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.

A new flavonoid glycoside, (-)-2S-8-methyl-5,7,4'-trihydroxyflavanone-7-O-β-D-glucopyranoside (1), along with five known ones, quercetin-3-O-(2"-galloyl)-α-L-arabinoside (2), kaempferol-3-O-α-L-arabinoside (3), guaijaverin (4), trifolin (5) and hyperin (6), was isolated from the leaves of Eucalyptus robusta. Their structures with absolute configurations were elucidated by NMR, HR-ESI-MS, CD spectra data and physicochemical methods. In addition, 2-6 were isolated from E. robusta for the first time.
Eucalyptus ; chemistry ; Flavonoids ; chemistry ; isolation & purification ; Glycosides ; chemistry ; isolation & purification ; Plant Leaves ; chemistry

Objective To investigate the role of intestinal fatty acid binding protein(I-FABP)in evaluating intestinal dysfunction of septic rats and the effect of glutamine on I-FABP expression.Methods Rats were divided into 3 groups,control group were only fed with Peptisorb,model group were fed with Peptisorb after intraperitoneal injection with E.coli endotoxin lipopolysaccharidegiven and glutamine group were added glutamine on basis of model group.The correlation between serum I-FABP level and intestinal mucosa damage index were analyzed and the concentrations of serum I-FABP in each group were observed and compared. Results The serum level of I-FABP in rats were correlated with the Chiu’s score of intestinal mucosa,mucosa thickness and villus length(P<0.05 ).Compared with control group,the concentration of serum I-FABP in model group and glutamine group were significantly increased(P<0.05),but which in glutamine group was lower than that in model group(P<0.05).Conclusions Serum I-FABP could be an non-invasive diagnosis index for evaluating acute intestinal dysfunction in septic rats.In addition,dietary glutamine supplementation may ameliorate sepsis-induced intestinal epithelial injury in rats.

Objective To investigate the correlation between sTREM-1 and inflammatory factors expression in critical patients and its effect on severity of disease and clinical prognosis .Methods sTREM-1 ,TNF-α,IL-6 ,IL-10 levels were checked in serum of 54 patients who admitted to intensive care unit (ICU) on the first day and only sTREM-1 was checked again on the third day .At the same time ,APACHEⅡand survival situation in 28 days were recorded .Results sTREM-1 level in critical patients was positive correlated with TNF-α,IL-6 and APACHEⅡ(P<0 .01) .There was positive correlation between APACHE Ⅱ and TNF-α,IL-6 ,but pearson correlation coefficient between sTREM-1 and APACHE Ⅱ was higher than TNF-α,IL-6 .Compared with the survivor group ,the concentrations of serum sTREM-1 was significantly higer in non-survivor group on the first day and the third day after entering ICU(P<0 .05) .Conclusion sTREM-1 level is positive correlated with inflammatory reaction and the severity of disease .It also has prognostic value for outcome in patients with critical illness .

Objective To explore the role of synaptic plasticity on the formation of visceral hyper- sensitivity induced by acute restraint stress in rats.Methods Twenty male Sprague-Dawley rats were randomly divided into control group and acute restraint stress group(model group).Visceral hypersensi- tivity was made by acute restraint stress for 1 h.The colorectal distension(CRD) with different pressure were performed and the abdominal electromyography(EMG) was recorded.The visceral sensitivity was determined by the frequency of EMG.The ultrastrueture of synapse was observed with transmission electron microscope.The expression of synaptophysin was measured by RT-PCR and Western-blot. Results①The frequency of EMG was significantly correlated with CRD pressure(control group,r=0.992, P=0.008;model group,r=0.978,P=0.022).The frequencies of EMG in model group(at 40,60 and 80 mm Hg) were significantly more than that in control group(P value=0.043,0.024,0.038,respectively).②There were more synaptic vesicles accumulated in presynaptical terminal.The post synaptic density was increased in model group compared to control group.③In the proximal and distant colon,the expressions of rnRNA and protein of synaptophysin were higher in model group (P

