Ten constituents have been isolated from the rhizomes of Cimicifuga foetida L.. Based on spectral evidence and by direct comparison with authentic samples, they were identified as isoferulic acid(Ⅰ ), 3-acetylcaffeic acid(Ⅱ ), caffeic ester glucoside(Ⅲ), cimifugin(Ⅳ),cimifugin glucoside(Ⅴ ), 6 -isoinosine (Ⅵ), cimidahurine(Ⅶ ), cimidahurinine(Ⅷ), D-glucose (Ⅸ) and sucrose (Ⅹ ).

【Objective】To observe the expression of PI3-K phosphorylated products and elucidate the correlation between PI3-K phosphorylated products and Th2 cytokine in peripheral blood mononuclear cell (PBMC).【Methods】14 patients with active lupus nephritis and 12 controls were selected,PI3-K phosphorylated products were detected by immunoprecipitation and Western blotting,RT-PCR was used to observe interleukin-6 mRNA and interleukin-10 mRNA expression.【Results】In either spontaneous condition or stimulated by anti-CD3 antibody,the expression of PI3-K phosphorylated products in patients with active lupus nephritis were higher than those of the controls(1.14±0.23 vs 0.46±(0.12，P=0.023;2.09±0.63 vs 0.65±0.14，P=0.016).The expression of PI3-K phosphorylated products in active lupus nephritis showed a positive correlation with interleukin-6 mRNA and interleukin-10 mRNA (r=0.652,P=0.008;r=0.718,P=0.007).PY294002,one of specific inhibitor of PI3-K,inhibited significantly the expression of interleukin-6 mRNA(2.32±0.51 vs 0.57±0.15,P=0.009) and interleukin-10 mRNA (1.71±0.33 vs 0.67±0.11,P=0.006) in stimulated PBMC in active lupus nephritis.【Conclusion】PI3-K can involve in the pathogenesis of lupus nephritis by inducing the overexpression of interleukin-6 and interleukin-10.

Crush syndrome in patients rescued from earthquake is a complex clinical syndrome with many medical conditions.The most complications are hyperkalemia,acute kidney injury,shock,infection,ARDS,malnutrition and multiorgan dysfunction.Managing these critical issues appropriately is essential for effective treatment of the crush syndrome.

Objective To investigate the relationship between triglyceride and serum polyunsaturated fatty acid (PUFA) in patients with metabolic syndrome (MS).Methods Totally 74 MS patients (MS group) and 62 healthy subjects (normal control group,NC group) were recruited from June 2011 to June 2012 in Shaoxing People's Hospital.Serum phospholipid fatty acid profiles were analyzed with capillary gas chromatography.Serum lipids were measured by enzymatic assay.Results The triglyceride concentration was significantly higher in MS group than that in NC group [(2.0 ±0.8) mmol/L vs.(1.3 ±0.5) mmol/L,P=0.000].The levels of n-3 PUFA,n-6 PUFA,and PUFA were significantly lower in MS group than those in NC group (9.8％ ±2.2％ vs.11.1％ ±2.4％,P=0.002; 35.4％ ±6.7％ vs.39.5％ ±7.8％,P=0.009; 45.2％ ±8.9％ vs.50.6％ ±10.1％,P =0.000).Triglyceride concentration was inversely correlated with n-3 PUFA and PUFA levels (r =-0.42,P =0.008 ; r =-0.23,P =0.013).Conclusions n-3 PUFA,n-6 PUFA,and PUFA decrease in MS patients.Triglyceride concentration is inversely correlated with PUFA.

