miR-124 and VAMP3 Act Antagonistically in Human Neuroblastoma.

Neuroblastoma (NB) is the most common extracranial solid tumor that affects developing nerve cells in the fetus, infants, and children. miR-124 is a microRNA (miRNA) enriched in neuronal tissues, and VAMP3 (vesicle-associated membrane protein 3) has been reported to be an miR-124 target, although the relationship between NB and miR-124 or VAMP3 is unknown. Our current work identified that miR-124 levels are high in NB cases and that elevated miR-124 correlates with worse NB outcomes. Conversely, depressed VAMP3 correlates with worse NB outcomes. To investigate the mechanisms by which miR-124 and VAMP3 regulate NB, we altered miR-124 or VAMP3 expression in human NB cells and observed that increased miR-124 and reduced VAMP3 stimulated cell proliferation and suppressed apoptosis, while increased VAMP3 had the opposite effects. Genome-wide mRNA expression analyses identified gene and pathway changes which might explain the NB cell phenotypes. Together, our studies suggest that miR-124 and VAMP3 could be potential new markers of NB and targets of NB treatments.

Kimura's disease successively affecting multiple body parts: a case-based literature review.

BACKGROUND: Kimura's disease is a rare, benign, chronic inflammatory disease that presents as painless, solid masses mainly affecting the deep subcutaneous areas of the head and neck, especially the salivary glands, parotid glands and nearby lymph nodes. It is characterized by elevated peripheral blood eosinophil and Immunoglobulin E (IgE) levels. CASE PRESENTATION: A 31-year-old Asian male presented with an orbital space-occupying lesion lasting for 1.5 years. Ten years prior, surgical excision of bilateral fossa cubitalis and groin masses was performed, and the pathological examination showed "lymphoproliferative disease". One year later, masses reappeared near the surgical sites; they grew slowly and shrank after glucocorticoid treatment. At this point, admission examinations showed in the peripheral blood an eosinophil proportion of 13.4%, a total IgE level of 26,900.00 IU/mL, prurigo present on the whole body, and multiple palpable masses near the bilateral fossa cubitalis and groin. The left eyeball was exophthalmic. The left elbow mass was excised, and the pathological examination confirmed Kimura's disease. Oral glucocorticoid therapy is taken and tapering regularly. The eosinophil count returned to normal, the IgE level gradually decreased, the orbital space-occupying lesion and elbow and groin masses shrank significantly, and the whole-body skin prurigo disappeared. Currently, the patient has been in a stable condition for eighteen months. CONCLUSION: Our case provides a novel insight that Kimura's disease should be involved in the differential diagnosis of inflammatory lesion mass of orbit and also supports systemic regular glucocorticoid as a valuable therapy of such condition, but close follow-up and long-term observation are crucial.

Clinical Features, Diagnostic Test Performance, and Prognosis in Different Subtypes of Chronic Pulmonary Aspergillosis.

OBJECTIVE: The aim of this study was to describe clinical features in different subtypes of chronic pulmonary aspergillosis (CPA)-simple aspergilloma (SA), chronic cavitary pulmonary aspergillosis (CCPA), chronic fibrosing pulmonary aspergillosis (CFPA), aspergillus nodule (AN), and subacute invasive aspergillosis (SAIA), respectively, and identify long-term prognosis of CPA. METHODS: We reviewed patients diagnosed with different subtypes of CPA from 2002 to 2020 at Nanjing Jinling Hospital, China. We analyzed the clinical and survival information of five different subgroups. A Cox regression model was used to explore proper antifungal duration and long-term survival factors of CCPA and SAIA. RESULTS: A total of 147 patients with CPA were included, consisting of 11 SA, 48 CCPA, 5 CFPA, 12 AN, and 71 SAIA. The most common underlying pulmonary disease was pulmonary tuberculosis (n = 49, 33%), followed by bronchiectasis (n = 46, 31.3%) and chronic obstructive pulmonary disease (COPD) or emphysema (n = 45, 30.6%), while in SAIA and CFPA groups, the most common was COPD or emphysema (45.1 and 100%). Cough (85%), expectoration (70.7%), hemoptysis (54.4%), and fever (29.9%) were common symptoms, especially in CCPA, CFPA, and SAIA groups. The common imaging manifestations included cavitation (n = 94, 63.9%), fungal ball (n = 54, 36.7%), pleural thickening (n = 47, 32.0%), and bronchiectasis (n = 46, 31.3%). SAIA and CFPA groups had a lower value of hemoglobin (HB) and serum albumin (ALB) with higher C-reactive protein and erythrocyte sedimentation rate. The positive rate of sputum culture, serum galactomannan (GM), and bronchoalveolar lavage fluid GM was 32.7% (36/110), 18.4% (18/98), and 48.7% (19/39), respectively. There were 64.6% (31/48) patients with CCPA and 25.4% (18/71) patients with SAIA who received surgery and the 5-year cumulative survival rate was 92.1 and 66.6%, respectively. SAIA, old age, male, low body mass index (BMI), COPD or emphysema, multiple distribution, low serum ALB, and positive sputum culture were adverse prognosis factors for SAIA and CCPA group, and BMI ≤ 20.0 kg/m2 was independently associated with increased mortality (hazard ratio (HR) 5.311, 95% CI 1.405-20.068, p = 0.014). Multivariable Cox regression indicated that surgery (HR 0.093, 95% CI 0.011-0.814, p = 0.032) and antifungal duration >6 months (HR 0.204, 95% CI 0.060-0.696 p = 0.011) were related to improved survival. CONCLUSION: The clinical features and laboratory test performance are different among SA, CCPA, CFPA, AN, and SAIA. Low BMI was an independent risk factor for survival. Selective surgery and antifungal duration over 6 months were associated with improved survival.

