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In order to obtain the lead compound for treatment of rheumatoid arthritis (RA), in this study, therapeutic efficacy of three bispecific antibodies (BsAB-1, BsAB-2 and BsAB-3) against both hIL-1beta and hIL-17 were compared on CIA model mice. First, by ELISA method we compared the binding capacity of the three bispecific antibodies to the two antigens. The results showed that all three antibodies could simultaneously bind both antigens, among these antibodies, BsAB-1 was superior over BsAB-2 and BsAB-3. CIA model was established with chicken type II collagen (CII) and developed RA-like symptoms such as ankle swelling, skin tight, hind foot skin hyperemia. The CIA mice were treated with three antibodies once every two days for total of 29 days. Compared with the CIA model mice, the RA-like symptoms of the antibody treated-mice significantly relieved, while the BsAB-1 treated-mice were almost recovered. CII antibody level in the serum and cytokines (IL-2, IL-1beta, IL-17A and TNF-alpha) expression in the spleen were examined. Compared with the CIA model mice, all three antibodies could significantly reduce CII antibody and cytokine expression levels. BsAB-1 antibody was more potent than BsAB-2 and BsAB-3. In summary, BsAB-1 is superior over BsAB-2 and BsAB-3 in amelioration of RA symptoms and regulation of CII antibody production and pro-inflammatory cytokine expression, therefore, BsAB-1 can be chosen as a lead compound for further development of drug candidate for treatment of RA.
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In order to enhance the antitumor efficacy of recombinant Newcastle disease virus, rNDV-IL15 was rescued in this study. Recombinant plasmid prNDV-IL15 was constructed, and BHK21 cells were transfected with the recombinant plasmid. Finally, the recombinant Newcastle disease virus rNDV-IL15 was successfully rescued. The growth curves of these two recombinant viruses were determined. Murine melanoma B16F10 cells were infected with rNDV-IL15 at MOI of 0.1, and the expression level of IL15 in the supernatant was detected by ELISA. The antitumor efficacy of rNDV-IL15 and rNDV was compared in vitro and in vivo. Results showed that prNDV-IL15 was constructed and recombinant virus rNDV-IL15 was successfully rescued. The growth curve of rNDV-IL15 showed that the growth of rNDV-IL15 had not been changed after insertion of IL15 gene. Results showed that there was high level of IL15 expression in the supernatant of rNDV-IL5-infected B16F10 cells (1 044.3 +/- 27.7 ng x mL(-1)). rNDV-IL15 and rNDV significantly inhibited the growth of B16F10 cells in vitro in a time-dependent manner. However, there was no significant difference between them. In animal experiments, rNDV-IL15 efficiently suppressed tumor growth in vivo when compared with rNDV, and the difference was statistically significant. The results suggested that rNDV-IL15 is a more effective antitumor agent.
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Objective To compare the efficacy and safety of liquid nitrogen cryotherapy combined with acyclovir and mecobalamin in the treatment of herpes zoster in elderly patients.Methods 520 elderly patients with herpes zoster were randomly divided into two groups,experimental group and control group (n=260,each).Patients in experimental group were treated with liquid nitrogen cryotherapy,using liquid nitrogen cotton swab to graze the skin lesions 2-3 times per day for successive 5 days,combined with acyclovir and mecobalamin.Patients in control group were treated with acyclovir and mecobalamin.New blisters and dry skin and crust were observed and compared between the two groups on the 5th,14th,30th day after treatment.The skin lesion situation and reaction times for pain complete remission,vesicular scab,postherpetic neuralgia (PHN) were recorded and analyzed.Results The effective rate was 93.9％ (244/260) in the experimental group versus 84.2％ (219/260) in the control group (x2 =12.32,P＜ 0.05).The reaction times for vesicular scab,pain complete remission and subside were shorter in experimental group than in control group [(2.63 ±0.78)d vs.(4.75±1.39)d,(8.17±1.68)d vs.(11.25±2.23)d,(9.24±2.53)d vs.(12.78±3.13)d,all P＜0.01].There was no significant difference in new blister time between the experimental group and the control group [(1.85±0.62) d vs.(1.79±0.83)d,P＞0.05].Postherpetic neuralgia incidence was lower in experimental group than in control group [6.9％ (18/260) vs.18.1％ (47/260),x2 =14.79,P＜0.01].Conclusions Treatment with liquid nitrogen cryotherapy combined with acyclovir and mecobalamin can shorten the reaction times of vesicular scab,and pain complete remission and subside,and reduce postherpetic neuralgia as compared to acyclovir and mecobalamin treatment in elderly patients with herpes zoster.
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Objective To detect the expression and effect of human tumor necrosis factor related apoptosis-inducing ligand (hTRAIL) in vivo,by using a novel double expressing adenoviral vector encoding hTRAIL and firefly luciferase ( luc ) gene ( ad -luc-hTRAIL),in which luc was used as reporter gene.Methods Lung cancer A549 cell xenografts in 16 nude mice models were established in subcutaneous inoculation way,the adenovirus vectors ( ad-luc-hTRAIL,ad-hTRAIL,ad-luc) and phosphate buffer saline (PBS) (n =4) as control were injected into tumor respectively.The size of the tumor was measured at different time points (4,7,10,14,21,28 d)after injection.The activity of luciferase in surface of the tumor was detected in vivo by using high-sensitivity cooled-charged coupled device(CCD) camera.The expression of hTRAIL was demonstrated by immunohistochemistry staining after sacrificing the animals at different time points,and immunohistochemical scores (IHS) were measured. The apoptosis rate of tumor cells was detected by using TUNEL and calculated. Analysis of variance,the paired t test and linear correlation analysis was used for the statistics. Results The growing speed of tumour xenografts was more slowly in ad-luc-hTRAIL and ad-hTRAIL groups than PBS group (t =2.71,2.72,P ＜ 0.05 ).The tumor volumes of ad-luc-hTRAIL,ad-hTRAIL,ad-luc and PBS groups 28 days after injection were (208.4 ± 42.3 ),( 181.5 ±23.9),( 403.1 ± 54.0 ) and ( 427.0 ± 59.3 ) mm3, respectively. There was no significant difference between ad-luc group and PBS group(t =2.07,P ＞ 0.05).The expression of luciferase in ad-luc-hTRAILgroup reached its peak at 7th day ( 1.37 ± 1.04),and then decreased quickly.The IHS and apoptosis rate in ad-luc-hTRAIL and ad-hTRAIL groups reached their peaks at 7th day,the peak values of IHS were 6.25 ±2.06 and 6.5 ± 2.89,the peak values of apoptosis rate were (60.75 ± 8.06 ) ％ and ( 61.50 ± 8.47 ) ％,respectively.The amount of luciferase expression ( absolute number of photons detected by CCD camera)was linear positive correlated with IHS and apoptosis rate ( rphotons/IHs =0.942,rph /rate =0.842,rIHs/rate =0.887,P ＜ 0.05 ).Conclusion The target gene hTRAIL can be transfected into lung cancer A549 cell xenografts nude mice models efficiently with a high level expression,and the therapeutic effect of hTRAIL can be monitored by detecting the expression of luc.
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A facial allotransplanted patient presented hyperglycemia with blood glucose ranged 14. 3 -33. 3 mmol/L after receiving immunosuppressive drugs and glucocorticoids. To control the blood glucose level, the patient was treated with two subcutaneous doses of 10 U human neutral protamine hagedorn (NPH) insulin, and the fasting glucose level came down to 3. 6 - 9. 4 mmol/L. Then the continuous subcutaneous infusion of insulin aspart ( Novo Industri) was administrated (from 96 to 21 U/d) , and the fasting blood glucose levels were 3. 9 -4. 6 mmol/L. With oral administration of Metformin and Repaglinide, the fasting blood glucose was maintained to 4. 3 -5.9 mmol/L. With these medications, the blood glucose level of the patient was under good control and the acute and chronic complications of hyperglycemia were effectively prevented.
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FGF21 (fibroblast growth factor 21) is a recently described member of the FGF family. It has been previously demonstrated that FGF21 is a potent regulator of glucose homeostasis. To improve stability of FGF21 for better efficacy, a new form of recombinant FGF21 was generated by fusion of a full length FGF21 gene and the Fc fragment of human IgG4 with flexible linker sequence. To examine the glucose regulation activity of FGF21-L-Fc, 3T3-L1 pre-adipocytes were differentiated into adipocytes, and glucose uptake activity of FGF21-L-Fc was examined by glucose oxidase and peroxidase (GOD-POD) assay. The results showed that in comparison with wild type FGF21, FGF21-L-Fc was more potent in stimulation of glucose uptake by 3T3-L1. In vivo studies on the modified protein demonstrated that FGF-L-Fc had a better efficacy in lowering blood glucose of the STZ-induced diabetic animals and controlled glucose level for a longer time. The results provided a sound basis for further studies.
