International Journal of General Medicine最新文献

Background and objective: Osteoporosis (OP) is a metabolic disease characterized by reduced bone mass and increased fracture risk. Tryptophan metabolism may play a crucial role in its pathogenesis, although the underlying mechanisms remain unclear. This study aimed to identify key regulatory genes and elucidate molecular mechanisms through integrated transcriptomic analysis.

Methods: OP-related datasets from Gene Expression Omnibus were analyzed using differential expression analysis, weighted gene co-expression network analysis, and tryptophan metabolism gene sets. Machine learning algorithms were applied to screen key genes and construct diagnostic models. Regulatory networks including protein-protein interaction, competing endogenous RNA, and transcriptional regulation were established. Key findings were validated through independent datasets, Mendelian Randomization, single-cell analysis, and RT-qPCR.

Results: Two key genes were identified: DVL1 (significantly downregulated) and RBM39 (significantly upregulated) in OP patients. DVL1 negatively correlated with resting memory CD4+ T cells and eosinophils, while RBM39 positively correlated with memory B cells and M2 macrophages. DVL1 (AUC = 0.75) and RBM39 (AUC = 0.91) demonstrated consistent expression patterns and excellent diagnostic performance. Functional enrichment revealed significant involvement in apoptosis, autophagy, and signaling pathways. Transcription factor YY1 was identified as a key regulator in the molecular network.

Conclusion: This bioinformatic study reveals the potential role of tryptophan metabolism in OP pathogenesis and identifies DVL1 and RBM39 as candidate diagnostic biomarkers and therapeutic targets through computational analysis. These findings are inferential based on transcriptomic data mining and require further validation through experimental approaches. Future studies should include functional characterization in cellular and animal models, prospective clinical cohort validation, and mechanistic investigations to confirm the diagnostic and therapeutic value of these candidates. If validated, these findings could provide a molecular foundation for developing non-invasive diagnostic tools and precision medicine approaches in OP management, potentially improving early detection and personalized treatment strategies for patients at risk of osteoporotic fractures.

Objective: To investigate the association between cognitive impairment and multimodal magnetic resonance imaging (MRI) markers in patients with cerebral microbleeds (CMBs), and to identify imaging predictors of CMB-related cognitive dysfunction.

Methods: This retrospective case-control study included 71 patients with CMBs confirmed by MRI between August 2022 and February 2024 and 65 age-matched healthy controls. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). All participants underwent multimodal MRI, including susceptibility-weighted imaging (SWI) for CMB detection and diffusion tensor imaging (DTI) for quantitative assessment of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in predefined brain regions. Spearman correlation analysis was performed to evaluate associations between CMB burden, DTI parameters, and cognitive scores. Multivariate linear regression analysis was used to identify independent risk factors for cognitive impairment.

Results: Compared with controls, patients with CMBs had significantly lower MoCA scores and higher CMB burden (both P < 0.05). FA values in the frontal-temporal lobe, parietal lobe, and basal ganglia were significantly reduced, while ADC values were increased (all P < 0.05). CMB number was negatively correlated with MoCA scores (r = -0.643, P < 0.001). Decreased FA and increased ADC in the frontal-temporal lobe and basal ganglia were significantly associated with cognitive decline. Regression analysis showed that CMB burden ≥10, reduced FA, elevated ADC, and basal ganglia involvement were independent risk factors for cognitive impairment.

Conclusion: Cognitive impairment in CMB patients is closely associated with lesion burden and microstructural white matter alterations detected by multimodal MRI. These imaging markers may facilitate early risk stratification and targeted monitoring, although longitudinal validation is warranted.

