not. A significant association was found between habitual tea consumption and a low prevalence of GERD (odds ratio [OR], 0.843; 95% confidence interval [CI], 0.779 - 0.911; p < 0.001) compared to non-drinkers. However, this association was only identified for semi- and non-fermented teas (OR, 0.832; 95% CI, 0.765 - 0.905; p < 0.001), but not fully fermented tea. Daily consumption of 1-2 cups (350-700 mL) (OR, 0.881 and 0.765, respectively) was significantly associated with a low prevalence of GERD, however drinking more than 3 cups per day was not significantly associated with GERD prevalence. Furthermore, drinking tea every day (OR, 0.847) was significantly associated with a low prevalence of GERD, while only drinking tea weekly or monthly was not.

Conclusion: The consumption of semi-fermented and non-fermented tea was associated with a low prevalence of GERD, but the association depended on the frequency and quantity of consumption. Further studies are needed to investigate the biological mechanisms of different types of tea and establish interventional strategies for those at high risk of GERD.

Background: High Pan-Immune-Inflammation Value (PIV) has been associated with poorer survival outcomes in men with metastatic prostate cancer. However, whether PIV is associated with adverse pathology and long-term oncological outcomes in localized prostate cancer treated with radical prostatectomy (RP) remains unclear.

Methods: We retrospectively evaluated 808 men who underwent RP for prostate adenocarcinoma at Kaohsiung Medical University Hospital between 2012 and 2023; 442 met the eligibility criteria and were included in the final analysis. PIV was dichotomized using a Youden-derived cutpoint (153) based on subsequent androgen deprivation therapy (ADT), defined as any adjuvant or salvage ADT administered after RP. We used multivariable logistic and Cox regression models to evaluate associations between preoperative PIV and adverse pathological features, subsequent ADT, biochemical recurrence (BCR), metastasis-free survival (MFS), and overall survival (OS).

Results: Median follow-up was 65.8 months. During follow-up, 100 men (22.6%) received subsequent ADT, 71 (16.1%) developed metastasis or died, and 54 (12.2%) died. High PIV was independently associated with ≥pT3 disease (adjusted odds ratio [aOR] 1.79, 95% confidence interval [CI] 1.14-2.81; p = 0.012), subsequent ADT (adjusted hazard ratio [aHR] 2.18, 95% CI 1.32-3.60; p = 0.002), shorter MFS (aHR 2.37, 95% CI 1.29-4.35; p = 0.006), and shorter OS (aHR 3.12, 95% CI 1.46-6.67; p = 0.003), but not with BCR.

Conclusions: High preoperative PIV was independently associated with ≥pT3 disease, subsequent ADT, shorter MFS, and shorter OS after RP, but not with BCR. These findings suggest that PIV may reflect disease progression beyond PSA-defined recurrence and may serve as a complementary preoperative biomarker. Further validation in independent cohorts is required.

Methylparaben (MEP), a widespread preservative, raises neurotoxicity concerns through oxidative stress and inflammation. Resveratrol (RES) is a natural polyphenol with antioxidant and anti-inflammatory properties. This study investigated whether RES protects against MEP-induced neurotoxicity in female rats. Female Wistar rats were divided into five groups (n=10/group): control, vehicle (5% DMSO), MEP alone (200 mg/kg, s.c., 15 days), RES alone (20 mg/kg, i.p., 15 days), and MEP+RES co-treatment. We evaluated anxiety-like behavior (elevated plus maze), brain histopathology (cortex/hippocampus), oxidative stress markers (GSH, SOD), stress-related gene expression (Nrf2, ASK1, PP-1cs, PP-2Acs by qPCR), inflammatory proteins (TNF-α, IL-6 by immunohistochemistry), and apoptotic markers (BAX, BCL-2). MEP exposure significantly increased anxiety-like behavior, caused structural damage in cortex and hippocampus, depleted GSH and SOD, upregulated Nrf2, ASK1, PP-1cs, and PP-2Acs, elevated TNF-α, IL-6, and pro-apoptotic BAX, while reducing BCL-2. RES alone caused no adverse effects. Remarkably, RES co-administration significantly attenuated and partially restored MEP-induced alterations, restoring behavior, tissue architecture, antioxidant defenses, gene expression, and immune balance. RES effectively attenuates MEP-induced neurotoxicity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, positioning it as a promising neuroprotective agent against environmental toxicants.