The aim of the experiments was to develop and characterize a murine model for investigating the effects of prenatal cocaine exposure on the mother and fetus. Pregnant mice were separated into three groups: group 1 was treated with cocaine HCl at 10 mg/kg twice daily (COC); group 2 was treated with saline at 10 ml/kg twice daily (SAL); and group 3 was pair-fed with the COC dams and was injected with saline following the same schedule (SPF) from embryonic day (E) 8 to 17. We utilized high-pressure liquid chromatography (HPLC) with UV detector and electrochemical detector to test the concentrations of cocaine, dopamine and serotonin, as well as HE staining to observe morphological alterations of liver and placenta. Though less food intake and lower weight gain were observed in COC and SPF groups but not in SAL dams, lower fetal body weight and brain weight were only seen in COC offspring. Pharmacological analysis revealed that cocaine was found in fetal plasma at 15 min following intraperitoneal administration on E17, accompanied with elevated concentrations of dopamine (DA) and serotonin (5-HT) in fetal brain. We also observed morphological changes in liver and placenta of cocaine-exposed fetuses. The present study indicates that pregnancy cocaine exposure can lead to maternal undernutrition and developmental abnormality of the fetal brain, liver and placenta. It is suggested that the developmental abnormality of the fetuses induced by cocaine is due to the toxicological effect of cocaine but not to maternal undernutrition.
Animals ; Brain ; metabolism ; pathology ; Cocaine ; adverse effects ; blood ; Disease Models, Animal ; Dopamine ; metabolism ; Female ; Fetus ; drug effects ; pathology ; Liver ; pathology ; Malnutrition ; Maternal Exposure ; adverse effects ; Maternal Nutritional Physiological Phenomena ; Mice ; Mothers ; Placenta ; pathology ; Pregnancy ; Serotonin ; metabolism

Objective To screen down regulated genes and find down regulated novel genes in gastric cancer. Methods Genes mRNA expression were detected between gastric cancer and normal gastric mucous membrane of five patients using cDNA microarray. Genes mRNA expression signals on hybridization membranes were analysized with computer software. Down regulated genes in gastric cancer were screened. cDNA suppression subtraction library was established by counterpart normal gastric mucous membrane mRNA(Tester) subtracting gastric cancer tissues mRNA(Driver) of five patients. After identification of the subtraction library, positive clones choosen randomly were sequenced , and down regulated novel genes in gastric cancer were screened. Some of the genes were identified by RT PCR.Results Down regulated genes in gastric cancer consist of 60 genes including tumor suppressing genes, apoptosis related genes, DNA replication and transcript or translate related genes, cell cycle related genes, cell migration related genes, etc. Two unknown gene fragments in gastric cancer were cloned. Conclusions Sixty down regulated genes in gastric cancer are confirmed. They are involved in gastric tumorigenicity and metastasis. cDNA subtraction library of gastric cancer was constructed successfully. Two down regulated novel gene fragments in gastric cancer was found.

The goal of this study is to investigate the population pharmacokinetics of oral tacrolimus in Chinese renal transplant patients and to identify possible relationship between covariates and population parameters. Details of drug dosage history, sampling time and concentration of 802 data points in 58 patients were collected retrospectively. Before analysis, the 58 patients were randomly allocated to either the model building group (n=41) or the validation group (n=17). Population pharmacokinetic data analysis was performed using the nonlinear mixed-effects model (NONMEM) program on the model building group. The pharmacokinetics of tacrolimus was best described by a one compartment model with first-order absorption and elimination. Typical values of apparent clearance (CL/F), apparent volume of distribution (V/F) were estimated. A number of covariates including demographic index, clinical index and coadministration of other drugs were evaluated statistically for their influence on these parameters. The final population model related clearance with POD (post operative days), HCT (haematocrit), AST (aspartate aminotransferase) and coadministration of nicardipine and diltiazem. Predictive performance of the final model evaluated with the validation group showed insignificant bias between observed and model predicted concentrations. Typical value of CL/F and V/F was 21.7 L x h(-1) and 241 L, inter-patient variability (RSD) in CL/F and V/F was 41.6% and 49.7%, respectively. The residual variability (SD) between observed and model-predicted concentrations was 2.19 microg x L(-1). The population pharmacokinetic model of tacrolimus in Chinese renal transplant patients was established and significant covariates on the tacrolimus model were identified.
Administration, Oral ; Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; blood ; pharmacokinetics ; Kidney Transplantation ; Male ; Metabolic Clearance Rate ; Middle Aged ; Models, Statistical ; Nonlinear Dynamics ; Retrospective Studies ; Tacrolimus ; administration & dosage ; blood ; pharmacokinetics ; Young Adult

