Objective To investigate the effects and related mechanism of iNO on erythrocyte deformability in septic acute lung injury(ALI).Methods Thirty anesthetized and mechanically ventilated young piglets(3-4weeks old)were allocated to 4 groups:(1)normal(group C,n=6):intraperitoneal injection of normal saline(NS).(2)normal+iNO(group CNO,n=4):NS followed by mechanical ventilation for 4 h,and then treated with iNO at 10 parts per million in volume(ppm).(3)model(group M,n=10):i.p.Escherichia coli at 5 × 109 cfu/ml,5 ml,and(4)NO(group MNO,n=10):i.p.Eschefichia coli at 5×109 cfu/ml lollowed by iNO-at 10 parts per million after ALI.Blood viscosity,malondialdehyde(MDA)in erythrocyte,Ca2+-Mg2+-ATPase and Na+-K+-ATPase of erythrocyte membrane were measured at basdine,establishment of ALI,12 and 24 h during the treatment.Results For normal age-matched piglets,there was little change of whole blood viscosity at high shear rate(110 s-1),which is a measure of erythrocyte deformability,so was the level of MDA in erythroeyte and the activity of erythroeyte membrane Ca2+-Mg2+-ATPase,Na+-K+-ATPase when iNO was provided for 12 or 24 h.At the time ALI was established,whole blood viscosity at high shear rate and MDA levels in erythroeyte increased significantly compared to the baseline level(P＜0.05),while the activity of erythrocyte membrane Ca2+-Mg2+-ATPase and Na+-K+-ATPase decreased significantly(P＜0.01,vsbaseline).Exposure of iNO for 12 h resulted in decreased whole blood viscosity at high shear rate and MDA levels in erythroeyte(P＜0.05,vs group C),and higher activity of erythrocyte membrane Ca2+-Mg2+-AT-Pase and Na+-K+-ATPase.When iNO was administered for 24 h,there was little difference of whole blood viscosity,activity of erythrocyte membrane Ca2+-Mg2+-ATPase,Na+-K+-ATPase and MDA levels in erythroeyte between the C and NO groups.Conclusion In the piglets with septic ALI,there was deterioration of erythrocyte deformability.Inhaled NO for 12 h may alter the deterioration,however,this effect is transient.

Child ; Humans ; Multiple Organ Failure

Background and purpose:A pressing obstacle in clinical chemotherapy is drug resistance in breast cancer.A nano-delivery system,which has many advantages as a drug carrier,such as carrying anticancer drugs,can be used effectively to overcome drug resistance in tumors.This paper examined a new nano-delivery system,called calcium phosphate and glycerophosphocholine-mPEG(CAP/GPC-MPEG)composite nanoparticle and its influence on the cellular drug uptake of BCRP-over expressing mitoxantrone(MIT)-resistant breast cancer cell MCF-7/MIT.This paper will also examine its effect on overcoming drug resistance in the MCF-7/MIT cells.Methods:After the calcium phosphate and GPC-mPEG composite nanoparticles were designed and prepared,the entrapment efficiency and in vitro drug release of mitoxantrone-loaded nanoparticles were investigated.Quantitative comparisons were made between cellular uptake of drug-loaded nanoparticles and free drugs.Finally,a confocal laser scanning microscopy Was used to compare the subcellular distribution of drug-loaded nanoparticles and the free drugs.Results:Calcium phosphate and GPC-mPEG composite nanoparticles were nanoporous spherical particles with diameters between 50-100 mn.The MIT-loaded nanoparticles have an entrapment efficiency of(89.45±0.05)%.Although the drug-loaded nanoparticles showed an initial burst of drug release,it was followed by a more sustained release.The concentration of mitoxantrone was 1.89 times treated with MIT-loaded nanoparticles for 1 h compared to that treated with free mitoxantrone for 1 h in MCF-7/MIT cells.and which was 2.33 times in MCF-7 cells.Fluorescent red mitoxantrone appeared in the cytoplasm and nucleus of the MCF-7 and MCF-7,MIT cells treated with MlT-loaded nanoparticles whereas it is almost undetected in both cells treated with free mitoxantrone.Conclusion:Calcium phosphate and GPC-mPEG composite nanoparticles Can promote the cellular uptake and entering of mitoxantrone to the nucleus in MCF-7 and its corresponding BCRP-over expressing MIT-resistant MCF-7/MIT breast cancer cell lines.This nanoparticle is a potential nano-carrier for overcoming drug resistance in tumors.

