Background: COVID-19, caused by SARS-CoV-2, has had a significant impact on global health. While the virus primarily affects the respiratory system, the intricate interplay between immune cells and the virus remains poorly understood. This study investigates the causal relationship between 731 immune cell phenotypes and COVID-19 using Mendelian randomization analysis.
Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was conducted using genetic variants strongly associated with immune cell phenotypes as instrumental variables. Data for 731 immune cell phenotypes were sourced from the GWAS Catalog, while data for COVID-19 susceptibility were obtained from the OPEN GWAS database. Five MR methods (IVW, MR-Egger, weighted median, simple mode, and weighted mode) were employed to estimate causal effects, with IVW as the primary analysis method.
Results: The study identified 57 immune cell phenotypes causally associated with COVID-19 risk across two independent GWAS datasets. Five immune cell phenotypes were consistently associated with COVID-19 risk across both datasets: CD3-lymphocyte %lymphocyte (protective), CD27 on CD20- (protective), CD20 on IgD+ CD38- unsw mem (increased risk), CD27 on IgD- CD38- (increased risk), and CD19 on B cell (increased risk). Sensitivity analyses confirmed the robustness of the findings.
Conclusion: This study provides compelling evidence for a causal relationship between specific immune cell phenotypes and COVID-19 risk. These findings highlight the potential for targeting these immune cell phenotypes as novel therapeutic targets for COVID-19 treatment and prevention.
Hepatitis B virus (HBV) infection is regarded as a major health concern worldwide. In patients with chronic HBV infection, exhausted virus-specific CD8+ T cells, resulting from the activation of the programmed cell death protein 1 and programmed death ligand 1 axis, play a key role in the chronicity of infection. Functional cure for HBV, defined as the seroclearance of hepatitis B surface antigen (HBsAg), is viewed as the optimal goal of chronic HBV infection treatment because HBsAg loss is associated with a low risk of hepatocellular carcinoma and a relatively favorable prognosis. Both interferon treatment and finite antiviral therapy have been found to be associated with positive HBV outcomes. Overall, combining immune checkpoint inhibitors with nucleos(t)ide analogs appears to be a promising approach for achieving HBsAg loss, particularly in patients with low HBsAg levels.
Background: Pediatric airway diseases are associated with complex challenges because of smaller and more dynamic airway structures in children. These conditions, along with specialized management by medical care staff, should be immediately and precisely recognized to prevent life-threatening obstructions and long-term respiratory complications. Recently, virtual reality (VR) has emerged as an innovative approach to clinical medical education. To evaluate and compare the effectiveness of VR-based education and traditional lectures in enhancing knowledge retention, clinical reasoning, and motivation among senior respiratory therapy students.
Methods: This experimental research was conducted between November 2020 and September 2022, involving 54 students from a School of Respiratory Therapy, with 43 completing a pre-test and undergoing random assignment into either a VR or a traditional education (non-VR) group. Samsung Gear VR Oculus headsets were used by the VR group for instructions on conditions such as laryngeal malacia, subglottic stenosis, and tracheomalacia. Theoretical exams, objective structured clinical examinations (OSCE), and instructional material motivation survey (IMMS) were used to evaluate participants' knowledge retention, clinical reasoning, and application capabilities, followed by statistical analysis comparing both study groups.
Results: No significant differences in pre-test scores were observed between the two groups. However, the VR group outperformed the non-VR group in OSCE scores significantly (p = 0.003) and demonstrated greater learning motivation and satisfaction based on IMMS scores. No notable difference in immediate post-education theoretical examination scores was observed between the groups.
Conclusion: VR-based education markedly improved the clinical reasoning and application skills of respiratory therapy students over traditional lecture methods. VR learning also increased students' motivation and satisfaction, indicating a more immersive and effective educational experience. These findings reveal that VR may be best utilized as a supplemental educational tool in clinical training programs. Future studies with larger samples and longer follow-up are warranted to further explore the optimal integration of VR in education.
Background: Induced pluripotent stem cell (iPSC) technology has emerged as a powerful tool for disease modeling, providing an innovative platform for investigating disease mechanisms. iPSC-derived organoids, including retinal organoids, offer patient-specific models that closely replicate in vivo cellular environments, making them ideal for studying retinal neurodegenerative diseases where retinal ganglion cells (RGCs) are impacted. N6-methyladenosine (m6A), a prevalent internal modification in eukaryotic mRNAs, plays a critical role in RNA metabolic processes such as splicing, stability, translation, and transport. Given the high energy demands of RGCs, mitochondrial dysfunction, which leads to impaired ATP production and increased ROS levels, is often central to the progression of retinal neurodegenerative disorders. However, the epigenetic mechanisms underlying m6A modification and their contributions to these conditions remain unclear.
