Objective To detect the level of anti-drug antibodies(AD As) against anti-tetanus toxin monoclonal antibodies in rhesus monkeys by bridging ELISA and affinity capture elution ELISA(ACE ELISA),and compare them in order to determine an efficient and rapid method for the detection of ADA.Methods The ADA level of anti-tetanus toxin monoclonal antibodies was detected by bridging ELISA and ACE ELISA,and the serum minimum dilution multiple,screening cut point(SCP) and confirmation cut point(CCP) were determined.The sensitivity,drug resistance and precision of the two methods were verified.Forty rhesus monkeys(half male and half female) were randomly divided into negative control group,low dose group,high dose group and intravenous group.The negative control group was inoculated with normal saline,while the other groups were given different doses of anti-tetanus toxin monoclonal antibodies.The blood samples were collected from limbs veins before administration,14 and 28 d after the initial administration and at the end of the recovery period,and the serum was separated,which was detected for the ADA by two methods.Results The minimum dilution multiple of serum was determined to be 1:10.The SCPs of bridging ELISA and ACE ELISA were 0.059 3 and 0.098 1,and the CCPs were 14% and 30%,respectively.The sensitivity of both bridging ELISA and ACE ELISA was 500 ng/mL,but the drug resistance of ACE ELISA at high concentration of positive control antibody(300 μg/mL) was better than that of bridging ELISA(480 ng/mL).The screening precision of bridging ELISA(<5%) was better than that of ACE ELISA(12.35%-21.36%).Four positive samples were detected in rhesus monkey serum samples by ACE ELISA,and three positive samples were confirmed;Eight positive samples were screened by bridging ELISA,while only one was positive after confirmation.The false positive rate of ACE ELISA(0.7%)was lower than that of bridging ELISA(5.2%).Conclusion ACE ELISA has high drug resistance in detecting anti-tetanus toxin monoclonal antibody ADA,which is superior to bridging ELISA,especially in the case of high drug concentration.Although ACE ELISA has slightly lower precision,it is still a reliable ADA detection method,suitable for preclinical research and clinical application of anti-tetanus toxin monoclonal antibodies

Hypoxia is an inherent feature of the majority of solid tumors,which can increase the resistance of tumor cells to radiotherapy and chemotherapy,promote tumor angiogenesis and lead to poor prognosis.Therefore,targeting the hypoxic tumor cells has become a spot in cancer therapy.Bioreduction drugs can be activated by a specific reduction to become cytotoxic metabolites,thus killing hypoxic tumor cells,while small molecular targeting inhibitors can selectively act on the key point of hypoxia pathway.They have paved a new way for hypoxia targeted therapy.

Objective To study the effect of selective COX-2 inhibitor NS398 on IL-10 and IFN-γexpression in human keratinocytes induced by UVA,and further to explore the effect on anti human skin photoaging.Methods HaCaT cells were divided into three groups:simple UV exposure group,NS398-intervene group and blank group.For UV radiation,simple UV exposure group and NS398-intervene group were irradiated with UVA at a dose of 30 J/cm2.In order to assess the effect of NS398,HaCat cells were treated with NS398 at the dose of 0,20,40,80μmol/L respectively and then incubated without irradiation for 2h,substrate changed and cultured for 24h,and then the expression of IL-10 and IFN-γ mRNA was detected via RT-PCR.Results Simple UV exposure group had obviously higher expression of IL-10 mRNA and lower expression of IFN-γ mRNA than that of control group,while NS398-intervened group had significantly lower expression of IL-10 mRNA and higher expression of IFN-γ mRNA than that of simple UV exposure group,and dose-dependency existed.Conclusions NS398 may delay photo-damage of human skin via inhibiting the expression of IL-10 mRNA and up-regulating the expression of IFN-γ mRNA in human keractinocytes.

Objective To evaluate the therapeutic effect of bone marrow mesenchymal stem cells (BMSC) transplantation via renal artery in treating experimental rats with adriamycin-induced chronic nephro -pathy.Methods A total of 50 male Sprague-Dawley (SD) rats were used as experimental animals.Two rats were used for the isolation and culture of BMSC.Twelve rats were designed as blank control group (group N);in other 36 rats adriamycin was injected through caudal vein to establish rat models of chronic nephropathy,these 36 rats were randomly and equally divided into three groups with 12 rats in each group:control group (group C,n=12),BMSC transplantation via renal artery group (group A,n=12),and BMSC transplantation via caudal vein group (group V,n=12).For the rats of group N,the same amount of normal saline was injected through caudal vein.Results At each observation point,the levels of blood urea nitrogen,serum creatinine,24 h urinary protein and 24 h urinary microprotein in group A,V and C were remarkably higher than those in group N (P＜0.01).One and two weeks after BMSC transplantation,the 24 h urinary microprotein level in group A was significantly lower than that in group C (P＜0.01);the serum creatinine level in group A was significantly lower than that in group C and group V (P＜0.01).One week after BMSC transplantation,both the 24 h urinary protein level and 24 h urinary microprotein level in group A were strikingly lower than those in group V (P＜0.01),but two weeks after BMSC transplantation these differences between group A and group V became not statistically significant.Conclusion BMSC transplantation via renal artery can improve cell-homing efficiency and improve the repair of damaged tissue as well.