Clinical features of cryptococcosis in patients with different immune statuses: a multicenter study in Jiangsu Province-China.

BACKGROUND: Current guidelines support different management of cryptococcosis between severely immunodeficient and immunocompetent populations. However, few studies have focused on cryptococcosis patients with mild-to-moderate immunodeficiency. We performed this study to determine the clinical features of pulmonary (PC) and extrapulmonary cryptococcosis (EPC) and compared them among populations with different immune statuses to support appropriate clinical management of this public health threat. METHODS: All cases were reported by 14 tertiary teaching hospitals in Jiangsu Province, China from January 2013 to December 2018. The trends in incidence, demographic data, medical history, clinical symptoms, laboratory test indicators, imaging characteristics and diagnostic method of these patients were then stratified by immune status, namely immunocompetent (IC, patients with no recognized underlying disease or those with an underlying disease that does not influence immunity, such as hypertension), mild-to-moderate immunodeficiency (MID, patients with diabetes mellitus, end-stage liver or kidney disease, autoimmune diseases treated with low-dose glucocorticoid therapy, and cancer treated with chemotherapy) and severe immunodeficiency (SID, patients with acquired immunodeficiency syndrome, haematologic malignancies, solid organ transplantation or haematologic stem cell transplantation, idiopathic CD4 lymphocytosis, agranulocytosis, aggressive glucocorticoid or immunosuppressive therapy and other conditions or treatments that result in severe immunosuppression). RESULTS: The clinical data of 255 cryptococcosis patients were collected. In total, 66.3% of patients (169) were IC, 16.9% (43) had MID, and 16.9% (43) had SID. 10.1% of the patients (17) with IC were EPC, 18.6% of the patients (8) with MID were EPC, and 74.4% of patients (32) were EPC (IC/MID vs. SID, p < 0.001). Fever was more common in the SID group than in the IC and MID groups (69.8% vs. 14.8% vs. 37.2%, p < 0.001). Of chest CT scan, most lesions were distributed under the pleura (72.7%), presenting as nodules/lumps (90.3%) or consolidations (10.7%). Pleural effusion was more common in SID group compared to IC group (33.3% vs. 2.4%, p < 0.001). Positivity rate on the serum capsular polysaccharide antigen detection (CrAg) test was higher in the SID group than in the other two groups [100.0% vs. 84.4% (MID) vs. 78.2% (IC), p = 0.013]. Positivity rate on the serum CrAg test was also higher in cryptococcal meningitis patients than in PC patients (100.0% vs. 79.5%, p = 0.015). CONCLUSIONS: The clinical presentation of MID patients is intermediate between SID and IC patients and is similar to that of IC patients. The serum CrAg test is more sensitive for the identification of SID or EPC patients.

Quantitative Analysis of Enhancement Intensity and Patterns on Contrast-enhanced Spectral Mammography.

CESM is an emerging digital mammography technology with a high breast cancer detection and a limited diagnostic specificity. In order to improve specificity, we quantitatively assessed enhancement intensity of breast lesions with different pathological types and hormonal receptor status and evaluated the consistency of enhancement patterns between CESM and DCE-MRI. A total of 145 lesions were enrolled, consisting of 43 malignant (17 non-infiltrating cancers and 26 infiltrating cancers) and 99 benign lesions. The diagnostic performance of enhancement intensity in the former positions was significantly higher than that in the latter positions (AUC: 0.834 vs. 0.755, p = 0.0008). Infiltrating cancers showed the highest enhancement intensity, while benign lesions the lowest (mean CNR1: 7.6% vs. 2.7%; median CNR1: 6.8% vs. 2.7%). Enhancement intensity of ER or PR positive group was weaker than negative group, while HER-2 positive group was stronger than negative group. 28 patients with 28 lesions performed both CESM and DCE-MRI examinations, showing a coincidence rate of 64.2% and moderate agreement (k = 0.515) between CESM and DCE-MRI. In conclusion, quantitative analysis of enhancement characteristics is feasible to the diagnosis practice on CESM.

Background Parenchymal Enhancement on Contrast-Enhanced Spectral Mammography: Influence of Age, Breast Density, Menstruation Status, and Menstrual Cycle Timing.

