The aging of glymphatic system in human brain and its correlation with brain charts and neuropsychological functioning.

This study aimed to investigate the aging of the glymphatic system in healthy adults, and to determine whether this change is correlated with the brain charts and neuropsychological functioning. Two independent brain 3.0 T MRI datasets were analyzed: a public dataset and our hospital-own dataset from two hospitals. The function of the glymphatic system was quantified by diffusion analysis along the perivascular space (ALPS) index via an automatic method. Brain charts were calculated online. Correlations of the ALPS index with the brain charts, age, gender, and neuropsychological functioning, as well as differences in ALPS index across age groups, were assessed. A total of 161 healthy volunteers ranging in age from 20 to 87 years were included. ALPS index was negatively correlated with the age in both independent datasets. Compared with that of the young group, the ALPS index was significantly lower in the elderly group. No significant difference was found in the ALPS index between different genders. In addition, the ALPS index was not significantly correlated with the brain charts and neuropsychological functioning. In conclusion, the aging of glymphatic system exists in healthy adults, which is not correlated with the changes of brain charts and neuropsychological functioning.

Clinical effectiveness of contrast medium injection protocols for 80-kV coronary and craniocervical CT angiography-a prospective multicenter observational study.

BACKGROUND AND OBJECTIVE: Decreasing X-ray tube voltage is an effective way to reduce radiation and contrast dose, especially in non-obese patients. The current study focuses on CTA in non-obese patients to evaluate image quality and feasibility of 80-kV acquisition protocols with varying iodine delivery rates (IDR) and contrast concentrations in routine clinical practice. METHODS: A prospective observational study in patients ≥ 18 years and ≤ 90 kg referred for coronary or craniocervical CTA at 10 centers in China (ClinicalTrials.gov: NCT02840903). Patients were divided into four groups: a standard 100-kV protocol (370 mgI/ml, IDR 1.48 gI/s), and three 80-kV protocols (370 mgI/ml, IDR 1.2 gI/s; 300 mgI/ml, IDR 1.2 gI/s; 300 mgI/ml, IDR 0.96gI/s). The primary outcome was contrast opacification of target vascular segments. Secondary outcomes were image quality (contrast-to-noise ratio, signal-to-noise ratio, visual image quality, and diagnostic confidence assessment), radiation, and iodine dose. RESULTS: From July 2016 to July 2017, 1213 patients were enrolled: 614 coronary and 599 craniocervical CTA. The mean contrast opacification was ≥ 300 HU for 80-kV 1.2 gI/s IDR scanned segments; IDR 0.96 gI/s led to lower opacification. Image quality and diagnostic confidence were fair to excellent (≥ 98% of images), despite lower contrast-to-noise ratios and signal-to-noise ratios in 80-kV images. Compared to the standard protocol, 80-kV protocols led to 44-52% radiation dose reductions (p < 0.001) and 19% iodine dose reductions (p < 0.001). CONCLUSION: Eighty-kilovolt 1.2 gI/s IDR protocols can be recommended for coronary and craniocervical CTA in non-obese patients, reducing radiation and iodine dose without compromising image quality. KEY POINTS: • Using low-voltage scanning CTA protocols, in which tube voltage and iodine delivery rate are reduced proportionally (voltage: 80 kV, IDR: 1.2 gI/s), reduces radiation and contrast dose without compromising image quality in routine clinical practice. • Reducing iodine delivery rate beyond direct proportionality to tube voltage is not beneficial.

Atypical presentations of coronavirus disease 2019 (COVID-19) from onset to readmission.