Objective To study the relationship between the genetic polymorphisms of carboxylesterase 1 gene (CESI) and the susceptibility to antituberculosis drug-induced hepatotoxicity (ATBDIH).Methods Genetic polymorphisms of CES1 in 473 tuberculosis patients with or without hepatotoxicity (200∶ 273) after antituberculosis chemotherapy were analyzed by PCR-MassArray.Results In4 tags of CES1 single nucleotide polymorphism (SNP),the frequency of the rs1968753 allele had statistical difference between the hepatotoxicity group and the no-hepatotoxicity group ( P =0.0236 ).The characteristics of anti-hepatotoxicity had been shown relationship with rs8192950 ( P =0.044,OR =0.649,95％ CI =0.426-0.989,AC/AA ) and rs1968753 ( P =0.048,OR =0.556,95％ CI =0.311-0.995,GG/AA).The diplotypes with ‘ CGC' haplotype exhibited significant protection against hepatotoxicity at one copy (P=0.048,OR=0.654,95％CI=0.430-0.996).Conclusions The genetic polymorphisms of CESI might have significant association with ATBDIH.SNP rs8192950 AC genotype and rs1968753 GG genotype might be the candidates for risk prediction of ATBDIH.

Objective To study the correlation between genetic polymorphisms of interleukin (IL)-1A/1B and susceptibility to tuberculosis (TB).Methods Genetic polymorphisms of IL-1A and IL1 B in 1032 TB patients and 1008 non-TB patients were analyzed using PCR-MassARRAY method.The correlation between genetic polymorphisms of IL-1A/1B and susceptibility to TB was statistically analyzed.Results Two tag SNPs of IL-1A and three tag SNPs of IL-1B were screened for the study.There were differences in the allele frequencies of rs2853550 and rs3783526 between TB group and non-TB group (P=0.047and P =0.034,respectively).IL-1 B SNP1 rs2853550 (P =0.025,OR =1.302,95 ％ CI =1.034-1.640,TC vs.CC) was found to be highly associated with TB,while the other SNPs showed no significant correlations with TB.Furthermore,IL-1B SNP1 rs2853550 [P=0.019,OR=1.308,95％ CI=1.045-1.638 for (TC+TT) vs.CC] in the dominant model conferred significant risk for TB,but IL-1A SNP2 rs3783526 [P=0.000,OR=0.764,95％ CI =0.591-0.988 for GG vs.(AA+GA)] in the recessive model showed protective effects against TB.The haplotype ‘TG’ in the IL-1B block showed a higher risk for TB compared with the common ‘ CA’ haplotype (P=0.032,OR=1.265,95％ CI=1.020-1.567).The diplotypes containing ‘ GA’ haplotype in IL-1A block and ‘ TG’ haplotype in IL-1B block were major risk factors for TB (for onecopy,adjusted P=0.014,OR=1.403 and 95％ CI=1.072-1.836; adjusted P=0.013,OR=1.339 and 95％ CI=1.063-1.688,respectively),but the diplotype with ‘CG’ in IL-1B block played a protective effect against TB (for two-copy,P=0.006,OR=0.664 and95％ CI=0.494-0.891).Conclusion The genetic polymorphisms of IL-1B rs2853550 might be closely associated with TB,but the GG genotype of IL1 A SNP rs3783526 might have the characteristic of anti-TB.

