Objective To investigate the effects of continuous venovenous hemodiafiltration (CVVHDF) on plasma lipopolysaccharide (LPS),interleukin(IL) 1β,IL-4,high mobility group box 1 (HMGB-1) in multiple organ dysfunction syndrome (MODS) dogs,to explore the therapeutic mechnism of CVVHDF.Methods Dogs were subjected to hemorrhagic shock plus resuscitation and endotoxemia to establish MODS model,then they were randomly divided into 2 groups:CVVHDF group (n=6) and MODS group (n=6).After endotoxin injection completed,the CVVHDF group received CVVHDF treatment for 24 h; MODS group did not receive CVVHDF treatment.The LPS,IL-1β,IL-4,HMGB-1 levels in plasma and ultrafiltrate were measured at different time points(before operation,before intravenous infusion of endotoxin,0 h,3 h,6 h,9 h,12 h,18 h,24 h after intravenous infusion completion of endotoxin),then the sieving coefficient (SC) was calculated.Results Compared with MODS group,the LPS,IL-1β,IL-4,HMGB-1 levels in plasma were significantly decreased in the CVVHDF group at 9 h,12 h,18 h,24 h (P ＜ 0.05).Some concentration of IL-1β,IL-4 and HMGB-1 was detected in the ultrafiltrate,the SC for IL-1β,IL-4 and HMGB-1 was 0.60±0.12,0.83±0.11,0.70±0.09 respectively,and LPS could not be detected in the ultrafiltrate,its SC was 0.After treatment,the damage level of lung and renal had been significantly reduced in CVVHDF group.Conclusion CVVHDF can effectively reduce the levels of pro-inflammatory mediator and anti-inflammatory cytokine related to MODS,cut off the vicious circle of cytokine network and reduce the damage level of organism in the treatment of MODS.

Objective To investigate the effect of allergen-specific immunotherapy on FEV1 and airway responsiveness in patients with idiopathic asthma.Methods 90 patients with idiopathic asthma from January 2013 to August 2015 in Deqing City People's Hospital were selected and randomly divided into control group and study group with 45 cases in each group.Control group were treated with anti-infection, relieving cough and eliminating phlegm, relieving spasm and relieving asthma, the study group was treated with allergen specific immunotherapy based on the control group, and a total of 3 months for a course of treatment.Blood samples were used to measure inflammatory mediators , airway sensitivity index, pulmonary function and airway responsiveness, at the same time, the clinical efficacy and complications were compared.Results Compared with before treatment, the levels of FVC, PEF, FEV1 and FEV1/FVC in the two groups increased, levels of AI, AO, T and WA decreased, levels of serum IL-4 decreased, levels of IL-10, IFN-γincreased, levels of serum IgE, SIgE, TIgE and EOS decreased, the difference was statistically significant (P<0.05), compared with the control group, the levels of FVC, PEF, FEV1 and FEV1/FVC in the study group were higher, the levels of AI, AO, T and WA were lower, serum IL-4 levels were lower after treatment, levesls of IL-10, IFN-γwere higher, levels of serum IgE, SIgE, TIgE and EOS were lower, the difference was statistically significant (P<0.05), and the effective rate in the control group (71.11%) was lower than the study group (88.89%), the difference was statistically significant(P <0.05).Conclusion Allergen-specific immunotherapy was effective for cough variant asthma, it can improve pulmonary function, inflammation and airway sensitivity.

Objective To observe the members' dynamic change of renin-angiotensin system (RAS) and angiotensin converting enzyme 2(ACE2)-Ang(1-7)-Mas axis during the continuous venovenous hemodiafiltration (CVVHDF) treating the dogs with multiple organ dysfunction syndrome (MODS),and to investigate the efficacy mechanism on cardiac function.Methods Dogs were subjected to hemorrhagic shock plus resuscitation and endotoxemia to establish MODS model,then they were randomly divided into 2 groups:CVVHDF group (n=8) and MODS group (n=6).After endotoxin injection completion,the CVVHDF group received CVVHDF for 12 h,MODS group didn't.Radioimmunoassay,euzymelinked mmunosorbent assay (ELISA) were used to detect the content of renin,Ang Ⅰ,Ang Ⅱ,Ang (1-7).Real-time PCR was used to detect the expression of renin mRNA and ACE2 mRNA.Western blotting was used to detect the protein content of renin,Ang Ⅱ,ACE2 and Ang (1-7).Results (1) Organ function:Compared with the MODS group,the vital signs,heart,lung and renal function were significantly ameliorated in the CVVHDF group,the difference had statistical significance (P＜ 0.05).(2) RAS changes:To detect index from the level of organs,genetic and molecular in arterial tissue,the results displayed that the content of renin,Ang Ⅰ,Ang Ⅱ,the expression of renin mRNA,the protein content of renin,Ang Ⅱ in CVVHDF group were lower than that in MODS group,the difference had statistical significance (P ＜ 0.01).(3)ACE2-Ang(1-7)-Mas axis's changes:Using the same methods above to detect corresponding indicators,the results displayed that the content of ACE2,Ang(1-7),the expression of ACE2 mRNA and the protein content of ACE2,Ang(1-7) in CVVHDF group were significantly improved than that in MODS group,the difference had statistical significance (P ＜ 0.01).Conclusions In the process of CVVHDF treating MODS,the ACE2 -Ang(1-7)-Mas axis plays the role which antagonizes the RAS system,and to protect the cardiac function.This research may be important for MODS' clinical rescue.

Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. We have previously identified the benzoyl sulfathiazole derivative II as a non-competitive PTP1B inhibitor with in vivo insulin sensitizing effects. Preliminary SAR study on this compound series has been carried out herein, and thirteen new compounds have been designed and synthesized. Among them, compound 10 exhibited potent inhibition against human recombinant PTP1B with the IC50 value of 3.97 micromol x L(-1), and is comparable to that of compound II.

Objective Plasma phospholipid metabolism analysis was employed to investigate plasma metabolic profile of acute renal graft rejection in order to find potential disease biomarkers and reveal its pathophysiological changes.Methods Selected 33 patients which did renal transplant in our hospital during 2009 to 2010,named preoperative group.14 patients were diagnosed as acute graft rejection,and 19 patients were non-acute graft rejection.Then use ultra performance liquid chromatography (UPLC) coupled with quadrupole time of flight mass spectrometry (qTOF-MS) to establish the metabolic fingerprint in those patients.The date was preprocessed with software Markerlynx,and analyzed with partial least squares discriminant analysis (PLS-DA),and data from conventional laboratory techniques were used for assessing renal function.Results In the plasma of renal transplant patients,seventeen biomarkers were discovered:creatinine,four sphingomyelins (SM),nine phosphatidylcholines (PC),three lysophosphatidylcholine (LPC).While the creatinine was increased,the others were reduced obviously.Conclutions UPLC-qTOF-MS based metabonomics can analyze the plasma phospholipid metabolism in patients with renal transplantation,reveal the law of phospholipids metabolic changes in the process of acute rejection.The levels of plasma phosphatidylcholine's esterlysis and fatty acids' β-oxidation are increased.The immunosuppressive therapy can reduce the activity of phospholipase,inhibit the level of plasma phosphatidylcholine's esterlysis and fatty acids' β-oxidation,which restraines the development of acute rejection after renal transplantation.Therefore it may be a promising new technology in diagnosing acute renal graft rejection after renal transplantation.

Jervine, a novel steroidal alkaloid from Veratrum nigrum L., exhibits both antitumor effect and potential toxicity. The aim of study was to characterize the pharmacokinetic behaviors and enterohepatic circu-lation of jervine in rats. A rapid and simple ultra-high performance liquid chromatography-tandem mass spectrometric method was developed and validated for quantification of jervine and alpinetin (internal standard) in rat plasma. After extraction from rat plasma by a simple protein-precipitation method, the analyte was separated on a C18 column (2.1 mm × 50 mm, 1.7μm) using water with 0.1％formic acid and acetonitrile as the mobile phase delivered at a flow rate of 0.4 mL/min. Jervine and alpinetin were determined in the positive mode with multiple reaction monitoring (MRM) of the ion transitions at m/z 426.3→108.8 and m/z 271.0→166.9, respectively. Molecular docking method was used to investigate the binding of jervine to p-glycoprotein and dehydroepiandrosterone sulfotransferase. The method was well validated within acceptance limits including specificity, matrix effect, recovery, precision, accuracy, and stability, and was successfully applied to the pharmacokinetic study of jervine after oral and intravenous administration to rats. Jervine presented a small volume of distribution, fast absorption, high oral bioavailability, and enterohepatic circulation. The enterohepatic circulation was first observed in veratrum alkaloids, and was further investigated by molecular docking studies, which was related to the binding of jervine to p-glycoprotein and dehydroepiandrosterone sulfotransferase. The pharmacokinetic properties and enterohepatic circulation of jervine in rats provided a significant basis for the drug-drug interaction and toxicity study in the future.

Objective:To evaluate the knowledge, attitudes and practices ( KAP) on National Essential Medi-cine System among pharmacists from secondary public hospitals in Shaanxi province. Methods: The quantitative re-search of KAP questionnaire is used, and the content of questionnaire includes personal information, knowledge, atti-tudes and practices. Results: A total of 520 copies of questionnaires were distributed and 82. 3% were effective. Respondents’ overall knowledge and attitudes are at the middle level;the main way to obtain knowledge is via training and meeting;respondents’ education level and frequency of participating in training have a significant impact on their level of knowledge;the degree of attention paid by hospitals has yet to be strengthened; and respondents are mostly concerned about the supply and distribution of essential drugs. Conclusion: In order to improve the awareness and recognition levels of pharmacists on the implementation of National Essential Medicine System in secondary public hospitals, the government should take the relevant measures, including introducing the high educated persons into secondary public hospitals, organizing related training programs and standardizing the daily monitoring of essential drugs in secondary public hospitals, etc.

