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 investigate the influence of iloprost on the expression of lung endothelin-1(ET-1) in rats with hypoxic pulmonary hypertension(HPH).Methods Thirty-two male SD rats were randomly divided into four groups:normal control (NC) group,normal treatment(NT) group,hypoxia control(HC) group,hypoxia treatment (HT) group.NC group and NT group raised under normal Oxygen conditions 3 weeks.HC and HT group placed in a low Oxygen chamber (O2 10％) were treated 3 weeks of hypoxia 8 hours per day.NT and HT group were treated daily iloprost by inhalation therapy (2μg/kg).Affer three weeks,measured mean pulmonary arterial pressure (mPAP),right ventricular systolic pressure (RVSP),index of right ventricular hypertrophy.HE staining was used to observe the morphological changes of pulmonary arteries and image analysis system was used to calculate the percentage of vascular wall thickness of small pulmonary arteries in each group,RT-PCR technique was used to assess the trends of ET-1 in lung tissue homogenates.Results The hemodynamics in HC group was significantly higher than other groups(P＜0.05),there was no significant statistically difference of the hemodynamics in HT group compare with normal control group.Pulmonary arteries morphology,vessel wall thickening and vessel lumina stenosis in HC group than NC、NT、group.These indicators were significant improved in HT group.ET-1 expression in lung tissue were significantly increased in HC group than NC groups.No significant difference was found between and NC group HT group.Conclusion Aerosol inhalation of iloprost has exact therapeutic effect for rats with HPH.Iloprost reduced ET-1 overexpression in lung tissue in HPH rats and prevent pulmonary vascular remodeling.

Objective To investigate effects of problem-based learning (PBL) and traditional learning (TL) on students' long-term memory and clinical practice ability. Methods Totally 79 5-year-program undergraduates of 2006, 2007, 2008 grade in school of clinical medicine of our hospital were randomly divided into PBL group (n=38) and TL group (n=41). The teaching effects were evaluated by two exams as well as teachers' subjective impression. SPSS 17.0 statistical analysis software was used;exam results were expressed as x±s; t test and rank sum test were used to analyze the exam results and subjective impression. α=0.05 was set as inspection level. Results In the second exam after 6 months, the mean exam scores were (76.66 ±5.94) and (73.59 ±5.74) in PBL group and TL group, without significant differences between the two groups (t=1.85, P=0.068). However, at clinical intern-ship stage, PBL group outperformed TL group based on the subjective evaluation (P=0.065, 0.277). Conclusion PBL can culture students' ability of problem-solving, but it is limited in culturing long-term memory.

OBJECTIVETo evaluate the association between p53 codon 72 polymorphism (R72P) and the risk of colorectal liver metastases.

METHODSThe p53 R72P genotype was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 78 consecutive colorectal cancer patients with liver metastases and 214 age- and sex-matched cases with nonmetastatic colorectal cancer.

RESULTSThe R allele of the p53 R72P polymorphism was more frequently found in metastatic cases than in nonmetastatic cases (P=0.075). Carriers of the 72R allele had a 2.25-fold (95% CI (confidence interval)=1.05 to approximately 4.83) increased risk of liver metastases. On the stratification analysis, 72R-carrying genotype conferred a 3.46-fold (95% CI=1.02 to approximately 11.72) and a 1.05-fold (95% CI=0.36 to approximately 3.08) increased risk of liver metastases for p53 overexpression-positive and negative colorectal cancers, respectively.

CONCLUSIONThese results demonstrate for the first time that the 72R allele of the p53 polymorphism has an increased risk for liver metastases in colorectal cancers positive for p53 overexpression.

Adenocarcinoma ; genetics ; metabolism ; pathology ; secondary ; Case-Control Studies ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; DNA, Neoplasm ; blood ; genetics ; Female ; Genes, p53 ; Genetic Predisposition to Disease ; Genotype ; Humans ; Liver Neoplasms ; genetics ; metabolism ; secondary ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics

AIMTo investigate the survival rate and the level of HaCaT cells damage with ultraviolet B (UVB) radiation at various doses, and observe the protective effects of ginsenoside Rg1 and Rb1 in vitro.

METHODSMTT assay was employed to analyze the cell survival rate after UVB radiation of 30, 60, 90 and 120 mJ x cm(-2). The damage of nucleolus and the protective effects of ginsenoside Rg1 and Rb1 were scanned by Hoechst 33258 staining and single cell gel electrophoresis assay (SCGE).

RESULTSIt was found that the cell survival rate decreased gradually and the damage of nucleolus aggravated as the radiation dose increased from 30 mJ x cm(-2) to 120 mJ x cm(-2). At the dose of 20 microg x mL(1-), obvious protective effect of ginsenoside Rg1 and Rb1 can be observed against UVB radiation-induced HaCaT cells growth inhibition and nucleolus damage.

CONCLUSIONUVB radiation inhibits HaCaT human keratinocytes growth and ginsenoside Rg1 and Rb1 can relief the damage.