OBJECTIVE: To observe the correlated serum inflammatory factor and cytokine changes in patients with coronary stent implantation, and to explore the significance of these changes.METHODS: Chinese Journal Full-Text Database was retrieved with search terms of coronary artery disease, percutaneous coronary interventions, inflammation, intimal hyperplasia, apoptosis and platelet-derived growth factor from 1995 to 2008. The language was restrained Chinese. A total of 17 literatures were collected, which concerns the changes of correlated inflammatory factor and cytokine levels and its significance. The literatures were sorted according to research object, experimental grouping,sample collection, assay method, experimental result, as well as experimental conclusion. Simultaneously, the patients received coronary stent implantation was analyzed to explore the significance of inflammatory factor and cytokine changes.RESULTS: The dynamic changed serum inflammatory factor and cytokine in patients with coronary stent implantation may be associated with the following mechanisms:①Endothelial cells were easily damaged in the balloon dilatation or stent implantation,therefore, inflammatory mediators or inflammatory factors were exposed to blood circulation, which stimulating neutrophilic granulocytes and up-regulating leukocyte adhesion molecule CD11b expression. ②Many stimulus could arise nuclear factor induced inflammatory reaction, produce interleukin 6, and stimulate C-reactive protein generation. ③The level of angiotensin Ⅱ increased at several days following stent implantation, and heightened with time prolonged, the proliferation of angiotensin Ⅱ was regulated by platelet-derived growth factor. By increasing the expression of endothelin, the synthesis of endothelin was accelerated, the proliferation and migration of vascular smooth muscle cells was promoted, which ultimately resulted in atherogenesis, balloon damage also involved in this process, which may be one of the mechanisms of restenosis.CONCLUSION: The changes of correlated inflammatory factor and cytokine can be served as inflammatory reaction indexes;moreover, soluble CD40 ligand, C-reactive protein and matrix metalloproteinase 9 may be associated with in-stent restenosis.

Objective:To investigate the effect of Liangxue Huoxue decoction on intestinal flora, intestinal barrier and NOD-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pyroptosis signaling pathway in mice model of sepsis-induced acute kidney injury (AKI).Methods:The model of AKI was established by cecal ligation and perforation (CLP). Thirty male C57BL/6 mice were randomly divided into sham operation group (Sham group), sepsis group (CLP group) and sepsis+Liangxue Huoxue decoction (CLP+LXHX group), with 10 mice in each group. Mice in Sham group only underwent laparotomy. Two hours before model establishment, mice in CLP+LXHX group were treated with Liangxue Huoxue decoction (6 g/kg) by gavage; mice in Sham group and CLP group were given equal volume of normal saline by gavages. After 24 hours of modeling, all mice were sacrificed under anesthesia, and the colon and kidney tissues and fresh feces in the colon were taken. The pathological changes of kidney and colon were observed by hematoxylin-eosin (HE) staining under light microscope. Real-time polymerase chain reaction (RT-PCR) was used to detect inflammatory factors (interleukins, IL-1β and IL-18) in renal tissue. The expressions of NLRP3, caspase-1 and GSDMD were detected by Western blotting. The changes of intestinal flora in mice were detected by 16S rDNA high-throughput sequencing.Results:Compared with the Sham group, the inflammatory cell infiltration of the kidney tissue was increased and the kidney became vacuolated in CLP group, the mRNA expressions of IL-1β, IL-18, and the protein expressions of NLRP3, caspase-1 and GSDMD were significantly increased in CLP group, the species richness of intestinal microflora decreased significantly, the relative abundance of Enterococcus and Escherichia-Shigella increased significantly, and the relative abundance of Ileibacterium, Alloprevotella, Lachnospiraceae, Klebsiella and Parasutterella increased significantly in CLP group. Compared with CLP group, Liangxue Huoxue decoction can significantly reduce the pathological changes of kidney and colon tissue, reduce the pathological score (1.75±0.43 vs. 3.50±0.50 for kidney tissue, 1.25±0.43 vs. 4.50±0.50 for colon tissue, both P < 0.05), improve the composition of intestinal flora, reduce the relative abundance of Enterococcus and Escherichia-Shigella, and significantly increase the relative abundance of Lactobacillus and Akkermansia. In addition, Liangxue Huoxue decoction can significantly reduce mRNA expressions of IL-1β and IL-18 in kidney tissue [IL-1β mRNA (2 -ΔΔCt): 1.59±0.05 vs. 4.61±0.88, IL-18 mRNA (2 -ΔΔCt): 1.69±0.17 vs. 2.86±0.63, both P < 0.05] and the protein expressions of NLRP3, caspase-1 and GSDMD (NLRP3/GAPDH: 0.71±0.04 vs. 0.89±0.01, caspase-1/GAPDH: 1.04±0.04 vs. 1.48±0.04, GSDMD/GAPDH: 0.90±0.01 vs. 1.41±0.02, all P < 0.05). Conclusions:Liangxue Huoxue decoction has obvious protective effect on AKI induced by sepsis. It can improve intestinal barrier by regulating intestinal flora, thereby inhibiting the activation of NLRP3/caspase-1/GSDMD signaling pathway in kidney tissue and reducing the expression of proptosis-related inflammatory factors.

