Advances in Clinical and Experimental Medicine最新文献

Background: Plasma ceramides are recognized biomarkers of cardiovascular risk; however, racial and ethnic differences in their levels, as well as their association with cardiovascular health (CVH) among African-American populations, remain insufficiently studied.

Objectives: This study aimed to assess the association between ceramide scores and CVH, as well as atherosclerotic cardiovascular disease (ASCVD) risk, among African-American adults, and to compare ceramide scores between African-American and White adults.

Material and methods: We conducted a secondary analysis of 2 U.S. studies including African-American and White adults. Collected data encompassed demographics, behavioral factors (e.g., diet) and clinical measures (e.g., plasma ceramide levels). Atherosclerotic cardiovascular disease risk was assessed using the American College of Cardiology/American Heart Association (ACC/AHA) 10-year pooled cohort equations, while CVH was evaluated using the American Heart Association (AHA) Life's Essential 8 (LE8) scoring system.

Results: Fifty-eight African-American adults (mean age: 54.6 years; 67.2% women) and 1,103 White adults (mean age: 64.5 years; 52.1% women) were included. Compared with White participants, African-Americans had significantly higher prevalence of obesity, hypertension, diabetes, and hyperlipidemia, but similar ASCVD risk (12.8% vs 12.6%; p = 0.65). No significant associations were observed between ceramide scores and either LE8 or ASCVD risk in African-Americans. Ceramide levels differed by race/ethnicity, with African-Americans showing lower concentrations of 18:0 (0.08 vs 0.10 μmol/L) and 24:1 (0.91 vs 1.17 μmol/L) species compared with White adults (both p < 0.001).

Conclusion: No association was observed between ceramide scores and CVH or ASCVD risk in African-American adults. Despite having a less favorable cardiometabolic profile, African-Americans exhibited lower ceramide levels than White adults. These findings suggest that ceramide scores may not accurately reflect cardiovascular risk in African-American populations.

Background: Initiating orthodontic treatment before the pubertal peak results in more pronounced long-term craniofacial changes in the maxilla and adjacent structures. Dental malocclusion correction through maxillary expansion has been shown to significantly increase the patency and decrease the airflow resistance in several airway compartments, ranging from the nares to the epiglottis plane.

Objectives: We aimed to assess the impact of treatment with a removable functional orthodontic appliance on the dimensions of selected sections of the upper respiratory tract in pediatric patients, with the goal of identifying the nasopharyngeal and oropharyngeal regions most susceptible to lateral maxillary and mandibular expansion.

Material and methods: We retrospectively reviewed the medical records and lateral cephalometric radiographs (LCRs) of all consecutive pediatric patients with deciduous or mixed dentition treated with a functional appliance between 2014 and 2019 at a private orthodontic practice in Racibórz, Poland. To assess the impact of the study group and gender on the dependent variables, a Multivariate Analysis of Covariance (MANCOVA) was performed. The variable T1 (age at treatment initiation) was included as a covariate in the model to control for its potential effect on the outcomes.

Results: The treatment group comprised 55 patients, while 24 subjects served as the control group. In contrast to the nasopharyngeal variables, the average annual increase in the oropharyngeal linear measurements was significantly greater in the treatment group. For the gender factor, after applying the Benjamini-Hochberg correction, no statistically significant differences were observed in any of the assessed variables. In contrast, after correction, the covariate T1 was statistically significant for the following variables: CVM1 and CVM2 (skeletal age before treatment initiation and after treatment completion, respectively), and T2 (chronological age after treatment completion).

Conclusions: Although treatment with a removable functional appliance does not significantly impact the nasopharyngeal airspace, it significantly increases oropharyngeal dimensions, which may help reduce the future risk associated with abnormal breathing patterns in treated patients.

Background: Recurrent miscarriage (RM), the loss of 2 or more consecutive pregnancies before 28 weeks' gestation, has become increasingly common in recent years, imposing significant physical and psychological burdens on affected women. Despite comprehensive evaluation, approx. 40-50% of RM cases remain unexplained and are therefore classified as idiopathic.

Objectives: This study aimed to investigate the expression of SMAD2 and SMAD3 and characterize Th1, Th2 and Th17 cytokine profiles in placental villous tissues from women with idiopathic RM.