Pelvic inflammatory disease (PID) is an inflammatory process of the upper genital tract that is mainly caused by sexually transmitted infections (STI). It can cause tubal factor infertility, ectopic pregnancy, or chronic pelvic pain. In recent years, its incidence has increased annually owing to various factors, such as sexually transmitted diseases and intrauterine surgery. Although empirical treatment, such as antibiotics or surgery, can alleviate the symptoms of pelvic inflammatory disease, the obstetric outcome is not ideal and the recurrence rate is high, which places a heavy physical and mental burden on women. Traditional Chinese medicine (TCM) is a complementary therapy to Western medicine that has a complete theoretical and practical system and has attracted international attention because of its excellent curative effect. An increasing number of people are accepting and trying to use traditional Chinese medicine to treat gynecological diseases, including infertility, polycystic ovary syndrome, and PID; however, its efficacy and mechanism are still controversial. Therefore, this article summarizes the related research on traditional Chinese medicine and Western medicine in the treatment of PID for clinical reference.

Background: Diabetic retinopathy (DR) is a leading cause of irreversible blindness globally. Analysis of dataset GSE221521 showed significant upregulation of FOXK1 in DR patient blood. Functional studies indicated that silencing FOXK1 promotes endothelial cell apoptosis, migration, and neovascularization under high glucose via the p-AKT/AKT pathway, suggesting FOXK1 plays a key role in DR. This study aims to identify FOXK1-related biomarkers in DR.

Methods: We integrated two DR-related datasets (GSE221521 and GSE189005). Candidate genes were identified through differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Biomarkers were subsequently screened using the Least Absolute Shrinkage and Selection Operator (LASSO) regression and validated based on their expression profiles. Further analyses included immune infiltration assessment, construction of a regulatory network, Gene Set Enrichment Analysis (GSEA), protein-protein interaction analysis via GeneMANIA, and drug prediction. The expression of key biomarkers was experimentally confirmed using reverse transcription quantitative polymerase chain reaction (RT-qPCR) on clinical peripheral blood samples.

Results: From seven initial candidate genes, SPDEF and SLC25A41 were validated as diagnostic biomarkers. A predictive nomogram constructed with these biomarkers showed significant prognostic value. Immune infiltration analysis revealed significantly higher levels of Macrophages M0, monocytes, and activated CD4 memory T cells in DR samples. The constructed TF-miRNA-mRNA network included 10 transcription factors and 2 microRNAs, with FOXC1 and hsa-mir-335-5p co-regulating both SPDEF and SLC25A41. GSEA identified 74 associated pathways, including oxidative phosphorylation. Drug prediction suggested 25 potential targeting compounds, with resveratrol, daunorubicin, and digitoxigenin emerging as promising candidates. Finally, RT-qPCR analysis confirmed the significant downregulation of both SPDEF and SLC25A41 in DR patients, consistent with the bioinformatics findings.

Conclusion: Our findings suggest that SPDEF and SLC25A41 serve as potential biomarkers for DR, which may aid in early detection and provide new insights into the pathogenesis of the disease.

Purpose: Tuberculosis remains a major cause of mortality in people living with HIV (PLWH), yet early diagnosis remains challenging. This study aimed to identify novel biomarker combinations and develop machine learning models, and to predict active TB in PLWH in a random and a chronological subset.

Patients and methods: We enrolled 760 PLWH with pulmonary symptoms. Demographic and clinical data and cytokine profiles were analyzed. Participants were first randomly split into training and validation sets. Subsequently, the whole dataset was re-analysed using the first 609 records as the training set and subsequent 151 records as the test set. Four models were developed with 10-fold cross-validation, incorporating feature selection and hyperparameter optimization. Model performance was assessed through ROC-AUC, sensitivity, specificity, and variable importance analysis.

Results: For the randomly split datasets, with active TB patients showed significantly elevated IFN-γ (median 5.7 vs 3.9 pg/mL, P<0.001) and IL-6 levels (25.3 vs 13.2 pg/mL, P<0.001) compared to without active TB cases. These two biomarkers were strong predictors based on the gradient boosting machine (GBM) model. AUCs (95% CI) on the randomly selected training dataset, was 0.96 (0.95, 0.97). That on the randomly selected test dataset was 0.73 (95% CI: 0.65-0.81). However, on chronological order, GBM model trained from the first 609 records AUC of 0.92 (0.91, 0.94) poorly predicted the 151 final records with the AUC of 0.66 (0.58, 0.75).

Conclusion: TB might have activated the two inflammatory biomarkers among the PLWH. The best predictive machine learning method still have limitation in generalizability to predict the outcome on other data sets.

