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Sirtuin 1 and Sirtuin 2 Gene Expressions in Colorectal Cancers

J Clin Pract Res. 2025 Oct 23;47(5):550-559. doi: 10.14744/cpr.2025.78739. eCollection 2025 Oct.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the immunoreactivity of sirtuin 1 (SIRT1) and sirtuin 2 (SIRT2) in colorectal cancer tissues using immunohistochemistry and to investigate their potential roles in the diagnosis and prognosis of colorectal cancer.

MATERIALS AND METHODS: Colon specimens from 104 patients diagnosed with colorectal adenocarcinoma at SBÜ Kartal Dr. Lütfi Kırdar City Hospital between 2016 and 2021 were analyzed. Immunohistochemical staining was performed to assess the immunoreactivity of SIRT1 and SIRT2. Associations between the clinicopathological parameters of colorectal cancer patients and the expression levels of SIRT1 and SIRT2 (categorized as low or high) were examined.

RESULTS: SIRT1 expression was significantly associated with K-RAS mutations (p=0.021) but showed no significant association with N-RAS (p=0.114) or B-RAF (p=0.624) mutations. SIRT2 expression levels were significantly associated with TNM stage (p=0.043), presence of metastasis (p=0.004), K-RAS mutations (p=0.047), and N-RAS mutations (p=0.020). Co-expression of SIRT1 and SIRT2 was significantly correlated with TNM stage (p=0.041), presence of metastasis (p=0.012), and mutations in K-RAS (p=0.028) and N-RAS (p=0.022).

CONCLUSION: SIRT2 expression levels were significantly correlated with TNM classification, as well as the presence of metastasis. In contrast, SIRT1 expression was not significantly associated with these parameters. Both SIRT1 and SIRT2 showed a statistically significant relationship with K-RAS mutations, highlighting their potential roles in the molecular pathology of colorectal cancer.

PMID:41347196 | PMC:PMC12673322 | DOI:10.14744/cpr.2025.78739

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Metabolomics Analysis-Based Machine Learning for Endometrial Cancer Diagnosis: Integration of Biomarker Discovery and Explainable Artificial Intelligence

J Clin Pract Res. 2025 Oct 23;47(5):503-511. doi: 10.14744/cpr.2025.58891. eCollection 2025 Oct.

ABSTRACT

OBJECTIVE: Endometrial cancer (EC) is the most frequent gynecological malignancy in women worldwide. This study aims to develop a predictive model integrating machine learning (ML) approaches with explainable artificial intelligence (XAI) using metabolomics panel data for significant biomarker discovery in EC.

MATERIALS AND METHODS: This study applied metabolomics and XAI to uncover diagnostic biomarkers for EC, the most common gynecologic malignancy. A total of 191 EC cases and 204 controls were analyzed using mass spectrometry. ML and XAI techniques were incorporated, including SHapley Additive exPlanation, Random Forest, BaggedCART, LightGBM, Adaptive Boosting, and Extreme Gradient Boosting.

RESULTS: Statistically significant differences (adjusted p<0.05) were found in 25 metabolites. Effect sizes (ES) of m/z=219.125 (ES=1.516), m/z=672.6961 (ES=0.913), and m/z=203.1564 (ES=0.839) were notably large, suggesting strong discriminatory ability. These metabolites are involved in lipid dysregulation, steroid hormone pathways, and oxidative stress, reflecting cancer-specific metabolic reprogramming. The ML models, particularly LightGBM, demonstrated high accuracy and good calibration. After training with the final feature dataset, SHapley Additive exPlanations (SHAP) analysis identified m/z=219.125, m/z=672.6961, and m/z=127.0769 as the top contributing features, aligning with their biological impact on EC pathogenesis.

CONCLUSION: This study suggests non-invasive biomarkers for early detection of EC screening, highlighting the heterogeneity of metabolic adaptation in EC and the need for multi-omics approaches to understand disease mechanisms. Limitations include diverse cohorts and reliance on tandem mass spectrometry. Nonetheless, these findings represent a step forward in precision oncology.

PMID:41347192 | PMC:PMC12673311 | DOI:10.14744/cpr.2025.58891

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Subclinical Spondyloarthritis Features in Patients with Hidradenitis Suppurativa: A Real-World Cross-Sectional Analysis

J Clin Pract Res. 2025 Oct 23;47(5):480-485. doi: 10.14744/cpr.2025.87060. eCollection 2025 Oct.

ABSTRACT

OBJECTIVE: The objective of this study is to investigate the frequency and clinical spectrum of subclinical spondyloarthritis (SpA) manifestations among patients with hidradenitis suppurativa (HS) and to evaluate their association with cutaneous disease severity and clinical characteristics.