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Objective To investigate the mechanism of mastoparan-1 (MP-1) antagonizing lipopolysaecharide (LPS) in vitro. Methods The affinity of MP-1 for lipid A was assayed by biosensor, and the neutralization of MP-1 on LPS (2 μg/L) was detected by kinetic turbidimetric limulus test. After exposing fluorescin isothiecyanate (FITC) labeled LPS (FITC-LPS) to MP-1 at different concentrations (5, 10, 20, 40 μmol/L), the binding of FITC-LPS to murine RAW264.7 cells was analyzed by laser scanning confocal microscopy. The influence of MP-1 on TLR4 expression in RAW264.7 cells stimulated by LPS (100 μg/L) was detected by immunoeytochemieal staining. The expressions of TLR4, TNF-α and IL-6 at the gene and protein level were detected by RT-PCR and ELISA after exposing LPS (100 μg/ L) stimulated RAW264.7 cells to MP-1 at different concentrations. The effect of MP-1 on the viability of RAW264.7 cells was detected by MTT assay. Results MP-1 had high affinity to lipid A and could neutralize LPS. MP-1 at 10 μmol/L significantly inhibited not only binding of FITC-LPS to RAW264.7 (P < 0.05), but also protein and gene expressions of TLR4, TNF-α and IL-6 in LPS stimulated RAW264.7 cells in a dose-dependent manner (P < 0.05). No toxic effect of MP-1 on the viability of RAW264.7 cells was found (P > 0.05). Conclusions MP-1 inhibits cell viability mediated by LPS, which may be related to its neutralization of LPS and inhibition of binding of LPS to RAW264.7 cell membrane receptors.
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Objective To investigate the status of musculoskeletal articles and musculoskeletal injury articles published in the major journals of radiology in China and compare with abroad during the last decade.Methods Statistic analysis and comparison were done with musculoskeletal injury articles published in the major journals of radiology in China and abroad.The number,category,exam methods,study region and study contents were analyzed respectively.The journals in China included Chinese Journal of Radiology,Journal of Clinical Radiology and Journal of Practical Radiology.The journals at abroad included Radiology,the American Journal of Roentgenology(AJR),the British Journal of Radiology(BJR)and Skeletal Radiology.Results The rate of musculoskeletal articles among the treatise articles was 13.O%(827/6352)in China and 10.4%(900/8659)in three kinds of compressive jonrnals at abroad.The rate of musculoskeletal injury articles in musculoskeletal articles was 21.5%(178/827)in China and 10.8%(97/900)abroad.Among the review articles,the rate was 9.9%(73/741)and 13.7%(10/73)in China.respectively,while that was 4.3%(34/783)and 23.5%(8/34),respectively abroad.Among the case reports,the rate was 17.0%(675/3971)and 3.4%(23/675)in China respectively,while that was 8.8%(177/2019)and 14.7%(26/177),respectively abroad.The rate of exam methods which onlv used X-ray plain film in injury articles was 11.7%(26/222),mainly CT was 42.8%(95/222)and mainly MR was27%(60/222)in China,while that was10.9%(32/295),9.8%(29/295)and 32.5%(96/295),respectively in four kinds of journals at abroad.The combination examination was 16.2%(36/222)in China and 42.0%(124/295)at abroad respectively,The other was 2.3%(5/222)in China and 4.8%(14/295)at abroad.As for the study region,the rate of vertebrate column was 22.5%(50/222).knee joint was 21.1%(47/222),cranial and facial bones was 15.3%(34/222),hip joint was 7.2%(16/222).thoracic region was 6.8%(15/222),foot and ankle was 4.5%(10/222),hand and wrist was 4.1%(9/222),respectively,while that was 14.6%(43/295),14.6%(43/295),1.7%(5/295).6.4%(19/295),3.7%(11/295),12.9%(38/295)and 7.5%(22/295)at abroad,respectively.As for the study contents,the rate of bone was 64.9%(144/222),articular capsule and ligament was 8.6%(19/222),cartilage and osteoepiphysis was 7.7%(17/222),dislocation with or without fracture was 5.8%(13/222),menisci was 5.4%(12/222),combination study was 4.0%(9/222)and the other was 3.6%(8/222),respectively,while that was 62.4%(184/295),24.1%(71/295),4.7%(14/295),0.3%(1/295),2.7%(8/295),2.4%(7/295)and 3.4%(10/295)at abroad,respectively,The number of experimental articles in Chinese Journal of Radiology was 7,while that of Radiology was 29.Conclusion The rate of article on bone and bone injury was lower in all articles.Emphasize should be laid on experimental research and non-bone musculoskeletal injury in china.