BACKGROUND: To investigate the CT imaging and clinical features of three atypical presentations of coronavirus disease 2019 (COVID-19), namely (1) asymptomatic, (2) CT imaging-negative, and (3) re-detectable positive (RP), during all disease stages. METHODS: A consecutive cohort of 79 COVID-19 patients was retrospectively recruited from five independent institutions. For each presentation type, all patients were classified into atypical vs. typical groups (i.e., asymptomatic vs.symptomatic, CT imaging-negative vs. CT imaging-positive, and RP and non-RP,respectively). The chi-square test, Student's t test, and Kruskal-Wallis H test were performed to compare CT imaging and clinical features of atypical vs. typical patients for all three presentation categories. RESULTS: In our COVID-19 cohort, we found 12.7% asymptomatic patients, 13.9% CT imaging-negative patients, and 8.9% RP patients. The asymptomatic patients had fewer hospitalization days (P=0.043), lower total scores for bilateral lung involvement (P< 0.001), and fewer ground-glass opacities (GGOs) in the peripheral area (P< 0.001) than symptomatic patients. The CT imaging-negative patients were younger (P=0.002), had a higher lymphocyte count (P=0.038), had a higher lymphocyte rate (P=0.008), and had more asymptomatic infections (P=0.002) than the CT imaging-positive patients. The RP patients with moderate COVID-19 had lower total scores of for bilateral lung involvement (P=0.030) and a smaller portion of the left lung affected (P=0.024) than non-RP patients. Compared to their first hospitalization, RP patients had a shorter hospitalization period (P< 0.001) and fewer days from the onset of illness to last RNA negative conversion (P< 0.001) at readmission. CONCLUSIONS: Significant CT imaging and clinical feature differences were found between atypical and typical COVID-19 patients for all three atypical presentation categories investigated in this study, which may help provide complementary information for the effective management of COVID-19.

A diagnostic model for coronavirus disease 2019 (COVID-19) based on radiological semantic and clinical features: a multi-center study.

OBJECTIVES: Rapid and accurate diagnosis of coronavirus disease 2019 (COVID-19) is critical during the epidemic. We aim to identify differences in CT imaging and clinical manifestations between pneumonia patients with and without COVID-19, and to develop and validate a diagnostic model for COVID-19 based on radiological semantic and clinical features alone. METHODS: A consecutive cohort of 70 COVID-19 and 66 non-COVID-19 pneumonia patients were retrospectively recruited from five institutions. Patients were divided into primary (n = 98) and validation (n = 38) cohorts. The chi-square test, Student's t test, and Kruskal-Wallis H test were performed, comparing 1745 lesions and 67 features in the two groups. Three models were constructed using radiological semantic and clinical features through multivariate logistic regression. Diagnostic efficacies of developed models were quantified by receiver operating characteristic curve. Clinical usage was evaluated by decision curve analysis and nomogram. RESULTS: Eighteen radiological semantic features and seventeen clinical features were identified to be significantly different. Besides ground-glass opacities (p = 0.032) and consolidation (p = 0.001) in the lung periphery, the lesion size (1-3 cm) is also significant for the diagnosis of COVID-19 (p = 0.027). Lung score presents no significant difference (p = 0.417). Three diagnostic models achieved an area under the curve value as high as 0.986 (95% CI 0.966~1.000). The clinical and radiological semantic models provided a better diagnostic performance and more considerable net benefits. CONCLUSIONS: Based on CT imaging and clinical manifestations alone, the pneumonia patients with and without COVID-19 can be distinguished. A model composed of radiological semantic and clinical features has an excellent performance for the diagnosis of COVID-19. KEY POINTS: • Based on CT imaging and clinical manifestations alone, the pneumonia patients with and without COVID-19 can be distinguished. • A diagnostic model for COVID-19 was developed and validated using radiological semantic and clinical features, which had an area under the curve value of 0.986 (95% CI 0.966~1.000) and 0.936 (95% CI 0.866~1.000) in the primary and validation cohorts, respectively.

Bisphenol A triggers the malignancy of acute myeloid leukemia cells via regulation of IL-4 and IL-6.

Acute myeloid leukemia (AML) is a cancer of hematopoietic stem cells with a rapid progression. The progression of AML can be regulated by estrogenic signals. Our present data showed that an industrial endocrine-disrupting chemical, bisphenol A (BPA), can promote the proliferation of AML cells and decrease their sensitivity to daunorubicin and cytarabine treatment. Among the tested cytokines, BPA treatment can decrease the expression of interleukin-4 (IL-4) while increasing the expression of IL-6. Overexpression of IL-4 or neutralization antibody of IL-6 (anti-IL-6) can attenuate BPA-induced proliferation of AML cells and reverse BPA-suppressed chemosensitivity. Furthermore, activation of nuclear factor kappa B is essential for BPA-induced upregulation of IL-6 in AML cells. As to IL-4, BPA can increase the expression of NFAT1 to inhibit its transcription. Collectively, our data showed that BPA can trigger the malignancy of AML cells via regulation of IL-4 and IL-6.

Overlapped differentially expressed genes between acute lymphoblastic leukemia and chronic lymphocytic leukemia revealed potential key genes and pathways involved in leukemia.

Common differentially expressed genes (DEGs) in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) might play critical roles in the pathogenesis and process of leukemia. We collected RNA sequencing (RNA-seq) data of human CLL, ALL samples, and normal peripheral blood CD19+ B cells as well as thymus samples, and analyzed similarities and differences between their transcriptomes using Cuffdiff2, DESeq, and edgeR. Compared with the RNA-seq data of normal peripheral blood CD19+ B cells and thymus samples, there were a large number of DEGs in ALL and CLL. DEGs in ALL and CLL not only have their distinguished features but also have a similar pattern. To figure out the common DEGs between CLL and ALL, we further identified 26 overlapped genes between CLL and ALL, among which 10 genes showed similar expression variation profiles whereas 16 genes showed opposite variation. The expression levels of 10 genes (SCML4, TNF-α, CD1C, FGFR1, MYO7B, DUSP1, PAP1GAP, MAN1C1, SLFN5, and CD8A) among the 26 genes were further confirmed by experiments, which was consistent with the results obtained by analyzing the RNA-seq data. The current study contributes to better understanding the pathophysiology of leukemia and unearthing novel potential prognostic markers and therapeutic targets of leukemia.

Increased glymphatic system activity in patients with mild traumatic brain injury.

Purpose: This study aims to investigate the glymphatic system activity changes in patients with mild traumatic brain injury (mTBI), particularly in MRI-negative patients, using analysis along the perivascular space (ALPS) technology. Methods: A total of 161 mTBI patients (age: 15-92 years old) and 28 healthy controls (age: 15-84 years old) were included in this retrospective study. The mTBI patients were divided into MRI-negative and MRI-positive groups. ALPS index was calculated automatically using whole-brain T1-MPRAGE imaging and diffusion tensor imaging. The Student's t and chi-squared tests were performed to compare the ALPS index, age, gender, course of disease, and Glasgow Coma Scale (GCS) score between groups. Correlations among ALPS index, age, course of disease and GCS score were computed using Spearman's correlation analysis. Results: Increased activity of the glymphatic system was suggested in mTBI patients based on ALPS index analysis, including the MRI-negative patients. There was a significant negative correlation between the ALPS index and age. In addition, a weak positive correlation between the ALPS index and course of disease was also observed. On the contrary, there was no significant correlation between the ALPS index and sex nor between the ALPS index and GCS score. Conclusion: Our study demonstrated that the activity level of the glymphatic system was enhanced in mTBI patients, even when their brain MRI scans were negative. These findings may provide novel insights for understanding the pathophysiology of mild TBI.

Efficacy of Stereotactic Body Radiotherapy for Recurrent or Residual Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization.

AIM: To evaluate the efficacy and toxicity of hypofractionated stereotactic body radiotherapy (SBRT) for patients with recurrent or residual hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). METHODS: Between June 2008 and July 2015, thirty-three patients with HCC were treated by SBRT. There were 63 lesions in 33 patients. A total dose of 39-45 Gy/3-5 fractions was delivered to the 70-80% isodose line. RESULTS: Objective response rate (CR + PR) was 84.8% at 6 months. The overall survival rate was 87.9%, 75.8%, 57.6%, and 45.5% at 6, 12, 18, and 24 months, respectively. Median overall survival was 19 months. At 3 months, AFP decreased by more than 75% in 51.5% of patients (17/33). Overall survival was significantly different (P < 0.001) between the group of patients for whom AFP decreased more than 75% and the group for whom AFP decreased by less than 75%. The AFP-negative rate was 48.5% (16/33) after 6 months. Eight patients (24.2%) had grade 1-2 transient fatigue, and 11 patients (33.3%) had grade 1-2 gastrointestinal reactions within 1 month. CONCLUSION: SBRT is a promising noninvasive and palliative treatment with acceptable toxicity for recurrent or residual HCC after TACE.