Methods: Patient-specific iPSCs were generated from individuals with Leber's hereditary optic neuropathy (LHON) and differentiated into retinal ganglion cells (RGCs) within retinal organoids. To analyze m6A methylation, we employed quantitative PCR and focused on differential expression of key m6A-modifying enzymes.
Results: iPSC-derived retinal organoids are adaptable for studying and investigating the epigenetic mechanisms of retinal neurodegenerative diseases. Our data demonstrated the profiling of global m6A-related gene expression levels in LHON patient-derived iPSC-RGCs compared with controls, highlighting specific disruptions in m6A modification pathways.
Conclusion: These findings suggest that differential m6A modifications may play pivotal roles in the pathogenesis of retinal neurodegenerative diseases and affect the progression of the disease in affected individuals.
Background: To investigate the effect of nimotuzumab (N) combined with nab-paclitaxel, cisplatin, and fluorouracil (APF) neoadjuvant chemotherapy on the surgical margin.
Methods: 55 patients were divided into three groups: neoadjuvant chemotherapy and surgery group (G1, 15 cases), chemotherapy and surgery group (G2 group, 20 cases), and surgery group (G3 group, 20 cases). Tissue samples of the tumor core zone (P0), adjacent (P1, 3-5mm from tumor), distal adjacent (P2, 7-10mm from tumor), and surgical margin (P3, 15mm from tumor) were collected. Morphological changes and pathological remission rates were observed. Immunohistochemistry was used to detect the expression of EGFR, elF4E, P53, and VEGF in each specimen by statistical analysis.
Results: In the G1 and G2 groups, various degrees of degeneration and necrosis were observed in the tumor retraction area. Nine cases of MPR (major pathologic response) and 4 cases of pCR (pathologic complete response) in the G1 group; 8 cases of MPR and 3 cases of pCR in the G2 group. The expressions of p53, eIF4E, and EGFR in the samples of the three groups decreased from P0 to P2 with statistical differences (p<0.05). In the molecular tumor shrinkage area, the expression levels of p53, eIF4E, and EGFR in the shrinkage zone were lower than those in the negative margin.
Conclusion: In summary, although there is no significant statistical difference between neoadjuvant chemotherapy with nimotuzumab combined with APF and APF alone in the pathological remission rate of locally advanced oral squamous cell carcinoma, there is a trend indicating that nimotuzumab combined with APF is superior.
Background: Epidural blood patching (EBP) is the primary treatment for spontaneous intracranial hypotension (SIH), although multiple attempts may sometimes be necessary. The SIH-EBP score, with a cutoff of ≥3, predicts the response to the first EBP. However, its generalizability requires further confirmation. This study aims to validate the clinical utility of the SIH-EBP score and determine the optimal cutoff for predicting the response to the first EBP in an independent cohort of SIH patients.
Methods: This retrospective study included patients with SIH who received at least one EBP at a tertiary medical center. Clinical data were extracted from electronic medical records, and brain and spinal magnetic resonance images were reviewed.
Results: Ninety-six patients (58F/38M, mean age 42.67 ± 10.16 years) were screened, with 49 analyzed (32F/17M, mean age 41.20 ± 9.13 years), including 30 responders (22F/8M, mean age 41.10 ± 10.14 years) (61.2%). There was a positive correlation between SIH-EBP scores and responder rates (p=0.001). A cutoff score of ≥3 was associated with a higher response rate than <3 (80.0% vs. 41.7%, p=0.006) (sensitivity=73.7%, specificity=66.7%, accuracy=69.4%). The optimal cutoff in this cohort was ≥2 (AUC=0.77, p<0.0001) (sensitivity=52.6%, specificity=90.0%, accuracy=75.5%).
Conclusion: In this cohort, the SIH-EBP score correlated with response rates to the first EBP. Although a score of ≥3 remains a valid predictor of treatment response, a cutoff of ≥2 proved to be more accurate and specific. However, its practical use is limited by a sensitivity of 52.6%. Further studies are needed to verify its role in other populations.
Background: Abdominal aortic aneurysm (AAA) is a significant global health concern, yet comprehensive population-based studies remain limited. This study aimed to evaluate the hospitalization rates, surgical trends, mortality, and reintervention rates for ruptured (r-AAA) and nonruptured (nr-AAA) AAA using data from a national health insurance database.
Methods: A population-based retrospective cohort study was conducted utilizing data from the Taiwanese National Health Insurance Research Database from 2007 to 2018. The study included individuals aged 20 years and older with a newly diagnosed AAA.