To evaluate the relationship of the extent and quantitative intensity of background parenchymal enhancement (BPE) on contrast-enhanced spectral mammography (CESM) with age, breast density, menstruation status, and menstrual cycle timing. This retrospective study included women who underwent CESM from July 2017 to March 2019 and who had menstruation status records. BPE category assessment was performed subjectively. BPE intensity was quantitatively measured using regions-of-interest. 208 subjects were included (150 were regular menstrual cycle and 58 were postmenopausal). The breast density was classified as category B in 11 subjects, category C in 231 subjects, and category D in 23 subjects. Subjects based on menstrual cycle timing, 24 at days 1-7, 55 at days 8-14, 48 at days 15-21, and 23 at days 22-28. Both quantitative and categorical analyses show a weak negative correlation between BPE and age in all subjects, but there was no significant correlation in premenopausal patients. Both the BPE pixel intensity value and BPE category was significantly lower in postmenopausal patients than in premenopausal patients, and there was no significant difference in breast density according to BPE. The minimum and maximum pixel values of BPE on days 8-14 of the menstrual cycle was significantly lower than those on days 15-21. There was no correlation between BPE level and menstrual cycle timing. Breast density with category D was more likely to have a lower BPE level than category C. We show here that BPE level is affected by menstruation status and menstrual cycle timing. We suggest that CESM should not be performed on days 15-21 of the menstrual cycle, but on days 8-14.

Contrast-enhanced spectral mammography: A potential exclusion diagnosis modality in dense breast patients.

BACKGROUND: China has an increasing burden of breast cancer. However, with a large population of dense breast patients, the diagnostic efficiency of conventional digital mammography is attenuated. METHODS: From July 2017 to October 2018, we retrospectively reviewed 397 dense breast patients who underwent contrast-enhanced spectral mammography (CESM) in West China Hospital. Among them, 53 patients who had both CESM and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) results and 114 patients who had pathological diagnoses were finally enrolled. All images were reviewed by two independent radiologists according to the 2013 Breast Imaging Reporting and Data System (BI-RADS) with all disagreements handed to an associate professor for final decisions. Correlation analyses between CESM and DCE-MRI were conducted. The diagnostic performance of CESM were investigated. RESULTS: The kappa value of the BI-RADS scores between CESM and DCE-MRI was 0.607 (P < .001), indicating high correspondence between CESM and DCE-MRI. As for lesion size measurement, moderate correlation (Kendall's tau coefficient: 0.556, P < .001) was detected between CESM and DCE-MRI. Using pathological diagnoses as the reference standard, the sensitivity, specificity, and area under the curve (AUC) of CESM were 82.4%, 96.4%, and 0.894, respectively. CONCLUSION: CESM demonstrated excellent overall diagnostic accuracy and a moderate correlation in lesion size estimation against DCE-MRI in dense breast patients, supporting it to be an alternative to DCE-MRI in breast cancer detection and diagnosis, especially for exclusion diagnosis.

Potential Anti-inflammatory Sesquiterpene Lactones from Eupatorium lindleyanum.

Eupatorium lindleyanum has traditionally been used as folk medicine in Asian countries for its therapeutic effects on tracheitis and tonsillitis. Investigation of the anti-inflammatory active constituents from E. lindleyanum led to the isolation of two novel sesquiterpene lactones, named eupalinolide L (1: ) and eupalinolide M (2: ), and seven known sesquiterpene lactones (3: -9: ). The structures and configurations of the new compounds were determined on the basis of spectroscopic analysis, especially 2D NMR techniques. In vivo experiments showed that the sesquiterpenes fraction significantly reduced mouse ear edema induced by xylene (18.6%, p < 0.05). In in vitro assays, compounds 1: -9: showed excellent anti-inflammatory activities, as they lowered TNF-α and IL-6 levels in lipopolysaccharide-stimulated murine macrophage RAW 264.7 cells (p < 0.001). The above results suggest that the sesquiterpene lactones from E. lindleyanum can be developed as novel potential natural anti-inflammatory agents.

Potential hypoglycaemic activity phenolic glycosides from Moringa oleifera seeds.

Moringa oleifera seed has remarkable curative effects on reducing blood pressure, blood sugar and enhancing human immunity. In this study, one novel phenolic glycoside (1) together with four known compounds 2-5 were isolated from the macroporous resin adsorption extract of M. oleifera seeds, and the compound 3 was reported for the first time from this plant. The structure of the new crystalline compound was determined on the basis of spectroscopic analyses including mass spectrometry, 1D and 2D NMR experiments. The hypoglycaemic activity of isolated compounds was investigated with HepG2 cell and STZ-induced mice. It was found that compound 1, 4 and 5 could promote the glucose consumption of insulin resistance cells and reduce blood glucose levels of STZ-induced mice. This study concludes that compound 1, 4 and 5 may be developed as new and safe hypoglycaemic drugs.