Objective To investigate the treatment,outcomes and disease burden of severe hand-foot-and mouth diseases(HFMD),and to evaluate the compliance to the 2011 guideline for treatment in regions with a high in-cidence of HFMD.Methods A collaborative study group was established including Children's Hospital of Fudan Uni-versity,Jiangxi Provincial Children's Hospital,Anhui Provincial Children's Hospital,Linyi People's Hospital and the Second People's Hospital of Fuyang City.Clinical manifestation,treatment,prognosis and other data of severe HFMD pa-tients were prospectively collected by filling out a survey form in real time from April 2014 to October 2016. Results Two hundred and twenty-six severe HFMD cases were collected during the research time,including 114 ca-ses in stage 2,75 cases in stage 3,and 37 cases in stage 4.Two hundred and twenty-one cases(97.8%)were given mannitol,with a mortality of 6.2%;91 cases(40.3%)were given mannitol and glycerol fructose,with a mortality of 3.3%;the combined use of mannitol and glycerol fructose might have a better result than the single use of mannitol. One hundred and ninety-eight cases(87.6%)were given intravenous immunoglobulin(IVIG).One hundred and ninety cases(84.1%)were given antiviral drugs.One hundred and forty-five cases(64.2%)were given hormone therapy,and the use of hormone could reduce temperature,but did not reduce the mortality.One hundred and fifty cases (66.4%)needed vasoactive agent,including milrinone,dobutamine,phentolamine and sodium nitroprusside. The vasoactive agent use in stage 3 and 4 were 88.0%(66/75 cases)and 91.9%(34/37 cases),respectively.Sixty-nine cases(30.5%)received continuous positive airway pressure(CPAP),91 cases(40.3%)with mechanical ventila-tion,peak inspiratory pressure(PIP)≥20 cmH2O(1 cmH2O=0.098 kPa)accounted for 61.6%(53/86 cases),po-sitive end-expiratory pressure(PEEP)≥10 cmH2O accounted for 36.3%(33/91 cases).The mean mechanical ven-tilation time was(125.9 ± 101.8)h.Eleven cases(4.86%)died or died after giving up treatment,in which the mortality in stage 3 was 6.7%(5/75 cases),and the mortality in stage 4 was 16.2%(6/37 cases).The death causes were respiratory failure,pulmonary hemorrhage,and circulatory failure. The average time from onset to death was (5.91 ± 5.26)(1-15)d.Length of stay in hospital was(9.18 ± 5.16)(1-37)d in which length of stay in hospi-tal in stage 3 and 4 were(11.3 ± 6.35)d,(11.4 ± 6.62)d,respectively,which were significantly longer than that in stage 2[(7.50 ± 3.04)d],and the difference was statistically significant(P <0.05). The cost was(19 136 ± 12 556)CNY,of which the cost in stage 3 and 4 was(23 121 ± 13 846)CNY,(29 849 ± 16 015)CNY,respectively, which were significantly higher than that in stage 2[(12 961 ± 4 272)CNY],and the difference was statistically sig-nificant(P<0.05). Multivariate analysis found that respiratory rhythm abnormality,capillary refill time more than 3 seconds were risk factors for the deaths in the severe HFMD.Conclusion The 2011 edition of guidelines for treat-ment of children with severe HFMD was well executed.Hormone,IVIG,antiviral drugs did not significantly reduce the mortality of severe HFMD in children.

Objective To investigate the clinical features of severe hand,foot and mouth disease (HFMD) in recent three years,and to analyse the risk factors of severe HFMD.Methods A multicenter collaborative research group was set up,including five children's hospitals(pediatric department)with high incidence of HFMD.Prospective epidemiologic approaches were adopted.After training,staffs from the col-laborative center executed the study by filling up the record forms.Results We collected 114 HFMD cases in stage 2,75 cases of HFMD in stage 3,37 cases of HFMD in stage 4 from April 2014 to October 2016.The age ranged from 2 months to 13 years old,the median age was 2 years old,younger than 3 years accounted for 86.3%.Fever was observed in all the severe HFMD,mean temperature was (39.2 ± 0.7) ℃,fever lasted for (4.54 ± 2.89)d.The mean heart rates in stage 2,3,4 were (128.2 ± 13.3,176.1 ± 22.2,184.2 ± 27.5) times/min,respectively.The mean arterial pressure was (84.4 ± 14.6) mmHg(1 mmHg=0.133 kPa),the mean respiratory rate was (39.0 ± 8.4)times/min,the mean respiratory rates in stage 2,3,4 were (37.8 ± 7.36,38.7 ± 8.13,43.4 ± 10.7) times/min,respectively. Respiratory rhythm abnormality in stage 2,3,4 were 9.6%,14.9% and 56.8%,respectively.The blood glucose increased gradually in 2,3 and 4 stages,the mean blood glucose in stage 4 was(12.4 ± 4.74)mmol/L.The incidence of coma in stage 4 was higher than those in stage 2 and 3. Multivariate Logistic regression analysis found that tachycardia,drowsiness,coma, respiratory rate increase,respiratory rhythm abnormality,capillary refilling time more than 3 seconds were risk factors for severe HFMD.Conclusion The incidence of severe HFMD is still high in children under 3 years of age in last three years.The severe patients have obvious changes in the nervous,respiratory and circulatory system. Tachycardia,drowsiness,coma,respiratory rate increase,respiratoy rhythm abnormality,capillary refilling time more than 3 seconds are risk factors for severe HFMD.

