Taizhou Fourth People's Hospital

Stress hyperglycemia is a common phenomenon in patients with critical illness, and its association with coronary microcirculation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) remains poorly understood. The coronary angiography-derived index of microcirculatory resistance (AMR) is a tool used to assess coronary microcirculation. This study aimed to investigate the relationship between stress hyperglycemia ratio (SHR) and AMR in STEMI patients undergoing pPCI. Three hundred sixty-two consecutive patients who underwent pPCI at Taizhou People’s Hospital between 2022 and 2023 were initially screened in this observational study. The study populations were classified as three groups according to fasting SHR tertiles: SHR1: SHR ≤ 0.76 (n = 114); SHR2: 0.76 < SHR < 0.96 (n = 110); and SHR3: SHR ≥ 0.96 (n = 113). Restricted cubic spline analysis was performed to explore the relationship between SHR and AMR. Logistic regression analysis was performed to identify independent predictors of high AMR (AMR ≥ 2.5). A total of 337 STEMI patients were included in this observational study. The AMR was significantly lower in SHR1 and SHR2 than that in SHR3 (all P < 0.05). The AMR were positively correlated with SHR (p for overall < 0.001, p for non-linear = 0.236). Multivariable logistic regression analysis identified SHR3 as an independent risk factor for high AMR after adjusting for other covariates (odds ratio: 1.78, 95% confidence interval: 1.040–3.058, p = 0.035). The SHR is an independent predictor of high AMR in STEMI patients undergoing pPCI. These results may offer new insights into the pathophysiology of STEMI and highlight the potential value of SHR as a clinical marker for coronary microcirculation status.

BackgroundWe investigated the potential of the preoperative neutrophil-to-lymphocyte ratio (NLR) and soluble urokinase-type plasminogen activator receptor (suPAR) as predictive biomarkers for biochemical recurrence (BCR) following radical prostatectomy in prostate cancer (PCa). By examining these markers individually and in combination, we aimed to enhance risk stratification and improve postoperative management.Material/MethodsA retrospective cohort of 245 patients with PCa who underwent laparoscopic radical prostatectomy were stratified into non-BCR (n=183) and BCR (n=62) groups based on a 2-year follow-up. We collected comprehensive clinical and pathological data, calculated preoperative NLR, and measured serum suPAR using ELISA. Cox regression analysis identified independent risk factors for BCR, while ROC curves evaluated the predictive power of NLR, suPAR, and their combination. Kaplan-Meier survival analysis assessed BCR risk associated with varying levels of these biomarkers.ResultsPreoperative NLR and suPAR levels were significantly higher in the BCR group. Multivariate Cox regression identified several independent risk factors for BCR, including preoperative PSA ≥20 ng/mL, pathological T3–T4 stage, positive surgical margins, and elevated NLR and suPAR levels. ROC analysis showed NLR and suPAR combined (AUC: 0.943, 95% CI: 0.911–0.975) significantly outperformed the predictive accuracy of each marker alone, with standalone AUCs of 0.873 for NLR and 0.881 for suPAR.ConclusionsElevated preoperative NLR and suPAR are strongly associated with increased BCR risk after radical prostatectomy in patients with PCa. Combined assessment of these biomarkers offers a superior predictive tool, facilitating personalized risk stratification and potentially guiding tailored postoperative management strategies in PCa care.

