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Objective The associations between the ratio of blood high-sensitivity C-reactive protein (hs-CRP) to high-density lipoprotein cholesterol (HDL-C) (hs-CRP/HDL-C ratio) and outcomes in patients with acute ischemic stroke (AIS) have yet to be established. This study is the first to examine the relationship between the hs-CRP/HDL-C ratio and three-month unfavorable outcomes in patients with AIS. Methods This secondary analysis utilized data from a prospective cohort study involving 1559 AIS patients recruited at a South Korean hospital between January 2010 and December 2016. We constructed a binary logistic regression model to explore the association between the hs-CRP/HDL-C ratio and unfavorable outcomes in patients with AIS. An attempt was made to use a generalized additive model (GAM) with smooth curve fitting to elucidate potential nonlinear interactions. Furthermore, inflection points were identified via a recursive method, and binary logistic regression models were developed for each side of these inflection points. Ultimately, a log-likelihood ratio test was used to identify the most appropriate model for explaining the connection between the hs-CRP/HDL-C ratio and unfavorable outcomes in patients with AIS. Results The incidence of unfavorable outcomes was 24.5%, with a median hs-CRP/HDL-C ratio of 3.64. After accounting for other factors, the binary logistic regression model revealed a statistically significant positive association between the hs-CRP/HDL-C ratio and the likelihood of poor outcomes in AIS patients (OR = 1.013, 95% CI: 1.005–1.022; P  = 0.002). A nonlinear relationship was observed, with the first inflection point of the hs-CRP/HDL-C ratio at 42.74. Each 1-unit increase in the hs-CRP/HDL-C ratio was associated with a 2.4% greater risk of unfavorable outcomes (OR = 1.024, 95% CI: 1.011–1.038, P  < 0.001). Conclusion This study provides evidence of a positive and nonlinear correlation between the hs-CRP/HDL-C ratio and poor three-month functional outcomes in AIS patients. When the hs-CRP/HDL-C ratio was less than 42.74, a positive association was observed with the risk of unfavorable outcomes. This finding offers a reference for optimizing early individualized therapy and aids in clinical counseling for patients with AIS.

The study was undertaken to determine the mechanism of miR-372-3p activating hepatic stellate cell (HSC). Transforming growth factor-β1 (TGF-β1) induced LX-2 cells were transfected with miR-372-3p mimics and/or RhoC overexpression vector (oe-RhoC), after which the miR-372–3 and RhoC expressions were detected and the biological functions of transfected cells were assessed. The relation between miR-372-3p and RhoC predicted online was validated using the dual-luciferase assay. Protein level of Collagen I (COL I), α-smooth muscle actin (α-SMA), and key proteins in the RhoC/ROCK pathway were determined using western blot. Activated LX-2 cells had decreased miR-372-3p and increased RhoC expression. Overexpression of miR-372-3p led to inhibited LX-2 cell proliferation, accelerated apoptosis, and decreased protein level of COL I and α-SMA, while such an expression pattern can be partially reversed by RhoC overexpression. miR-372-3p can bind and target RhoC expression. miR-372-3p inhibited RhoC expression to block the activation of the Rho/ROCK pathway and thus mediate LX-2 cell proliferation and apoptosis. miR-372-3p mediated RhoC/ROCK pathway to inhibit HSC activation.

