ABSTRACT
OBJECTIVE@#Cassiae Semen (CS, Juemingzi in Chinese) has been used for thousands of years in ancient Chinese history for relieving constipation, improving liver function as well as preventing myopia. Here we aimed to elucidate the anti-steatosis effect and underlying mechanism of CS against non-alcoholic fatty liver disease (NAFLD).@*METHODS@#High-performance liquid chromatography (HPLC) was used to identify the major components of CS water extract. Mice were fed with a high-fat and sugar-water (HFSW) diet to induce hepatic steatosis and then treated with CS. The anti-NAFLD effect was determined by measuring serum biomarkers and histopathology staining. Additionally, the effects of CS on cell viability and lipid metabolism in oleic acid and palmitic acid (OAPA)-treated HepG2 cells were measured. The expression of essential genes and proteins involved in lipid metabolism and autophagy signalings were measured to uncover the underlying mechanism.@*RESULTS@#Five compounds, including aurantio-obtusin, rubrofusarin gentiobioside, cassiaside C, emodin and rhein were simultaneously identified in CS extract. CS not only improved the diet-induced hepatic steatosis in vivo, as indicated by decreased number and size of lipid droplets, hepatic and serum triglycerides (TG) levels, but also markedly attenuated the OAPA-induced lipid accumulation in hepatocytes. These lipid-lowering effects induced by CS were largely dependent on the inhibition of fatty acid synthase (FASN) and the activation of autophagy-related signaling, including AMP-activated protein kinase (AMPK), light chain 3-II (LC3-II)/ LC3-1 and autophagy-related gene5 (ATG5).@*CONCLUSION@#Our study suggested that CS effectively protected liver steatosis via decreasing FASN-related fatty acid synthesis and activating AMPK-mediated autophagy, which might become a promising therapeutic strategy for relieving NAFLD.
ABSTRACT
Objective@#To analyze the clinical features, etiological distribution and drug sensitivity of primary nephrotic syndrome (PNS) complicated with urinary tract infection (UTI) in children.@*Methods@#The clinical data and etiological characteristics of 221 PNS patients complicated with UTI were retrospectively analyzed, who were hospitalized from January 2008 to December 2017 in the Department of Nephrology, Children′s Hospital of Chongqing Medical University.@*Results@#The PNS patients complicated with UTI were mainly preschoolers (129/221 cases, 58.4%). The incidence of relapsed PNS with UTI (134/822 cases, 16.3%) was higher than that of initial PNS with UTI (87/1 663 cases, 5.2%), and the difference was statistically significant (χ2=83.200, P<0.05). The clinical manifestation was mainly present with asymptomatic bacteriuria (173/221 cases, 78.3%). The proportions of relapsed PNS (112/173 cases) and using prednisone and/or immunosuppressant(126/173 cases) in asymptomatic UTI group were respectively significantly higher than those of the symptomatic UTI group (22/48 cases and 27/48 cases, respectively), and the difference was statistically significant (χ2=5.627, 4.850, all P<0.05). The incidence of recurrent UTI (RUTI)was 13.1% (29/221 cases). Compared with initial UTI group, RUTI group had longer course [(9.3±3.5) months vs.(4.4±3.7) months, t=9.427, P<0.05], and significantly higher proportions of relapsed PNS (29/29 cases vs.105/192 cases, P<0.05), using prednisone and/or immunosuppressant (26/29 cases vs.127/192 cases), decreased hemoglobin(Hb)(14/29 cases vs.51/192 cases) and complement C3 (14/29 cases vs.31/192 cases) and higher abnormal rate of urinary system (7/29 cases vs.6/192 cases) (χ2=5.480, 5.721, 16.039, 20.094, all P<0.05). Gram-negative bacteria were the dominant pathogens (174/263 cases, 66.1%), and Escherichia coli was the main bacteria (54/263 cases, 20.5%). The proportions of Escherichia coli, Pseudomonas aeruginosa and extended-spectrum β-lactamases(ESBLs) producing bacteria were significantly higher in RUTI group than those in initial UTI group(26/62 cases, 11/62 cases, 21/62 cases vs.28/201 cases, 15/201 cases, 15/201 cases)(χ2=22.776, 5.620, 27.970, all P<0.05). The drug sensitivity test indicated that gram-negative bacteria were more sensitive to Amikacin, Meropenem, and Piperacillin/Tazobactam, and gram-positive bacteria were more sensitive to Vancomycin, Linezolid and Teicoplanin.@*Conclusions@#Preschoolers with PNS and relapsed PNS are prone to UTI.The clinical manifestation of UTI was mainly presented with asymptomatic bacteriuria.UTI should be considered when children with PNS relapsed.PNS with longer course, anemia, decreased complement, and urinary system abnormity may be more likely to develop RUTI.Gram-negative bacteria were the dominant pathogens.Escherichia coli was the main bacteria with high drug resistance and ESBLs producing bacteria may be more common in RUTI.Piperacillin/Tazobactam could be the first choice of empirical antimicrobial agents for PNS complicated with UTI.