1.The comparison between mild cases and severe cases of hand-foot-mouth disease
Guoshun MAO ; Ling LUO ; Xiaolin LIU ; Lichun WANG ; Lifeng LIU ; Zhifeng QIU ; Yang HAN ; Yong ZHAO ; Ying ZHU ; Jing XIE ; Qihan LI ; Taisheng LI
Chinese Journal of Infectious Diseases 2008;26(7):387-390
Objective To compare the simple cases of hand-foot-mouth disease(HFMD) with HFMD patients complicated with encephalitis and HFMD cases complicated with pulmonary edema (PE). To explore predictor factors of disease progression and unfavorable prognosis. Methods Forty-one EV71-infected children admitted to the Fuyang First People's Hospital in Anhui Province from March to May in 2008 were investigated in the research, who were classified as encephalitis-complicated cases ( encephalitis group, n = 15 ), PE-complicated cases ( PE group, n = 15 ) and simple cases (simple group, n= 11 ). Their clinical manifestation, laboratory findings, and immunophenotypes of peripheral blood lymphocyte were analyzed to find predictors associated with disease progression and unfavorable outcomes. Results The mortality rate in PE group was 66.7%, which was significantly higher than that in encephalitis group. Ninty-three point three percent cases in PE group and encephalitis group were younger than 3 years old, with statistic difference compared to simple group. Patients in PE group had higher total blood white cell (WBC) counts and higher absolute neutrophil counts and tended to have higher breathing rate, heart i'ate and glucose level than encephalitis group. The percentages of T cells and natural killer (NK) cells were significantly lower among patients complicated with encephalitis than simple HFMD patients.Conclusions PE is one predictor for poor prognosis. Factors correlated with unfavorable outcome include high WBC, high absolute neutrophil counts; elevated breathing rate, heart rate and glucose level. The immunophenotypes of peripheral blood lymphocytes can also predict the disease progression.
2.Airborne fine particle decreases the cell viability and induces inflammation in human bronchial epithelial cells
Zhicong HONG ; Xianyang LUO ; Chengfu CAI ; Jian XU ; Guoshun ZHUANG
Journal of Central South University(Medical Sciences) 2017;42(9):1042-1047
Objective:To investigate the effects of airborne fine particle on cell viability and inflammation in human bronchial epithelial cells.Methods:Atmospheric PM2.5 samples were collected by PM2.5 sampler.PM2.5 morphology was observed by scanning electron microscope (SEM).Human bronchial epithelial cells (BEAS-2B) were treated with PM2.5 at different concentrations (0,50,100,200,400,800 μg/mL) for 12,24 or 48 hours,and the cell activity were evaluated by cell counting kit-8 (CCK-8).The mRNA expression levels of (granulocyte-macrophage colony stimulating factor,GM-CSF) and TNF-α were detected by quantitative real-time PCR (qRT-PCR).Western blot was used to detect the protein expressions of GM-CSF and TNF-α.Results:According to SEM,the shape of PM2.5 varied,and the diameter was different and mostly equal to or less than 2.5 μm.CCK-8 assay showed that different concentrations of PM2.5 exposure for 12 hours,24 hours and 48 hours resulted in loss of cell viability of BEAS-2B cells (P<0.05).Different concentrations of PM2.5 increased the mRNA and protein expression of GM-CSF and TNF-α,and the higher concentration of PM2.5 induced higher expression,which have statistical significant difference between the groups (P<0.05).Conclusion:Atmospheric PM2.5 can cause inflammatory response in human bronchial epithelial cells.They can reduce cell viability,which may be related to the PM2.5 trigger and aggravation of bronchopulmonary inflammatory diseases.
3.Discovery of an orally active VHL-recruiting PROTAC that achieves robust HMGCR degradation and potent hypolipidemic activity
Guoshun LUO ; Zhenbang LI ; Xin LIN ; Xinyu LI ; Yu CHEN ; Kun XI ; Maoxu XIAO ; Hanlin WEI ; Lizhe ZHU ; Hua XIANG
Acta Pharmaceutica Sinica B 2021;11(5):1300-1314
HMG-CoA reductase (HMGCR) protein is usually upregulated after statin (HMGCR inhibitor) treatment, which inevitably diminishes its therapeutic efficacy, provoking the need for higher doses associated with adverse effects. The proteolysis targeting chimera (PROTAC) technology has recently emerged as a powerful approach for inducing protein degradation. Nonetheless, due to their bifunctional nature, developing orally bioavailable PROTACs remains a great challenge. Herein, we identified a powerful HMGCR-targeted PROTAC (