Humanized monoclonal antibodies(mAbs) are increasingly widely used in targeted therapy for cancer and some other major diseases.Complementarity-determining region(CDR) grafting makes quantities of humanized mAbs available.Herein,we provide an overview on the strategy and progress of CDR grafting.

Objective To explore different socio-demographic and clinical characteristics for early onset patients (EOP) with psoriasis and late onset patients (LOP) with psoriasis in Chinese population and to provide scientific evidences for establishing comprehensive prevention and treatment strategy for psoriasis.Methods Cross-sectional study was performed.A total of 942 diagnosed psoriasis patients who paid a visit to outpatient clinic in a tertiary hospital in China from 12th September 2013 to 19th May 2015 was consecutively enrolled and investigated.Exploratory analysis was conducted to detect the association between disease onset age and patients features.Results Among 942 enrolled psoriasis outpatients,the average age was (40.6 ± 13.6) years with a range from 5 to 80 years.The sex ratio was 2.1 in favor of male.The most observed type of psoriasis in the present study was psoriasis vulgaris (98.3％).The average psoriasis area and severity index (PASI) for patients were 9.47 ±7.63.Comorbidity was combined in 20.2％ cases.Patients with EOP had a significantly higher likelihood of family history of disease.Compared EOP to LOP,LOP had a significantly higher likelihood of comorbidities involvement (P ＜ 0.05) and significant higher BMI index (P ＜ 0.05).Conclusions The present study supports the hypothesis that there are clinical differences between EOP and LOP in Chinese population.Both dermatologists and patients should pay more attention to psoriasis-associated features,such as family history and comorbidity diseases involvements.

Objective To investigate the cytolytic activity of extracellular cytolytic toxin rVVC of Vibrio vulnificus on the apoptosis of human ECV304 cells, and to analyze the activities of Caspase-3,-8 and -9. Methods The cytotoxic effect of refolded rVVC on the growth and apoptosis of ECV304 cells was identified by MTT, Hochest33342/PI fluorescent staining, flow cytometry and DNA agarose electrophoresis analysis, respectively. The activities of Caspase-3, -8 and -9 was measured using a colorimetric method. Results The viability of human ECV304 cells exposed to rVVC was inhibited by rVVC after 24 h. 2.0 HU/ml rVVC groups had a better cytotoxic effect to human ECV304 than that of 0.5 HU /ml rVVC groups. The apoptosis of human ECV304 cells in 2.0 HU/ml rVVC+40 μmol/L Z-VAD-FMK groups was relative reduced than that of 2.0 HU/ml of rVVC groups. After 0.5 h treatment with 2.0 HU/ml of rVVC, the Caspase-3 activity in human ECV304 cells increased gradually and reached the peak at 3 h (versus control groups, P<0.01). The activity of Caspase-8 and -9 remained unchanging. Conclusion The rVVC has cytotoxic effect on human ECV304 and the cytolysin is probably correlated with Caspase-3.

OBJECTIVETo explore the effect of Ginkgo biloba extract (GBE) on the function of alveolar polymorphonuclear neutrophils (PMN) in severe acute pancreatitis (SAP) rats complicated with lung injury (LI).

METHODSForty-eight adult SD rats were randomly divided into three groups, i.e., the sham-operation group, the SAP group, and the GBE treatment group, 16 in each group. The SAP model was successfully induced by retrograde injection of 5% sodium taurocholate solution into the biliopancreatic duct. Rats in the sham-operation group only received flipping of the duodenum. Those in the GBE treatment group received GBE intervention based on SAP model. Equal volume of normal saline was given to rats in the sham-operation group and the SAP group. Rats were sacrificed at 6 and 12 h after operation respectively. The lung tissue was sampled to evaluate the LI score. The wet/dry ratio (W/D) of lung tissues was detected. The activity of myeloperoxidase (MPO) was measured. Alveolar PMN was harvested by bronchoalveolar lavage. The content of neutrophil elastase (NE) in bronchoalveolar lavage fluid (BALF) was measured by enzyme-linked immunoabsorbent assay (ELISA). The percentage of CD11b/CD18 double positive PMN was detected using flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and NE protein in the lung tissue was detected by Western blot.

