Advances in Clinical and Experimental Medicine最新文献

Background: High levels of PM2.5 air pollution pose serious health risks, especially in rapidly urbanizing areas. While its effects on organs such as the heart and lungs are well documented, its effects on the cornea remain less well understood. Emerging evidence links PM2.5 exposure to corneal damage through processes such as autophagy, inflammation, and oxidative stress; however, the precise molecular pathways remain largely unknown.

Objectives: This study aimed to identify key genes and signaling pathways in PM2.5-exposed human corneal epithelial cells (HCECs) using RNA sequencing and bioinformatics analysis.

Material and methods: Human corneal epithelial cells were cultured and exposed to 25 μg/mL PM2.5 for 24 h. High-throughput sequencing was performed after total RNA extraction and library construction for mRNA and microRNA (miRNA). Clean reads were mapped to the reference genome after filtering out low-quality reads. The Differential Expression Sequencing 2 (DESeq2) R package was used to identify differentially expressed (DE) mRNAs and miRNAs with a fold change ≥2 or ≤0.5 and a false discovery rate (FDR) ≤ 0.001.. Bioinformatics analyses included hierarchical clustering, protein-protein interaction network construction, target gene prediction, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment.

Results: The analysis identified 45 DE mRNAs, including 14 upregulated and 31 downregulated transcripts, along with 16 upregulated miRNAs. A gene interaction network was constructed comprising nine mRNAs (6 upregulated and 3 downregulated), while a combined miRNA-mRNA network included 14 miRNAs and 21 mRNAs, forming 73 interaction pairs. Functional enrichment analysis of these genes revealed 30 significantly enriched GO terms, as well as 27 KEGG signaling pathways.

Conclusions: This study constructed regulatory networks and identified genes DE in the corneal response to PM2.5 exposure, particularly those involved in autophagy, inflammatory responses, and oxidative stress-related pathways. These results lay the groundwork for further research into the effects of PM2.5 on ocular surface health and provide insights into the molecular mechanisms underlying PM2.5-induced damage to human corneal epithelial cells, potentially guiding the development of targeted diagnostics or therapies to mitigate ocular surface injury caused by PM2.5.

Background: Many hospitals worldwide implement nurse-led sedation protocols to prevent both underand over-sedation and to enhance comfort and safety for mechanically ventilated patients in intensive care units (ICUs); however, definitive conclusions regarding their effectiveness remain limited.

Objectives: To assess the efficacy of nurse-led sedation protocols on clinical outcomes in mechanically ventilated adults within ICUs.

Material and methods: A systematic search was conducted across 4 electronic databases - PubMed, Embase, Scopus, and the Cochrane Library - to identify relevant studies published in peer-reviewed journals. The standard mean difference (SMD) and risk ratio (RR), along with their corresponding 95% confidence intervals (95% CIs), were calculated. Heterogeneity among studies was assessed using the Cochran's Q test and I2 statistic, with significance determined by the appropriate p-value. All statistical analyses were performed using Review Manager (RevMan) v. 5.4.

Results: This meta-analysis of 10 randomized controlled trials (RCTs; n = 1,151 patients) indicates that a nurse-led sedation protocol is significantly more effective than usual care in reducing ICU mortality (RR = 0.34 (95% CI: 0.25 to 0.45); I2 = 38%, p < 0.001), duration of mechanical ventilation (SMD = -1.94 (95% CI: -2.16 to -1.72); I2 = 73%, p < 0.001), length of hospital stay (SMD = -1.70 (95% CI: -1.80 to -1.59); I2 = 79%, p < 0.001), length of ICU stay (SMD = -1.58 (95% CI: -1.76 to -1.40); I2 = 66%, p < 0.001), and incidence of delirium (RR = 0.47 (95% CI: 0.39 to 0.57); I2 = 15%, p < 0.87).

Conclusion: Compared to usual care, nurse-led sedation protocol can improve ICU mortality and other clinical outcomes in mechanically ventilated ICU patients safely and effectively.

Background: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, out-of-field locoregional relapse remains common. The optimal longitudinal expansion from gross tumor volume (GTV) to clinical target volume (CTV) varies across practice, and its impact on local control is not fully defined.

Objectives: To explore the relationship between GTV-CTV margin expansion and inflammatory biomarkers and their combined impact on prognosis to determine a more optimal target volume range for esophageal cancer (EC).