Background: Raynaud's syndrome (RS) is traditionally considered a benign vasospastic disorder; however, emerging evidence suggests that it may reflect systemic vascular dysfunction and a prothrombotic state. Emerging epidemiological evidence suggests an association between RP and VTE, but further validation across different populations and analytical approaches is needed.

Methods: We conducted a retrospective cohort study with the TriNetX global electronic health record database. Adult patients diagnosed with RS between 2015 and 2024 were identified and matched 1:1 with individuals without RS by using propensity score matching, adjusting for demographics, comorbidities, medical utilization, and laboratory parameters. Patients with autoimmune diseases, malignancy, thrombophilia, vascular disease, pregnancy, or anticoagulant and hormonal contraceptive use were excluded to minimize confounding. The primary outcome was incident VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), assessed with Cox proportional hazards models.

Results: After matching, 93,263 patients were included in each group. During follow-up, VTE occurred in 1,407 patients in the RS group and 1,179 patients in the non-RS group. RS was associated with a significantly increased risk of VTE (hazard ratio [HR] 1.33; 95% confidence interval [CI] 1.24-1.44). Increased risks were observed for both DVT (HR: 1.30; 95% CI: 1.18-1.43) and PE (HR: 1.38; 95% CI: 1.24-1.54). Subgroup analyses showed a more pronounced association in younger individuals and consistent effects across sexes.

Conclusions: RS is associated with an increased risk of venous thromboembolism independent of major confounding conditions.

Background: Mitochondrial dysfunction is a hallmark of acute and chronic kidney diseases. This study investigates the expression landscape and potential association of FNDC5 with renal injury.

Methods: We integrated human scRNA-seq, mouse spatial transcriptomics (ischemia-reperfusion injury model), in vitro high-glucose (HG) models in proximal tubule cells and podocytes, and a constitutive Fndc5 knockout mouse model. Candidate transcription factor occupancy at the FNDC5 promoter was examined by ChIP-qPCR, and associations were assessed in a non-insulin-dependent diabetes mellitus mouse model.

Results: scRNA-seq localized FNDC5 to specific tubules, showing downregulation in diabetic nephropathy. Spatial transcriptomics confirmed a distinct loss of cortical Fndc5 following ischemia-reperfusion injury. In vitro, HG treatment suppressed FNDC5, reduced cell viability, and triggered mitochondrial fragmentation, evidenced by increased DRP1 phosphorylation and downregulated MFN1/OPA1. ZEB1 and CREB1 were identified as candidate transcription factors showing occupancy at the FNDC5 promoter. Genetic deletion of Fndc5 reproduced this fission-permissive shift and reduced PGC1α expression under basal, non-diabetic conditions, providing loss-of-function evidence that Fndc5 deficiency is sufficient to reproduce this phenotype, independent of any additional metabolic stressor. In vivo, diabetic mice exhibited diminished FNDC5 levels, which correlated with an oxidative stress-associated marker (4-HNE) and reduced expression of the biogenesis-associated marker PGC1α.

Conclusion: FNDC5 downregulation is a conserved feature of renal injury associated with mitochondrial fission, and genetic loss-of-function data indicates that Fndc5 deficiency is sufficient to reproduce selected features of this fission-permissive mitochondrial phenotype; whether FNDC5 acts through a defined downstream pathway remains to be established.

Background: Human cytomegalovirus (CMV) infection is frequently detected in patients with ulcerative colitis (UC), particularly in severe or refractory disease. Its impact on disease activity, long-term course, and clinical outcomes remains controversial.

Methods: In this retrospective single-center cohort study conducted at the University Hospital Münster (Germany), adult UC patients undergoing colonoscopy between May 2002 and May 2024 were included. CMV status was determined by tissue-based PCR from colonic biopsies at baseline colonoscopy (BL). Patients with at least one follow-up colonoscopy (FU) were analyzed. Clinical and endoscopic disease activity (total Mayo score [tMayo], endoscopic Mayo score [eMayo]), remission rates, treatment exposure, and outcomes were compared between patients with CMV-positive and CMV-negative biopsies at BL and FU.

Results: A total of 181 UC patients were included (63 CMV-positive, 118 CMV-negative biopsies). At BL, CMV-positive patients had significantly higher endoscopic disease activity (eMayo, p = .03) and numerically higher clinical activity. At FU (median interval 34 vs. 45 months), both groups showed improvement; however, CMV-positive patients continued to exhibit significantly higher disease activity (tMayo p = .001; eMayo p < .001). Rates of clinical/endoscopic remission were significantly lower in CMV-positive patients at both BL and FU. No significant association was observed between CMV status of biopsies and colectomy rates (p = .21). Antiviral therapy was administered in 60% of CMV-positive patients and was associated with higher baseline disease activity but not with differences at FU.