Material and methods: Forty-nine women with idiopathic RM in early pregnancy and 41 gestational age-matched women with normal pregnancies (NP) were recruited at Shanxi Maternal and Child Health Hospital (Taiyuan, China) . Following informed consent, placental villous tissues were obtained via ultrasound-guided vacuum aspiration, rinsed in saline and stored at -80°C. Total RNA was extracted from each sample, and SMAD2 and SMAD3 mRNA levels were quantified using real-time quantitative PCR (qPCR) using the 2-ΔΔCq method. Parallelly, tissue homogenates were assayed with enzyme-linked immunosorbent assay (ELISA) for Th1 cytokines (interleukin (IL)-2, intereron gamma (IFN-γ), tumor necrosis factor alpha (TNF-α)), Th2 cytokine (IL-10), and Th17 cytokines (IL-6, IL-17). Spearman's rank correlation was used to evaluate associations between SMAD2/3 expression and cytokine concentrations. All statistical analyses were performed in IBM SPSS v. 27.0, with two-tailed p < 0.05 denoting significance.

Results: The qPCR analysis demonstrated that SMAD2 mRNA levels in villous tissues were significantly higher in the RM group than in NP controls (p < 0.05). Consistent with this, ELISA revealed a marked increase in IL-6 concentration (p < 0.05) alongside significant reductions in IL-2, IL-10, TNF-α, and IFN-γ levels in RM samples vs NP (all p < 0.05). Spearman correlation analysis showed that SMAD2 expression was inversely correlated with IFN-γ (ρ < 0, p < 0.05), while SMAD3 expression was negatively associated with both IL-2 and IFN-γ levels (ρ < 0, p < 0.05).

Conclusions: SMAD2/3 can affect the expression of Th1 and Th17 cytokines, which may in turn affect normal embryonic development.

Cornelia de Lange syndrome (CdLS) is a complex genetic disorder affecting multiple body systems. It is characterized by distinctive facial features, skeletal anomalies, neurological and developmental impairments, physiological cutaneous manifestations such as hirsutism and synophrys, and numerous other signs and symptoms. Among affected individuals, the clinical presentation of CdLS varies widely, ranging from relatively mild to severe forms. Additionally, CdLS increases the frequency of certain dermatoses, including cutaneous bacterial infections and idiopathic thrombocytopenic purpura. Six genes have been identified in association with CdLS: NIPBL (Nipped-B-like protein), RAD21 (double-strand break repair protein rad21 homolog), SMC1A and SMC3 (structural maintenance of chromosomes 1A and 3), BRD4 (bromodomain-containing protein 4), and HDAC8 (histone deacetylase 8). Cornelia de Lange syndrome is estimated to occur in 1 out of every 10,000-30,000 live births, making it a rare condition and posing diagnostic challenges due to its low incidence. The present review aims to raise awareness of CdLS among dermatologists by providing a brief overview of the syndrome and summarizing the current literature on its dermatological manifestations.

Background: Major depressive disorder (MDD) is frequently comorbid with mild cognitive impairment (MCI), yet its molecular basis remains unclear.

Objectives: This study aimed to identify shared differentially expressed genes (DEGs) and biological pathways that may underlie the comorbidity between MDD and MCI. Using integrative bioinformatics approaches applied to transcriptomic datasets, we sought to uncover molecular biomarkers that could inform early diagnosis and provide novel targets for mechanism-based therapeutic strategies.

Material and methods: Transcriptomic datasets from MDD (GSE58430) and MCI (GSE140831) patients were analyzed to identify DEGs. Functional enrichment analyses were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Protein-protein interaction (PPI) networks were constructed to identify core genes.

Results: A total of 301 DEGs were shared between MDD and MCI. Gene Ontology and KEGG enrichment analyses revealed key biological processes involved in neuroinflammation, oxidative stress, synaptic dysfunction, and apoptotic signaling. The PPI network analysis identified nine hub genes with high connectivity: HSP90AB1, CDC42, NFKB1, CD8A, CALM3, PARP1, CD44, H2BC21, and MYH9.

Conclusions: These findings reveal shared molecular biomarkers and pathways linking MDD and MCI, providing insights into their comorbidity. The identified core genes, particularly PARP1 and CDC42, may serve as novel targets for early diagnosis and mechanism-based therapeutic strategies in psychiatry and neurodegenerative disorders.

Background: Hyperlipidemia is a major risk factor for cardiovascular diseases and is associated with complications such as atherosclerosis and tendon injury. Though atorvastatin reduces cholesterol, genetic variants (CYP2D6-4, SULT1A1, CYP2C192) affect its response. These genetic variations influence atorvastatin metabolism, thereby affecting its therapeutic effectiveness.