Ferroptosis and insulin resistance (IR) play crucial roles in the development of gestational diabetes mellitus (GDM). This study aims to analyze the effects of perillaldehyde (PAE) on ferroptosis and IR in human trophoblast cells, as well as its underlying mechanism in these effects. In this study, human trophoblasts (HTR-8/SVneo cells) treated with high glucose or in combination with insulin were used as in vitro models of GDM. The protective effects of PAE were evaluated by detecting insulin resistance and ferroptosis. GSE datasets (GSE154414 and GSE54157), SwissTargetPrediction, and GeneCards were used for gene target prediction. Results showed that PAE mitigated the decrease in HTR-8/SVneo cell viability caused by HG treatment. PAE exerted a protective effect against HG-triggered ferroptosis in HTR-8/SVneo cells by reducing ROS, Fe2+, and MDA levels, while increasing GSH and GPX4 levels and SOD activity. PAE alleviated IR in HTR-8/SVneo cells by increasing IRS1 and GLUT4 mRNA levels and glucose uptake, while decreasing IGF-1 mRNA level. PAE inhibited the expression of PTPN1 in HTR-8/SVneo cells with HG treatment. PTPN1 overexpression reversed the effect of PAE on ferroptosis in HTR-8/SVneo cells with HG treatment. PTPN1 overexpression counteracted the effects of PAE on IR in HTR-8/SVneo cells. PAE activated the Akt/Foxo signaling pathway by downregulating PTPN1 in HTR-8/SVneo cells under HG conditions. Akt/Foxo1 activation counteracted the effects of PTPN1 overexpression on ferroptosis and IR in HTR-8/SVneo cells with HG treatment. In conclusion, PAE attenuated IR and high glucose-triggered ferroptosis in trophoblast cells via regulation of the PTPN1/Akt/Foxo1 signaling pathway.

Hyperlipidemia is a prevalent condition that accelerates the development of cardiovascular diseases. Traditional treatments targeting lipid regulation often have limitations, such as hepatotoxicity. This study investigates the dual action of a novel compound, 5-(4-(3-thioxo- 3H-1,2-dithiol-5-yl)phenoxy)pentanoic acid (TDPPA), in reducing lipid levels and protecting the liver. TDPPA was synthesized and structurally confirmed by 1H-NMR, 13C-NMR, and HRMS. Its lipid-lowering efficacy was first assessed in Triton WR-1339-induced acute hyperlipidemic mice. Mechanistic studies were then conducted in a high-fat emulsion-induced chronic hyperlipidemia model, incorporating histopathological analysis of the liver (H&E and Oil Red O staining). Liver index, serum lipid panels, hepatic function markers, HⁿS content, oxidative stress parameters, and pro-inflammatory cytokines were quantified via ELISA, while the interaction between TDPPA and PPAR-α was evaluated by molecular docking and Western blotting. TDPPA significantly reduced serum triglyceride (TG), total cholesterol (TC), and lowdensity lipoprotein cholesterol (LDL-C) in both acute and chronic models, while increasing highdensity lipoprotein cholesterol (HDL-C). Histology revealed marked reductions in hepatic lipid accumulation and inflammatory infiltration. Biochemical assays showed decreases in AST and ALT, enhanced antioxidant capacity (higher SOD and HⁿS, lower MDA), and suppression of TNF- α, IL-6, and IL-1β. Molecular docking and Western blot analysis indicated that these effects were associated with upregulation of PPAR-α protein expression. TDPPA demonstrates potent lipid-lowering, antioxidant, and antiinflammatory activities, likely through a dual mechanism involving PPAR-α activation and HⁿSmediated hepatoprotection. These findings position TDPPA as a promising therapeutic candidate for hyperlipidemia with the benefit of liver protection.

The characteristic asymmetric motor symptoms of Parkinson's disease (PD) may be associated with asymmetric deposition of α-synuclein. The impaired glymphatic system may promote pathological deposition of α-synuclein, leading to disease progression. The aim of this study was to investigate the function of the glymphatic system in PD patients with unilateral motor symptom onset using diffusion tensor image analysis along the perivascular spaces (DTI-ALPS) method, and to elucidate the relationship between glymphatic system asymmetry and the side of motor symptom onset. We conducted diffusion tensor imaging scans on 36 left-onset PD (LPD) patients, 27 right-onset PD (RPD) patients, and 49 healthy controls (HCs). Bilateral hemispheric ALPS indices were calculated to assess glymphatic function, and an asymmetry index (AI) was derived to quantify interhemispheric asymmetry in glymphatic function. Compared to HCs, RPD patients exhibited a significant reduction in the left ALPS index, while both left and right ALPS indices were significantly reduced in LPD patients. In both LPD patients and HCs, the right ALPS index was lower than the left, suggesting a natural leftward asymmetry. However, this asymmetry was diminished in RPD patients, as indicated by a lower AI. Moreover, in RPD patients, the Unified Parkinson's Disease Rating Scale Part III score showed a negative correlation with the left ALPS index and with AI. This study demonstrated that PD patients with lateralized motor symptom onset exhibit different patterns of glymphatic system function. The glymphatic system asymmetry may provide new insights into the mechanism underlying the lateralized onset of PD.

