Development and validation of a new diagnostic prediction model of ENHO and NOX4 for early diagnosis of systemic sclerosis.

Objective: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis. The challenge of early diagnosis, along with the lack of effective treatments for fibrosis, contribute to poor therapeutic outcomes and high mortality of SSc. Therefore, there is an urgent need to identify suitable biomarkers for early diagnosis of SSc. Methods: Three skin gene expression datasets of SSc patients and healthy controls were downloaded from Gene Expression Omnibus (GEO) database (GSE130955, GSE58095, and GSE181549). GSE130955 (48 early diffuse cutaneous SSc and 33 controls) were utilized to screen differentially expressed genes (DEGs) between SSc and normal skin samples. Least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) were performed to identify diagnostic genes and construct a diagnostic prediction model. The results were further validated in GSE58095 (61 SSc and 36 controls) and GSE181549 (113 SSc and 44 controls) datasets. Receiver operating characteristic (ROC) curves were applied for assessing the level of diagnostic ability. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to verify the diagnostic genes in skin tissues of out cohort (10 SSc and 5 controls). Immune infiltration analysis were performed using CIBERSORT algorithm. Results: A total of 200 DEGs were identified between SSc and normal skin samples. Functional enrichment analysis revealed that these DEGs may be involved in the pathogenesis of SSc, such as extracellular matrix remodeling, cell-cell interactions, and metabolism. Subsequently, two critical genes (ENHO and NOX4) were identified by LASSO and SVM-RFE. ENHO was found down-regulated while NOX4 was up-regulated in skin of SSc patients and their expression levels were validated by above three datasets and our cohort. Notably, these differential expressions were more pronounced in patients with diffuse cutaneous SSc than in those with limited cutaneous SSc. Next, we developed a novel diagnostic model for SSc using ENHO and NOX4, which demonstrated strong predictive power in above three cohorts and in our own cohort. Furthermore, immune infiltration analysis revealed dysregulated levels of various immune cell subtypes within early SSc skin specimens, and a negative correlation was observed between the levels of ENHO and Macrophages M1 and M2, while a positive correlation was observed between the levels of NOX4 and Macrophages M1 and M2. Conclusion: This study identified ENHO and NOX4 as novel biomarkers that can be serve as a diagnostic prediction model for early detection of SSc and play a potential role in the pathogenesis of the disease.

Impact of the 'weekend effect' on hospital-acquired pneumonia after aneurysmal subarachnoid hemorrhage.

OBJECTIVES: Weekend admission has been reported to be associated with poor clinical outcomes of various diseases. This study aimed to determine whether weekend admission increases the incidence of hospital-acquired pneumonia (HAP) in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We retrospectively analyzed aSAH patients admitted to our hospital between 2014 and 2020. These patients were divided into weekend and weekday groups. We compared the incidence of HAP and other clinical outcomes between the two groups. Risk factors for HAP were identified by logistic regression analysis. RESULTS: Of 653 included aSAH patients, 145 (22%) were admitted on weekends and 508 (78%) were admitted on weekdays. The incidence of HAP in the weekend group was significantly higher than that in the weekday group (25% vs 16%, P = 0.01). The weekend group showed worse clinical outcomes, including worse neurological outcome (74% vs 65%, P = 0.03), higher risk of intensive care unit (ICU) admission (21% vs 13%, P = 0.01) and longer length of stay (21.3 vs 16.4 days, P < 0.01). Age ≥ 60 years (odds ratio [OR] = 2.0, 95% confidence interval [CI] = 1.3-3.0, P < 0.01), modified Fisher score (MFS) ≥ 3 (OR = 1.7, 95% CI = 1.1-2.6, P = 0.02), weekend admission (OR = 1.8, 95% CI = 1.1-2.8, P = 0.02) and operative treatment (OR = 2.3, 95% CI = 1.2-4.5, P = 0.02) were risk factors for HAP following aSAH. CONCLUSION: Weekend admission was associated with a higher incidence of HAP in aSAH patients. This study suggested that medical administrators may need to optimize healthcare services on weekends.

Antiplatelet therapy may be safe in ischemic stroke patients with cerebral microbleed.

OBJECTIVE: We examined whether antiplatelet therapy is safe for ischemic stroke patients with cerebral microbleed. METHODS: We retrospectively analyzed ischemic stroke patients admitted to our hospital from 2015 to 2018. Baseline information was extracted from the computerized database. Adverse events, including symptomatic cerebral hemorrhage, recurrent cerebral infarction, and death, were collected by phone. RESULTS: A total of 184 ischemic stroke patients were examined, including 106 with and 78 without cerebral microbleed. No patient experienced symptomatic cerebral hemorrhage after discharge. Patients with cerebral microbleed had a higher prevalence of hypertension (92% vs 74%) and suffered from more serious leukoaraiosis (3.0 ± 1.7 vs 1.3 ± 1.4 points on the Fazekas scale). Leukoaraiosis scores were correlated with the number of cerebral microbleeds (r = 0.42). CONCLUSIONS: Antiplatelet therapy may be safe for ischemic stroke patients with cerebral microbleed. The risk-benefit ratio should be carefully evaluated before withholding antiplatelet therapy.

Proton magnetic resonance spectroscopy as a diagnostic biomarker in mild cognitive impairment following stroke in acute phase.

To investigate proton magnetic resonance spectroscopy (HMRS) as a diagnostic biomarker to identify mild cognitive impairment (MCI) following stroke in the acute phase. A total of 72 stroke patients were recruited in the acute phase of stroke from the Department of Neurology, including 36 stroke patients with MCI and 36 stroke patients without MCI. All patients underwent brain MRI/MRS examination on a 3.0 T scanner and a neuropsychological test in the acute phase of stroke. Single-voxel HMRS was performed to obtain hippocampal metabolism intensities and brain infarcts were assessed on MRI. Group difference in metabolite ratios was analyzed using a T-test. Spearman rank correlation was used to study the correlation between metabolite ratios and Montreal Cognitive Assessment scores. The hippocampal n-acetylaspartate/creatine (NAA/Cr) ratio was found to be significantly lower in stroke patients with MCI compared with stroke patients without MCI (P<0.02). However, we found no differences in the metabolite ratios between hippocampus ipsilateral to infarctions and the contralateral side (P>0.05) in stroke patients with MCI. Furthermore, a correlation was found between hippocampal NAA/Cr ratios and Montreal Cognitive Assessment scores in stroke patients with MCI (P<0.01). HMRS could be a biomarker to identify MCI following stroke in the acute phase by capturing neurodegenerative changes.