Material and methods: A retrospective analysis of 209 ESCC patients undergoing radical CRT was conducted. Patients were categorized into small (SM), medium (MM) and large (LM) margin groups based on GTV-CTV expansion. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and their respective fold changes were calculated and analyzed for correlations with CTV margin expansion and patient prognosis.

Results: Larger radiation fields led to higher post-treatment inflammatory markers with significant fold changes. Kaplan-Meier (KM) curves and receiver operating characteristic (ROC) curves indicated that the LM group, low pre-treatment NLR, low post-treatment NLR, PLR and SII, and fold changes in NLR, PLR and SII before and after treatment could predict local recurrence-free survival (LRFS). However, Cox analysis identified pre-treatment NLR, the change in SII from preto post-treatment, and GTV-CTV margin expansion as independent predictors.

Conclusions: Although inflammatory biomarkers offer prognostic value, primary GTV-CTV margin expansion has a stronger influence on LRFS in ESCC patients undergoing CRT. Further multi-institutional studies are needed to validate these findings and address current study limitations, including single-center design, small sample size and exclusion of in-field recurrences.

Genetic mutations and their phenotypic manifestation have been recognized as critical factors in tumorigenesis. However, the relationship between these mutations and the pathogenesis of uterine leiomyomas (UL) remains inadequately characterized. There is compelling evidence to suggest a genetic underpinning in UL development, alongside influences from epigenetics, environmental stimuli, growth hormones, and growth factors. A plethora of studies have tried to elucidate the genetic and epigenetic etiologies associated with UL, but the definitive implications of these findings remain unclear. An extensive systematic review was conducted to investigate the genetic etiologies of UL. This systematic review aimed to consolidate current knowledge on genetic and epigenetic causes of UL, offering a comprehensive perspective on the evidence and its relevance in other solid tumors. A secondary focus was to identify the most significant genetic association with the genesis of UL. A total of 60 articles were identified, and 10 chromosomes and 51 genes were found to be implicated in the development of UL. The main trend in fibroid research focuses on genetic abnormalities and aberrations as the etiology of UL development. It has been estimated that 40% of UL can be associated with chromosome-specific aberrations. Chromosomal gain, loss, rearrangement, single nucleotide polymorphism (SNP), and translocation are the most common aberrations associated with UL development. The most recurrent ones include chromosome X and 7q deletions, and rearrangements of 12q15, 6p21 and 10q22. MED12 has been identified as a gene of particular importance in the development of UL.

Background: Regulatory T (Treg) cells and plasmacytoid dendritic cells (pDCs) are involved in the pathogenesis of drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).

Objectives: To compare circulating Treg cells and pDCs at different stages among patients with DRESS/DIHS, patients with maculopapular drug eruption (MPE), and healthy subjects, and to assess circulating Treg cells and pDCs at post-steroid cessation in DRESS/DIHS.

Material and methods: This was a cross-sectional study that enrolled adult patients diagnosed with DRESS/DIHS and MPE. Blood samples were obtained from the patients at the initial presentation (acute phase), 1 week later (subacute phase), during the 3rd week (resolution phase), and post-steroid cessation for DRESS/DIHS. Healthy subjects' blood samples were also taken. Peripheral blood mononuclear cells were isolated for flow cytometry analysis.

Results: A total of 22 patients participated in this study: patients with DRESS/DIHS (n = 9), patients with MPE (n = 8), and healthy subjects (n = 5). During the acute stage of DRESS/DIHS and MPE, the mean percentage of Treg cells and pDCs significantly decreased compared to healthy subjects. However, Treg cells showed a progressive increase towards the resolution phase in both conditions, while pDCs continued to decrease towards the resolution phase. Following steroid discontinuation in DRESS/DIHS, both Treg cells and pDCs showed a progressive increase in number.

Conclusions: Treg cells and pDCs play a role in DRESS/DIHS and MPE pathogenesis, evidenced by the fluctuation in their percentages at each stage of both conditions. However, increased circulating Treg cells may crucially mitigate inflammation in both conditions.

Uncovering objective biomarkers of mild traumatic brain injury (mTBI) may lead to earlier and more accurate identification of this injury, improved prognostic assessment and earlier targeted treatments. Emerging evidence highlights the potential of salivary biomarkers, particularly proteins, as a noninvasive, inexpensive and objective method for diagnosing mTBI, due to their presence in saliva following blood-brain barrier disruption; however, consensus on their utility remains limited. Our aim was to explore the diagnostic potential of salivary protein biomarkers in the identification of mTBI. A comprehensive search was conducted from April to September 2024 across the PubMed, Embase and Google Scholar databases. Original observational studies examining the diagnostic utility of salivary protein biomarkers for mTBI in human populations were included. Seven (1.7%) studies out of 411 identified reports met the inclusion criteria. A total of 49 salivary proteins demonstrated significant differential expression. Subgroup analysis based on the mechanism of injury (sports-related and non-sports-related) identified 4 overlapping proteins: ALOX5, ITGB2, ADRB2, and HRH1. ALOX5 and ITGB2 were significantly upregulated in both subgroups, while ADRB2 and HRH1 were downregulated in sports-related cases and upregulated in non-sports-related cases, which may reflect differential expression related to the region of impact and progression of injury pathophysiology. These findings suggest that salivary proteins such as ALOX5, ITGB2, ADRB2, and HRH1 may serve as promising noninvasive biomarkers for the diagnosis of mTBI. Their involvement in key processes in mTBI pathology supports further investigation in larger, rigorously designed clinical studies to validate their diagnostic utility.

Background: Procedural sedation reduces pain, anxiety, and discomfort during emergency department (ED) procedures. Analgesics, sedatives and anxiolytics ensure patient comfort but can cause respiratory, cardiovascular, neurological, and gastrointestinal (GI) side effects.

Objectives: To synthesize data on adverse events and procedural efficacy from randomized controlled trials (RCTs) involving the use of different drugs/drug combinations used for procedural sedation.

Material and methods: A systematic literature review was conducted using MEDLINE and CENTRAL databases for RCTs that involved adult patients who were administered drugs for procedural sedation in the ED. Outcomes such as hypoxia, hypotension, apnea, agitation, GI disturbances (nausea, vomiting), and bradycardia/dysrhythmia were extracted from the trials. A meta-analysis was performed using OpenMeta (Analyst) software to determine the pooled incidence of each adverse outcome and procedural success for the different drugs and drug combinations.

Results: A total of 50 RCTs were included in the meta-analysis with information from 5,398 patients. Meta-analysis of the data showed a pooled incidence of 136 events/1,000 sedations (95% confidence interval (95% CI): 112-160) for hypoxia, 23 events/1,000 sedations (95% CI: 15-31) for hypotension, 143 events/1,000 sedations (95% CI: 110-177) for agitation, 51 events/1,000 sedations (95% CI: 38-64) for apnea, 45 events/1,000 sedations (95% CI: 30-60) for GI disturbances, and 30 events/1,000 sedations (95% CI: 19-41) for bradycardia/dysrhythmia. The procedural success rate was 921 events/1,000 sedations (95% CI: 896-946).

Conclusion: The results of this meta-analysis shed light on the adverse effects of various procedural sedation agents used for different procedures in the ED. Ketamine-propofol combinations were associated with less hemodynamic instability, whereas propofol caused hypotension and respiratory events and GI disturbances were associated with the administration of fentanyl and ketamine. Thus, individual patient factors such as age and comorbidities and the risk profile of different agents should be considered during procedural sedation protocols. This meta-analysis summarizes the side effects of several drugs to help physicians administer them safely.

Background: Inguinal hernia repair ranks among the most prevalent surgical interventions worldwide. Effective postoperative pain management is paramount for enhancing patient comfort, facilitating early mobilization and optimizing recovery outcomes.

Objectives: This study aimed to rigorously evaluate the efficacy of a modified ultrasound-guided (USG) lower abdominal nerve block in conjunction with local anesthetic (LA) injection during inguinal hernia surgery in elderly patients.

Material and methods: This prospective cohort study included 50 elderly male patients (mean age 71.84 ±5.56 years) who underwent ultrasound-guided transinguinal hernia surgery from May 2022 to June 2023. Patients were divided into the intervention group (n = 28) and the control group (n = 22). Pain scores were assessed using the visual analogue scale (VAS) multiple times as initial, during and within the first 24 h post-surgery. Secondary outcomes, encompassing vital signs, analgesic consumption and overall patient satisfaction, were also monitored.