Objectives: To advance personalized therapeutic drug monitoring and improve lipid profile management, this study aims to develop a robust and LC-MS/MS method for quantifying atorvastatin levels in human plasma. Additionally, to investigate the influence of genetic polymorphisms - particularly CYP2D6-4-on plasma concentrations of atorvastatin in patients with hyperlipidemia.

Material and methods: Ethical approval for the study was obtained from the appropriate institutional review boards, and written informed consent was obtained from all participants. Atorvastatin was measured using LC-MS/MS. PCR-based methods were used for genotyping. Statistical analyses were performed to evaluate relationships between plasma atorvastatin levels and genetic variants.

Results: The LC-MS/MS method demonstrated excellent linearity, accuracy, precision, and stability, for the quantification of atorvastatin in human plasma. Higher atorvastatin concentrations were tied to CYP2D6-4. Furthermore, the study validated the analytical method for consistent and reliable measurement of atorvastatin levels in clinical samples.

Conclusions: This study successfully developed and validated a straightforward and reliable LC-MS/MS method for quantifying atorvastatin levels in human plasma. Significant CYP2D64 - atorvastatin links highlight the value of pharmacogenetic dosing. Integrating pharmacogenetics - especially in the Jordanian population - may enhance the safety, efficacy, and individualization of atorvastatin therapy.

Background: The precise causal relationship between circulating inflammatory factors and sepsis has not yet been fully elucidated.

Objectives: To identify biomarkers that enable earlier and more accurate diagnosis of sepsis.

Material and methods: The causal relationships between 41 circulating inflammatory factors, C-reactive protein (CRP), and procalcitonin (PCT) with sepsis and 28-day sepsis-related mortality were evaluated using two-sample bidirectional Mendelian randomization (MR) analyses.

Results: This study revealed negative causal associations between genetically predicted circulating inflammatory factors-interleukin-6 (IL-6) (odds ratio [OR] = 0.923; 95% confidence interval [CI], 0.854-0.998; p = 0.044), RANTES (OR = 0.926; 95% CI, 0.862-0.994; p = 0.033), and macrophage inflammatory protein-1β (MIP1β) (OR = 0.957; 95% CI, 0.919-0.996; p = 0.032) - and the risk of sepsis. Furthermore, positive causal relationships were observed between CRP and sepsis (OR = 1.140; 95% CI: 1.055-1.232; p = 0.001), as well as between CRP and 28-day sepsis-related mortality (OR = 1.241; 95% CI: 1.034-1.489; p = 0.020). Platelet-derived growth factor-BB (PDGF-BB) levels were also elevated in sepsis (OR = 1.136; 95% CI: 1.003-1.286; p = 0.044). Mediation analysis indicated that CRP mediated the effects of IL-6 and RANTES on sepsis, accounting for 25.87% (OR = 0.980; 95% CI: 0.961-0.998) and 2.04% (OR = 1.002; 95% CI: 0.991-1.012) of the total effect, respectively. The robustness of these associations was confirmed through leave-one-out sensitivity analysis and funnel plots.

Conclusions: This study enhances our understanding of the mechanisms underlying sepsis and its associated mortality, and underscores the therapeutic potential of targeting inflammatory factors in its management.

Background: Acute cholecystitis (AC) is a common biliary disorder, most often caused by gallstones obstructing the cystic duct and leading to gallbladder inflammation.

Objectives: This study aimed to compare the therapeutic efficacy and complication rates of laparoscopic cholecystectomy (LC) performed using the Calot's triangle approach vs traditional LC techniques in the treatment of AC.

Material and methods: A retrospective analysis was conducted on 120 patients diagnosed with AC, with 60 patients undergoing LC using the Calot's triangle approach (study group) and 60 patients treated with traditional LC techniques (control group). Surgical parameters, including operation time, intraoperative hemorrhage, postoperative recovery times, and 30-day postoperative complications were recorded. Intraoperative adhesion formation was evaluated through direct visualization and graded based on severity. Postoperative pain was assessed using the visual analogue scale (VAS).

Results: There was no statistically significant difference in the baseline characteristics between the 2 groups, confirming their comparability. The study group (Calot's triangle approach) demonstrated significantly shorter average operation time, postoperative exhaust time, and diet recovery time compared to the control group. Additionally, patients in the study group had significantly lower intraoperative bleeding, lower VAS pain scores at 24 h and 72 h postoperatively, and a lower overall complication rate compared to the control group (p < 0.05).