MATERIALS AND METHODS: In this prospective, cross-sectional real-world study, 120 adults with a confirmed diagnosis of HS were systematically assessed for musculoskeletal involvement. The evaluation included clinical examination for inflammatory back pain, peripheral arthritis, enthesitis, and targeted magnetic resonance imaging (MRI) for sacroiliitis when indicated. Laboratory analyses included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and human leukocyte antigen B27 (HLA-B27) status. Spearman’s rank correlation was used to analyze relationships between SpA-related features and HS clinical parameters, including the International Hidradenitis Suppurativa Severity Score System (IHS4) score, Hurley stage, and smoking.

RESULTS: Among the cohort, MRI-confirmed sacroiliitis was detected in 13.3%, enthesitis in 18.3%, HLA-B27 positivity in 12.5%, and peripheral arthritis in 10.0% of patients. A total of 12.5% fulfilled the modified New York criteria for ankylosing spondylitis. No statistically significant correlations were observed between SpA findings and HS severity indices. Weak associations were noted between smoking and both HLA-B27 positivity (ρ=0.27) and peripheral arthritis (ρ=0.21).

CONCLUSION: Subclinical axial and peripheral SpA features are frequently encountered in patients with HS, often in the absence of musculoskeletal complaints. The lack of correlation with skin disease activity highlights the need for routine rheumatologic evaluation in this population to enable early recognition and tailored treatment of inflammatory joint disease.

PMID:41347191 | PMC:PMC12673314 | DOI:10.14744/cpr.2025.87060

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Georeferenced checklist and occurrence dataset of slime moulds (Eumycetozoa) across Central and Eastern Europe emphasising forest ecosystems

Biodivers Data J. 2025 Nov 25;13:e175486. doi: 10.3897/BDJ.13.e175486. eCollection 2025.

ABSTRACT

BACKGROUND: A continental-scale, georeferenced checklist of slime moulds (Eumycetozoa) for Central and Eastern Europe, supplemented with standardised environmental covariates and with a particular emphasis on forest ecosystems, has not previously been available. The absence of a harmonised corpus has constrained statistically supported tests of habitat- and substrate-related patterns and limited objective gap-mapping, particularly within forest ecosystems, where microclimatic buffering, dead-wood continuity and stand history are expected to be decisive; it has also hindered rigorous evaluation of slime moulds’ role as bioindicators of forest habitat types, substrate associations and gradients in anthropogenic pressure (naturalness).

NEW INFORMATION: Literature discovery spanned multidisciplinary and domain-specific platforms; inclusion required a determinable taxon, a locality at least to country level and a year. Records were de-duplicated conservatively; names were harmonised to a single authority (Eumycetozoa.com) with GBIF Species backbone as a fallback and higher taxonomy was filled consistently. The resource comprises presence-only occurrences, a taxonomically standardised checklist and a reference set; the curated bibliography comprises 528 bibliographic entries. Coverage spans Austria, Belarus, Czechia, Estonia, Germany, Hungary, Latvia, Liechtenstein, Lithuania, Moldova, Poland, Russia (European part), Slovakia, Slovenia, Switzerland and Ukraine. Event dates range from 1857 to 2025-08-01 and support ranges and mixed precision. Environmental content includes elevation, consolidated forest class, substrate category, habitat pressure, microhabitat, pH, air temperature, annual precipitation and stand age; controlled vocabularies comprise eight consolidated forest classes, ten substrate categories and seven habitat-pressure classes. The dataset is released under CC-BY-4.0 (Creative Commons Attribution 4.0 International), employs reproducible DwC mapping and stable identifier versioning and is suited to ecological and biogeographic analyses, including forest-focused modelling and gap analyses.

PMID:41347183 | PMC:PMC12673333 | DOI:10.3897/BDJ.13.e175486

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Different interventions in preventing sufentanil-induced cough: a systematic review and network meta-analysis

Front Pharmacol. 2025 Nov 19;16:1619920. doi: 10.3389/fphar.2025.1619920. eCollection 2025.

ABSTRACT

BACKGROUND: Sufentanil-induced cough (SIC) is prevalent in anesthesia practice. A variety of interventions have been employed to prevent SIC. However, the optimal intervention remains elusive.