RESULTSCompared with the sham-operation group, significant pathologic lesion occurred in the lung tissue of rats in the SAP group; the pathologic LI score, lung tissue W/D ratio, MPO, and NE content in BALF significantly increased, the expression of ICAM-1 and NE in the lung tissue was obviously up-regulated, and the percentage of CD11b/CD18 double positive PMN significantly increased (P < 0.01). Compared with the SAP group, pathological lesion of the lung tissue was obviously attenuated, and the above indices were all significantly declined in the GBE treatment group (P < 0.01).

CONCLUSIONSExpression of ICAM-1 in the lung tissue and the percentage of D11b/ CD18 double positive PMN were up-regulated in SAP rats complicated with LI, resulting in the adherence of PMN to pulmonary vascular endothelial cells, and then activating PMN to release NE and aggravate LI. GBE could alleviate LI through down-regulating the expression ICAM-1 and CD11b/CD18, and hindering the adherence and activation of PMN to pulmonary vascular endothelial cells.

Animals ; Bronchoalveolar Lavage Fluid ; cytology ; Ginkgo biloba ; chemistry ; Intercellular Adhesion Molecule-1 ; metabolism ; Lung Injury ; drug therapy ; etiology ; metabolism ; Neutrophils ; metabolism ; Pancreatic Elastase ; metabolism ; Pancreatitis ; complications ; drug therapy ; metabolism ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley

Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; immunology ; metabolism ; T-Lymphocytes, Regulatory ; metabolism ; Th17 Cells ; metabolism

Objective To study the therapeutic effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on acute liver failure ( ALF) induced by D-galactosamine (D-gal) and lipopolysaccharide (LPS) in rats. Methods The ALF model was obtained through intraperitoneal injection of D-gal(300 mg/kg)and LPS (20μg/kg)in Wister rats. The hUCMSCs were transplanted after intoxication. All rats were divided into four groups, and each group received either hUCMSCs or 0.9% NaCl solution through intraperitoneal or tail-intravenous injection. To evaluate the liver function of each group, the levels of alanine aminotransferase (ALT), total bilirubin (TBil) and serum albumin (Alb) were measured on the day of hUCMSCs transplantation and the following 1, 2, 3, 5 and 7 days. All rats were then sacrificed to examine the liver histology at day 7. Analyses were done by using Fisher's exact test, unpaired t test and Mann-Whitney U test. Results There were no significant differences of survival rates among four groups (Fisher's exact test, both P = 1. 00). The levels of ALT, TBil and Alb in group receiving hUCMSCs intraperitoneally were (804. 9 ± 88. 0) U/L,(17. 4±2. 7) μmol/L and (20. 9±0. 8) g/L, respectively after 2 days of injection, whereas in the corresponding control group, those were (1294. 3± 171. 4) U/L, (32. 3±5. 5) μmol/L and (16. 1±0. 9) g/L, respectively, which indicated that hUCMSCs transplantation significantly improved the liver function (t = 2. 640, P =0.020;t=2.529, P = 0. 025;t= - 3. 833, P = 0. 002). Both of hUCMSCs-transplanted groups showed no significant differences. Liver histological data showed that transplantation of hUSMSCs through either intraperitoneal or tail-intravenous injection alleviated liver damage (U=4. 500, P = 0. 005;U=4. 500, P = 0. 008) and the mitotic index also increased in hUCMSCs-transplanted groups (U=4. 000, P = 0. 005; U=5. 500, P = 0. 013). Conclusions The levels of ALT, TBil and Alb can rapidly normalize in ALF rats after injected with hUCMSCs either intraperitoneally or tail-intravenously. hUCMSCs application raises the mitotic index, enhances hepatocellular regeneration and improves histological status.

