Abstract: Objective　To investigate the influences of notoginsenoside R1 (NGR1) on cell injury and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway of alveolar epithelial cells infected by Klebsiella pneumoniae (Kp). Methods　A549 cells were grouped into five groups: control group (C group), infection group (Infect group), infection + low NGR1 group (Infect + L-NGR1 group), infection + high NGR1 group (Infect + H-NGR1 group), and infection+high NGR1+JAK2/STAT3 pathway inhibitor group (Infect+H-NGR1+SD-1029 group). Cell proliferation was measured using CCK8; ELISA kits were applied to detect the contents of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ) in the culture medium; flow cytometry was applied to detect apoptosis; RT-qPCR was applied to detect the expressions of JAK2/STAT3; Western blot was applied to detect JAK2/STAT3 pathway, autophagy protein microtubule-associated protein 1 light chain 3 (LC3), autophagy-relatedgene5 (Atg5), autophagy-related gene (Atg) 6 (Beclin-1), apoptosis protein B-cell lymphoma 2 (Bcl-2), Bcl-2-accociated protein (Bax), cysteinyl aspartate specific proteinase (cleaved-caspase-3) proteins expression. Results　Compared with the C group, the 72 h cell viability, the protein levels of Bcl-2, LC3-II/I, Atg5, Beclin-1, the mRNA relative expressions and protein phosphorylation levels of JAK2, STAT3 in the Infect group were obviously decreased (P<0.05); the contents of IL-1β, TNF-α, IFN-γ, apoptosis rate, the protein levels of Bax and cleaved-caspase-3 were obviously increased (P<0.05). Compared with Infect group, the 72 h cell viability, the protein levels of Bcl-2, LC3-II/I, Atg5, Beclin-1, the mRNA relative expressions and protein phosphorylation levels of JAK2, STAT3 in the Infect+L-NGR1 group and Infect+H-NGR1 group were obviously increased (P<0.05); the contents of IL-1β, TNF-α, IFN-γ, apoptosis rate, the protein levels of Bax and cleaved-Caspase-3 were obviously decreased (P<0.05). Compared with Infect+H-NGR1 group, the 72 h cell viability, the protein levels of Bcl-2, LC3-II/I, Atg5, Beclin-1, the protein phosphorylation levels of JAK2, STAT3 in the Infect+H-NGR1+SD-1029 group were obviously decreased (P<0.05), and the contents of IL-1β, TNF-α, IFN-γ, apoptosis rate, the protein levels of Bax and cleaved-caspase-3 were obviously increased (P<0.05). Conclusions NGR1 can activate the JAK2/STAT3 signaling pathway, promote autophagy of alveolar epithelial cells, and inhibit Kp-induced inflammatory injury and apoptosis of alveolar epithelial cells.

Objective To compare the immunoregulatory effects of Radix Millettia Speciosa (RM Speciosa) and Radix Millettia Championi (RM Championi)on immunosuppressed mice.Methods Kunming mice were randomly divided into normal control group,CTX model group,LMS positive group,RM Speciosa groups and RM Championi groups (20,10 and 5 g/kg).The mice were treated respectively with drug or NS once a day for consecutive 20 days.Mice in the other groups were injected intraperitoneally with CTX at days 8,10 and 12 to establish immunosuppressed mice model except the normal group.The changes of body weight,immune organ weight,white blood cell (WBC)number,carbon particle clearance capability of macrophages and delayed type hypersensitivity (DTH)of mice in all groups were determined and compared.Results Compared with that in CTX group,the WBC number was significantly increased (P<0.01 or P<0.05)and the degree of DTH (P<0.01) was enhanced at different doses in RM Speciosa groups and RM Championi groups.The activity of macrophages and the index of thymus and spleen were also improved in the treatment groups (P<0 .0 5 or P<0 .0 1 ).The index of thymus and the degree of DTH in RM Speciosa groups (20 and 10 g/kg)were slightly higher than those in the corresponding RM Championi groups (P<0.01 or P<0.05).For other indicators,RM Speciosa groups did not significantly differ from RM Championi groups (P>0.05).Conclusion Both RM Speciosa and RM Championi can improve the immune function of CTX-induced immunosuppressed mice,and RM Speciosa is slightly superior to RM Championi in improving specific cellular immunity.