Objective:To investigate the detection rate of intestinal colonization of carbapenem-resistant Enterobacterales (CRE) in inpatients, and to analyze the molecular epidemiological characteristics of CRE strains.Methods:This was a prospective study. Stool, rectal swab or perianal swab specimens of 213 inpatients in the surgical intensive care unit (SICU), medical intensive care unit (MICU) and the department of hematology (transplantation ward) in The Second Hospital of Anhui Medical University were collected from March to December, 2019. MacConkey plate containing carbapenems was used to screen CRE strains, and bacteria identification and drug susceptibility test were conducted. Key strains were selected for whole genome sequencing (WGS). Besides, multilocus sequence typing, capsular serotype, drug resistance gene, virulence gene and plasmid carrying characteristics of these strains were analyzed. Using KPN FJ723042 sequence as a reference, the single-nucleotide polymorphism (SNP) of all strains was analyzed.Results:Twenty-three CRE strains were detected, with a detection rate of 10.8%(23/213), which included 15(65.2%) carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates, three (13.0%) Escherichia coli strains, three (13.0%) Enterobacter cloacae strains and two (8.7%) Citrobacter freundii strains. SNP cluster analysis showed that the 15 CRKP strains had two main clonotypes, which were both predominant in SICU. Fifteen strains of CRKP were type ST11-K64. All these strains carried β-lactamase Klebsiella pneumoniae carbapenemase 2 ( blaKPC-2 ), and 12 strains carried regulator of mucoid phenotype gene A2 ( rmpA2) and iucABCD. Conclusions:The detection rate of intestinal colonization of CRE in inpatients is high, and most strains are CRKP of type ST11-K64. These CRKP strains have both multidrug resistance and virulence characteristics, which are risks for hospital transmission.

Objective:The whole-genome sequencing and virulence characteristics analysis of a Klebsiella pneumoniae isolate that caused lower limb gas gangrene were performed to provide a reference for the comprehensive understanding of molecular virulence characteristics of K. pneumoniae causing severe community-acquired infection. Methods:The patient was admitted to the emergency department for treatment on March 13, 2018.The main clinical symptoms of the patients were high fever, gas gangrene of the left lower limb, and diabetic ketoacidosis. The pus specimen was collected for the bacterial culture, isolates identification and antimicrobial susceptibility testing. Hypermucoviscous phenotype was detected by string test. The whole genome of the isolate was sequenced and the multi-site sequence typing, capsular serotyping, plasmid characteristics, virulence and antimicrobial resistance genes of the isolate were analyzed. Plasmid curing and conjugation experiments were used to analyze plasmid characteristics. The virulence of the strain was assessed by serum killing and Galleria mellonella lethality assays. A two-sample t-test was used to compare the differences in the lethal dose of 50% (LD 50) between the tested strains and reference strains against the G. mellonella larvae. Results:K. pneumoniae strain KPN41053 was identified, it was only resistant to ampicillin and was negative for hypermucoviscous phenotype. Whole genome sequencing showed that the length of KPN41053 chromosome was 5 377 071 bp, belonging to ST660 type, and the capsular type was K16. A IncFIB(K)/HI1B virulence plasmid (207 506 bp) with a sequence that was highly similar to pLVPK was harbored by KPN41053. The plasmid carried a variety of virulence genes, among which rmpA and rmpA2 were pseudogenes. The plasmid could not be transferred horizontally by conjugation. The variation strain KPN41053_PC was obtained by plasmid curing. Serum killing analysis showed that KPN41053 was serum resistant (Grade 6), and KPN41053_PC was serum intermediately sensitive (Grade 3). The lgLD 50 of KPN41053 had no difference with that of the hypervirulent control strain (ST23-K1 type) ( t=0.32, P=0.765), and was significantly lower than that of KPN41053_PC ( t=5.97, P=0.004). Conclusions:KPN41053 was an atypical hypervirulent K. pneumoniae that belonged to ST660 but without a hypermucoviscous phenotype. The virulence plasmid harbored by KPN41053 was its key virulence factor. Hypervirulent K. pneumoniae can lead to community-acquired gas gangrene in diabetic patient, which deserves clinical attention.

OBJECTIVETo study the hypolipidemic active compounds from Crataegus pinnatifida and mechanism of action of those.

METHODGuided by the inhibitory activity to HMG-CoA reductase, the active compounds were separated and purified with macroporous resin and silica gel.

RESULTFour active compounds were obtained, which were quercetin, hyperoside, rutin and chlorogenic acid, the sum of their inhibitory rate was 50.01%, and the total inhibitory rate of the mixture of four active compounds matched was 79.48%.

CONCLUSIONQuercetin and hyperoside were the principle active components inhibiting HMG-CoA reductase in Hawthorn fruit, and there were synergistic action among them.

Crataegus ; chemistry ; Fruit ; chemistry ; Hydroxymethylglutaryl CoA Reductases ; analysis ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Plant Extracts ; pharmacology