Bosnian Journal of Basic Medical Sciences (BJBMS)
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Construction of the prognostic nomogram and treatment recommendation in patients with mixed endometrial carcinoma treated with hysterectomy
Get PDFMixed endometrial carcinomas (MECs) account for approximately 3%–10% of all endometrial carcinomas (ECs). These are defined as a combination of two or more distinct histologic subtypes, with at least one being a type II tumor that constitutes at least 5% of the overall tumor. However, the associated prognostic factors and treatment of MECs remain unclear. The study aimed to identify theindependent prognostic factors of MEC patients treated with hysterectomy and to explore the optimal treatment modalities for overall survival (OS) and cancer-specific survival (CSS). Using the Surveillance, Epidemiology, and End Results (SEER) database, a total of 12,848 MEC patients treated with hysterectomy were screened. Independent prognostic factors were identified by Cox regression analysis and used to construct the nomogram. The concordance indices (C-indices) of OS and CSS were 0.807 and 0.834 in the training set. Validation of the nomogram revealed that the receiver operating curve (ROC) maintained good discrimination, the decision curve analysis (DCA) had a high net benefit rate, and the calibration curves showed high consistency. Patients were grouped by the nomogram formula and the number of positive regional lymph nodes (NPR-Lymph node) to evaluate the therapeutic outcomes of chemotherapy, radiotherapy, neoadjuvant treatment, and lymph node operation. Survival analysis revealed that chemotherapy could improve the prognosis for OS and CSS in the high-risk group and in the group with NPR-Lymph node counts above 1 (P < 0.05). Radiotherapy was associated with better OS and CSS in the intermediate-risk and high-risk groups, and in the group with NPR-Lymph node counts above 0 (P < 0.05). Lymphadenectomy was found to prolong OS and CSS in the high-risk group (P < 0.05), while neoadjuvant treatment did not prolong OS and CSS in any group. Thus, in this study, the nomogram for MEC patients treated with hysterectomy was successfully built and validated which could effectively predict the prognosis and identify at-risk population to guide clinical decision making. The NPR-Lymph node was identified as a potentially strong prognostic indicator with good clinical value
Response to the Letter regarding “The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders”
Get PDFDear Editor, In relation to the letter expressing concerns about some important points of the article entitled “The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders”, we would like to comment on the following.
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Histopathologic degenerative score as a predictor of minimal clinically important difference in pain and functionality following surgical treatment for disc herniation
Get PDFLumbar disc herniation (LDH) often results in significant pain and disability, and histopathologic (HP) evaluation of intervertebral discs (IVDs) offers critical insights into treatment outcomes. This prospective observational study explores HP changes in IVDs and their association with clinical outcomes following surgical treatment for LDH. A cohort of 141 patients undergoing MRI-confirmed LDH surgery underwent HP evaluation using a semi-quantitative HP degeneration score (HDS). Preoperatively and at a six-month follow-up, the comprehensive clinical assessment included the Oswestry disability index (ODI) and visual analog scale (VAS), with a minimal clinically important difference (MCID) calculated from ODI and VAS. Results indicated significant associations between higher HDS and adverse clinical outcomes, including persistent pain and greater disability post-surgery. Specifically, an HDS ≥ 7 was predictive (OR = 6.25, 95% CI: 2.56–15.23) of disability outcomes measured with MCID-ODI (AUC: 0.692, 95% CI: 0.609–0.767, P < 0.001), and HDS ≥ 8 was predictive (OR = 1.72, 95% CI: 1.04–2.77) of persistent pain measured with MCID-VAS (AUC = 0.628, 95% CI: 0.598–0.737, P = 0.008), highlighting the diagnostic potential of HDS in assessing postoperative recovery. This study underscores the potential of HP evaluation using HDS to provide valuable insights into disease progression and outcomes in LDH patients, complementing conventional radiologic methods. The findings support the application of personalized treatment strategies based on HP findings while acknowledging challenges in interpretation and clinical implementation
Exploring the therapeutic potential of diterpenes in gastric cancer: Mechanisms, efficacy, and clinical prospects
Get PDFGastric cancer (GC) remains a significant global health challenge, particularly prevalent in East Asia. Despite advancements in various treatment modalities, the prognosis for patients, especially those in advanced stages, remains poor, highlighting the need for innovative therapeutic approaches. This review explores the promising potential of diterpenes, naturally occurring compounds with robust anticancer properties, derived from diverse sources such as plants, marine organisms, and fungi. Diterpenes have shown the ability to influence reactive oxygen species (ROS) generation, ferroptosis, and autophagy, positioning them as attractive candidates for novel cancer therapies. This review explores the mechanisms of action of diterpenes and their clinical implications for the treatment of GC. Additionally, it addresses the challenges in translating these compounds from preclinical studies to clinical applications, emphasizing the need for further research to enhance their therapeutic profiles and minimize potential side effects. The discussion underscores the importance of diterpenes in future anticancer strategies, particularly in the fight against gastric cancer
