Bosnian Journal of Basic Medical Sciences (BJBMS)
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Chronic otitis media with effusion in children with adenoidal hypertrophy: Development of a diagnostic prediction model
Chronic otitis media with effusion (COME) is a prevalent condition that poses significant risks to the growth and development of children with adenoidal hypertrophy (AH). This study investigates the risk factors associated with COME in children diagnosed with AH and establishes a clinical prediction nomogram to enhance diagnostic accuracy. The study included 311 children with AH, diagnosed through lateral nasopharyngeal radiographs, from the Department of Otorhinolaryngology Head and Neck Surgery at the First Affiliated Hospital of Anhui Medical University. Risk factors were identified using the least absolute shrinkage and selection operator (LASSO), while Firth\u27s penalized logistic regression analysis was employed to further refine the variables and develop a predictive model. The model\u27s performance was assessed using the C-index, calibration curve, and decision curve analysis, with internal validation conducted through bootstrapping. The resulting predictive nomogram included four key risk factors: young age, vitamin D3 deficiency, degree of AH, and tympanometry results. The model exhibited strong predictive capabilities, achieving a C-index of 0.945 (95% confidence interval: 0.941, 0.949). Bootstrapping validation confirmed a high C-index of 0.934. The calibration curve demonstrated good alignment, while the decision curve indicated a net benefit across thresholds of 10%–90%. This nomogram—incorporating tympanometry, AH degree, serum vitamin D3 levels, and age—serves as a valuable tool for clinicians and families in assessing the risk of COME in children with AH
Circulating microRNAs in prostate cancer — Non-invasive biomarkers for diagnosis, prognosis and therapy: A review
Prostate cancer (PC) is a common malignancy driven by interacting genetic, environmental, and lifestyle factors, including hereditary mutations (BRCA1/2, HPC1, AR variants), premalignant lesions [proliferative inflammatory atrophy (PIA), prostatic intraepithelial neoplasia (PIN)], and Western dietary patterns. This narrative review aims to synthesize evidence on the role of microRNAs (miRNAs) in PC pathogenesis and clinical management across diagnosis, prognosis, therapy, and recurrence prediction. We searched PubMed/MEDLINE (2004–present) using predefined terms, screened reference lists, excluded outdated records, and prioritized biomarker studies with AUC ≥ 0.85. Current diagnostic pathways—digital rectal examination, prostate-specific antigen (PSA) testing, multiparametric MRI, and Gleason-based International Society of Urological Pathology (ISUP) grading—are complemented by molecular tools (4Kscore, PHI, SelectMDx, TMPRSS2–ERG, PCA3, ConfirmMDx). MiRNAs, key post-transcriptional regulators, contribute to PC via dysregulated biogenesis and modulation of androgen receptor signaling within an inflamed, remodeled tumor microenvironment. Circulating and exosomal miRNAs (notably miR-21, miR-375, and miR-182-5p) exhibit greater specificity and stability than PSA, enabling non-invasive diagnosis, risk stratification, treatment monitoring, and recurrence prediction. Therapeutic approaches—antagomirs, sponges, miRNA masks, and CRISPR editing—show preclinical promise, while chemical modifications [peptide nucleic acids (PNAs), locked nucleic acids (LNAs), C2′ modifications] improve stability and delivery but remain limited by biodistribution, tissue penetration, off-target effects, and immunogenicity. In conclusion, standardized workflows and multicenter validation, integrated with clinical and imaging data, are essential to translate miRNA-based tools into precision PC management
Association between the CRP–TyG index and lupus nephritis risk
Assessment of insulin resistance is increasingly emphasized in patients with systemic lupus erythematosus (SLE) due to its significant role in predicting kidney injury and cardiovascular risk. Given that sustained inflammation is a hallmark of SLE, the novel C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which comprehensively reflects insulin resistance and inflammation, has emerged as a valuable biomarker. This study aimed to investigate the association between the CTI and the risk of lupus nephritis (LN) risk and further explore its predictive potential in SLE patients. A cohort of 195 SLE patients stratified by renal involvement or CTI tertiles were included. Spearman’s correlation analysis was performed to assess the relationship between the CTI and clinical parameters of lupus activity. Logistic regression analysis was utilized to identify the association between the CTI and risk of LN. The receiver operating characteristic (ROC) curve was employed to evaluate the CTI and the TyG index in predicting LN. The results demonstrated significantly elevated CTI levels in the LN group compared to the non-LN group. Multivariate-adjusted regression analysis indicated that a unit increase in CTI corresponded to enhanced risk of LN (adjusted OR =2.062; 95% CI: 1.208 – 3.522), particularly among patients in the third tertile compared to those in the first tertile (adjusted OR = 4.368; 95% CI: 1.411 – 13.520). Subgroup analysis revealed that SLE patients with a SLEDAI-2K score greater than 6 exhibited an increased LN risk associated with higher CTI levels. ROC analysis illustrated the higher sensitivity of CTI (AUC = 0.6592; 95%CI, 0.576 – 0.742) compared to the TyG index (AUC = 0.6327; 95%CI, 0.546 – 0.719) in predicting LN risk. These findings indicate that elevated CTI is strongly associated with an increased risk of LN, suggesting its potential as a valuable predictor of LN risk in SLE patients
Association of PPARγ2 Pro12Ala polymorphism with gestational diabetes mellitus risk: A systematic review and meta-analysis
Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication that poses significant risks to both mothers and their offspring, with genetic susceptibility believed to play a role in its pathogenesis. This study examined the association between the Pro12Ala (Pro [C]→Ala [G]) polymorphism in the peroxisome proliferator-activated receptor γ2 (PPARγ2) gene and the risk of developing GDM. A systematic literature search was conducted across databases including PubMed/Medline, Web of Science, Embase, and the Cochrane Library, identifying clinical studies that evaluated the relationship between the PPARγ2 Pro12Ala variant and GDM. Strict inclusion criteria ensured that all case groups comprised exclusively women diagnosed with GDM. Data on study characteristics, sample sizes, and allele frequencies were extracted, and meta-analyses were performed using RevMan 5.3 and Stata with Hartung-Knapp random-effects models. Fifteen studies were included in the analysis. The Pro12Ala polymorphism showed no significant association with GDM risk across allelic (Ala [G] vs. Pro [C]), dominant (CG+GG vs. CC), and recessive (GG vs. CG+CC) models (allelic: OR=0.90, 95% CI=0.75–1.08, p=0.26; dominant: OR=0.92, 95% CI=0.74–1.13, p=0.42; recessive: OR=0.82, 95% CI=0.54–1.25, p=0.33; all p>0.05). Subgroup analyses by ethnicity indicated a potential protective association of the Ala (G) allele with GDM in East Asian populations, while no significant associations were found in European or Middle Eastern populations; ethnicity was identified as a significant effect modifier (p<0.05). There were no meaningful differences in subgroups categorized by study quality and sample size. Sensitivity analyses confirmed the robustness of the findings, and small-study effects detected by Egger’s test did not substantially alter the pooled estimates. In conclusion, the PPARγ2 Pro12Ala polymorphism was not significantly associated with GDM risk in the general population. The potentially protective trend observed in East Asian women warrants cautious interpretation due to concerns regarding multiple testing, allele-frequency variation, and limited statistical power
Genetic risk of alcohol-related liver cirrhosis: Associations of PNPLA3, TM6SF2, and a two-variant polygenic risk score
A minority of individuals who consume excessive alcohol develop cirrhosis. Variants in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) and the transmembrane 6 superfamily member 2 gene (TM6SF2) have been previously identified as associated with alcohol-related cirrhosis (ALC). This study aimed to examine the variants of PNPLA3 and TM6SF2 and to develop and assess a polygenic risk score (PRS) for ALC. We enrolled 118 patients diagnosed with ALC and 131 control subjects, who were either abstainers or low-level alcohol consumers without evidence of liver disease. Genotyping of risk variants was performed using PCR-RFLP methodology. PRS, based on independent allelic effect size estimates from genotyped genetic loci, were computed and compared