Objective To determine the associations between matrix metalloproteinase-2 (MMP-2, encoded by the MMP2 gene) 1306C/T and 735C/T polymorphisms and first and recurrent ischemic stroke in a Chinese population. Methods Patients with first and recurrent ischemic stroke were included. Serum MMP-2 was measured, and MMP2 1306C/T and 735C/T polymorphisms were detected. The associations between MMP2 1306C/T and 735C/T polymorphisms and first and recurrent ischemic stroke were analyzed. Results Serum MMP-2 in patients with first and recurrent ischemic stroke was significantly higher compared with controls, and patients with recurrent ischemic stroke had higher MMP-2 than those with first ischemic stroke. The frequency of the CC genotype and C allele of MMP2 735C/T was highest in patients with recurrent ischemic stroke, followed by patients with first ischemic stroke, and controls. Conversely, the genotype and allele of MMP2 1306C/T did not significantly differ between groups. The CC genotype of MMP2 735C/T was independently associated with first and recurrent ischemic stroke (odds ratios = 1.45 and 1.64, respectively), as was the C allele of MMP2 735C/T (odds ratios = 1.68 and 1.77, respectively). Conclusions The CC genotype and C allele of MMP2 735C/T were associated with first and recurrent ischemic stroke in a Chinese population.

Abstract Objective To assess the efficacy and safety of peripherally acting mu-opioid receptor antagonists (PAMORAs) for the treatment of opioid-induced constipation (OIC). Methods Randomized controlled trials (RCTs) were searched for OIC therapy comparing PAMORAs with placebo. Both a pairwise and network meta-analysis were performed. The surface under the cumulative ranking area (SUCRA) was used to determine the efficacy and safety of OIC treatment using different PAMORAs. Results The primary target outcome was a response that achieves an average of three or more bowel movements (BMs) per week. In the network meta-analysis, four PAMORAs (naldemedine, naloxone, methylnaltrexone, and alvimopan) showed a better BM response than the placebo. Naldemedine was ranked first (odds ratio [OR] = 2.8, 95% credible interval [CrI] = 2–4.5, SUCRA = 89.42%), followed by naloxone (OR = 2.9, 95% CrI = 1.6–5.3, SUCRA = 87.44%), alvimopan (OR = 2.2, 95% CrI = 1.3–3.5, SUCRA = 68.02%), and methylnaltrexone (OR = 1.7, 95% CrI = 1.0–2.8, SUCRA = 46.09%). There were no significant differences in safety found between the PAMORAs and the placebo. Conclusions We found that PAMORAs are effective and can be safely used for the treatment of OIC. In network meta-analysis, naldemedine and naloxone appear to be the most effective PAMORAs for the treatment of OIC.

Uric acid (UA) is the final oxidation product of purine metabolism. Hyperuricemia has been previously reported to contribute to vascular endothelial dysfunction and the development of cardiovascular diseases, metabolic syndrome and chronic kidney diseases. In addition, it has been reported that fibroblast growth factor 21 (FGF21) can exert regulatory effects on UA-induced lipid accumulation. Therefore, the present study aimed to investigate the possible role of FGF21 in HUVEC cell injury induced by UA. The study used UA to induce HUVEC cell injury, inhibited sirtuin 1 (Sirt1) expression using EX527 and overexpressed FGF21 by transfection. Subsequently, reverse transcription-quantitative PCR was performed to measure the mRNA expression levels of FGF21, Sirt1 and inflammatory cytokines TNF-α, IL-1β and IL-6, whereas western blotting was performed to measure their corresponding protein expression levels including FGF21, Sirt1, NLR family pyrin domain containing 3, pro-caspase1, apoptosis-associated speck-like protein containing a CARD, activating transcription factor 4, C/EBP homologous protein and eukaryotic initiation factor 2. Furthermore, dichloro-dihydro-fluorescein diacetate staining was performed to measure intracellular reactive oxygen species (ROS) generation in HUVECs. The levels of ROS and nitric oxide were also quantified using commercial assay kits. The results demonstrated that overexpression of FGF21 significantly inhibited UA treatment-induced endoplasmic reticulum (ER) stress, inflammation and oxidative stress in HUVECs. Furthermore, overexpression of FGF21 significantly activated Sirt1. The sirt1 inhibitor, EX527, significantly abrogated the suppressive effects of FGF21 overexpression on ER stress, inflammation and oxidative stress in UA-stimulated HUVECs. To conclude, results of the present study suggested that FGF21 may attenuate UA-induced ER stress, inflammation and vascular endothelial cell dysfunction by activating Sirt1. Therefore, FGF21 may be a potential effective target for the future treatment of vascular endothelial cell dysfunction.