Objective: To compare the value of digital breast tomosynthesis (DBT) and flly-field digital mammography (FFDM) in evaluating breast architectural distortion (AD) lesions, and the value of DBT and ultrasound in differentiating benign and malignant breast AD. Methods: DBT, FFDM and ultrasound data of 58 patients with AD lesions detected with DBT were retrospectively analyzed. Taken pathological outcomes as standards, the sensitivity, specificity and accuracy of DBT and FFDM in evaluating breast AD were compared and analyzed. The consistency of results of DBT and ultrasound in differentiating benign and malignant breast AD with pathological results was analyzed. ROC curve of DBT and ultrasound for differentiating benign and malignant breast AD were drawn, and the diagnostic efficacies were compared. Results: All patients underwent FFDM, and 41 of them also underwent ultrasound examination. Among 58 cases of breast AD detected with DBT, only 23 AD were found with FFDM (χ2=33.03, P<0.05). The sensitivity (80.65% [25/31]) and accuracy (78.00% [39/50]) of DBT in diagnosis of dense breast with AD were higher than those of FFDM (35.48% [11/31], 48.00% [24/50], χ2=12.98, 9.65, both P<0.05), but the specificity (73.68% [14/19]) was no statistically different with that of FFDM (68.42% [13/19], χ2=0.13, P>0.05). Median consistency of DBT and ultrasound results was observed in differentiating benign and malignant breast AD and pathological results (Kappa=0.65, 0.71, both P<0.05). The sensitivity, specificity of DBT and ultrasound in differentiating benign and malignant breast AD was 91.30% (21/23), 72.22% (13/18) and 82.61% (19/23), 88.89% (16/18), respectively (Z=1.45, P>0.05). Conclusion: The sensitivity and accuracy of DBT in evaluating breast AD are higher than FFDM. DBT is comparable to ultrasound in differentiating benign and malignant breast AD. AD detected with DBT has relatively high malignancy, so it is recommended to conduct timely biopsy for correct diagnosis.

Implant surface modified coating can improve its osteoinductivity, about which simple calcium phosphate coating has been extensively studied. But it has slow osteointegration speed and poor antibacterial property, while other metal ions added, such as nano zinc ion, can compensate for these deficiencies. This paper describes the incorporation form, the effect on physical and chemical properties of the material and the antibacterial property of nano zinc, and summarizes the material's biological property given by calcium ion, zinc ion and inorganic phosphate (Pi), mainly focusing on the influence of these three inorganic ions on osteoblast proliferation, differentiation, protein synthesis and matrix mineralization in order to present the positive function of zinc doped calcium phosphate in the field of bone formation.
Biocompatible Materials ; Calcium ; Calcium Phosphates ; chemistry ; Cell Differentiation ; Cell Proliferation ; Humans ; Ions ; Metal Nanoparticles ; chemistry ; Osteoblasts ; cytology ; Osteogenesis ; Phosphates ; chemistry ; Zinc ; chemistry

Objective To compare the repair effect on renal function between different times of bone marrow mesenchymal stem cells (BMSCs) transplant via renal artery route in experimental rats with adriamycininduced nephropathy.Methods Adriamycin-induced nephropathy model was established in 32 rats through injection of adriamycin though the caudal vein.Based on the scheduled times of BMSCs transplant,the experimental rats were randomly and equally divided into M0 group (zero time),M1 group (one time),M2group (2 times) and M3 group (3 times) with 8 rats in each group.Other 8 SD rats were used as normal control group (N group).Single dose of 0.5 rnl BMSC suspension (2×106 cells/ml) was transplanted to the rats of M0 group (zero time),M1 group (one time),M2 group (2 times) and M3 group (3 times),for the rats of the groups not receiving BMSC transplant a single dose of 0.5 ml L-DMEM culture medium,used as a placebo,was adopted to replace BMSC suspension.The transplant interval was one week.Before transplant as well as one and two weeks after last time of transplant,the serum urea nitrogen,serum creatinine,24 h urine protein and 24 h urine microprotein were tested,and one week after last time of transplant pathological sections were made for laser focusing microscope examination to observe renal pathological changes and the distribution of BMSC cells in the kidney.Results The values of serum urea nitrogen,serum creatinine,24 h urine protein and 24 h urine microprotein determined at each observation time point in M0 group,M1 group,M2 group and M3 group were significantly higher than those in N group (P＜0.001).The values of 24 h urine protein and 24 h urine microprotein determined at one week after last time of transplant in M2 group and M3 group were strikingly lower than those in M1 group (P＜0.05),but these differences between M2 group and M3 group were not statistically significant (P=0.063).Conclusion For the treatment of adriamycin-induced nephropathy in experimental rats,two times of using BMSCs transplant via renal artery route can achieve optimal curative effect.