Objective To explore the relationship between left ventricular diastolic function and the dynamic changes of myocardial ultrastructure and argyrophilic fiber in diabetic rats on the different periods of lesions(week 4,12 and 24).Methods The diabetes mellitus(DM)in healthy male Sprague-Dawley rats was induced by a single injection of streptozotocin(STZ,Sigma)into intraperitoneal at a dose of 65 mg/kg body weight.The left ventricular diastolic function was measured by Color Doppler Flow Imaging-Pulsed Wave(CDFIPW)and Doppler Tissue Imaging(DTI)echocardiography.Heart tissue at the apex was obtained rapidly for transmission electron microscope study.Argyrophilic staining was used in the study of argyrophilic fiber volume fraction(APFVF)in heart interstitial tissue.Results Diastolic dysfunction of left ventricle was detected in STZinduced diabetic rats by CDFI-PW(E/A ＜ 1)at week 4,and progressed gradually.Pseudonormal filling (E/A ＞ 1)was found in diabetic rats at week 24,which could be identified by DTI(Ea/Aa ＜ 1).Diastolic function of normal rats was not impaired(E/A ＞ 1 and Ea/Aa ＞ 1).Transmission electron microscopy revealed a spectrum of subcellular remodeling in myocardium which was characterized by myofibril content decrease,disorganization,mitochondrial degeneration,sarcoplasmic reticulum,structural disorder.Compared with the control group,APFVF in myocardium was increased significantly in diabetic rats(P ＜ 0.05).Conclusion The diastolic dysfunction in STZ-induced diabetic rats correlates with damage of ultrastructure and increase of myocardial argyrophilic fiber.

OBJECTIVEA high performance liquid chromatography (HPLC) method was developed to determine the concentration of nitidine chloride in plasma and successfully applied to study pharmacokinetics after i.v. administration in rabbits.

METHODTwelve rabbits, randomized into 2 groups , were given i.v. at the dose of 4, 6 mg x kg(-1) respectively. Chloramphenicol was used as an internal standard. Nitidine chloride was extracted from plasma with ion pair reagent, and was determined by HPLC.

RESULTThe calibration curves of nitidine chloride was linear in the range of 0.03-2.04 mg x L(-1). Its recoveries were more than 95%, intra-day and inter-day precisions were lower than 6%. The concentration-time curve of nitidine chloride in rabbits after i.v. of 4 and 6 mg x kg(-1) were shown to fit a two-compartment model, the main pharmacokinetic parameters showed no significant difference between the low and high dosage, and the AUC values are directly relative to doses. T1/2alpha were (5.46 +/- 0.89), (4.76 +/- 0.33) min respectively, T1/2beta were (263.33 +/- 16.4), (274.71 +/- 16.52) min respectively, AUC were (46.56 +/- 1.80), (69.19 +/- 2.30) microg x min(-1) x mL(-1) respectively.

CONCLUSIONIt is first time to establish the HPLC method to determine the concentration of nitidine chloride in rabbits plasma. The method is sensitive, accurate and reproducible. It is first time to study the pharmacokinetic characters of nitidine chloride in rabbits after i.v. administration, the elimination of nitidine chloride is linear pharmacokinetics.

Animals ; Benzophenanthridines ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Female ; Male ; Rabbits ; Random Allocation

OBJECTIVETo develop a method for elucidating " chromatography-efficacy" relation of the extract of Zanthoxylum nitidum on the gastric cancer cells.

METHODAfter obtaining the tumor inhibition rate and fingerprint peak data through MTT and HPLC, "chromatography-efficacy" relation was established by an appropriate statistical method.

RESULTThe gastric cancer "chromatography-efficacy" relation of Z. nitidum was established by step-back technique.

CONCLUSIONThe "chromatography-efficacy" relation has statistically significant and practical significance, so it has reference value in some way.

Antineoplastic Agents, Phytogenic ; analysis ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Humans ; Stomach Neoplasms ; drug therapy ; physiopathology ; Zanthoxylum ; chemistry

Objective To study whether crystal-8 exerts analgesic effect on the central nervous system,and to observe the relationship between crystal-8 and receptors. Methods A total of 32 SD rats were randomly divided into the 0.9% sodium chloride solution group, positive control group ( rotundine 2 mg·kg-1 ) , high dose of crystal-8 group ( 2 mg·kg-1 ) and low dose of crystal-8 group ( 1 mg · kg-1 ) . The changes of pain threshold were measured by the thermal stimulation test following intracerebroventricular (ICV) injection.The SD rats or mice were randomly divided into the 0.9% sodium chloride solution group, receptor tool medicine group ( including naloxone, reserpine, haloperidol, scopolamine) , crystal-8 group, receptor tool medicine plus crystal-8 group. The pain threshold was detected by the thermal stimulation test at 15, 30, 45, 60, 90, 120 min after dosing, then the influence of analgesic effect of crystal-8 on the neurotransmitter was observed. Results Compared with the 0.9% sodium chloride solution group, the pain threshold of rats was improved after taking the crystal-8 by intracerebroventricular (ICV) injection(P<0.01).Compared with the crystal-8 group, the naloxone plus crystal-8 group, the haloperidol plus crystal-8 group, the scopolamine plus crystal-8 group couldn't increase the pain threshold, there was no significant difference among these groups(P>0.05).However, Reserpine plus crystal-8 group could significantly decrease the pain threshold in rats compared with the crystal-8 group(P<0.01).The analgesic effect of crystal-8 was interfered by reserpine. Conclusion The analgesic effect of crystal-8 may be involved in the central mechanism,which relates to monoamine neurotransmitters, but has nothing to do with the opioid receptor, M receptor, and the inhibition of central DA receptor.