This meta-analysis aimed to compare the diagnostic effectiveness of [ Ga]Ga-FAPI-04 PET and [ F]FDG PET for detecting lymph node metastasis in digestive system cancer patients. A comprehensive search of PubMed, Web of Science, and Embase databases was conducted to identify relevant articles up to June 2024. Studies were included if they evaluated the diagnostic performance of [ Ga]Ga-FAPI-04 PET and [ F]FDG PET in detecting lymph node metastasis in digestive system cancer patients. Sensitivity and specificity were assessed using the DerSimonian and Laird method and were transformed using the Freeman-Tukey double arcsine transformation. Fifteen articles, encompassing a total of 617 patients, were included in this study. The overall sensitivity of [ Ga]Ga-FAPI-04 PET for diagnosing lymph node metastasis in digestive system cancers was 0.82 (95% CI: 0.67-0.93), and the specificity was 0.91 (95% CI: 0.84-0.97). In comparison, the sensitivity of [ F]FDG PET was 0.51 (95% CI: 0.38-0.63), with a specificity of 0.81 (95% CI: 0.64-0.94). These results suggest that [ Ga]Ga-FAPI-04 PET has a significantly higher sensitivity ( < 0.01) and similar specificity ( = 0.20) compared to [ F]FDG PET in detecting lymph node metastasis in digestive system cancers. Our meta-analysis indicates that [ Ga]Ga-FAPI-04 PET has higher sensitivity and similar specificity compared to [ F]FDG PET in diagnosing lymph node metastasis in digestive system cancers. However, the high heterogeneity among the studies may impact the robustness of the current evidence. Therefore, future research should prioritize larger prospective studies with more diverse populations and specific cancer subtypes to draw more definitive conclusions. https://www.crd.york.ac.uk/PROSPERO/view/CRD42024572412, Unique Identifier: CRD42024572412.

The treatment of idiopathic short stature (ISS) with recombinant human growth hormone (rhGH) has been a subject of extensive research. This study aims to perform a bibliometric analysis of publications related to rhGH treatment for ISS, identifying research hotspots, key publications, and international collaboration networks. A literature search was conducted on the Web of Science Core Collection, covering literature from 1991 to 2024. Bibliometric tools including CiteSpace, VOSviewer and \"bibliometrix\" package of R were used to analyze publication trends, authorship, institutional contributions, and citation networks. Keyword co-occurrence and burst detection were performed to identify emerging research topics. This area of study had experienced significant growth and maturation over the past three decades, characterized by increasing interest and investment in research pertaining to rhGH interventions for ISS. The majority of research output was concentrated in China. Leading contributors to this body of work included the University of Ulsan. The most prolific academic journals in this field were the . The keyword co-occurrence analysis identified \"gene,\" \"mutations,\" and \"genotype,\" highlighting genetic factors in rhGH therapy for ISS. Keyword burst analysis, however, emphasized recent trends like \"safety\" and \"growth hormone deficiency,\" reflecting growing attention to treatment risks and patient-specific care. This bibliometric analysis highlights the progression of rhGH research for ISS, shifting from foundational studies to contemporary priorities such as tailored therapies and clinical outcomes. Future research should focus on advancing precision medicine and optimizing treatment protocols while addressing safety concerns and long-term effectiveness.

This meta-analysis evaluated diagnostic performance of deep learning (DL) algorithms using whole slide images (WSIs) for detecting microsatellite instability-high (MSI-H) in colorectal cancer (CRC). PubMed, Embase, and Web of Science were searched until January 2025. Nineteen studies comprising 33,383 samples were included. Bivariate random-effects models calculated pooled sensitivity/specificity with 95% CIs. The revised QUADAS-2 tool was used for quality assessment. Pooled patient-based internal validation showed a sensitivity of 0.88 and specificity of 0.86, while external validation revealed higher sensitivity of 0.93 but lower specificity of 0.71. Image-based analysis showed similar accuracy. Meta-regression identified center, reference standard, and tile size as major sources of heterogeneity, with no significant differences observed between internal and external performance. Overall, DL algorithms demonstrate excellent sensitivity in detecting MSI-H; however, their lower specificity in external validation suggests overfitting and highlights the need for algorithm standardization to improve generalizability and clinical utility.