across groups. The development of ALC was significantly associated with CG and GG genotypes of PNPLA3 (CG: OR: 1.82; 95% CI: 1.05-3.17; p=0.033; GG: OR: 7.64; 95% CI: 3.06-19.07; p<0.001) and the CT genotype of TM6SF2 (OR: 2.43; 95% CI: 1.27-4.63; p=0.007), controlling for age and sex. Patients with cirrhosis exhibited a significantly higher mean PRS compared to controls (0.32 vs. 0.167, p = 1.8e-07). The odds ratios (ORs) and 95% confidence intervals for the group with the highest PRS score compared to the reference group were 6.707; 95% CI: 3.313-13.581, p<0.001. In our ALC patient cohort, the PNPLA3 rs738409 and TM6SF2 rs58542926 variants were associated with an increased risk of ALC development. Moreover, the PRS derived from these two variants effectively identified the genetic components linked to cirrhosis within the study population
Phenolic-derived compounds in osteoporosis–Mechanisms, clinical evidence, and drug delivery: A review
Osteoporosis is a degenerative skeletal disorder characterized by reduced bone mass and the deterioration of bone microarchitecture, resulting in an increased risk of fractures. Its development is driven by an imbalance in bone remodeling, where osteoclastic bone resorption surpasses osteoblastic bone formation. Factors such as oxidative stress, chronic inflammation, ferroptosis, and hormonal changes, particularly estrogen deficiency in postmenopausal women, contribute to this imbalance. Metabolites derived from phenolic compounds have emerged as promising natural agents for osteoporosis prevention due to their antioxidant, anti-inflammatory, and hormone-modulating properties. Key phenolic groups, including flavonoids (quercetin), isoflavones (genistein and daidzein), and stilbenes (resveratrol), have demonstrated significant osteoprotective effects by regulating receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG) signaling, activating Wnt and β-catenin pathways, and suppressing inflammatory cytokines. Clinical findings indicate that these compounds may enhance bone mineral density and modulate bone turnover markers in populations at risk for osteoporosis. However, their clinical application is limited by low bioavailability and rapid metabolism. Advances in drug delivery systems, including nanoencapsulation, liposomal formulations, and prodrug design, have improved stability, absorption, and targeted delivery to bone, thereby enhancing therapeutic potential while minimizing systemic effects. This review discusses the molecular mechanisms underlying osteoporosis, emphasizing oxidative and hormonal dysregulation, and highlights the therapeutic relevance of phenolic compounds. Additionally, it summarizes recent clinical observations and formulation strategies aimed at enhancing therapeutic efficacy. Overall, phenolic compounds represent promising plant-based strategies for the prevention and management of osteoporosis
Association of laryngopharyngeal reflux with chronic rhinosinusitis prevalence in adults: A systematic review and meta-analysis
Laryngopharyngeal reflux (LPR) has been implicated in the pathogenesis of chronic rhinosinusitis (CRS), but the evidence from individual studies remains inconsistent. This meta-analysis aims to clarify the association between LPR and CRS in adults. We systematically searched PubMed, Embase, Web of Science, CNKI, and Wanfang for observational studies that evaluate the relationship between LPR and CRS in adult populations. Heterogeneity among studies was assessed using the Cochrane Q test and the I² statistic. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using a random-effects model to account for heterogeneity. A total of eight cross- sectional studies involving 3,456 participants were included in the analysis. The results indicated a significant association between LPR and a higher prevalence of CRS in adults (OR = 4.77, 95% CI 2.51 to 9.07; p < 0.001; I² = 63%). Sensitivity analysis restricted to high-quality studies (Newcastle-Ottawa Scale score ≥ 7) produced similar results with no observed heterogeneity (OR = 5.98, 95% CI 3.60 to 9.92; I² = 0%). Exploratory subgroup analyses suggested a stronger association in studies with smaller sample sizes and when both LPR and CRS were diagnosed using objective methods. No significant evidence of publication bias was detected through Egger’s test (p = 0.35); however, this analysis was underpowered and should be interpreted cautiously in the context of the small-study effect. In conclusion, LPR may be associated with an increased prevalence of CRS in adults, especially when both conditions are diagnosed using objective criteria. Further prospective studies are needed to confirm this association and explore the underlying mechanisms