Objective To identify the genetic loci associated with bipolar disorder in Chinese population by the ge?nome scan on chromosome 20 in bipolar disorder patients and healthy people from Shandong peninsula. Method Geno?typing was conducted on DNA pool samples of 104 bipolar disorder patients and 1000 controls using thirteen microsatel?lite markers on chromosome 20 spaced at intervals of approximately 10 cM and GeneMapper 4.0 software. CLUMP soft?ware was used to analyze multiallelic markers. Result Significant difference of allele frequencies was found at marker D20S186 (20p12.2) between patients and controls (P=0.022). Conclusion The data suggest that the D20S186 locus (20p12.2) is significantly associated with susceptibility to bipolar disorder in a Chinese Han population in Shandong pen?insula. Future studies should focus on the fine mapping of this region and assessment of candidate genes.

Objective To conduct the molecular epidemiologic analysis of Staphylococcus aureus (S.aureus) in the intensive care units(ICUs) and general wards and to compare their clinical characteristics.Methods Ninety-six clinically isolated strains of S.aureus(43 strains from the emergency intensive care unit(EICU) and neurosurgical intensive care unit(NICU) and 53 strains from the general wards) collected from Sepetember 2015 to April 2016 were performed the bacterial identification and antibiotic susceptibility test.The molecular typing was performed by adopting staphylococcal protein A (spa) typing method.Results Among 96 strains of S.aureus,the detection rate of methicillin-resistant S.aureus(MRSA) was 40.6%(39/96),which among 43 strains in ICU was 62.8%(27/43) and which among 53 strains in the general words was 22.6%(12/53).The resistance rates of strains from ICUs to gentamicin,levofloxacin,clindamycin,fosfomycin and minocycline were 23.3%,48.8%,46.5%,32.6% and 32.5% respectively,while which from the general wards were 7.5%,24.5%,18.9%,2.1% and 0% respectively.The Spa typing results showed that the main types of ICUs were t002,t091 and t311.The major epidemic strain was t002(n=16,37.2%) and mainly isolated from EICUs(12 strains),26 spa types were identified among the general wards trains,mainly were t189,t377,t571,t034,t091,t127.Conclusion The detection rate of MRSA in ICUs is higher than that in the general wards,these strains have high resistant rate to routine antibacterial drugs.t002 is the major epidemic strain.The general wards have more spa types with higher genetic diversity.

Objective To investigate the role of scavenger receptor class B type 1 (SR-B1) signaling pathway in serum amyloid A (SAA)-induced angiogenesis in rheumatoid arthritis (RA).Methods The expression and location of SR-B1 in RA and osteoarthritis (OA) synovial tissues were observed by immunohistochemistry.And SR-B1 expression in the resting human umbilical vein endothelial cells (HUVECs) was detected by immunoflourescence.Wound repair assessement and tube formation assessement were employed to evaluate the effect on cell migration and tube formation stimulated by SAA and/or anti-SR-B1 antibody.The t-test and one-way analysis of variance (ANOVA) were used for statistical analysis.Results ① SR-B1 was significantly highly expressed in RA tissue samples (A=6 788±819) when compared to the minimal expression in OA (A =31 849±6 977,t=3.567,P＜0.01).Positive staining of SR-B1 was observed in RA synovial vascular endothelial cells and perivascular areas.② Strong staining for SR-B1 was observed in all HUVECs tested.③ Significant wound healing induced by SAA (MI=2.50±0.17) was found compared with the untreated controls (MI=1.00±0.09,q=14.38,P＜0.01),and the effects were inhibited in the presence of anti-SR-B1 antibody (MI=1.16±0.14,q=13.02,P＜0.01).④ Compared to the untreated group (branch point number:6.6±0.8),there was an enhanced formation of branched and capillary-hke tube structure followed by SAA stimulation (branch point number:19.0±1.1,q=25.04,P＜0.01) after culturing for 72 h,whereas,tube formation decreased markedly upon pre-treated with anti-SR-B1 antibody (branch point number:7.6±1.3,vs SAA,q =23.32,P＜0.01).Conclusion Our present study suggests that serum amyloid A may induce angiogenesis via SR-B1 signaling pathway in RA.