ObjectiveTo study the expression of p27 and its relationship with CpG island methylation phenotype (CIMP) in insulinoma.MethodsExpression of p27 was tested in 27 insulinoma tissues and 11 paired control tissues by immunohistochemistry staining.CpG island methylation of p16,MLH1,RAR-β,MGMT,THBS1 (CIMP) was detected in 27 insulinoma tissues and 11 paired cantrol tissues by methylation specific PCR (MSP).The data of p27 and CIMP expression were correlated with the clinicopathological characteristics.ResultsThe positive expression rate of p27 in insulinoma tissues was significantly lower than that in paired control tissues (48％ vs 91％,P =0.008).High rate of CIMP occurrence in insulinoma tissues was 33％ (9/27),while it was 18％ (2/11) in paired control tissues,and difference between the two groups was not statistically significant ( P =0.350 ).The methylation of MGMT was reversely associated with p16 methylation ( P =0.004).p27 expression in insulinoma tissues was reversely associated high rate of CIMP occurrence but it was not statistically significant ( P =0.420).Neither the expression of p27 nor the occurrence of CIMP was associated with the clinicopathological features.ConclusionsDown-regulation of p27 and high rate of CIMP occurred in insulinomas,suggesting that the inactivation of p27 and epigenetic alterations of several genes might contribute to the carcinogenesis of insulinoma.

ObjectiveTo investigate whether neuronal intermediate filament protein(NF-66) could be used as a molecular marker for the determination of malignancy of insulinoma.MethodsThe expression of NF-66 protein was detected in insulinoma and pana - cancerous tissues and 3 insulinoma cell lines by immunohistochemistry staining. The relationship between the expression of NF-66 protein and the clinicopathological characteristics,survival was analyzed by univariate and multivariate statistical analysis.ResultsExpression of NF-66 was found in 102(77％ ) out of 132 insulinomas and none of 98 paired control (P =4.86 × 10-31 ).NF-66 was highly expressed in 3 insulinoma cell lines.The expression of NF-66 was found in 96 (81％) out of 118 benign tumors (P =0.003),while out of 14 malignant insulinomas,6(43％ ) were found to express NF-66 ( P =0.003 ).The expression of NF-66 was significantly associated with tumor size (3 cm as the cut-off point),distant metastasis (38％ vs 81％,P =0.013) and distant plus lymph node metastasis (46％ vs 81％,P =0.009),respectively.The expression of NF-66 was not correlated with age,gender,recurrence and overall survival.ConclusionsDown-regulation of NF-66 was significantly associated with tumor malignancy,suggesting that NF-66 could be a potentially novel molecular bionarker to distinguish malignancy from benign insulinoma.

Objective To study the effectiveness and feasibility of low intensity of aerobic bicycle ergometer training on hemiplegic stroke patients unable to perform assistive or independent ambulation.Methods Thirty stroke patients unable of assistive or independent ambulation were randomly divided into a control group and a aerobic training group.Patients in the aerobic training group performed low intensity of aerobic bicycle ergometer training for 30 min,3 times a week for 6 weeks in addition to a routine rehabilitation regime.The training duration and course of routine rehabilitation training were the same in both groups.The related cardiovascular response in aerobic training and changes in motor performance as well as the risk factors for stroke were observed in both groups.Results Twenty-four patients(12 patients in each group)completed the experiment.Patients in aerobic training group performed all training regime safely without any adverse response.Their motor function(including FMA score,Rivermead index,BI ADL ability),exercise endurance duration in exercise test,glucose level at 2 h in oral glucose tolerance test,fasting insulin level and HOMA-IR index all improved greatly as compared to the control group(P ＜ 0.05).Conclusion Low intensity of aerobic bicycle ergometer training can be safely and effectively administered in hemiplegic stroke patients unable of assistive ambulation or independent ambulation.

Adult ; Age Factors ; Air Pollutants, Occupational ; toxicity ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Police ; Pulmonary Diffusing Capacity ; physiology ; Pulmonary Ventilation ; physiology ; Respiratory Function Tests ; Smoking ; adverse effects ; Vehicle Emissions ; toxicity