Conclusions: Molecular detection of CMV in the intestinal mucosa is associated with increased mucosal inflammation and a less favorable long-term disease course in UC, but has no effect on hard outcome parameters such as colectomy. Antiviral therapy has no effect on clinical outcome parameters. These findings indicate that further studies are needed to clarify the pathophysiological influences of CMV infection on disease course in ulcerative colitis and its impact on the efficacy of advanced therapies.

Loss of neurogenesis leads to cognitive impairment and is one of the main causes of neuron degeneration diseases. Mulberry, an economic plant used as Chinese traditional herb, exhibits multiple biological properties. This study investigated the protective molecular mechanisms of mulberry leaf extracts (MLWE) and neochlorogenic acid (nCGA) on scopolamine-induced neuron cell death and cognitive dysfunction. Administration of MLWE and nCGA significantly improved cognitive functions in the Y-maze test of scopolamine-treated mice. MLWE and nCGA reversed scopolamine-reduced brain-derived neurotrophic factor (BDNF) expression and its downstream pathways. Immunohistochemical staining or Western blot analysis showed that MLWE and nCGA increased the expression of neurogenetic proteins such as nestin, NeuN, and doublecortin (DCX) in scopolamine-treated mice. They also reversed the hippocampus structure and neuronal proliferation, decreased Bax expression, and increased Bcl2 expression, thereby attenuating scopolamine-induced neural apoptosis. MLWE (0.5 mg m/L) and nCGA (10 μM) rescued scopolamine-induced cell death in SH-SY5Y cells. MLWE and nCGA repressed scopolamine-induced apoptosis, as evidenced by decreasing sub-G1 phase population through regulation of Bcl2 and Bax expression. Moreover, MLWE and nCGA promoted neurogenesis marker expression in SH-SY5Y cells. Our findings revealed that MLWE and nCGA significantly reversed scopolamine-induced neuron damage through enhanced adult hippocampus neurogenesis.

Background: Nephrolithiasis remains a major global health burden with limited non-invasive tools for early diagnosis and monitoring. Urinary small extracellular vesicle (sEV)-associated microRNAs (miRNAs) are stable molecular signatures that reflect renal pathophysiological shifts. This study aims to identify candidate urinary sEV-associated miRNAs for nephrolithiasis in a clinical discovery cohort and prioritize candidate biomarkers by integrating human urinary sEV miRNA profiles with publicly available murine nephrolithiasis datasets.

Methods: Small RNA sequencing was performed on RNA isolated from urinary sEVs obtained from a clinical discovery cohort (25 patients with nephrolithiasis and 8 healthy controls) to identify candidate biomarkers associated with nephrolithiasis. Differentially expressed miRNAs (DEmiRNAs) were identified using a |log₂ fold change| > 1 and adjusted P < 0.05 threshold. Functional enrichment (GO/KEGG) was conducted on predicted target genes. To prioritize biologically relevant candidates, human DEmiRNAs were intersected with an available murine kidney miRNA dataset (GSE186793) and the ExoCarta database. The lead candidate, miR-223-3p, was further validated via RT-qPCR in human urinary sEV samples and urinary sEVs isolated from an independent CaOx-induced mouse model.

Results: We identified 111 significantly dysregulated urinary sEV-associated miRNAs (105 upregulated, 6 downregulated) in patients with nephrolithiasis. Functional analysis linked these miRNAs to endocytosis, mitochondrial organization, and the MAPK/Wnt signaling pathways. Integrative analysis of the human urinary sEV, the murine kidney miRNA datasets (GSE186793), and the ExoCarta database prioritized a conserved five-miRNA signature (miR-223-5p, miR-223-3p, miR-342-3p, let-7i-5p, and miR-29c-3p). Among these candidates, miR-223-3p demonstrated the strongest translational potential and was therefore selected for further validation. RT-qPCR confirmed that miR-223-3p was significantly upregulated in both human urinary sEVs and urinary sEVs from the CaOx-induced mouse model.

Conclusion: Our findings characterize a distinct urinary sEVs-associated miRNA landscape within this discovery cohort and identify miR-223-3p as a promising candidate biomarker for nephrolithiasis. Given the relatively small, clinically heterogeneous discovery cohort and the absence of an independent validation cohort, these findings should be considered hypothesis-generating and require validation in larger, independent, clinically stratified prospective studies before clinical application.