Results: The mean age of the cohort was 71.84 ±5.56 years, with a mean body mass index (BMI) of 24.96 ±1.59 kg/m2. A substantial proportion of patients (82%) presented with comorbidities, including hypertension and cerebral infarction. The post-surgery VAS score was significantly decreased in both groups in comparison to the pre-group (in the control group: pre vs post Z = -3.494 p = 0.005, in the intervention group: pre vs post Z = -4.373 p ≤ 0.001). The primary VAS scores were at the highest level at admission time in both groups; however, duringand post-VAS scores were significantly lower in the intervention group than in the control group at time points during and after surgery (p < 0.001, U = 610; and p < 0.001, U = 471, respectively).

Conclusions: The implementation of a modified ultrasound-guided lower abdominal nerve block markedly enhances postoperative analgesia, reduces opioid requirements and improves patient satisfaction in elderly patients undergoing transinguinal hernia repair. These findings underscore the importance of effective pain management strategies in this vulnerable population.

Background: Osteoarthritis (OA), particularly knee and hip osteoarthritis (KOA and HOA), is a leading cause of disability. Although diabetes-related factors and lipid abnormalities have been implicated in OA development, the causal nature of these associations remains unclear.

Objectives: This study investigates the relationships between diabetes-related factors (type 2 diabetes (T2D), fasting insulin and glycated hemoglobin (HbA1c)), blood lipid risk factors (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides), and OA using Mendelian randomization (MR) analysis.

Material and methods: A bidirectional MR design was applied, using genetic data from publicly available genome-wide association studies (GWAS) that included 403,124 KOA cases and 393,873 HOA cases, along with datasets on diabetes-related and blood lipid risk factors. Genetic variants were used as instrumental variables, and causal relationships were assessed using the TwoSampleMR (v. 0.5.7) package in R. The primary analytical methods included inverse-variance weighted (IVW) analysis, weighted median (WM) analysis, and MR-Egger regression.

Results: The forward MR analysis did not identify a causal relationship between diabetes-related factors or blood lipid markers and OA. However, this does not exclude the possibility of indirect pathways or small effects that may not have been detected. In the reverse MR analysis, fasting insulin demonstrated a potential causal relationship with HOA (odds ratio (OR) = 2.568, 95% confidence interval (95% CI): 1.192-5.536, p = 0.016). Additionally, HbA1c (OR = 1.675, 95% CI: 1.254-2.238, p < 0.01), T2D (OR = 1.082, 95% CI: 1.008-1.162, p = 0.03), and LDL-C (OR = 0.799, 95% CI: 0.688-0.928, p < 0.01) were associated with KOA. Glycated hemoglobin and T2D appeared to be potential risk factors for KOA, whereas LDL-C showed a protective association.

Conclusions: This study provides evidence supporting causal associations between diabetes-related factors, blood lipid levels, and the risk of KOA and HOA. These findings suggest that effective blood glucose control and lipid management may help prevent or slow the progression of OA.

Background: In the contemporary era, acquiring online information has become a prevalent practice. As with any affliction, individuals are inclined to investigate the potential therapeutic avenues for erectile dysfunction (ED) on the internet.

Objectives: To evaluate the quality, comprehensibility and informative content of YouTube videos on penile prosthesis implantation, with a focus on videos produced by healthcare professionals, and to address the videos according to the class of physician producing the video.

Material and methods: A search for "penile prosthesis" was conducted on YouTube using a censored network to ensure privacy and prevent bias. The first 100 relevant videos uploaded in the last decade were analyzed. They were categorized by source (academicians, government or private hospital physicians, and non-physicians) and assessed for quality using the modified Quality Criteria for Consumer Health Information (DISCERN) scale, Global Quality Scale (GQS) and a newly developed Total Informative Score based on the European Association of Urology Patient Information Forms. The Kruskal-Wallis H test, Kendall's tau correlation test and Spearman's test were used for statistical analysis.

Results: Of the videos analyzed, 87% provided informative content, with the majority (51%) uploaded by academic sources. The median duration time was 185 s (111-397). The average modified DISCERN score was low (median: 2, Q1-Q3: 2-3), indicating generally inadequate quality, with 54% rated as poor. No statistical significance occurred between GQS scores for the videos published by the upload source. Videos by government hospital physicians scored the highest in quality measures, while non-physician videos garnered more views and likes. The Patient Education Materials Assessment Tool (PEMAT) understandability and actionability scores showed that videos from healthcare professionals had higher understandability (70%) than those from other sources.

Conclusions: The overall quality of YouTube videos on penile prostheses is low, despite most being informative. Videos created by physicians are more reliable and easier to understand. Implementing stricter guidelines for content creators and promoting public awareness initiatives are recommended to improve patient access to high-quality information.