Mechanism study of chlorogenic acid alleviating macrophage activation / 中国药房

OBJECTIVE To observe the effects of chlorogenic acid on the activation of macrophage induced by lipopolysaccharide （LPS）， and to explore the role of triggering receptors expressed on myeloid cells-2 （TREM2） in the action. METHODS To find a suitable LPS concentration， the cells were cultured with 1， 10 and 100 ng/mL LPS for 24 h. The level of interleukin 6 （IL-6） in the cell culture supernatant and protein expression of inducible nitric oxide synthase （iNOS） in the cells were detected. To search for a suitable chlorogenic acid concentration， the cells were divided into control group， LPS group and three chlorogenic acid （0.01， 0.1 and 1 μmol/L）+LPS groups. The levels of tumor necrosis factor α （TNF-α） and IL-1β in the cell culture supernatant， the protein expressions of iNOS and TREM2 in the cells and cell viability were detected. To observe the effects of TREM2 in chlorogenic acid alleviating macrophage activation， TREM2-small interfering RNA （TREM2-siRNA） was taken to intervene in TREM2 protein expression. The cells were divided into control group， LPS group， chlorogenic acid+LPS group， TREM2-siRNA+chlorogenic acid+LPS group and SC-siRNA+chlorogenic acid+LPS group. After 24 h incubation， the levels of TNF- α and IL-1β in the cell culture supernatant and protein expressions of TREM2， iNOS and nuclear factor κB p65 （NF-κB p65） in the cells were detected. RESULTS 10 ng/mL LPS promoted IL-6 release and increased iNOS protein expression， and 10 ng/mL LPS was taken in the next experiments. Compared with the LPS group， 0.1 μmol/L chlorogenic acid decreased TNF-α jiaji1981@126.com and IL-1β levels， and down-regulated iNOS expression，meanwhile increased TREM2 expression without effect on cell viability， and 0.1 μmol/L chlorogenic acid was taken in the next experiments. Compared with the control group， the protein expressions of iNOS and NF- κB p65 in the LPS group were significantly increased （P＜0.05）； compared with the LPS group， the protein expressions of iNOS and NF- κB p65 in the chlorogenic acid+LPS group were significantly decreased， the protein expressions of TREM2 was significantly increased （P＜ 0.05）； compared with the chlorogenic acid+LPS group， the protein expressions of iNOS and NF-κB p65 of TREM2-siRNA+ chlorogenic acid+LPS group were significantly increased， the protein expressions of TREM2 was significantly decreased （P＜0.05）. TREM2-siRNA could significantly reverse the above effects of chlorogenic acid， while SC-siRNA did not significantly affect the above anti-inflammatory effects of chlorogenic acid. CONCLUSIONS Chlorogenic acid can inhibit the LPS-induced macrophage activation， and its anti-inflammatory may be mediated by TREM2 protein.

The impact of goggle-associated harms to health and working status of nurses during management of COVID-19

BackgroundTo investigate the impact of goggles on their health and clinical practice during management of patients with COVID-19. Methods231 nurse practitioners were enrolled who worked in isolation region in designated hospitals to admit patients with COVID-19 in China. Demographic data, goggle-associated symptoms and underlying reasons, incidence of medical errors or exposures, the effects of fog in goggles on practice were all collected. Data were stratified and analyzed by age or working experience. Risk factors of goggle-associated medical errors were analyzed by multivariable logistical regression analysis. FindingsGoggle-associated symptoms and foggy goggles widely presented in nurses. The most common symptoms were headache, skin pressure injury and dizziness. Headache, vomit and nausea were significantly fewer reported in nurses with longer working experience while rash occurred higher in this group. The underlying reasons included tightness of goggles, unsuitable design and uncomfortable materials. The working status of nurses with more working experience was less impacted by goggles. 11.3% nurses occurred medical exposures in clinical practice while 19.5% nurses made medical errors on patients. The risk factors for medical errors were time interval before adapting to goggle-associated discomforts, adjusting goggles and headache. InterpretationGoggle-associated symptoms and fog can highly impact the working status and contribute to medical errors during management of COVID-19. Increased the experience with working in PPE through adequate training and psychological education may benefit for relieving some symptoms and improving working status. Improvement of goggle design during productive process was strongly suggested to reduce incidence of discomforts and medical errors.