Objective To study the levels of plasma catecholamine( norepinephrine,epinephrine and dopamine) in children with severe hand,foot and mouth disease( HFMD) ,and to assess the influence of cate-cholamine on the pathogenesis of severe HFMD. Methods A collaborative study group was established, including Children′s Hospital of Fudan University, Jiangxi Provincial Children′s Hospital, Anhui Provincial Children′s Hospital,Linyi People′s Hospital and No. 2 People′s Hospital of Fuyang City. Blood samples from children with severe HFMD were collected from April 2014 to October 2016. The levels of blood epineph-rine,norepinephrine,dopamine were measured at 2 h,24 h and 48 h after diagnosis for HFMD. Results The level of epinephrine at 24 h after diagnosis was ( 213. 0 ± 139. 8 ) ng/L in children with pulmonary edema, which was significantly higher than that of children without pulmonary edema[(137. 8 ± 45. 5)ng/L)](P=0. 022). The level of epinephrine at 24 h after diagnosis was (373. 2 ± 298. 1)ng/L in the dead children,and was (144. 2 ± 42. 5)ng/L in the survival children. The concentration of norepinephrine at 24 h after diagnosis was (1935. 7 ± 1824. 1)ng/L in the dead children,and was (858. 3 ± 212. 7)ng/L in the survival children. The levels of epinephrine and norepinephrine of those who died from HFMD were significantly higher than those of survival children at 24 h after diagnosis. There were no significant differences in catecholamine con-centrations among stage 2,3,4 HFMDs at 2 h,24 h and 48 h after diagnosis. Sex and enterovirus 71 virus infection had no significant influences on plasma catecholamine concentrations in children with severe HFMD. Conclusion Plasma epinephrine levels increase in children with HFMD complicated with pulmonary edema. Epinephrine and norepinephrine may play an important role in the death of children with severe HFMD.

Objective To explore the changes and clinical significance of joint fluid TNF-α and TNF-β1 levels in patients with knee osteoarthritis (KOA). Methods A total of 90 patients with KOA hospitalized in our hospital were selected. They were assigned to group A with 30 patients at early stage, group B with 30 patients at medium stage,and group C with 30 patients at advanced stage according to the stage of X ray; 30 healthy volunteers were in the con-trol group. Levels of joint fluid TNF-αand TNF-β1 were tested in four groups of patients. Results Levels of joint fluid TNF-β1 at medium and advanced stages of KOA were significantly lower than those in the control group, and the dif-ferences were significant (P<0.01); Levels of joint fluid TNF-α at medium and advanced stages of KOA were signifi-cantly higher than those in the control group, and the differences were significant(P<0.01); the difference of levels of joint fluid TNF-α and TNF-β1 at early stage of KOA was not significant compared with those in the control group(P>0.05);levels of TNF-α/TNF-β1 at early,medium and advanced stage of KOA were significantly higher than those in the control group(P<0.01);TNF-αwas positively correlated with KOA stage(r=0.930,P<0.01);TNF-β1 was nega-tively correlated with KOA stage(r=-0.849,P<0.01);TNF-α/TNF-β1 was positively correlated with KOA stage(r=0.828,P<0.01). Conclusion TNF-α and TNF-β1 are involved in the formation and progression of OA, and levels of joint fluid TNF-α and TNF-β1 are able to reflect the severity of KOA lesions; joint fluid TNF-α/TNF-β1 is able to detect KOA early.