Periplocin improves the sensitivity of oxaliplatin-resistant hepatocellular carcinoma cells by inhibiting M2 macrophage polarization
Get PDFThe aim of this research was to investigate the impact of periplocin (PPLN) on oxaliplatin (OXA) resistance in hepatocellular carcinoma (HCC) cells and offer insights for improving clinical treatment of HCC. The IC50 value of HCC cell lines against OXA was detected by the CCK-8 assay, and an OXA-resistant HepG2 cell line (HepG2/OXA) was constructed. THP-1 cells were induced into M1 or M2 macrophages, and M2 macrophage-conditioned medium (M2-CM) was prepared. M1 and M2 macrophage polarization were detected using RT-qPCR and flow cytometry. CCK-8, EdU staining, clone formation assay, flow cytometry, and western blotting were used to assess the proliferation and apoptosis of HepG2/OXA cells treated with PPLN and M2-CM. Additionally, a nude mouse subcutaneous graft tumor model was constructed. PPLN enhanced the sensitivity of HepG2/OXA cells to OXA, reduced their clone-forming ability, and promoted their apoptosis. Notably, PPLN hindered M0 macrophage polarization to M2 macrophages, while M1 polarization remained unaffected. The proliferation-inhibiting and apoptosis-promoting effects of OXA+PPLN on HepG2/OXA cells were significantly attenuated by the addition of M2-CM, suggesting that PPLN improves the OXA sensitivity of HepG2/OXA cells by hindering M2 macrophage polarization. Furthermore, PPLN inhibited M2 macrophage polarization and improved the OXA sensitivity of HepG2/OXA cells in vivo. In conclusion, PPLN inhibited the proliferation of HepG2/OXA cells, promoted their apoptosis, and inhibited M2 macrophage polarization both in vivo and in vitro, which in turn enhanced the OXA sensitivity of HepG2/OXA cells
Co-expression of miRNA players in advanced laryngeal carcinoma – Insights into the roles of miR-93-5p, miR-145-5p, and miR-210-3p
Get PDFAdvanced laryngeal squamous cell carcinoma (LSCC) is the second most prevalent type of head and neck squamous cell carcinoma (HNSCC). Identifying microRNAs (miRNAs) related to key regulatory molecules or mechanisms could offer an alternative approach to developing new treatment strategies. The aim of our study is to evaluate significant correlations among deregulated miRNAs in advanced laryngeal carcinoma and to analyze, in silico, their strength of association, targets, and the most deregulated pathways. Several miRNAs demonstrated promising co-expression results, specifically miR-93-5p, miR-145-5p, and miR-210-3p. Their expressions were explored and further validated in a large set of in vivo advanced LSCC samples, which were subsequently used for bioinformatics and enrichment analyses. Our results highlight the significant roles of miR-93-5p, miR-145-5p, and miR-210-3p in regulating major pathways linked to the cell cycle via epithelial-to-mesenchymal transition (EMT), PI3K/Akt signaling, hypoxia, metabolism, apoptosis, angiogenesis, and metastasis. The associations between the expressions of these miRNAs and patients\u27 clinical features could be central to the progression of advanced LSCC. Overall, our study provides important insights into the co-expression and regulatory networks of miR-93-5p, miR-145-5p, and miR-210-3p in advanced laryngeal carcinoma, underscoring their potential as therapeutic targets or biomarkers for this aggressive cancer. Further research is needed to elucidate the specific mechanisms through which these miRNAs contribute to the pathogenesis and progression of laryngeal carcinoma
Clinical significance of HIF-1α, ET-1, and NO as biomarkers in chronic obstructive pulmonary disease patients with pulmonary hypertension
Get PDFPulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), with repeated infections and airflow limitation leading to endothelial dysfunction. The objective of this study was to retrospectively investigate the clinical significance of serum hypoxia-inducible factor 1-alpha (HIF-1α), plasma endothelin-1 (ET-1), and nitric oxide (NO) as non-invasive blood biomarkers for diagnosing patients with acute exacerbation of COPD (AECOPD). A total of 230 AECOPD patients were assessed for serum HIF-1α, plasma ET-1, and NO levels using Doppler echocardiography and blood tests. Clinical characteristics, including age, COPD duration, and comorbidities, were compared between patients with and without PH. The diagnostic value was determined through receiver operating characteristic analysis. Pearson correlation and multivariate logistic analyses explored the correlation of biomarkers in AECOPD with PH. Serum HIF-1α, plasma ET-1, and NO levels showed significant differences between COPD patients with and without PH. The combination model (0.027 * HIF-1α + 0.028 * ET-1 − 0.049 * NO) demonstrated an area under the curve of 0.89, indicating superior diagnostic value compared to individual biomarkers. Multivariate logistic analysis identified smoking, higher Global Initiative for Chronic Obstructive Lung Disease grade, hypertension, and elevated levels of HIF-1α, ET-1, and NO as independent risk factors for AECOPD. Positive correlations were observed between serum HIF-1α and plasma ET-1 levels with pulmonary artery systolic pressure, while NO demonstrated a negative correlation. Serum HIF-1α, plasma ET-1, and NO were associated with AECOPD and PH, and detecting individual or combined levels of these biomarkers in the blood can predict COPD-related PH