CAFs-derived MFAP5 promotes bladder cancer malignant behavior through NOTCH2/HEY1 signaling.

Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment and contribute to tumor cell proliferation and metastasis. Microfibrillar-associated protein 5 (MFAP5), a component of elastic microfibers and an oncogenic protein in several types of tumors, is secreted by CAFs. However, the role of MFAP5 in the bladder cancer remains unclear. Here, we report that MFAP5 is upregulated in bladder cancer and is associated with poor patient survival. Downregulation of MFAP5 in CAFs led to an impairment in proliferation and invasion of bladder cancer cells. Luciferase reporter assays and electrophoretic mobility shift assays (EMSA) showed QKI directly downregulates MFAP5 in CAFs. In addition, CAFs-derived MFAP5 led to an activation of the NOTCH2/HEY1 signaling pathway through direct interaction with the NOTCH2 receptor, thereby stimulating the N2ICD release. RNA-sequencing revealed that MFAP5-mediated PI3K-AKT signaling activated the DLL4/NOTCH2 pathway axis in bladder cancer. Moreover, downregulation of NOTCH2 by short hairpin RNA or the inactivating anti-body NRR2Mab was able to reverse the adverse effects of MFAP5 stimulation in vitro and in vivo. Together, these results demonstrate CAFs-derived MFAP5 promotes the bladder cancer proliferation and metastasis and provides new insight for targeting CAFs as novel diagnostic and therapeutic strategy.

Can SARS-CoV-2-infected women breastfeed after viral clearance? / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The recently emerged novel coronavirus pneumonia, named the coronavirus disease 2019 (COVID-19), shares several clinical characteristics with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and spread rapidly throughout China in December of 2019 (Huang et al., 2020). The pathogen 2019 novel coronavirus (2019-nCoV) is now named SARS coronavirus 2 (SARS-CoV-2) and is highly infectious. As of Apr. 9, 2020, over 80 000 confirmed cases had been reported, with an estimated mortality rate of 4.0% (Chinese Center for Disease Control and Prevention, 2020). Person-to-person transmission and familial clustering have been reported (Chan et al., 2020; Nishiura et al., 2020; Phan et al., 2020). However, there is no evidence of fetal intrauterine infection in pregnant women who have been infected with SARS-CoV-2 in their third trimester (Chen et al., 2020). It is unclear whether breastfeeding transmits the virus from previously infected and recovered mothers to their babies. Here we report the clinical course of a pregnant woman with COVID-19. In order to determine whether SARS-CoV-2 can be transmitted to newborns through breastfeeding, we measured viral RNA in the patient's breastmilk samples at different time points after delivery.

Transmission risk of patients with COVID-19 meeting discharge criteria should be interpreted with caution / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

As of Apr. 22, 2020, the World Health Organization (2020) has reported over 2.4 million confirmed coronavirus disease 2019 (COVID-19) patients and 169 151 deaths. Recent articles have uncovered genomic characteristics and clinical features of COVID-19 (Chan et al., 2020; Chang et al., 2020; Guan et al., 2020; Zhu et al., 2020), while our understanding of COVID-19 is still limited. As suggested by guidelines promoted by the General Office of National Health Commission of the People's Republic of China (2020) (from Versions 1 to 6), discharged standards for COVID-19 were still dependent on viral real-time polymerase chain reaction (RT-PCR) tests of respiratory specimens, showing that recovered COVID-19 patients with twice negative RT-PCR could meet discharge criteria. Here, we examined two cases in which nucleic acid test results were inconsistent with clinical and radiological findings, leading to suboptimal care.