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Objective To investigate the relationship between systemic lupus erythematosus and Epstein-Barr virus infection. Methods Expression of EBV-DNA was detected by fluorescent quantitative PCR assay in SLE patients (n=40) and normal control individuals (n=40). Results EBV-DNA in 11 were positive of the 40 patients and 3 were positive of the 40 normal control individual,and there was significant different(P
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Objective To investigate the change of monocyte autophagy in patients after trauma.Methods ①According to Injury Severity Score(ISS) or Abbreviated Injury Scale(AIS),we divided our 51 subjected trauma patients into 3 groups,the minor injury group(n=21),the moderate trauma group(n=19) and the severe trauma group(n=11).Another 14 healthy volunteers served as control.We collected the peripheral blood in 24 h,3,5 and 10 d after trauma,then harvested the monocytes by density gradient centrifugation with adherence separation.Then we observed the autophagy phenomenon by using laser confocal microscopy and transmission electron microscopy;② After the isolated monocytes were dyed with MDC and lysed,they were detected and quantified for fluorescent intensity by fluorospectrophotometer(excitation wavelength 380 nm and emission wavelength 525 nm);③Blood sugar level of all patients were measured in 24 h,3 and 5 d respectively after trauma,and the correlation between autophagy and blood sugar was analyzed.Results Compared with control group,more autophagy in monocytes was observed and quantified in trauma patients than in health volunteers(P
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<p><b>BACKGROUND</b>To evaluate the relationship between estrogen receptor (ER) expression and level of serum sexual hormones in male patients with lung cancer.</p><p><b>METHODS</b>The levels of serum estradiol (E 2), testosterone (T), follicle stimulating hormone (FSH) and lutenising hormone (LH) were measured in 25 patients with lung cancer and 30 healthy men by enzyme immunoassay magnetic solid phase (IEMA), the ER expression was detected in 25 cancer tissues, 25 paracancerous tissues, and 11 benign pulmonary tissues by immunocytochemistry (ICC).</p><p><b>RESULTS</b>The level of plasma E₂ in male patients with lung cancer was significantly higher than that in normal controls [(22.4±15.7) ng/L [WTBX]vs ( 12.6±4.8) ng/L, P=0.001 9] while the level of T was significantly lower while the level of T was significantly lower [(2.9±1.3) μg/L [WTBX]vs (4.1±1.5) μg/L, P= 0.003 0]. The ratio of E₂/T of male patients with lung cancer was also remarkably higher than that of control . The ratio of E₂/T of male patients with lung cancer was also remarkably higher than that of control [(9.7±10.0) ×10⁻³[WTBX]vs ( 3.4±1.6)×10⁻³, P=0.004 6]. The expression rate of ER in lung cancer tissue samples was 60.0% (15/25), but no ER expression was found in the paracancerous tissues and benign pulmonary tissues. The level of E₂ had positive correlation with the expression of ER in male patients with lung cancer (. The expression rate of ER in lung cancer tissue samples was 60.0% (15/25), but no ER expression was found in the paracancerous tissues and benign pulmonary tissues. The level of E₂ had positive correlation with the expression of ER in male patients with lung cancer (r=0.916 7, P < 0.001).</p><p><b>CONCLUSIONS</b>There are disorders and imbalances of sexual hormone metabolism in male patients with lung cancer, and these imbalances relate to the expression of ER. The elevation of E₂ level in peripheral blood might be related to the overexpression of ER.</p>
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ObjectiveTostudycellularimmunefunctioninpatientswithsyphilis.MethodsUsingflowcytometry,thecharacteristicofperipheralbloodlymphocyteimmophenotypes(PBLI)of23casesofsyphilis,andtherelationshipbetweenthePBLIandtherapeuticeffectwereanalyzed.Meanwhile,serumlevelofsIL-2Rofthepa-tientswasdetectedbyELISA.ResultsTheresultsshowedthatthepercentagesofpanT,TH,NKcellsandtheratioofTH/TSwerelower(P