INTRODUCTION:The association between earlobe crease (ELC) and cerebral small vessel disease, including white matter hyperintensities (WMHs) and brain atrophy, is unclear, especially in the setting of acute ischemic stroke (AIS). Here, we aimed to investigate the association between ELC and WMHs as well as brain atrophy among AIS patients. METHODS:A total of 730 AIS patients from China were enrolled. Patients were divided into groups without and with ELC, unilateral and bilateral ELC according to pictures of bilateral ears. Logistic regression models were employed to assess the impact of ELC, bilateral ELC on WMHs, periventricular hyperintensities (PVHs), deep white matter hyperintensities (DWMHs), and brain atrophy, as measured by the Fazekas scale and global cortical atrophy scale, in brain magnetic resonance imaging. RESULTS:There were 520 (71.2%) AIS patients with WMHs, 445 (61.0%) with PVH, 462 (63.3%) with DWMH, and 586 (80.3%) with brain atrophy. Compared to those without ELC, patients with ELC were significantly associated with an increased risk of PVH (odds ratio [OR] 1.79; 95% confidence interval [CI], 1.15-2.77) and brain atrophy (OR: 6.18; 95% CI: 3.60-10.63) but not WMHs and DWMH. The presence of bilateral ELC significantly increased the odds of WMHs (OR: 1.60; 95% CI: 1.00-2.56), PVH (OR: 1.87; 95% CI: 1.18-2.96), and brain atrophy (OR: 8.50; 95% CI: 4.62-15.66) when compared to individuals without ELC. Furthermore, we discovered that the association between bilateral ELC and WMHs, PVH, and DWMH was significant only among individuals aged ≤68 (median age) years (all p trend ≤0.041). However, this association was not observed in patients older than 68 years. CONCLUSIONS:In Chinese AIS patients, the presence of the visible aging sign, ELC, especially bilateral ELC, showed independent associations with both WMHs and brain atrophy, particularly among those younger than 68 years old.

Chronic graft-versus-host disease (cGVHD), characterized by chronic tissue inflammation and fibrosis involving multiple organs, remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF) is an anti-inflammatory drug approved for the treatment of multiple sclerosis and psoriasis. We previously reported that DMF effectively inhibits acute GVHD (aGVHD) while preserving the graft-versus-leukemia effect. However, the role of DMF in cGVHD progression remains unknown. Here, we found that DMF administration significantly suppresses follicular helper T cell (Tfh) differentiation, and germinal center formation and alleviates disease severity in different murine cGVHD models. Mechanistically, DMF treatment downregulates IL-21 transcription by activation of Nrf2, thus orchestrating Tfh-related gene programs both in mice and humans. The inhibitory role of DMF on Tfh cell differentiation was diminished in Nrf2 deficient T cells. Importantly, the therapeutic potential of DMF in clinical cGVHD has been validated in human data whereby DMF effectively reduces IL-21 production and Tfh cell generation in peripheral blood mononuclear cells from active cGVHD patients and further attenuates xenograft GVHD. Collectively, our findings reveal that DMF potently inhibits cGVHD development by repressing Tfh cell differentiation via Nrf2, paving the way for the treatment of cGVHD in the clinic.

Background: The involvement of N7-Methylguanine (m7G) RNA methylation regulators in the progression of different types of solid cancers in humans has been established. However, the specific impact of m7G-related genes on Acute myeloid leukemia (AML) remains uncertain. Our research aims to build a novel signature of M7Gs that could enhance our understanding of the molecular heterogeneity in leukemia.Methods: The RNA-seq and clinical data of patients with AML were acquired from the UCSC XENA website. Prognostic-related genes were selected using LASSO to construct a risk-scoring model. External datasets were utilized to validate the effectiveness of the model, and the mRNA expressions of candidate genes were measured using RT-qPCR.Results: A prognostic model was developed using a risk-scoring approach based on three candidate genes (IFIT5, EIF4E2, and LARP1) and their respective risk coefficients. Multivariate Cox regression analysis revealed a significant association between the risk score and overall survival (p<0.001). In both the experimental and validation cohorts, individuals classified as high risk exhibited a poorer prognosis. The 5-year area under the curve (AUC) was calculated as 0.715 for the TCGA-LAML cohort and 0.646 for GSE37642. Additionally, analysis using ssGSEA demonstrated that the high-risk group exhibited higher levels of immune cell infiltration compared to low-risk group. RT-qPCR results indicated that the expression levels of LARP1, EIF4E2 and IFIT5 were consistent with the results of the bioinformatic analysis.Conclusions: In summary, the m7G-related genes are potential prognostic biomarkers for patients with AML.