METHODS: A comprehensive search of the literature was conducted on the PubMed, Embase, Web of Science, Cochrane Library (CENTRAL) and China National Knowledge Infrastructure (CNKI) databases. The search was limited to publications prior to July 5, 2025. A network meta-analysis (NMA) was conducted using the R software. A Bayesian framework was employed for this NMA. Comparisons of competing models based on the deviance information criterion (DIC) were used to select the optimal model for NMA. The primary outcome is the overall incidence of SIC. The secondary outcomes included the incidence of mild SIC and moderate to severe SIC.

RESULTS: The NMA included 37 randomized controlled trials (RCTs) with 5,105 patients and 18 interventions. Pairwise meta-analysis results indicate that the intervention group significantly decreases the overall incidence of SIC (7.6% vs. 34.8%; OR 0.13; 95% CI 0.09 to 0.18; P < 0.0001; I2 = 53.0%), the incidence of mild SIC (4.0% vs. 13.0%; OR 0.28; 95% CI 0.22 to 0.35; P = 0.369; I2 = 5.7%), and the incidence of moderate to severe SIC (3.4% vs. 21.7%; OR 0.13; 95% CI 0.10 to 0.16; P = 0.040; I2 = 30.6%). NMA results suggested that nalbuphine, dezocine, and butorphanol significantly reduced the overall incidence of SIC, as well as the incidence of mild and moderate-to-severe SIC. Additionally, remifentanil and esketamine were effective in reducing both the overall incidence of SIC and the incidence of moderate to severe SIC. The use of a mechanical dropper was also effective in reducing the incidence of moderate to severe SIC.

CONCLUSION: Three pharmacological interventions-nalbuphine, dezocine, and butorphanol significantly reduced the overall incidence of SIC, as well as the incidence of mild and moderate-to-severe SIC. Additionally, remifentanil and esketamine were effective in reducing the overall incidence of SIC and the incidence of moderate to severe SIC. The application of a mechanical dropper was also effective in reducing the incidence of moderate to severe SIC. The remaining interventions indicated a trend toward reducing SIC incidence; however, this was not statistically significant.

SYSTEMATIC REVIEW: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024581866 , PROSPERO (CRD42024581866).

PMID:41347178 | PMC:PMC12673273 | DOI:10.3389/fphar.2025.1619920

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Metabolomic changes associated with treatment response of neoadjuvant chemotherapy with TEC regimen in HER2-negative breast cancer

Front Pharmacol. 2025 Nov 19;16:1707223. doi: 10.3389/fphar.2025.1707223. eCollection 2025.

ABSTRACT

INTRODUCTION: This study aimed to characterize time-dependent metabolic alterations and identify metabolites associated with treatment response in HER2-negative breast cancer patients undergoing neoadjuvant chemotherapy (NAC) with the TEC regimen (docetaxel, epirubicin, and cyclophosphamide).

METHODS: A total of 60 plasma samples were collected from 20 patients at three time points: baseline (T1), after three cycles of NAC (T2), and before surgery (T3). Pathological assessment classified patients into three response groups: pathologic complete response (pCR, n = 5), pathologic partial response (pPR, n = 7), and pathologic stable disease (pSD, n = 8).

RESULTS: After three cycles of NAC, a greater decrease in glycochenodeoxycholate was associated with poorer treatment response, whereas a larger reduction in LysoPC(18:1) correlated with better response. Following six cycles, elevated epinephrine levels were positively associated with therapeutic efficacy, while increased cysteine levels were linked to unfavorable outcomes. Ursodeoxycholic acid showed an upward trend in pCR patients but declined in pPR and pSD groups. Combined analysis of ursodeoxycholic acid and cysteine improved the predictive performance for treatment response.

DISCUSSION: These findings reveal dynamic metabolic reprogramming during NAC and suggest that ursodeoxycholic acid and cysteine may serve as potential predictive biomarkers of therapeutic efficacy in HER2-negative breast cancer patients treated with the TEC regimen.

PMID:41347169 | PMC:PMC12673219 | DOI:10.3389/fphar.2025.1707223

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Comparative effectiveness and pharmacological fingerprints of indobufen versus rivaroxaban in patients with chronic kidney disease: a single-center, real-world study

Front Pharmacol. 2025 Nov 19;16:1694163. doi: 10.3389/fphar.2025.1694163. eCollection 2025.

ABSTRACT

INTRODUCTION: Antithrombotic management in Chronic Kidney Disease (CKD) is a clinical dilemma. This study aimed to empirically evaluate the “de facto interchangeability” of the antiplatelet indobufen and the anticoagulant rivaroxaban by comparing their real-world effectiveness and safety in hospitalized CKD patients.