Conclusions: The LC Calot's triangle approach demonstrated shorter operation times and lower rates of certain complications compared with traditional LC techniques. However, the absence of statistically significant differences in some key outcomes highlights the need for further research to fully evaluate its clinical advantages and long-term benefits.

Background: Hepatocellular carcinoma (HCC) shows significant differences in incidence and mortality between genders.

Objectives: This study investigates the mechanisms by which estrogen receptors (ER), specifically ERα, influence HCC outcomes.

Material and methods: Bioinformatics approaches were used to study estrogen and its related pathways in relation to HCC. Estrogen receptor expression levels, along with downstream circular RNAs (circRNAs) and microRNAs (miRNAs), were measured in MHCC97H cells via quantitative reverse transcription polymerase chain reaction (RT-qPCR). Western blot was used to assess estrogen receptor 1 (ESR1) and SMAD family member 7 (SMAD7) protein expression. Cell proliferation, migration and cell cycle status of MHCC97H cells were measured using Cell Counting Kit-8 (CCK-8), Transwell assays and flow cytometry for cell cycle analysis.

Results: Bioinformatics analysis revealed that ERα acts as a transcription factor (TF) for 9 circRNAs with differential expression in HCC. We constructed the ERα/circRNA/miRNA/SMADs network based on the downstream targets of circRNAs, which were associated with the SMADs family. Survival studies revealed that ESR1 is correlated with favorable patient survival in liver cancer. In MHCC97H cells, qRT-PCR findings showed low expression of ESR1, hsa_circ_0004913 and SMAD7, but significant expression of hsa-miR-96-5p. Overexpression of ESR1 significantly increased the expression of hsa_circ_0004913 and SMAD7 while suppressing hsa-miR-96-5p. Western blot analysis confirmed these findings. Furthermore, ESR1 overexpression reduced MHCC97H cell proliferation and migration while inhibiting growth through G1 phase arrest. ESR1 acts as a TF that binds to the promoter of hsa_circ_0004913, as demonstrated using chromatin Immunoprecipitation followed by chromatin immunoprecipitation-quantitative real-time PCR (ChIP-qPCR). A dual-luciferase reporter experiment confirmed that hsa_circ_0004913 targets and regulates hsa-miR-96-5p.

Conclusions: ERα can function as aTF, modulating the expression of various circRNAs with differential expression in HCC. Through this regulation, it modulates the circRNA/miRNA/SMADs network, thereby inhibiting the progression of HCC.

Background: Noninvasive ventilation (NIV) is an important treatment modality in the management of chronic obstructive pulmonary disease (COPD) by reducing respiratory distress, improving gas exchange and reducing exacerbations without the need for intubation and invasive airways.

Objectives: To synthesize data from randomized controlled trials (RCTs) and perform a meta-analysis to understand the beneficial effects of NIV across different COPD stages.

Material and methods: A systematic literature review was performed using MEDLINE (PubMed) and Cochrane Register of Controlled Trials (CENTRAL) al databases for RCTs that involved the administration of NIV vs usual treatment (oxygen supplementation, pharmacological agents, nasal cannulation) in patients with stable COPD, acute exacerbations of COPD (AECOPD), and post-exacerbation COPD (PECOPD). Mortality, exacerbation and intubation rates, and arterial blood gases (PaCO2 and PaO2 levels) were assessed in both groups. RevMan software was used to assess the risk of bias and calculate the pooled odds ratio (OR), mean differences (MDs) and subgroup analyses with a random-effects model.

Results: A total of 51 RCTs were included in the meta-analysis with information from 3,775 patients. Meta-analysis of the data showed that there was a significant decrease in mortality outcomes (p < 0.001), intubation frequency (p < 0.001) and PaCO2 levels (p < 0.001) but no significant improvement in exacerbation frequency (p = 0.12) and PaO2 levels (p = 0.69). Subgroup analyses demonstrated no significant difference between COPD stage on mortality outcomes (p = 0.32), PaCO2 level (p = 0.12) and PaO2 level (p = 0.64). There was a significant decrease in intubation rate in AECOPD patients receiving NIV and a statistically nonsignificant difference in exacerbation frequency in stable COPD patients using NIV.

Conclusion: The findings of this meta-analysis indicate a substantial overall enhancement in the frequency of exacerbations and intubations, mortality outcomes, and arterial gas levels among patients in various stages of COPD. Consequently, it is imperative to identify patients with COPD that are most likely to benefit from the use of NIV.