Background Inflammation is a potential mechanism underlying the development of white matter lesions (WMLs) and cerebral atrophy. We aimed to investigate the relationship of fibrinogen levels with WMLs and cerebral atrophy in patients with acute ischemic stroke (AIS). Methods A total of 701 AIS patients were enrolled. Participants were divided into four groups according to the quartiles of fibrinogen levels: Q1 < 2.58 g/L, Q2: 2.58-3.12 g/L, Q3: 3.12-3.67 g/L, Q4: ≥ 3.67 g/L. White matter hyperintensity (WMH), periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) were defined according to the Fazekas scale. Cerebral atrophy was defined according to global cortical atrophy scores. Univariate and multivariate logistic regression were used to explore the relationship of fibrinogen levels and WMHs, PVH, DWMH and cerebral atrophy. Results Among 701 AIS patients, 498 (71.0%), 425 (60.6%), 442 (63.1%), and 560 (79.9%) had WMHs, PVH, DWMH and cerebral atrophy, respectively. After adjustment for potential covariates, the highest fibrinogen quartiles were significantly associated with increased risk of WMHs (odds ratio [OR] 1.97, 95% confidence intervals [CI] 1.10-3.50), PVH (OR 1.85, 95% CI 1.08-3.16) and cerebral atrophy (OR 2.53, 95% CI 1.19-5.40) but not DWMH (OR 1.37 95% CI 0.81-2.31) compared with the lowest fibrinogen quartile. Moreover, the association between elevated fibrinogen levels and the risk of WMLs and cerebral atrophy remained significant as continuous variables. Conclusions Increased baseline fibrinogen levels were independently associated with WMHs, PVH and cerebral atrophy in patients with ischemic stroke. Fibrinogen could be the potential blood biomarker of WMLs and cerebral atrophy.

Natural killer (NK) cells have been demonstrated as a promising cellular therapy as they exert potent anti-tumor immune responses. However, applications of NK cells to tumor immunotherapy, especially in the treatment of advanced hematopoietic and solid malignancies, are still limited due to the compromised survival and short persistence of the transferred NK cells in vivo . Here, we observed that fucosyltransferase (FUT) 7 and 8 were highly expressed on NK cells, and the expression of CLA was positively correlated with the accumulation of NK cells in clinical B cell lymphoma development. Via enzyme-mediated ex vivo cell-surface fucosylation, the cytolytic effect of NK cells against B cell lymphoma was significantly augmented. Fucosylation also promoted NK cell accumulation in B cell lymphoma-targeted tissues by enhancing their binding to E-selectin. Moreover, fucosylation of NK cells also facilitated stronger T cell anti-tumor immune responses. These findings suggest that ex vivo fucosylation contributes to enhancing the effector functions of NK cells and may serve as a novel strategy for tumor immunotherapy.

Little is known about oropharyngeal colonization microorganisms in patients during allogeneic hematopoietic stem cell transplantation (allo-HSCT), and updated epidemiologic investigations are advisable. This study aimed to characterize oropharyngeal colonization microorganisms in patients during allo-HSCT and confirm whether they were related to clinical outcomes. This retrospective, matched case-control study included 1267 consecutive patients undergoing allo-HSCT between January 2018 and December 2020 at our institution. Patients with oropharyngeal colonization microorganisms were those with a positive throat swab before or on the day of transplantation without the occurrence of any symptoms of infection. Propensity score matching was used. Characteristics of oropharyngeal colonization microorganisms were evaluated among patients in the transplant medicine wards and compared with clinical outcomes within 100 days in positive and negative colonization groups. A total of 127 patients had oropharyngeal colonization microorganisms before or on the day of transplantation. Using propensity score matching, we matched the 127 patients in the positive colonization group with 508 patients in the negative colonization group at a 1:4 ratio (total of 635 cases). None of the differences in clinical traits between the 2 groups remained significant. Among the 127 patients with oropharyngeal colonization microorganisms, 90 patients suffered from the documented infection subsequently, and the others were asymptomatic. A total of 82 single gram-negative bacteria were identified in 127 isolates. There were no differences between the positive and negative colonization groups in the occurrence of oral mucositis, Epstein-Barr virus, or acute graft-versus-host disease and relapse within 100 days. However, the rate of neutrophil or platelet recovery was significantly lower in the positive colonization group compared with the negative colonization group (hazard ratio [HR], .71; 95% confidence interval [CI], .59 to .84; P < .001; HR .69; 95% CI, .58 to .83; P = .003; separately). The risk of bloodstream infection was higher in the positive colonization group compared with the negative colonization group (HR, 6.09; 95% CI, 3.16 to 11.75; P < .001). The continency rate between the bacteria isolated from the blood samples and oropharyngeal colonization microorganisms among the patients with positive results was 73.3%. Patients in the positive colonization group were more vulnerable to cytomegalovirus infection compared with the negative colonization group (HR, 1.41; 95% CI, 1.00 to 1.99; P = .049). The nonrelapse mortality at day +100 was higher in the positive colonization group (HR, 3.46; 95% CI, 1.69 to 7.08; P < .001). The survival probability within 100 days was significantly lower in the positive colonization group (HR, 3.38; 95% CI, 1.78 to 6.41; P < .001). Our data show that the presence of oropharyngeal colonization microorganisms is related to clinical outcomes, and that oropharyngeal microorganism monitoring may be useful during allo-HSCT.

Extraskeletal osteosarcoma is an uncommon and high-grade soft tissue malignancy. The incidence is even lower when the lung and pulmonary artery are the primary site. The purpose of this report is to present the radiological features of this neoplasm in a 52-year-old man. In our case, contrast-enhanced CT and 3D-CT reconstruction clearly showed the primary lesion and its invasion into surrounding tissues. Although wide local excision of the primary tumor is the treatment of choice, local recurrence and metastasis rates remain high, and this progression can be clearly shown on CT and SPECT/CT examinations.