Morinda Officinalis

Varicoceles (VCs) are the predominant cause of male infertility and are a risk factor for chronic venous disease. Morinda officinalis (M. officinalis) is a traditional Chinese medicine used to tonify the kidney and strengthen yang. In this study, we evaluated the effects of water-soluble polysaccharides extracted from M. officinalis (MOPs) on gonadotropin-release hormone (GnRH) secretion in a classic experimental left VC (ELV) rat model. Intragastric administration of MOPs at a dose ranging from 50 mg kg−1 to 100 mg kg−1 facilitated improvements in sperm parameters and seminiferous epithelial structures, modulated serum hormone profiles, and stimulated GnRH synthesis and release in the hypothalamus. MOPs also promoted spinogenesis and functional spine maturation in the arcuate nuclei (Arc), wherein they acted mainly on Kiss1 and GnRH neurons. Moreover, MOP-mediated Kisspeptin-GPR54 pathway upregulation and MAPK phosphorylation activation may have been responsible for increases in GnRH synthesis and release. Collectively, the findings of this study indicate that MOPs were effective in stimulating GnRH secretion, possibly by upregulating the Kiss1/GPR54 pathway and enhancing synaptic plasticity, and that MOPs can serve as a therapy for early VCs

Spatiotemporal Distribution of Eutrophication in Lake Tai as Affected by Wind

One common hypothesis is that wind can affect concentrations of nutrients (i.e., nitrogen and phosphorus) and chlorophyll-a (Chl-a) in shallow lakes. However, the tests of this hypothesis have yet to be conclusive in existing literature. The objective of this study was to use long-term data to examine how wind direction and wind speed affect the spatiotemporal variations of total nitrogen (TN), total phosphorus (TP) and Chl-a in Lake Tai, a typical shallow lake located in east China. The results indicated that the concentrations of nutrients and Chl-a tended to decrease from the northwest to the southeast of Lake Tai, with the highest concentrations in the two leeward bays (namely Meiliang Bay and Zhushan Bay) in the northwestern part of the lake. In addition to possible artificial reasons (e.g., wastewater discharge), the prevalent southeastward winds in warm seasons (i.e., spring and summer) and northwestward winds in cool seasons (i.e., fall and winter) might be the major natural factor for such a northwest-southeast decreasing spatial pattern. For the lake as a whole, the concentrations of TN, TP and Chl-a were highest for a wind speed between 2.1 and 3.2 m·s-1, which can be attributed to the idea that the wind-induced drifting and mixing effects might be dominant in the bays while the wind-induced drifting and resuspension effects could be more important in the other parts of the lake. Given that the water depth of the bays was relatively larger than that of the other parts, the drifting and mixing effects were likely dominant in the bays, as indicated by the negative relationships between the ratios of wind speed to lake depth, which can be a surrogate for the vertical distribution of wind-induced shear stress and the TN, TP and Chl-a concentration. Moreover, the decreasing temporal trend of wind speed in combination with the ongoing anthropogenic activities will likely increase the challenge for dealing with the eutrophication problem of Lake Tai. © 2017 by the authors

An empirical study of bugs in software build systems

NSF

Chemotherapy induced nausea and vomiting may cause anxiety and depression in the family caregivers of patients with cancer

ObjectiveTo investigate the impact of chemotherapy induced nausea and vomiting (CINV) on the anxiety and depression of the primary family caregivers of patients with cancer.MethodsThis study screened family caregivers of patients with cancer undergoing highly emetogenic chemotherapy (HEC) containing a 3-day cisplatin regime. Caregivers who did not experience anxiety or depression at baseline screening were enrolled in this study. Based on the patients’ CINV status during chemotherapy, their family caregivers were divided into two groups: patients who experienced CINV (CINV group) and patients who did not experience CINV (No-CINV group). All enrolled family caregivers completed the Hospital Anxiety and Depression Scale (HADS) questionnaire on the fourth and 8 days of chemotherapy.ResultsA total of 256 family caregivers were screened for this study, of which 195 caregivers without anxiety or depression at baseline were included. A total of 150 (76.9%) patients undergoing chemotherapy experienced acute CINV; 63 (42%) of their family caregivers experienced anxiety, and 65 (43.3%) developed depression. This was significantly higher than the experiences of the No-CINV group (2.2%, P < 0.001; 0%, P < 0.001, respectively). Among the patients undergoing chemotherapy, 86 (44.1%) experienced delayed CINV. The incidence of anxiety and depression in the family caregivers of patients with delayed CINV were 27.9 and 36%, respectively, both of which were significantly higher than that in the family caregivers of the No-CINV group (0.9%, P < 0.001; and 0.9%, P < 0.001, respectively).ConclusionAcute and delayed CINV occurring in patients during chemotherapy may induce anxiety and depression in their family caregivers

Dementia Literacy among Community-Dwelling Older Adults in Urban China: A Cross-sectional Study