Objective:To investigate the synergistic effects and molecular mechanisms of dihydroartemisinin(DHA) and sorafenib(SOR) in inducing ferroptosis in anaplastic thyroid cancer(ATC) cells.Methods:CCK-8 and flow cytometry assays were performed to detect the effects of DHA and SOR on the proliferation and ferroptosis of ATC cells(CAL-62). Real-time fluorescence quantitative PCR and Western blotting assays were performed to detect the expressions of ferroptosis-related genes glutathione peroxidase 4(GPX4), solute carrier family 7 member 11 gene(SCL7A11), lipoxygenase-15(LOX-15), and p53. The levels of iron death intermediate metabolites including lactate dehydrogenase(LDH), glutathione(GSH), malondialdehyde(MDA), ferrous ion(Fe 2+ ), nitric oxide(NO), and reactive oxygen species(ROS)were measured by corresponding assay kits. The corresponding inhibition of DHA and SOR on ATC in vivo was analyzed in a tumor model in nude mice. Results:Compared with the control group, DHA, SOR, and DHA+ SOR treatment significantly inhibited cell proliferation and apoptosis in a dose-dependent manner( P<0.001), with increased LDH, Fe 2+, MDA, and ROS contents and reduced GSH activity( P<0.001), which were promoted by ferrous sulfate(FeSO 4)and reversed by ferroptosis inhibitor-1. Compared with the control group and the drug monotherapy group, 15-LOX-2 and p53 expressions were upregulated in DHA+ SOR group while GPX4 and SCL7A11 expressions were decreased( P<0.001), without significant difference in 15-LOX-1 protein content. In addition, NO level was significantly increased in DHA+ SOR group( P<0.001). DHA and SOR inhibited tumor growth of ATC in vivo. Conclusion:DHA and SOR synergistically induced ferroptosis via upregulating the expression of 15-LOX-2 gene and inhibiting NO synthesis in ATC cells.

Objective:To assess the bacterial profiles and antimicrobial susceptibility patterns in uropathogens, and help to inform the empiric treatment decisions for urinary tract infection in outpatient settings.Methods:A single institutional retrospective analysis was performed on positive urine cultures from outpatient settings between January 1998 and December 2018. To analyze changes over time, trends analysis were undertaken on bacterial profiles, antimicrobial susceptibility and resistance.Results:A total of 1.172 pathogenic bacteria were isolated after exclusion of duplicate strains originated from the same patient, including 991(84.6%) Gram-negative bacterial strains and 181(15.4%) Gram-positive strains. The most common Gram-negative uropathogens were Escherichia coli (60.8%) and Klebsiella pneumonia (8.1%). Enterococcus faecalis (4.6%) was the predominant Gram-positive strain. The detection rate of Escherichia coli increased significantly, from 50.8% to 63.2% ( χ2=7.978, P=0.046), and no significant difference was observed in the distribution of major uropathogenic bacteria over the 20 years (all P>0.05). The proportion of extended-spectrum β-lactamase (ESBLs) producing strains increased significantly across the 20 years ( P<0.05). The resistance rates of Escherichia coli to amoxicillin and clavulanate potassium, aztreonam, ceftazidime, ciprofloxacin and sulbactam + cefoperazone increased significantly (all P<0.05). All the isolates sustained high susceptibility to tazobactam + piperacillin, amikacin, imipenem and nitrofurantoin (95.0%, 95.7%, 97.9% and 91.1%). Similar to those of Escherichia coli, Klebsiella pneumoniae remained a high and stable sensitivity to tazobactam+piperacillin, amikacin and imipenem during the 20 years (79.1%, 88.0% and 80.3%). However, the proportion of ESBLs producing strains increased significantly ( P<0.05). Among Gram-positive bacteria isolates, the sensitivity rates of Enterococcus faecalis to ampicillin, nitrofurantoin and penicillin G were 100.0%. No vancomycin resistant strain was detected in Gram-positive bacteria. Conclusions:From 1998 to 2018, Escherichia coli and Klebsiella pneumoniae are the most common Gram-negative bacteria uropathogens obtained in outpatient settings. Significant increases of resistance to some antimicrobial agents such as second- and third-generation cephalosporins and fluoroquinolones are observed during the 20 years and high susceptibilities to tazobactam+piperacillin, amikacin, imipenem and nitrofurantoin sustain over time. Local treatment strategies of urinary tract infections on outpatient basis should be made according to epidemiology of drug resistance and individual characteristics to control the spread and curb the prevalence of drug resistant.