Purpose: This qualitative study aimed to explore the patient-perceived barriers to early help-seeking, diagnosis, and surgical treatment among rural patients with venous leg ulcers.

Methods: Semi-structured face-to-face interviews were conducted with 16 rural patients with venous leg ulcers who underwent primary varicose vein surgery for the first time. The data were analyzed inductively and in accordance with reflexive thematic analysis. The generated themes were systematically mapped onto the corresponding intervals of the Model of Pathways to Treatment.

Results: We identified 11 barrier themes across the four intervals. During the symptom appraisal interval, barriers were symptom normalization, self-treatment, and avoidant coping with symptoms. When seeking help, patients faced disease misattribution, reliance on familial support and decision-making, and low public awareness of vascular surgery. The diagnosis interval was plagued by misdiagnosis or missed diagnosis and delayed specialist referrals. Finally, pre-surgery barriers included emotional and cognitive resistance to surgery, peer influence bias, and disparities in medical resources distribution.

Conclusion: This study identified diverse barriers across four stages of the treatment pathway for venous leg ulcers among rural patients, which were associated with disease-related, patient-related, and healthcare system-related factors. To address these barriers, a multifaceted healthcare system approach is essential, including enhanced public education, the implementation of age-friendly services, the establishment of evidence-based referral criteria, strengthened primary care competencies, and an expanded vascular surgery workforce to serve underserved areas.

Background: Sarcopenia, characterized by a progressive decline in muscle mass and function associated with aging, impacts around 10% of older adults worldwide and leads to heightened morbidity, increased hospitalization, and escalating healthcare costs. Early detection is crucial for timely intervention. The SARC-F questionnaire is a brief and validated screening tool utilized globally to identify individuals at risk of sarcopenia. Nevertheless, a validated Arabic version is currently unavailable.

Methods: The SARC-F questionnaire was translated into Arabic employing a forward-backward translation method, followed by cultural adaptation, including the conversion of metric units. Content validity was evaluated by two domain experts using a 4-point relevance scale. Face validity was assessed through cognitive interviews conducted in a sample of 15 Arabic-speaking participants (range = 25-40). Internal consistency was measured using Cronbach's alpha in a sample of 120 adults (31.76 years (SD = 10.43, range = 20-68)). Test-retest reliability was analyzed utilizing the Intraclass Correlation Coefficient (ICC) in a sample of 86 participants over an interval of 10 to 14 days. Inter-item associations were examined using Spearman's rank-order correlations.

Results: Following an expert review and gender-inclusive modifications, the content validity index improved from 2.0 to 4.0. Face validity testing demonstrated high clarity and acceptability across all items. The internal consistency analysis yielded a Cronbach's alpha of 0.648, indicating moderate reliability. Furthermore, the test-retest reliability displayed a commendable ICC value of 0.767 (95% CI: 0.663-0.841). The strongest inter-item correlation was found between assistance in walking and stair climbing (ρ = 0.419, p <0.001).

Conclusion: The Arabic version of the SARC-F exhibits acceptable content and face validity, moderate internal consistency, and good test-retest reliability. This tool is poised to enhance the early detection of sarcopenia in Arabic-speaking populations and support clinical decision-making for preventative strategies.

With the widespread use of antiretroviral therapy (ART), the life expectancy of people living with HIV (PLWH) has significantly improved. However, the incidence of cardiovascular disease (CVD) in this population has progressively increased. PLWH exhibit a significantly higher risk of cardiovascular diseases compared to the general population. Consequently, CVD has become one of the leading contributors to mortality not related to AIDS. The pathogenesis may involve several factors: HIV-related proteins exacerbating endothelial injury and inflammation; immune activation and chronic inflammation; adverse effects of ART; and traditional cardiovascular risk factors. Although multiple inflammatory cytokines are implicated in HIV-associated CVD, interleukin-32 (IL-32) stands out due to its distinctive multifunctional properties. Compared with other cytokines, Interleukin-32 (IL-32), a multifunctional pro-inflammatory cytokine, plays key roles in inducing the release of inflammatory cytokines, promoting endothelial dysfunction, and driving monocyte migration. IL-32 is closely associated with the development of HIV-associated CVD and shows potential as a novel biomarker and therapeutic target. This review aims to summarize recent advances in understanding the role of IL-32 in HIV-associated CVD. It also provides new insights for the diagnosis and treatment of CVD in PLWH.