METHODS: In this retrospective cohort study (2020-2024), we analyzed CKD patients treated with indobufen or rivaroxaban. A multi-stage analysis first used machine learning to assess baseline cohort comparability, overcoming limitations of p-value-based tests. Subsequently, a Linear Mixed Model (LMM), adjusted for confounders including polypharmacy, assessed independent drug effects on in-hospital thrombosis, hemorrhage, and longitudinal laboratory markers.

RESULTS: Machine learning demonstrated the clinical comparability of the indobufen and rivaroxaban cohorts. The incidence of in-hospital thrombosis was numerically lower in the indobufen group (3.65% vs. 7.58%; P = 0.101), while hemorrhage rates were similar (2.19% vs. 2.27%; P = 1). The LMM analysis, beyond verifying indobfen’s expected antiplatelet activity (modulating MPV, PDW), revealed pleiotropic effects (increased prealbumin, HDL-C) and a significant reduction in urine occult blood (P < 0.001), suggesting renal safety. Notably, the model demonstrated that apparent effects on hemoglobin and eGFR were attributable to confounding by co-medications, not a direct drug effect.

CONCLUSION: In this real-world CKD cohort, indobufen and rivaroxaban demonstrated comparable clinical effectiveness and safety. Combining machine learning with longitudinal models helps to statistically adjust for complex confounders like polypharmacy, thereby providing a more robust estimate of a drug’s independent effect.

PMID:41347166 | PMC:PMC12672237 | DOI:10.3389/fphar.2025.1694163

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Qianyang Yuyin Granules for vascular damage in mild-to-moderate hypertensive patients: a systematic review with meta-analysis and trial sequential analysis

Front Pharmacol. 2025 Nov 19;16:1612508. doi: 10.3389/fphar.2025.1612508. eCollection 2025.

ABSTRACT

OBJECTIVE: The purpose is to evaluate the clinical efficacy and safety of Qianyang Yuyin Granules in the treatment of vascular damage in essential hypertension systematically.

METHODS: Relevant literature databases include CNKI, Wanfang Data, VIP, CBM, PubMed, Web of Science, Cochrane Library. DeepSeek-V3 was used for AI-assisted retrieval. The time limit for searching was from the establishment of the database to 15 April 2025. Eligible randomized controlled clinical trials were screened according to inclusion and exclusion criteria. Publication bias assessment and quality evaluations were analysed by using the Cochrane Handbook and meta-analysis was performed by using RevMan 5.3 software. Finally, using Trial Sequential Analysis 0.9Beta software to perform the trial sequential analysis.

RESULTS: 21 studies were finally included, with a total sample of 1,419 cases, 728 cases in the experimental group and 691 cases in the control group. Meta-analysis suggested that the trial group using Qianyang Yuyin Granules was effective in lowering PWV-BS [MD = -0.58, 95%CI: (-0.88, -0.29), P < 0.0001], PWV-ES [MD = -0.79, 95%CI: (-1.22, -0.36), P = 0.0003] in the elderly population with essential hypertension (≥60 years old), lowering inflammatory factor-related indexes including CRP [SMD = -0.37, 95%CI: (-0.58, -0.16), P = 0.0005] and TNF-α [SMD = -0.44, 95%CI: (-0.70, -0.18), P = 0.001], lowering systolic blood pressure [MD = -3.86, 95%CI: (-5.33, -2.39), P < 0.00001] and diastolic blood pressure [MD = -2.24, 95%CI: (-3.39, -1.10), P = 0.0001] were all superior to the control group that only used basic treatment and the differences were statistically significant; The incidence rate of adverse reactions in the experimental group was not statistically significant when compared with that of the control group [OR = 0.71, 95%CI: (0.26, 1.93), P = 0.51]. The sequential analysis further suggested that the addition of Qianyang Yuyin Granules to reduce PWV and CRP in peripheral blood had a precise role.

CONCLUSION: The addition of Qianyang Yuyin Granules in the treatment of vascular damage in mild-to-moderate essential hypertension can improve the clinical efficacy without increasing the adverse effects of conventional drugs, and has further clinical application value. However, further research with larger scale and stricter quality control is needed.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42025641482.

PMID:41347150 | PMC:PMC12672466 | DOI:10.3389/fphar.2025.1612508

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Inflammatory storm and metabolic disorders: unraveling heterogeneity in mortality risk for comorbid diabetes mellitus and heart failure via the C-reactive protein-triglyceride-glucose index

Front Endocrinol (Lausanne). 2025 Nov 19;16:1689238. doi: 10.3389/fendo.2025.1689238. eCollection 2025.