Serum cytokine profiles in children with IgA vasculitis with nephritis
Get PDFThis study aimed to discover novel serum biomarkers for IgA vasculitis with nephritis (IgAVN). The serum of IgA vasculitis (IgAV) patients without nephritis and IgAVN patients not treated with glucocorticoids was analyzed for 440 proteins using a novel quantitative planar protein microarray. To verify the biomarkers, semiquantitative immunofluorescence analysis was performed on selected differential cytokines in a separate cohort of kidney tissue samples. A total of 41 proteins were differentially expressed between the IgAVN and IgAV groups out of the 440 proteins analyzed. Five differentially abundant proteins, including VEGF R3, ADAM12, TIM-3, IL-12p40, and CEACAM-5, were further validated by semiquantitative immunofluorescence analysis in kidney tissue from independent cohorts. ADAM12, TIM-3, IL-12p40, and CEACAM-5 were expressed in kidney tissue. A linear relationship was observed between the pathological grade of IgAVN and the expression levels of ADAM12 and CEACAM-5. Furthermore, while the prognosis of children with IgAVN may have a linear relationship with CEACAM-5, the results did not indicate a significant statistical difference, which may be related to the sample size. The expression of ADAM12 and CEACAM-5 were positively correlated with the pathological grade. More importantly, we found that CEACAM-5 may be related to the prognosis of IgAVN, which could serve as a significant biomarker for assessing disease severity and monitoring disease progression
Association between lactate dehydrogenase and 28-day all-cause mortality in patients with non-traumatic intracerebral hemorrhage: A retrospective analysisof the MIMIC-IV database
Get PDFLactate dehydrogenase (LDH), a nonspecific inflammatory biomarker, has been used in the assessment of acute myocardial infarction, acute hepatitis, acute lung injury, and other severe diseases. However, no studies have evaluated the prognostic value of LDH in patients with non-traumatic intracerebral hemorrhage (ICH). This cohort study aims to assess the association between LDH levels and 28-day all-cause mortality in patients with non-traumatic ICH. Data for this retrospective cohort analysis were obtained from the MIMIC-IV (v2.2) database, and the study included patients with non-traumatic ICH as defined by the International Classification of Diseases, 9th and 10th editions. Patients were categorized into four distinct groups based on their LDH levels. The primary outcome of interest was the 28-day mortality rate. To analyze these associations and assess the consistency of interactions, subgroup analyses, Cox regression analysis, Kaplan–Meier (K–M) curves, and nonlinear analysis were conducted. A total of 406 patients with non-traumatic ICH were enrolled in the study and were divided into quartiles based on LDH levels. The K–M curve indicated that the 28-day all-cause mortality rate of patients in the Q4 group (LDH > 287.25) was significantly higher than in the Q1 (LDH < 194.7) (P < 0.001) and Q2 (194.7 < LDH < 233.0) (P < 0.001) groups, though not significantly different from Q3 (P = 0.140). Multivariate Cox proportional hazards analysis revealed that patients in the highest LDH quartile had a significantly increased risk of mortality compared to those in the lowest quartile across three models: unadjusted [HR, 3.401; 95% CI, 1.719–6.731; P < 0.001], partially adjusted [HR, 2.422; 95% CI, 1.211–4.846; P = 0.012], and fully adjusted [HR, 3.054; 95% CI, 1.522–6.126; P = 0.002]. Restricted cubic spline (RCS) models revealed an L-shaped association between LDH levels and the 28-day all-cause mortality rate, indicating a nonlinear relationship (P < 0.001). No significant interactions were observed between LDH levels and other factors in the subgroup analyses (all P for interaction > 0.05). Our findings indicate a significant association between 28-day all-cause mortality and LDH levels in patients with non-traumatic ICH. Specifically, patients with elevated LDH levels within the first 24 h of ICU admission are at a higher risk of mortality
Inhibitors of the Wnt pathway in osteoporosis: A review of mechanisms of action and potential as therapeutic targets
Get PDFThe Wnt signaling pathway is one of the most important and critical signaling pathways for maintaining cellular functions, such as cell proliferation and differentiation. Increasing evidence substantiates that the Wnt signaling pathway also plays a significant role in the regulation of bone formation in osteoporosis. Accordingly, inhibitors of this pathway, such as sclerostin, Dickkopf-1 (DKK1), WNT inhibitory factor 1 (WIF1), and secreted frizzled-related proteins (SFRPs), have a negative regulatory role in bone formation and may serve as effective therapeutic targets for osteoporosis. This review examines the mechanisms of action of Wnt signaling pathway inhibitors in osteoporosis, the relationship between the Wnt pathway and its inhibitors, and new molecular targets for osteoporosis treatment. Overall, the regulatory mechanisms of Wnt pathway inhibitors are summarized to provide scientific and theoretical guidance for the treatment and prevention of osteoporosis