Response to the Letter regarding “Sugammadex vs neostigmine in post-anesthesia recovery: A systematic review and meta-analysis”
This response addresses feedback on our systematic review and meta-analysis comparing sugammadex with neostigmine for neuromuscular block reversal. We acknowledge high heterogeneity for time-based outcomes, likely due to differences in clinical settings and anesthetic/surgical protocols, but pooled effects consistently favored sugammadex for faster and more complete reversal. We agree hypnotic depth and other perioperative factors may modify emergence and airway safety, yet these variables were inconsistently reported and could not be analyzed quantitatively. We also clarify that time outcomes were synthesized using standardized mean differences to account for different reporting units, and any presentation inconsistencies will be corrected. Overall, our findings support pharmacologic superiority of sugammadex with reductions in selected complications, while emphasizing that broader recovery quality may not uniformly improve and should be interpreted in clinical context
NEIL3 and TOP2A as key drivers of esophageal cancer through WNT signaling
Esophageal cancer (EC) is a highly aggressive malignancy with limited treatment options. Nei like DNA glycosylase 3 (NEIL3) and DNA topoisomerase II alpha (TOP2A) have been identified as potential therapeutic targets, though their roles in EC remain unclear. This study investigates the effects of NEIL3 overexpression and TOP2A knockdown, focusing on the WNT signaling pathway. ECA109 esophageal cancer cells were used to assess the impact of NEIL3 overexpression and TOP2A knockdown on proliferation, colony formation, migration, invasion, and apoptosis. The involvement of the WNT signaling pathway was also explored. NEIL3 overexpression significantly enhanced proliferation, colony formation, migration, and invasion while reducing apoptosis. In contrast, TOP2A knockdown suppressed these functions and promoted apoptosis, independent of NEIL3. NEIL3 overexpression could not reverse the effects of TOP2A knockdown. Both NEIL3 and TOP2A acted through the WNT signaling pathway. In vivo, NEIL3 knockdown reduced tumor size and weight via WNT pathway modulation. NEIL3 and TOP2A play key roles in EC progression through the WNT signaling pathway. Targeting these molecules may offer promising therapeutic strategies for EC
Diagnostic accuracy of two-dimensional shear wave elastography and point shear wave elastography in identifying different stages of liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease: A meta-analysis
To assess the diagnostic accuracy of two-dimensional shear wave elastography (2-D SWE) and point shear wave elastography (pSWE) in detecting liver fibrosis stages in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), a comprehensive search was conducted across four databases up to February 9, 2024. A bivariate random-effects model was used to analyze the diagnostic accuracy of the methods. After screening, 13 studies involving pSWE included 1527 patients, while nine studies involving 2-D SWE included 1088 patients. The areas under the summary receiver operating characteristic (SROC) curves for diagnosing significant fibrosis (F ≥ 2), advanced fibrosis (F ≥ 3), and cirrhosis (F = 4) using pSWE and 2-D SWE were as follows: 0.84 (95% CI 0.80–0.87), 0.91 (95% CI 0.88–0.93), and 0.94 (95% CI 0.91–0.95) for pSWE; 0.83 (95% CI 0.79–0.86) 0.85 (95% CI 0.82–0.88), and 0.89 (95% CI 0.86–0.91) for 2-D SWE, respectively. The pooled sensitivity for pSWE and 2-D SWE for stages F ≥ 2, F ≥ 3, and F = 4 were 0.71 (95% CI 0.63–0.78), 0.81 (95% CI 0.72–0.88), and 0.81 (95% CI 0.63–0.91) for pSWE, and 0.77 (95% CI 0.68–0.84), 0.80 (95% CI 0.72–0.87), and 0.92 (95% CI 0.75–0.98) for 2-D SWE, respectively. The pooled specificity of pSWE and 2-D SWE for these stages were 0.83 (95% CI 0.76–0.88), 0.87 (95% Cl: 0.81–0.92), and 0.91 (95% CI 0.86–0.94) for pSWE, and 0.76 (95% CI 0.66–0.84), 0.76 (95% CI 0.69–0.82), and 0.83 (95% CI 0.78–0.85) for 2-D SWE, respectively. In conclusion, both 2-D SWE and pSWE demonstrated high diagnostic performance in identifying various stages of liver fibrosis in MASLD patients