Results: Among 70 457 patients diagnosed with aortic aneurysm or dissection, 22 538 (32%) adult patients (≥20 years) were identified with AAA. The annual incidence of AAA ranged from 7.7 to 10.3 per 100 000 population, with r-AAA decreasing from 1.3 to 0.8 per 100 000 and nr-AAA from 9.0 to 6.8 per 100 000. Most patients with AAA were older adults (85%), with 15 392 (68%) hospitalized and 4885 (32%) undergoing surgery within 14 days of diagnosis. The use of endovascular aneurysm repair (EVAR) significantly increased from 28% to 96% over the study period. Long-term survival was higher in patients who underwent open surgical repair (OSR) compared to those who received EVAR or conservative management, irrespective of whether they had r-AAA or nr-AAA.
Conclusion: AAA predominantly affects older individuals, and the annual incidence shows a declining trend. Since the introduction of EVAR, its use has steadily increased while OSR rates have decreased. Although both EVAR and OSR are associated with reduced mortality in patients with r-AAA, OSR is linked to superior long-term survival outcomes.
Background: This retrospective study investigated whether disturbances in circulating T-lymphocyte subsets could predict the incidence of acute kidney injury (AKI) and in-hospital mortality in patients with sepsis.
Methods: Clinical data from patients with sepsis admitted to the intensive care unit were reviewed. Logistic regression analyses were used to identify independent predictors of in-hospital mortality and the development of AKI.
Results: Of 81 patients with sepsis, 50 developed AKI. Both nonsurvivors and patients with septic AKI exhibited higher Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. Nonsurvivors exhibited more organ damage, with significantly lower levels of peripheral T-lymphocyte subsets, including total circulating lymphocytes, and CD3 + , CD3 + CD4 + , and CD3 + CD8 + T-lymphocytes. Patients with septic AKI exhibited fewer total peripheral lymphocytes and fewer CD3 + , CD3 + CD4 + , and CD3 + CD8 + T-lymphocytes, with higher serum lactate levels and lower nadir platelet counts. Independent predictors of 30-day hospital mortality included maximum SOFA and APACHE II scores, occurrence of encephalopathy, and peripheral CD3 + and CD3 + CD8 + T-lymphocyte counts. Moreover, the maximum SOFA score and CD3 + and CD3 + CD8 + T-lymphocyte counts demonstrated good predictive power for AKI in receiver operating characteristic (ROC) curve analyses, with an area under the ROC curve of 0.810 (95% confidence interval [CI], 0.712-0.908) for SOFA score, 0.849 (95% CI, 0.764-0.934) for CD3 + T-lymphocytes, and 0.856 (95% CI, 0.772-0.941) for CD3 + CD8 + T-lymphocytes.
Conclusion: Patients with sepsis-induced AKI experienced T lymphopenia and increased in-hospital mortality. Higher maximum SOFA scores and reduced peripheral CD3 + and CD3 + CD8 + T-lymphocyte levels were associated with in-hospital mortality and the development of AKI in patients with sepsis.
Background: Diabetes and insulin resistance alter the physiological state of serum albumin (SA), which is a prognostic marker for stable coronary artery disease (CAD). However, whether the SA concentration is associated with long-term cardiovascular (CV) outcomes in diabetic patients with stable CAD remains unclear.
Methods: In total, 1148 patients were retrospectively identified from a nationwide multicenter cohort study on patients with stable CAD. They were categorized into four groups according to their diabetes mellitus (DM) status and SA concentration (cutoff: 4 g/dL).
Results: The patients' mean age was 62.5 years, and 83.5% were male. Of the total patients, 405 were included in group 1 (SA ≥4/non-DM), 322 in group 2 (SA <4/non-DM), 201 in group 3 (SA ≥4/DM), and 220 in group 4 (SA <4/DM). Group 4 had the oldest age and a higher prevalence of prior myocardial infarction and stroke. During the median 4.5-year follow-up (interquartile range: 1.5-6.7 years), the highest and lowest survival rates in terms of all-cause and CV mortality were found in groups 1 and 4, respectively. However, no prognostic differences were noted in nonfatal stroke and myocardial infarction among the groups. The data were consistent after covariate adjustment. Using group 1 as the reference, hazard ratio (HRs) (95% CIs) for all-cause mortality in groups 2, 3, and 4 were 3.64 (1.22-10.83), 3.26 (0.95-11.33), and 5.74 (1.92-16.95), respectively, and those for CV mortality were 2.8 (0.57-13.67), 2.62 (0.40-17.28), and 6.15 (1.32-28.58), respectively.
Conclusion: In diabetic patients with stable CAD, a low SA concentration (<4 g/dL) was associated with increased long-term mortality regardless of all-cause or CV reasons but not nonfatal CV events.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：