Genomic Analysis Reveals Distinct Subtypes in Two Rare Cases of Primary Ovarian Lymphoma

Primary (localized) non-Hodgkin lymphoma (NHL) of the ovary is extremely rare; only a few cases have been reported in the literature. We report two cases of primary ovarian lymphoma (POL), one involving bilateral ovaries in a 15-year-old girl and other involving one ovary in a 5-year-old girl. This report describes detailed clinical, histopathological, and imaging findings, along with the review of literature of primary diffuse large B-cell lymphoma (DLBCL) arising from an ovary. In addition, we describe findings of targeted capture panel sequencing on both tumors and identify the major genetic mutations that are recurrently mutated in pan-cancers. Compared to the genomic mutation features of major subtypes of DLBCL, we distinguish that each POL belongs to distinctive subtypes, GCB (germinal center B-cell subtype) DLBCL and ABC (activated B-cell subtype) DLBCL, respectively. The findings from the genomic analysis may help to understand the pathogenesis of POL and to guide potential targeted therapy in the future.     

RAGE: a new frontier in chronic airways disease

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern-recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern-recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically. One pattern-recognition receptor that has recently come to attention in chronic airways disease is the receptor for advanced glycation end products (RAGE). RAGE is a member of the immunoglobulin superfamily of cell surface receptors that recognizes pathogen- and host-derived endogenous ligands to initiate the immune response to tissue injury, infection and inflammation. Although the role of RAGE in lung physiology and pathophysiology is not well understood, recent genome-wide association studies have linked RAGE gene polymorphisms with airflow obstruction. In addition, accumulating data from animal and clinical investigations reveal increased expression of RAGE and its ligands, together with reduced expression of soluble RAGE, an endogenous inhibitor of RAGE signalling, in chronic airways disease. In this review, we discuss recent studies of the ligand–RAGE axis in asthma and COPD, highlight important areas for future research and discuss how this axis might potentially be harnessed for therapeutic benefit in these conditions.     

安眠小复方对小鼠促眠作用的机制研究

目的探讨中药安眠小复方对小鼠脑神经肽P物质(SP)及睡眠相关细胞因子的影响,以揭示其促眠作用机制。方法60只KM小鼠随机分为6组,安眠小复方高、中、低剂量组分别灌胃给予安眠小复方4.16g/kg,2.08g/kg,1.04g/kg,百乐眠组灌胃给予百乐眠胶囊0.28g/kg,地西泮组灌胃给予地西泮片1.30mg/kg,连续给药7d。末次给药30min后,处死动物,取脑组织,检测小鼠脑内神经肽SP、白介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)含量。结果与空白对照组比较,安眠小复方高、中、低剂量组均能明显降低小鼠脑组织中SP含量(P0.05或P0.01)和IL-1β含量(P0.01);安眠小复方高、中、低剂量组亦能降低小鼠脑组织中TNF-α含量,其中高、低剂量组与空白对照组比较差异有统计学意义(P0.05)。结论中药安眠小复方可能通过降低脑内SP含量、破坏觉醒中枢同时调节睡眠相关细胞因子而发挥促眠作用。     

Deep learning applied to two-dimensional color Doppler flow imaging ultrasound images significantly improves diagnostic performance in the classification of breast masses: a multicenter study

BackgroundThe current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images.MethodsTaking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR−), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists.ResultsThe accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87–0.91, 0.89–0.92, 0.87–0.91, and 0.86–0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%).ConclusionsThe CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists.Trial registrationChictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.     

CyclinB1 deubiquitination by USP14 regulates cell cycle progression in breast cancer

Breast cancer is the most common malignant tumor among women in China, which seriously threatens women's physical and mental health. Tumorigenesis is closely related to the dysregulation of cell cycle. The cell cycle progression includes interphase and mitotic phase (M phase). Cyclin B1 is a key protein in regulating M phase, which is essential for the whole cell cycle progression. CyclinB1 can be degraded through ubiquitination mediated by the anaphase promoting complex/cyclosome (APC/C). However, the mechanism of how CyclinB1 is deubiquitinated in breast cancer still remains unclear. In this study, we discovered that CyclinB1 interacted with ubiquitin-specific peptidase 14 (USP14). Based on the deubiquitinating function of USP14, we detected the effect of USP14 on the ubiquitination of CyclinB1. Inhibiting the activity of USP14 or USP14 knockdown significantly increased the ubiquitination of CyclinB1. In accordance with this, knocking down USP14 arrested cell cycle at G2/M phase. Knocking down USP14 with siRNAs significantly inhibited the proliferation and migration of breast cancer cells. In conclusion, our study demonstrated that USP14 regulated the cell cycle of breast cancer cells by regulating the ubiquitination of CyclinB1, which will provide a solid theoretical basis for the development of anti-cancer drugs targeting USP14.     