ObjectiveDelay in seeking diagnosis of dementia is common in China. Misinformation and poor knowledge about dementia may contribute to it. The study was designed to explore the nationwide dementia literacy among older adults in urban China and to investigate the factors associated with overall dementia literacy.MethodsIn a cross-sectional study, a convenience sample of 3,439 community-dwelling old adults aged 60 and over was recruited from 34 cities in 20 provinces between June 20 and August 20, 2014. All participants were administered the face-to-face mental health literacy questionnaire, which included the prevalence, symptoms, intention, and options for treatment of dementia. Stepwise multivariate regression analysis was used to explore factors associated with overall dementia literacy.ResultsThe response rate was 87.4%. The overall dementia literacy was 55.5% (SD = 20.9%) among all respondents. The correct response rate was higher for questions on symptoms (58.7–89.6%), but lower for questions on the prevalence (22.2%) and choosing appropriate professional care personnel (22.2%). Being male [OR = 1.256, 95% CI (1.022–1.543)], having lower per capita annual income [OR = 1.314, 95% CI (1.064–1.623)], lower education [OR = 1.462, 95% CI (1.162–1.839)], and suspected depression [OR = 1.248, 95% CI (1.009–1.543)] were negatively associated with overall dementia literacy.ConclusionDementia literacy among community-dwelling older adults in urban China remains very low, in particular about the impact of dementia and appropriate treatment personnel. Community educational programs aiming to close this knowledge gap are encouraged to focus on those in the population at highest risk of low dementia literacy

Cardiovascular mortality by cancer risk stratification in patients with localized prostate cancer: a SEER-based study

PurposeThe risk of cardiovascular disease (CVD) mortality in patients with localized prostate cancer (PCa) by risk stratification remains unclear. The aim of this study was to determine the risk of CVD death in patients with localized PCa by risk stratification.Patients and methodsPopulation-based study of 340,806 cases in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with localized PCa between 2004 and 2016. The proportion of deaths identifies the primary cause of death, the competing risk model identifies the interaction between CVD and PCa, and the standardized mortality rate (SMR) quantifies the risk of CVD death in patients with PCa.ResultsCVD-related death was the leading cause of death in patients with localized PCa, and cumulative CVD-related death also surpassed PCa almost as soon as PCa was diagnosed in the low- and intermediate-risk groups. However, in the high-risk group, CVD surpassed PCa approximately 90 months later. Patients with localized PCa have a higher risk of CVD-related death compared to the general population and the risk increases steadily with survival (SMR = 4.8, 95% CI 4.6–5.1 to SMR = 13.6, 95% CI 12.8–14.5).ConclusionsCVD-related death is a major competing risk in patients with localized PCa, and cumulative CVD mortality increases steadily with survival time and exceeds PCa in all three stratifications (low, intermediate, and high risk). Patients with localized PCa have a higher CVD-related death than the general population. Management of patients with localized PCa requires attention to both the primary cancer and CVD

Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: A randomised, double-blind, placebo-controlled trial

Objectives Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebocontrolled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy. Methods A randomised, double-blind and placebocontrolled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets. Results At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells. Conclusions Low-dose IL-2 might be effective and tolerated in treatment of SThe work was supported by the National Natural Science Foundation of China (31530020,31570880,81471601,81601417 and 81701598), Peking-Tsinghua Center for Life Sciences to ZG LI, Beijing Sci-Tech Committee Z171100000417007,Clinical Medicine Plus X-Young Scholars Project of Peking University (PKU2019LCXQ013) supported by the Fundamental Research Funds for the Central Universities, Beijing Nova Program Z171100001117025, National Key Research and Development Program of China (2017YFC0909003 to DY), BellberryViertel Senior Medical Research Fellowship to DY and Beijing SL PHARM

Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity

该研究成果揭示了吞噬性细胞内Hippo信号通路关键激酶Mst1和Mst2通过活化Rac家族蛋白来调节线粒体向吞噬小泡募集并释放ROS来清除病原体，这个生物学过程在天然免疫和宿主防御中发挥着重要作用。该成果解析了人的Mst1基因缺失或Rac2基因突变引发免疫缺陷综合症的致病机理，为研究人类感染性疾病提供了全新的视角。 该论文的主要工作由2012级博士生耿晶、2013级博士生孙秀峰以及王平、张世浩和王晓珍等学生共同承担，并与厦门市第一医院、台湾长庚大学、中国科学技术大学等单位合作完成，通讯作者为周大旺教授和陈兰芬教授。该研究工作获得了“青年千人计划”、国家自然科学基金委和科技部的资助。Mitochondria need to be juxtaposed to phagosomes for the synergistic production of ample reactive oxygen species (ROS) in phagocytes to kill pathogens. However, how phagosomes transmit signals to recruit mitochondria has remained unclear. Here we found that the kinases Mst1 and Mst2 functioned to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activated the GTPase Rac to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for the recruitment of mitochondria to phagosomes. Inactive forms of Rac, including the human Rac2D57N mutant, disrupted the TRAF6-ECSIT complex by sequestering TRAF6 and substantially diminished ROS production and enhanced susceptibility to bacterial infection. Our findings demonstrate that the TLR-Mst1-Mst2-Rac signaling axis is critical for effective phagosome-mitochondrion function and bactericidal activity.Supported by the National Basic Research Program (973) of China (2015CB910502 to L.C.), China's 1000 Young Talents Program (D.Z. and L.C.), the 111 Projects (B12001 and B06016), the Fundamental Research Funds for the Central Universities of China-Xiamen University (CXB2014004 to J.Z.; 20720140551 to L.C.; and 2013121034 and 20720140537 to D.Z.), the National Natural Science Foundation of China (31270918, 81222030 and J1310027 to D.Z.; 81372617, 81422018 and U1405225 to L.C.; 81472229 to L.H.; and 81302529 to X.L.), the Natural Science Foundation of Fujian (2013J06011 to D.Z. and 2014D007 to X.L.), the US National Institutes of Health (RO1 CA136567 for J.A.) and institutional funds from Massachusetts General Hospital (for J.A.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript