Objective To investigate the expressions of interferon γ(IFNγ), interferon inducible protein-10(IP-10). chemokine receptor CXCR3 and their significance in infection-associated hemophagocytic syndrome(IAHPS). Methods Forty-three patients with IAHPS, 35 infection patients without HPS and 25 healthy controls were included in the study. The serum IFNγ and IP-10 levels were measured by enzyme linked immunosorbent assay(ELISA). The expression of CXCR3 on cell surface of CD_4~+ and CD_8~+ T cells in peripheral blood was determined by flow cytometry. SPSS 13.0 was used for data processing, and independent-sample t test was performed to compare the differences among the groups. Results The serum IFNγ and IP-10 levels in patients with IAHPS were( 608±135) pmol/L and(939±141) pmol/L respectively, which were significantly higher than those in without HPS group[(154±45) pmol/L and (385±119) pmol/L, t=4.97 and 4.02, P<0.05] and healthy controls[(56±18) pmol/L and (248±98) pmol/L, t=5.27 and 4.77, P<0.05]. The expressions of CXCR3 on CD_4~+ and CD_8~+ T cells in IAHPS group were (35±11)% and (23±8)% respectively, which were significantly higher than those in without HPS group[(24±7)% and (16±7)%, t=3.12 and 3.62, P<0.05] and healthy controls[(20±6)% and (12±5)%, t=4.46 and 4.93, P<0.05]. Conclusion The expressions of IFNγ, IP-10 and CXCR3 are increased significantly in patients with IAHPS, which may be related to the disease pathogenesis.

Objective To evaluate the effectiveness of free highly active antiretroviral therapy (HAART) in adult infected with human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome (AIDS) patients in Dehong area. Methods Clinical data of 1039 adult HIV/AIDS patients from five counties/cities in Dehong area who initiated HAART during the period from July 1st 2004 to June 30th 2008 were retrospectively analyzed to examine their virological and immunological responses to HAART. Data were analyzed by Chi-squared test or F test. Results Among the 1039 HIV/AIDS cases, 611 were males and 428 were females. The mean age was (37.0±9.9) years and the mean treatment duration was (22. 41 ± 12. 69) months. Complete viral suppression (HIV viral load＜50 copy/mL) was achieved in 781 cases (75. 17%). The percentage of patients achieving complete viral suppression rates were 76.95%, 76.49%, 70.65% and 77. 73% in patients treated for 6-12,13-24, 25-36 and more than 37 months, respectively (x2=8.646, P=0.194). The meanCD4+ T cell counts were (164.93±118.05) × 106/L at baseline, and (330.85±201.73) × 106/L, (356.24±205.49) × 106/L, (434.53±250.65) × 106/L and (396.31±202.62) × 106/L in patients treated for 6- 12, 13-24, 25-36 and more than 37 months, respectively. CD4- T cell counts were significantly different in patients treated for 6-12 and 13-24 months (F= 19. 423 , P＜0. 01). Successful immune reconstitution was achieved in 927 ( 90.88 % ) cases. Seven hundred and seventeen (70.29% ) cases achieved both virological suppression and immunological reconstitution with HAART, whereas 40 cases (3. 92%) failed to achieve both virological and immunological responses. Conclusion HIV/AIDS patients in Dehong area show good virological and immunological responses to HAART.

Objective To investigate the effects of Dihuangyinzi(DHYZ) on behaviors and RAGE/p38 pathway in APP/PS1 mice.MethodTwenty APP/PS1 dementia mice were randomly divided into model group(n=10) and Chinese medicine group(n=10).The blank group was C57 BL/6 J normal mouse(n=10).The mice in Chinese medicine group were intragastric administration with DHYZ (9.75 g·kg-1·d-1).The mice in model group and blank group were treated with distilled water.After 30 days,the abilities of learning and memory of mice were detected by Morris water maze.The expression of amyloid-beta1-42(Aβ1-42) in the hippocampus and cortex was detected by immunohistochemistry.Reactive oxygen species of brain tissue were detected by DCFH-DA Methods in the brain of APP/PS1 mice.Gene expression level of receptor for advanced glycation end products(RAGE) was measured by real-time polymerase chain reaction (RT-PCR) in the cortex and hippocampus of APP/PS1 mice.The expression of phospho-mitogen-activated protein kinases (p38) was analyzed with Western blot and immunofluorescence analysis in the cortex and hippocampus of APP/PS1 mice.Results Behavioral Results showed that DHYZ significantly increased the distance((23.088±7.083)cm) and residence time((1.961±1.230)s)of effective area in Morris water maze on the fifth day(P<0.05,P<0.01)and remarkably increased the number of effective area crossings((1.607±0.405) times) and plats((0.893±0.283) times) in Morris water maze on the fifth day(P<0.01,P<0.05).DHYZ also significantly reduced the intracelluar ROS level(122.611±7.630) in the brain(P<0.01),and DHYZ could depress the expression of RAGE(1.467±0.081,7.983±0.136) and phosphorylation of p38 (0.376±0.026,0.538±0.016)in the cortex and hippocampus of APP/PS1 mice(P<0.01,P<0.05).Conclusions The Results demonstrate that DHYZ can partly improve memory impairment of APP/PS1 mice by the inhibition of RAGE/p38 pathway.

Objective To investigate the effects of Dihuang Yinzi (DY) on the receptor for advanced glycation end-products(RAGE)/reactive oxygen species(ROS)/apoptosis pathway in SH-SY5Y cells induced by amyloid-beta1-42 (Aβ1-42) oligomer. Methods Firstly, we adopted methyl thiazolyl tetrazolium(MTT) method to detect the cell vitality in fetal bovine serum (FBS) group, blank serum group, and low-, middle- and high- dose DY-containing serum groups, so as to confirm the optimal concentration and treatment time of DY-containing serum. Secondly, we applied MTT method to detect cell vitality and applied Annexin V/propidium iodide (PI) staining method to observe the apoptosis of SH-SY5Y cells treated with 0~20 μmol/L Aβ1-42 for 24 and 48 h, so as toconfirm the optimal concentration and treatment time of Aβ1-42 for establishing Alzheimer's disease (AD) model in vitro. Thirdly, MTT method was used for the detection of cell vitality, and Annexin V/PI staining method was used for detection of the apoptosis of SH-SY5Y cells in blank serum group, model group, western medicine control group and low-, middle-and high-dose DY-containing serum groups, and Dihydroethidium (DHE) method was used for the assay of ROS contents, so as to observe the effect of DY on the recovery of injured SH-SY5Y cells induced by Aβ1-42. Finally, we applied Western blot method to detect the expression level of RAGE in SH-SY5Y cells of blank group, model group and DY-containing serum group; after Aβ1-42-induced SH-SY5Y cells were transfected with RAGE gene, we adopted DHE staining method and Annexin V/PI staining method to detect ROS content and cell apoptotic rate in all of the above groups, so as to observe the effect of DY on SH-SY5Y cell apoptosis and RAGE expression. Results The cell vitalities were increased in low- and middle-dose DY-containing serum groups at 24 h (P < 0.05 or P < 0.01 compared with that in the blank serum group). The conditions for the establishment of AD model in vitro were as follows: the optimal concentration of Aβ1-42 was 5μmol/L, and the treatment time was 24 h. The cell vitalities were significantly enhanced, the cell apoptotic rate and ROS content were significantly lowered in Aβ1-42-induced SH-SY5Y cells of the medication groups(P <0.05 or P < 0.01 compared with those in the model group) , and the cell vitality was the highest and the cell apoptotic rate was the lowest in the middle-dose DY-containing serum group. The RAGE expression level was decreased in Aβ1-42-induced SH-SY5Y cells of the middle-dose DY-containing serum group(P < 0.05 compared with that in the model group) . ROS content and cell apoptotic rate were decreased in Aβ1-42-induced SH-SY5Y cells transfected with RAGE gene in the middle-dose DY-containing serum group (P<0.01). Conclusion DY may play an anti-oxidative role through inhibiting the production of ROS and cell apoptosis, thus to suppress RAGE protein and to achieve the preventive and therapeutic effect for AD.

AIM: To study the effect of cholecystokinin octapeptide(CCK-8) on lipopolysaccharide (LPS)-stimulated pulmonary interstitial macrophage(IM) in vitro. METHODS: Pulmonary IM were isolated and cultured in the presence of LPS, CCK-8, proglumide(the antagonist of CCK receptors) and vehicle alone or together. The expression of mCD14 protein was assayed by flow cytometry, and sCD14 in the supernatant was analyzed semi-quantitatively by Western blot, and TNF-? in the supernatant was detected with ELISA. RESULTS: CCK-8, at concentrations from 10 -7 mol/L to 10 -6 mol/L inhibited significantly the expression of mCD14, the release of sCD14 and TNF-? to the supernatant up-regulated by LPS(1 mg/L). The effect of CCK-8 was inhibited by proglumide. CONCLUSION: CCK-8 modulated negatively several functions of LPS-stimulated pulmonary IM through CCK receptors, which may be one of the mechanisms for CCK-8 to alleviate the inflammation in lung tissues during endotoxemia.

Objectives To access the bacteriology in patients with sepsis due to biliary tract infection to provide a basis for empirical selection of proper antibiotic treatment.Methods This is a single-center retrospective study on 214 patients with biliary tract infection admitted from August 2014 to July 2016 to the surgical intensive care units (ICU) of The First Affiliated Hospital of Sun Yat-sen University.To study the demographic information,sequential organ failure assessment (SOFA),usage of antibiotics before ICU and duration of ICU were analyzed.Bile,peritoneal drainage and blood samples were collected.Results 47 septic shock patients and 25 septic patients due to biliary tract infection were enrolled in the trial.The two groups (the shock group vs.the sepsis group) had a significant difference in the duration of ICU stay [(6.4 ± 4.6) d vs.(2.3 ± 1.8) d,P ＜ 0.05].48 strains of pathogens were isolated from the bile samples.The major pathogens were Escherichia coli (E.coli) (n =23,47.9％),Enterococcus faecalis (n =8,16.7％) and Enterococcus faecium (n =2,4.2％).80 strains of pathogens were isolated from the peritoneal drainage culture samples.E.coli,pseudomonas aeruginosa,and Klebsiella pneumoniae ranked the top 3 species,accounting for 26.3％,11.3％ and 7.5％,respectively.The sensitivity of E.coli isolated from bile to amikacin,imipenem and panipenem were all over 90.0％.Conclusions E.coli was the principal gram-negative bacterium in biliary infection induced sepsis.Early administration of carbapenemes may reduce the occurrence of septic shock in these patients.

Objective To investigate the effect of schisandrin (SCH) treatment on learning and memory abilities and their mechanism in APP/PS1 dual transgenic dementia mice,and explore the effect of Chinese medicine on Alzheimer's disease (AD).Methods Thirty-five APP/PS1 dementia mouse models were randomly assigned into APP/PS1 model group (n=17) and APP/PS1+SCH group (n=18);another 10 male C57BL/6J mice were chosen as blank control group.The mice in the APP/PS1+SCH group were given intragastric administration of SCH at 2.6 mg/(kg· d) for 30 d;the mice in the APP/PS1 model group and blank control group were treated with distilled water for 30 d.The learning and memory abilities of these APP/PS1 mice (n=7) were detected by Morris water maze.Mice from the three groups were sacrificed;Nissl staining was used to observe Nissl bodies of neurons in brain tissues;real-time fluorescence quantitative PCR (qPCR) was used to detect the mRNA content of terminal glycosylationend products receptor (RAGE) in brain tissues;Western blotting was used to detect the expressions of RAGE and phosphorylated P38 mitogen-activated protein kinase (p-p38) in brain tissues.Results (1) The results of water maze space exploration experiment showed that the times of crossing the platform area in the three groups were statistically significant (P＜0.05);as compared with the APP/PS1 modelgroup,the times of crossing the platform area in the APP/PS1+SCH group were significantly increased (P＜0.05).(2) Nissl staining results showed that the contents of Nissl bodies in the hippocampal CA1 area and cortical neurons of the APP/PS 1 model group were significantly reduced,with light staining and cell body atrophy;the lesions in mice of the APP/PS1+SCH group were less severe than those of APP/PS1 model group,some neurons were atrophic,and the content of the neuronal nileite bodies in the hippocampal CA1 region was relatively abundant.(3) The qPCR results showed that there were statistically significant differences in RAGE mRNA expression levels in the cortex and hippocampus of the three groups (P＜0.05);as compared with the APP/PS1 model group,the APP/PS1+SCH group had significantly reduced RAGE mRNA expression in the hippocampal area (P＜0.05).(4) Western blotting results showed that RAGE and p-p38 protein expression levels in two parts of mice of APP/PS1+SCH group were significantly reduced as compared with those in the APP/PS1 model group (P＜0.05).Conclusion SCH may improve the functional status of hippocampal and cortical neurons and improve the spatial exploratory memory ability of APP/PS1 mice by down regulating the RAGE and P38 expressions.

Objective To investigate the effect ofDihuangyinzi (DHYZ)-medicated serum on receptor for advanced glycation end product (RAGE)/p38 miotgen-activated protein kinase (MAPK) /nuclear factor (NF)-κB pathway in SH-SY5Y cells induced by Aβ1-42.Methods Male SD rats were randomly divided into normal control group and experimental group (n=20);natural sera medium and DHYZ sera medium were prepared.(1) SH-SY5Y cells were divided into control group,model group and DHYZ treatment group;natural sera medium,natural sera medium+Aβ1-42 oligomer,and DHYZ sera medium+Aβ1-42 oligomer were given to the cells,respectively.Westem blotting was used to detect the protein expressions of NF-κB p65,p38 and phosphorylate (p)-p38.(2) SH-SY5Y cells were given DHYZ sera medium+Aβ1-42 oligomer treatment,and at different time points of Aβ1-42 oligomer treatment (15 min,30 min,60 min,12 h,24 h,48 h and 72 h),Western blotting was used to detect the protein expressions of p38 and p-p38.(3) SH-SY5Y cells were divided into 6 groups:mock-transfected RAGE blank group,transfected RAGE blank group,mock-transfected RAGE model group,transfected RAGE model group,mock-transfected RAGE herb group and transfected RAGE herb group;herb groups were given DHYZ-medicated serum;inflammatory factors,interleukin (IL)-1β,IL-6,and tumor necrosis factor (TNF)-a,were measured by ELISA and cytometric bead array.Results (1) As compared with model group,DHYZ treatment group had significantly decreased NF-κB p65 and p-p38/p38 protein expression.(2) The p-p38 protein expression began to increase 30 min after Aβ1-42 treatment,reached to its peak level 24 h after Aβ1-42 treatment,and began to decrease 48 h after Aβ1-42 treatment.(3) The IL-1β,IL-6 and TNF-α levels were increased significantly in the transfected RAGE model group as compared with those in the mock-transfected RAGE model group (P＜0.05);the IL-1β,IL-6 and TNF-α levels were increased significantly in the transfected RAGE herb group as compared with those in the mock-transfected RAGE herb group (P＜0.05);the IL-1β,IL-6 and TNF-α levels were decreased significantly in the mock-transfected RAGE herb group as compared with those in the mock-transfected RAGE model group (P＜0.05);the IL-1β,IL-6 and TNF-α levels were decreased significantly in the transfected RAGE herb group as compared with those in the transfected RAGE model group (P＜0.05).Conclusion DHYZ-medicated serum could inhibit the RAGE-p38 pathway and improve the inflammatory reaction in Aβ1-42-induced SH-SY5Ycells transfected with RAGE gene to protect the SH-SY5Y cells.

BACKGROUNDEndostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP.

METHODSFour hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety .

RESULTSOf 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group .

CONCLUSIONSThe addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .

OBJECTIVETo examine the proportion and influencing factors on HIV-infected individuals who rejecting the antiretroviral therapy among all the HIV positives, in Dehong prefecture, Yunnan province.

METHODSA cross-sectional analysis was conducted on all the local HIV-infected survivals aged over 16 year old who refused to receive antiretroviral therapy (ART) by the end of 2013 in Dehong prefecture.

RESULTSThe proportion of those rejecting the ART among HIV-infected survivals and aged over 16 years old in Dehong prefecture, was 7.4% (605/8 136). Factors related to the 'rejection' among the 605 refusals would include: being male (72.9%), aged 31-45 years (57.2%), peasants (75.4%), married (52.2%), with minor ethnicity (41.3%), illiterate or only having primary school education (58.7%), infected through sexual contacts (61.2%), and with CD4(+)T cell counts >350 cells/mm(3) (66.6%). Data from the multiple logistic regression analysis indicated that rejecting the ART was significantly associated with areas, gender, age, ethnicity and CD4(+)T cell counts of the HIV patients. Those who were from Yingjiang county, female, aged 31-45 years old had lower proportions of ART refusals than those who were from Ruili city, male, aged ≤30 year old. Those who were of Dai minority and had no records on CD4(+)T cell counts, had higher proportions of ART refusals than those who were of Han ethnicity and had CD4(+)T cell counts ≤350 cells/mm(3). Reasons for the 605 HIV-infected patients with rejection to the ART would include fear of disclosure of HIV infection status (84, 13.9%), misunderstandings of the effectiveness and side effects of ART (111, 18.3%), self-realized wellness(340, 56.2%) and others (70, 11.6%). Of them, reasons for the 181 patients with CD4(+)T cell counts ≤350 cells/mm(3) that rejecting ART would include fearfulness on the disclosure of HIV infection status(40, 22.1%), misunderstandings of the effectiveness and side effects of ART (36, 19.9%), self-realized wellness (84, 46.4%) and others (21, 11.6%). Among those who rejected ART, reasons for that would vary by areas, gender, age, marital status and routes of HIV transmission, according to the results from Chi-squared tests.

CONCLUSIONA substantial proportion of HIV-infected individuals rejected ART in Dehong prefecture of Yunnan province. It was urgently needed to enhance health education programs of ART tailored for those HIV-infected patients, according to different characteristics and reasons for rejection, so as to promote the ART in this prefecture.

Adult ; Anti-Retroviral Agents ; therapeutic use ; China ; Cross-Sectional Studies ; Ethnic Groups ; Female ; HIV Infections ; drug therapy ; Health Education ; Health Services Needs and Demand ; Humans ; Male ; Marital Status ; Marriage ; Middle Aged ; Minority Groups ; Sexual Behavior ; Treatment Refusal