Objective To investigate the effects of different early enteral nutrient (EN) emulsions of TPF-T and TP on nutritional status and intestinal mucosal barrier in patients with septic shock. Methods From May 2017 to May 2018, 112 patients with septic shock were continuously enrolled in the Department of Intensive Care Unit of the First People's Hospital of Taizhou, and they were randomly divided into a TPF-T group and TP group, each group with 56 cases. After admission, the patients in both groups were all treated according to the 2016 Saving Sepsis Campaign (SSC) Guidelines for septic shock. Both groups were supported with EN, TPT-T group was given TPF-T EN emulsion rich in fish oil, while TP group was supported with standard TP EN emulsion, and the therapeutic course was consecutive 7 days in both groups. The differences in nutritional status, inflammatory response, immune function, intestinal mucosal barrier, gastrointestinal symptoms and prognosis were compared between the two groups. Results After EN, the nutrition indicators such as albumin (Alb), prealbumin (PA), transferrin (TRF) and immune indexes (IgA, IgG), human leukocyte DR antigens (HLA-DR) and D-lactic acid were increased in both groups, reaching the peaks on the 7th day after EN application, Alb, PA, TRF, IgA, IgG, HLA-DR in the TPF-T group were significantly higher than those in the TP group [Alb (g/L): 34.43±5.81 vs. 33.59±5.34, PA (mg/L): 269.83±47.56 vs. 252.67±41.92, TRF (g/L): 3.43±0.64 vs. 3.32±0.81, IgA (mg/L): 159.45±34.56 vs. 143.31±33.81, IgG (mg/L): 4 947.68±871.66 vs. 4 583.75±841.54, HLA-DR: (68.22±9.11)% vs. (62.21±9.69)%], and after EN, the D-lactic acid in the TPF-T group was significantly lower than that in the TP group (mg/L: 30.42±6.79 vs. 33.34±7.31). The inflammatory indicators of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), procalcitonin (PCT), endotoxin and diamine oxidase (DAO) were all gradually reduced in two groups, reached the lowest levels on the 7th day after EN application, and all the above-mentioned indicators in the TPF-T group were significantly lower than those in the TP group [TNF-α (ng/L):95.43±20.69 vs. 109.59±23.45, CRP (mg/L): 21.33±16.35 vs. 32.36±17.83, PCT (μg/L): 1.24±1.21 vs. 4.18±1.32, endotoxin (U/L): 10.32±2.31 vs. 11.54±2.69, DAO (g/L): 19.45±8.49 vs. 25.47±9.41]. The incidences of gastric retention, diarrhea and paralysis of lower digestive tract in TPF-T group were significantly lower than those in TP group [gastric retention: 14.29% (8/56) vs. 32.14% (18/56), diarrhea: 12.50% (7/56) vs. 35.71% (20/56), paralysis of lower digestive tract: 7.14% (4/56) vs. 23.21% (13/56)], the length of hospital stay was significantly shorter in the TPF-T group than that in the TP group (days: 18.77±5.08 vs. 21.71±6.67, P < 0.05); however, there was no significant difference in mortality between the two groups [14.29% (8/56) vs. 21.43% (12/56), P > 0.05]. Conclusion TPF-T could more effectively maintain nutritional status, reduce inflammatory reaction, improve immunity, protect intestinal mucosal barrier function, and has fewer adverse reactions, which was helpful to improve the prognosis of septic shock patients.

Objective To investigate the possibility of in vitro expression of human neurotrophin-3 (NT-3) gene in mouse embryonic stem (ES) cells. Methods The reconlbinant eukaryotic expression vector,PCDNA-3.1(+)-NT-3 was transiently transfected into ES cells by means of liposome mediated method. NT-3 protein and mRNA were tested by immunohistochemical method and RT-PCR,respectively.NT-3 protein secretion in the supernatant of cell culture was detected by ELISA.Results By immunohistochemistry, ES cells were red stained in cytoplasma, showing that the transfected NT-3 plasmid was expressed in the ES cells.RT-PCR got a 200 bp segment in the transfected cells,and the NT-3 protein secretion in the supernatrdnt of transfected cell culture detected by ELISA was dramatically higher than that of control group(P＜0.05). Conclusions Successful transfection of recombinant PCDNA-3.1(+)-NT-3 into the ES cells that leads to stable expression of NT-3 gene can be a potential effective gene delivery approach in the treatnlent of Parkinson's disease.