ABSTRACT

INTRODUCTION: Acute decompensated heart failure (ADHF), a critical cardiovascular emergency, is driven by a metabolic and inflammatory imbalance that serves as the central mechanism of disease progression. This study aims to analyze the heterogeneity of mortality risk in patients with comorbid diabetes mellitus (DM) and HF using the C-reactive protein-triglyceride-glucose index (CTI).

METHODS: This study evaluated 1,051 ADHF patients from the Jiangxi-ADHF II cohort. The Boruta algorithm, a fully automated feature selection method, was applied to identify key predictive variables and rank their importance. Cox proportional hazard models were constructed to assess the association between the CTI and 30-day mortality risk in ADHF patients, stratified by DM status. To further elucidate the nonlinear characteristics of risk associations, restricted cubic splines were employed to construct dose-response relationship curves. Additionally, heatmaps were used to assess the joint association of CTI components with mortality risk.

RESULTS: The 30-day follow-up revealed a mortality rate of 8.3%. Through the Boruta algorithm and multivariate Cox regression analysis, we identified CTI as a key prognostic factor for short-term mortality risk in ADHF patients, especially in those with comorbid DM. The restricted cubic splines model further confirmed the linear and non-linear associations between CTI and mortality in ADHF patients with and without DM. Additionally, heatmaps visualized the association between CTI components and mortality: to summarize, the mortality risk is relatively low when the triglyceride-glucose index remains within specific ranges (8.25-9.0 for patients with DM; 7.0-9.0 for non-DM patients) and the C-reactive protein level is maintained below 50 mg/L. Further subgroup analyses highlighted distinct risk modulation patterns: non-DM ADHF patients exhibited mortality risk heterogeneity across gender, hypertension, and stroke subgroups; however, the DM comorbid group demonstrated uniform risk profiles with no statistically significant differences.

DISCUSSION: This study demonstrates the clinical utility of the novel inflammatory-metabolic index CTI in mortality risk assessment for ADHF patients, with superior risk stratification efficacy observed in those with DM comorbidity.

PMID:41347140 | PMC:PMC12672285 | DOI:10.3389/fendo.2025.1689238

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Clinical and Treatment Characteristics of 3795 Adults Consecutively Hospitalized for Major Depressive Disorder in the OASIS-D Study

Depress Anxiety. 2025 Nov 26;2025:4470169. doi: 10.1155/da/4470169. eCollection 2025.

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) is common and associated with high social and economic burden. Knowledge of characteristics of hospitalized adults with MDD can help identify clinical treatment and prevention targets.

METHODS: The multicenter “Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression” (OASIS-D) study assessed characteristics of patients aged 18-75 years hospitalized between October 2020 and December 2024, who were admitted to a psychiatric inpatient unit for MDD at eight German centers. Baseline illness-, treatment-, and suicidality-related characteristics of the overall sample are reported.

RESULTS: Among 3795 patients (median age = 42.0, interquartile range [IQR] = 27.5-57.0 years; females = 53.9%) with MDD (severe episode = 75.3%, psychotic features = 7.9%; first episode = 34.9%; treatment-resistant depression [TRD] = 18.2%). Psychiatric comorbidities of MDD were present in 46.2% and included substance use disorder (18.9%), personality disorders (8.4%), stress/adjustment disorders (7.6%), and phobic/other anxiety disorders (6.6%). In 42.5%, the admission was prompted by a psychiatric emergency, primarily due to suicidality (35.0%), followed by stupor/refusal/intoxication/acute agitation (0.9%-1.5%), or danger to others/delirium (0.1%-0.3%). Overall, 72.0% of patients had active or passive suicidal thoughts, and 11.5% had attempted suicide within 2 weeks prior to admission. Furthermore, 83.9% had lifetime suicidal thoughts, and 36.0% had lifetime suicide attempts. Altogether, 76.8% had received outpatient psychiatric care within their lifetime (62.3% within 6 months), and 57.8% of patients had lifetime inpatient treatment for MDD. At admission, 71.6% of patients were prescribed psychiatric medications: antidepressants = 59.8%; antipsychotic = 25.1%, anxiolytics/hypnotics = 11.8%, and mood stabilizers = 8.6%. Additionally, 4.0% had previously received electroconvulsive therapy (ECT). The median hospitalization duration was 31.0 (IQR = 13.0, 57.0) days.

CONCLUSION: Almost half of admissions in adults with MDD were considered emergencies, with 90% being related to suicidality, and only <60% received antidepressants at admission. These data underscore the need for early identification and treatment of adults with MDD, especially those with suicidality. Outcomes of this population required further study. Trial Registration: ClinicalTrials.gov identifier: NCT04404309.

PMID:41347111 | PMC:PMC12674865 | DOI:10.1155/da/4470169