Background: Delayed cord clamping (DCC) has significant impact on health and well-being of preterm and term infants locally and worldwide. Effect of autotransfusion from delayed cord clamping has demonstrated significant beneficial effects in decreasing neonatal morbidity and mortality. However, this implementation has not been routinely established in clinical practice.

Aim: To improve the percentage of eligible infants who receive DCC among preterm newborns at tertiary hospital in Riyadh, Saudi Arabia.

Methods: The study was conducted between June 2023 and June 2024 at tertiary hospital, Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi Arabia. We applied Plan-Do-Study-Act (PDSA) as a structured approach. The study population was defined as preterm infants aged <35 weeks. Interventions that were used included: workforce education, improving standardized procedures, monitoring and evaluation, and resources management. The DCC compliance rate was measured, in addition to employee training attendance and documentation methods.

Results: At the beginning of this study, the rate of DCC procedure was very low, and accounted only for 0% to 3%. After the interventions (Education and training, policy development, process monitoring and audits, and resource allocation) were applied, the rate of DCC increased to 92%, and this prevalence remained above the benchmark (60%), plateauing at above 90%. There were no reported maternal or neonatal adverse events.

Conclusion: This study confirmed that the rate of DCC increased after using the appropriate organized interventions. Applying the same or similar approach in other medical settings may be a valuable contributor in improving neonatal outcomes in addition to improve the standards related to DCC practices.

Purpose: Out-of-hospital cardiac arrest (OHCA) remains a critical emergency with low survival rates despite advanced prehospital interventions. Emerging evidence suggests that early administration of epinephrine is associated with improved outcomes compared to delayed epinephrine administration, particularly in non-shockable rhythms. While intravenous (IV) access is the standard route for drug delivery, it is often difficult to obtain in the prehospital setting. Intraosseous (IO) access offers a viable alternative, but its comparative survival benefit remains unclear. Few studies have examined the association of IO access on outcomes relative to patients who received no prehospital vascular access. This study aims to assess survival outcomes among OHCA patients receiving different prehospital vascular access strategies.

Patients and methods: This retrospective cohort study included adult patients with non-traumatic OHCA in Taoyuan, Taiwan (June 2021-June 2024). Patients were grouped based on the final attempted route: IV, IO, failed IV, or no-access attempt. The primary outcome was survival to discharge; secondary outcomes were prehospital ROSC, survival over 2 hours, and favorable neurological outcome. Multivariable logistic regression was performed, with sensitivity analyses including early treatment (≤15 min), EMT-P-level providers, and epinephrine stratification.

Results: Among 5093 adult OHCA patients, compared with the no-access attempt group, IO access was associated with higher survival to discharge (aOR 1.44; 95% CI 1.08-1.91). IV access also showed increased survival to discharge (aOR 1.25; 95% CI 1.01-1.58). However, in the subgroup analysis of patients treated by EMT-P providers, IV access demonstrated a stronger association with survival to discharge (aOR 3.65; 95% CI 1.16-11.49) compared to IO access (aOR 2.29; 95% CI 1.28-7.24). Failed IV attempts yielded the poorest outcomes. Sensitivity and stratified analyses demonstrated that early vascular access (≤15 min) significantly improved survival for both IO (aOR 2.03; 95% CI 1.45-2.85) and IV (aOR 1.25; 95% CI 1.11-1.49) routes, with treatment timing, provider level, and epinephrine use modifying these associations.

Conclusion: Prehospital vascular access, either IV or IO, was associated with improved survival compared with no access attempt. Failed IV attempts were linked to the poorest outcomes, underscoring the potential harm of procedural delays. Early transition to IO may serve as an effective rescue strategy when IV access is difficult; however, successful IV or humeral IO should be preferred when feasible.