Objective To explore the direct economic loss caused by healthcare-associated infection(HAI)in general hospitals in China.Methods 68 hospitals were selected,a retrospective 1:1 matched survey was conducted to compare the direct medical cost in patients with and without HAI between January 1,2015 and December 31,2015. Results A total of 2 123 pairs of patients with and without HAI were included in the survey.The average cost of hospitalization in HAI and non-HAI groups were ￥25 845.30 and ￥12 006.14 respectively,￥13 839.16 on average was increased due to HAI.The average economic loss in provincial and ministerial levels of hospitals were￥21 409.83.The average economic loss in different regional hospitals were ￥9 725.42-￥18 909.59,and north China ranked the first.Economic loss caused by bloodstream infection and lower respiratory tract infection were more than other sites,which were ￥23 190.09 and ￥18 194.50 respectively.Conclusion HAI resulted in considerable direct economic loss.Prevention and control of HAI,especially bloodstream infection and lower respiratory tract infection should be paid more attention.

Objective To investigate the epidemiological characteristics of device-associated infection (DAI)in neonatal intensive care units(NICUs)of tertiary first-class hospitals in China,and provide scientific evidence for the prevention and control of neonatal DAI.Methods Neonates in NICUs at 17 hospitals of 9 provinces from October 2013 to September 2014 were selected for multicenter study,DAI was surveyed prospectively according to the uni-form diagnostic criteria and methods.Results A total of 12 998 neonates were monitored,the total patient-days were 126 125 d,13 cases of central line-associated bloodstream infection (CLABSI)and 70 cases of ventilator-asso-ciated pneumonia (VAP)occurred,central line utilization rate was 15.56%,incidence of CLABSI was 0.66/1 000 device-days;ventilator utilization rate was 7.67%,incidence of VAP was 7.23/1 000 device-days.Utilization rates of central line and respirator in neonates with body weight ≤ 1 000 g was the highest,which were 61 .06% and 29.91 % respectively;In NICUs with 20-30 beds,utilization rate of central line was the highest(16.67%),and res-pirator was the lowest(4.11 %);of hospitals in different regions,central line and respirator utilization rate in south-west China was the highest.Of different sizes of ICUs,VAP per 1 000 device-days was the lowest in NICUs with 20-30 beds(2.36 ‰).Difference in incidence of CLABSI and VAP per 1 000 device-days in neonates at NICUs of different regions were significantly different;incidence of CLABSI and VAP per 1 000 device-days was highest in southern China(2.68 ‰ and 31 .06‰ respectively),followed by southwest region.Of different quarters,incidence of CLABSI,and VAP per 1 000 device-days were not significantly different(all P >0.05).Conclusion Device utili-zation rate and incidence of DAI in China are both high,and are different in neonates of different birth weight,at different sizes of NICUs,as well as different regions,monitoring should be intensified,prevention and control measures should be implemented according to infection characteristics.

Objective To evaluate the effect of evidence-based bundle intervention strategy on reducing the inci-dence of central line-associated bloodstream infection (CLABSI).Methods Prospective and multicenter study was adopted,patients admitted to 54 intensive care units (ICUs)of 41 hospitals and with central venous catheters (CVCs)between October 1 ,2013 and September 30,2014 were monitored .Baseline data between October 2013 and March 2014 were collected as pre-intervention data;from April to September 2014,the participated hospitals performed intervention strategy,post-intervention data were compared with pre-intervention data.Results The usage rate of CVCs before and after intervention was significantly different (44.18% vs 44.63%,χ2 =5.526,P =0.019).Incidence of CLABSI before and after intervention was not significantly different(RR ,0.82[95%CI ,0.59-1 .13],P =0.10).Constituent ratio of catheter insertion sites between pre-and post-intervention was significantly different (χ2 =76.264,P <0.001),femoral vein catheterization rate as well as proportion of two and above catheter insertion sites after intervention decreased(17.25% VS 13.72%;2.27% VS 1 .44%,respectively);hand hygiene implementation rate and accuracy rate after intervention were both higher than before intervention (79.73% vs 76.14%,P <0.001 ;91 .47% vs 74.26%,P <0.001 ,respectively);constituent ratio of skin disinfectant applica-tion before and after intervention was significantly different(χ2 =3.861 ,P <0.001 ),proportion of chlorhexidine ethanol increased (29.62% VS 50.56%);except daily assessment and record,compliance to other prevention and control measures before and after intervention were all significantly different(all P <0.001);utilization rate of max-imal sterile barrier,qualified rate of dressing of operators,and port disinfection were all significantly enhanced. Conclusion Bundle intervention in intubation and maintenance are implemented effectively,but intervention effect on CLABSI needs further study.