Apoptosis ; drug effects ; radiation effects ; Cell Line ; Cell Survival ; drug effects ; radiation effects ; DNA Damage ; drug effects ; radiation effects ; Dose-Response Relationship, Radiation ; Ginsenosides ; isolation & purification ; pharmacology ; Humans ; Keratinocytes ; cytology ; drug effects ; radiation effects ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Protective Agents ; isolation & purification ; pharmacology ; Ultraviolet Rays ; adverse effects

BACKGROUND AND OBJECTIVEAccumulating data indicate that docetaxel plus cisplatin and 5-fluorouracil has certain effect on advanced gastric or gastro-oesophageal junction adenocarcinoma. This study was to evaluate the efficacy and toxicity of docetaxel plus nedaplatin and 5-fluorouracil (DNF regimen) in treating advanced esophageal carcinoma.

METHODSForty-three patients with pathologically confirmed advanced esophageal carcinoma treated by DNF regimen: intravenous infusion of docetaxel (75 mg/m(2)) over 1 h, intravenous infusion of nedaplatin (100 mg/m(2)) over 3 h, intravenous infusion of leucovorin (CF, 200 mg/m(2)) over 2 h, intravenous injection of 5-fluorouracil (375 mg/m(2)) over 10 min, followed by a 46-hour infusion of 5-fluorouracil (2.6 g/m(2)). The cycle was repeated every three weeks. Treatment efficacy was evaluated every two weeks according to the WHO standards. All patients received at least two cycles of chemotherapy.

RESULTSPatients received a total of 144 cycles of treatment, and all were evaluable for efficacy and toxicity. Of the 43 patients, 2 (4.65%) achieved complete response (CR), 25 (58.14%) achieved partial response (PR), 9 (20.93%) had stable disease (SD), and 7 (16.28%) had progressive disease (PD). The overall response rate was 62.8%. The median time-to-progression (TTP) was 201 days and the median survival time (MST) was 310 days. Grade III/IV adverse events mainly included neutropenia (20.93%), febrile neutropenia (4.65%), thrombocytopenia (6.98%) and vomiting (9.30%). One patient died of grade IV thrombocytopenia.

CONCLUSIONDNF regimen is effective for and well tolerated by patients with advanced esophageal carcinoma.

Adenocarcinoma ; drug therapy ; pathology ; secondary ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; secondary ; Esophageal Neoplasms ; drug therapy ; pathology ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia ; chemically induced ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Remission Induction ; Survival Rate ; Taxoids ; administration & dosage ; adverse effects ; Thrombocytopenia ; chemically induced

OBJECTIVETo investigate the influence of maternal staphylococcal enterotoxin B (SEB) administration during pregnancy on CD3⁺ TCR Vβ8⁺T cells of adult offspring rats.

METHODSPregnant maternal rats at gestational day (GD) 16 were injected intravenously with 15 µg SEB in 0.2 ml PBS (SEB group), and the control rats receive the same volume of PBS. Flow cytometry was used to determine the levels of CD3⁺ TCR Vβ8⁺T cells in both the thymus and peripheral blood of adult offspring rats and the response of these cells to a secondary SEB administration.

RESULTSMaternal SEB administration during pregnancy significantly decreased the percentages of CD3⁺TCR Vβ8⁺T cells in the thymus in adult female (1.760-2.714) and male (1.098-2.088) offspring rats (P<0.05). The change of CD3⁺TCR Vβ8⁺T cells in the peripheral blood was similar to that in the thymus. In the control adult offspring rats, SEB administration at adulthood significantly reduced the percentages of CD3⁺TCR Vβ8⁺T cells in both the thymus and peripheral blood (P<0.05). But in SEB group, a secondary SEB administration in adult offspring rats significantly increased the percentage of CD3⁺TCR Vβ8⁺T cells in the peripheral blood (P<0.05) but not in the thymus (P>0.05).

CONCLUSIONMaternal SEB administration during pregnancy can change the response of CD3⁺ TCR Vβ8⁺T cells of adult offspring rats to a secondary SEB administration.

Animals ; Enterotoxins ; adverse effects ; Female ; Male ; Maternal Exposure ; adverse effects ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; T-Lymphocyte Subsets ; drug effects

OBJECTIVETo investigate α-toxin-induced apoptosis of umbilical vein endothelial cells and explore its role in vertical infection of Staphylococcus aureus L-form.

METHODSHUV-EC-C cells exposed to different concentrations (0, 10, 30, 90, and 270 ng/ml) of α-toxin for different time lengths (0, 2, 4, 6, and 8 h) were examined for apoptosis using flow cytometry with Annexin V-PI staining. The levels of tumor necrosis factor-α (TNF-α) and the activities of, caspase-3 and caspase-8 in the cell culture were detected by ELISA and colorimetric method, respectively. α-Toxin-induced cell apoptosis was also analyzed in HUV-EC-C cells treated with a neutralizing antibody of TNF-α or with the inhibitory peptides of caspase-3 (zDEVD-FMK) and caspase-8 (zIETD-fmk).