Human pegivirus (HPgV) is a blood-borne RNA virus belonging to the family Flaviviridae, and contains two types HPgV-1 and HPgV-2. HPgV-1 infection does not cause acute diseases in healthy individuals but was demonstrated to play beneficial roles in individuals coinfected with HIV-1. HPgV-1 has a high prevalence in blood donors and the general population worldwide. The long-term consequence of HPgV-1 infection in healthy individuals remains unknown. High prevalence of HPgV-1 in blood donors raises concerns about the risk of transfusion transmission. Development of rapid and accurate point-of-care testing (POCT) of HPgV-1 will facilitate the screening of HPgV-1 infection among blood donors. Here, we reported a novel high-fidelity loop-mediated isothermal amplification (HiFi-LAMP) assay for detection of HPgV-1 and evaluated its performance in 175 healthy adults from Taizhou, China. The assay exhibits high specificity and sensitivity with limits of detection (LODs) of 122.6-135.7 copies of viral RNA/25 μL reaction for various HPgV-1 variants and can be completed within 30 min. Clinical validation showed that the assay had a 100% concordance with a previously described RT-qPCR assay for 175 sera from healthy adults, showing 100% sensitivity and specificity. Furthermore, we reported a 28.0% (111/397) prevalence of HPgV-1 in healthy adults in Taizhou, China, with no significant differences between genders and ages. The prevalence is obviously higher than a pooled HPgV-1 prevalence of 3.3% in blood donors in China. The novel HPgV-1 HiFi-LAMP assay offers a robust, rapid, and cost-effective tool for HPgV-1 surveillance to mitigate transfusion risk, especially in resource-limited areas. High prevalence of HPgV-1 in healthy adults underscores its potential public health relevance.

Cisplatin is a common anticancer drug, but its frequent nephrotoxicity limits its clinical use. Small GTP-binding protein GDP dissociation stimulator (smgGDS), a small GTPase chaperone protein, was considerably downregulated during cisplatin-induced acute kidney injury (CDDP-AKI), especially in renal tubular epithelial cells. SmgGDS-knockdown mice was established and found that smgGDS knockdown promoted CDDP-AKI, as demonstrated by an increase in serum creatine, blood urea nitrogen levels and the appearance of tubular patterns. RNA sequencing suggested that protein kinase RNA-like ER kinase (PERK), which bridges mitochondria-associated ER membranes, was involved in smgGDS knockdown following CDDP-AKI, and then identified that smgGDS knockdown increased phosphorylated-PERK in vivo and in vitro. Furthermore, we confirmed that smgGDS deficiency aggravated apoptosis and ER stress in vivo and in vitro. And the ER stress inhibitor 4-Phenylbutyric acid and the inhibition of PERK phosphorylation mitigated smgGDS deficiency-induced ER stress related apoptosis following cisplatin treatment, while the eIF2α phosphorylation inhibitor could not reverse the smgGDS deficiency accelerated cell death. Furthermore, the over-expression of smgGDS could reverse the ER stress and apoptosis caused by CDDP. Overall, smgGDS regulated PERK-dependent ER stress and apoptosis, thereby influencing renal damage. This study identified a target for diagnosing and treating cisplatin-induced acute kidney injury.