Introduction This study evaluated the predictive value of glucose response curve shape during the oral glucose tolerance test (OGTT) for macrovascular complications in patients with type 2 diabetes mellitus (T2DM). Research design and methods A retrospective observational analysis was conducted involving 75 subjects with normal glucose tolerance (NGT) and 496 patients with T2DM, all of whom underwent a 3-hour OGTT, along with insulin and C-peptide release tests. Multivariate linear regression models assessed the cross-sectional associations between glucose response curve shapes and common carotid artery (CCA) diameter and intima-media thickness (IMT) in T2DM patients. Risk factors for carotid atherosclerosis analyzed using multivariate logistic regression. Results Among patients with type 2 diabetes who underwent OGTT, the group with monophasic curves ( n  = 282) showed higher blood glucose levels, increased insulin resistance, and poorer pancreatic β-cell function compared to the multiphasic curve group ( n  = 214). Larger CCA diameters were independently associated with monophasic curves compared to multiphasic curves (regression coefficient: 0.134 [0.016, 0.252], P  = 0.026). Increased IMT was independently associated with monophasic curves compared to multiphase curves (regression coefficient: 0.038 [0.001, 0.075], P  = 0.045). Independent risk factors for carotid atherosclerosis in T2DM patients included monophasic curve (odds ratio [OR] 2.014, 95% confidence interval [CI] 1.300-3.121, P  = 0.002), age (OR 1.040, 95% CI 1.020–1.059, P  < 0.001), male sex (OR 2.107, 95% CI 1.364–3.256, P  = 0.001), and duration of diabetes (OR 1.043, 95% CI 1.009–1.078, P  = 0.012). Conclusion The shape of the glucose response curve during OGTT was significantly linked to the risk of macrovascular complications in T2DM patients. Those with monophasic glucose curves were at an elevated risk of developing such complications.

Right ventricular (RV) dysfunction is known to be highly correlated with mortality and morbidity; nevertheless, imaging-based assessment of RV anatomy and physiology lags far behind that of the left ventricle. In this study, we advance RV imaging using cardiac magnetic resonance (CMR) to accomplish the following aims: (i) track the motion of six tricuspid annular (TA) sites using a semi-automatic tracking system; (ii) extract clinically important TA measurements—systolic velocity (Sm), early diastolic velocity (Em), late diastolic velocity (Am), and TA plane systolic excursion (TAPSE)—for each TA site and compare these CMR-derived measurements in healthy subjects vs. patients with heart failure, repaired tetralogy of Fallot, pulmonary hypertension, and hypertrophic cardiomyopathy; (iii) investigate how the TA motion related measurements compare with information provided by invasive right heart catheterization (RHC); (iv) evaluate the rate of change in surface area swept out by the reconstructed tricuspid annulus over time and (v) assess the reproducibility of this CMR-based technique. Results indicate that TA motion parameter data obtained in three dimensions using the proposed CMR-based systematic methodology achieve superior diagnostic performance (Sm: AUC = 0.957; TAPSE: AUC = 0.981) compared to two-dimensional CMR imaging. Both Sm and TAPSE from CMR correlated positively with dP / dt max /IP from RHC (Sm: r  = 0.621, p  < 0.01; TAPSE: r  = 0.648, p  < 0.01). Our highly reproducible and robust methodology holds potential for extending CMR imaging to characterization of TA morphology and dynamic behaviour, eventually leading to deeper understanding of RV function and improved diagnostic capability.