Galectin-3 may serve as a marker for poor prognosis in colorectal cancer: A meta-analysis

Galectin-3 has an important function in the development of tumors. The purpose of this meta-analysis was to explore the relationships between the expression of galectin-3 on clinicopathological features and prognosis of colorectal cancer (CRC). A comprehensive literature search was used to identify eligible studies, and Stata software was conducted using in this meta-analysis. A total of 15 studies, including 1661 cases, were matched in the inclusion criteria. The pooled analysis indicated that galectin-3 expression was related to the poor overall survival (OS) in CRC patients (HR: 1.77, 95% CI: 1.36–2.31, P < 0.0001). Our meta-analysis also showed that cancerous tissues have higher levels of galectin-3 expression than normal tissues. Besides, positive galectin-3 expression was also related to advanced TNM stages(III/IV vs. I/II: OR 5.30, 95% CI: 2.42–11.61, P < 0.0001), higher Duke’s stages (C/D vs. A/B: OR 4.00, 95% CI: 2.22–7.22, P < 0.0001), venous invasion (venous invasion vs. not: OR 3.02, 95%CI: 1.75–5.22, P < 0.0001) and higher CEA level (CEA≥5 ng/ml vs. ≤ 5 ng/ml: OR 2.09, 95% CI: 1.09–4.03, P = 0.03). In summary, our results indicated that overexpression of galectin-3 is significantly related to the tumor progression and could be a efficient in predicting the prognosis of patients with CRC.     

Acute effects of alcohol on brain perfusion monitored with arterial spin labeling magnetic resonance imaging in young adults

While a number of studies have established that moderate doses of alcohol increase brain perfusion, the time course of such an increase as a function of breath alcohol concentration (BrAC) has not yet been investigated, and studies differ about regional effects. Using arterial spin labeling (ASL) magnetic resonance imaging, we investigated (1) the time course of the perfusion increase during a 15-minute linear increase of BrAC up to 0.6 g/kg followed by a steady exposure of 100 minutes, (2) the regional distribution, (3) a potential gender effect, and (4) the temporal stability of perfusion effects. In 48 young adults who participated in the Dresden longitudinal study on alcohol effects in young adults, we observed (1) a 7% increase of global perfusion as compared with placebo and that perfusion and BrAC are tightly coupled in time, (2) that the increase reaches significance in most regions of the brain, (3) that the effect is stronger in women than in men, and (4) that an acute tolerance effect is not observable on the time scale of 2 hours. Larger studies are needed to investigate the origin and the consequences of the effect, as well as the correlates of inter-subject variations.     

Preventing preeclampsia and its fetal complications with low-dose aspirin in East Asians and non-East Asians:A systematic review and meta-analysis

Background: Low-dose aspirin can reduce the incidence of preeclampsia and intrauterine growth restriction (IUGR). However, the effects of ethnicity upon low-dose aspirin’s efficacy has not been analyzed. Here, we comparatively evaluated the efficacy of low-dose aspirin in preventing preeclampsia and related fetal complications in East Asian and non-East Asian pregnant women at risk for preeclampsia. Methods: Several databases were searched for randomized controlled trials (RCTs) comparing low-dose aspirin with either placebo or no treatment in pregnant women at risk for preeclampsia. Odds ratios (ORs) and associated 95% confidence intervals (CIs) for preeclampsia and related fetal outcomes were tabulated. Results: Low-dose aspirin significantly reduced preeclampsia risk in both East Asians (OR = 0.20, 95% CI: 0.11–0.35) and non-East Asians (OR = 0.84, 95% CI: 0.77–0.92). Low-dose aspirin significantly reduced IUGR risk in East Asians (OR = 0.36, 95% CI: 0.20–0.67) but not in non-East Asians (OR = 0.85, 95% CI: 0.41–1.77). Low-dose aspirin did not significantly reduce the risk of cesarean section in either East Asians (OR = 0.67, 95% CI: 0.14–3.22) or non-East Asians (OR = 1.01, 95% CI: 0.86–1.19). Conclusions: Low-dose aspirin is effective in reducing preeclampsia risk in both East Asians and non-East Asians and has differential effects in East Asians and non-East Asians with respect to IUGR.