RESULTSα-Toxin induced apoptosis of HUV-EC-C cells in a dose- and time-dependent manner and caused significantly enhanced expression of TNF-α and the activation of both caspase-3 and caspase-8. Inhibition of TNF-α with its neutralizing antibody and the inhibitory peptides of caspase-3 or -8 all significantly decreased α-toxin-induced cell apoptosis, and the caspase-3 inhibitor completely blocked α-toxin-induced cell apoptosis.

CONCLUSIONα-Toxin-induced apoptosis is partially mediated by the extrinsic cell death pathway of TNF-α and caspase-8 and plays an important role in the vertical infection of S. aureus L-form to affect fetal growth and development.

Apoptosis ; Bacterial Toxins ; toxicity ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; L Forms ; Staphylococcal Infections ; Staphylococcus aureus ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo study the changes of partial pressure of brain tissue oxygen (PbtO2) and brain temperature in acute phase of severe head injury during mild hypothermia therapy and the clinical significance.

METHODSOne hundred and sixteen patients with severe head injury were selected and divided into a mild hypothermia group (n=58), and a control group (n=58) according to odd and even numbers of hospitalization. While mild hypothermia therapy was performed PbtO2 and brain temperature were monitored for 1-7 days (mean=86 hours), simultaneously, the intracranial pressure, rectum temperature, cerebral perfusion pressure, PaO2 and PaCO2 were also monitored. The patients were followed up for 6 months and the prognosis was evaluated with GOS (Glasgow outcome scale).

RESULTSThe mean value of PbtO2 within 24 hour monitoring in the 116 patients was 13.7 mm Hg +/- 4.94 mm Hg, lower than the normal value (16 mm Hg +/- 40 mm Hg ) The time of PbtO2 recovering to the normal value in the mild hypothermia group was shortened by 10 +/- 4.15 hours compared with the control group (P<0.05). The survival rate of the mild hypothermia group was 60.43%, higher than that of the control group (46.55%). After the recovery of the brain temperature, PbtO2 increased with the rise of the brain temperature.

CONCLUSIONSMild hypothermia can improve the survival rate of severe head injury. The technique of monitoring PbtO2 and the brain temperature is safe and reliable, and has important clinical significance in judging disease condition and instructing clinical therapy.

Adult ; Blood Gas Monitoring, Transcutaneous ; Body Temperature ; Brain ; metabolism ; Brain Chemistry ; Craniocerebral Trauma ; metabolism ; therapy ; Female ; Humans ; Hypothermia, Induced ; Male ; Oxygen ; metabolism ; Partial Pressure ; Regional Blood Flow ; Treatment Outcome

OBJECTIVETo explore the feasibility of autologous fascia as a scaffold for the reconstruction of skeletal muscle in vivo.

METHODSTwenty-eight healthy New Zealand rabbits were employed in the study. The anterior tibial muscle in both legs were divided to create a gap of 10 mm in each muscle. One leg was used in the experiment (E, n = 28), while the contralateral as self-control (C). The legs in C group were further divided into 3 groups (C1, C2 and C3). While defects in the midportion of anterior tibial muscle in the hind legs were created in all rabbits. In E group, each defect was filled with a tubule made of autologous fascia lata, and the fascial tubule was filled with tiny muscular granules (< 1 mm x 1 mm x 1 mm). In C1 group (n = 10), the defect was also filled with fascial tubule but with no muscle filling. The defect in C2 group (n = 10) was only filled with muscle granules without fascial tubule. The defect in C3 group (n = 8) received no treatment. The survival rate of the transplantation was grossly observed, and the tissue samples were harvested for histological and ultra-structural examination and immunohistochemical identification of desmin at 2, 3, 4, 6 and 9 post-operation weeks. The expression level of alpha-actin DNA in the tissue samples from the midportion of grafted fascia was assessed by RT-PCR (reverse transcription polymerase chain reaction) in E and C1 groups.

RESULTS(1) Survival rate of the transplantation: In E group, it was 93.33% with near normal tissue contour in the grafting area. The muscle defects were not completely repaired in C1, C2 and C3 groups. (2) Under light and electronic microscopy, marked proliferation of muscular cells surrounding fibrous tissue could be discerned at 2 and 3 post-operation weeks in E group, while only necrotic tissue and fibrosis were observed in C1 and C2 groups, and no definite tissue could be discernible in C3 group. (3) Immunohistochemical staining revealed that over 85% of the cells were positive for desmin in E group, while only less than 25% in C1 group. (4) The expression level of alpha-actin DNA was significantly higher in E group than that in C2 group (P < 0.05).

CONCLUSIONThese results suggested that autologous fascia as a scaffold is beneficial for skeletal muscle reconstruction in vivo.

Animals ; Disease Models, Animal ; Fascia ; transplantation ; Muscle, Skeletal ; surgery ; Rabbits ; Soft Tissue Injuries ; surgery ; Tissue Culture Techniques ; Tissue Scaffolds ; Transplantation, Autologous