Objective To study the effect of interleukin 2(IL-2)of clinical dose range,on the proliferation of human peripheral blood T cells,with special emphasis on the number and functional phenotype of γδT cells.Methods Human peripheral blood mononuelear cells(PBMCs)were isolated by density gradient centrifugation and cultured for 2 weeks at different IL-2 concentrations.Ratio and phenotype of different T cell subpopulations before and after in vitro expansion were explored by immunofluorescence staining.Cell number was estimated by trypan blue staining and cell counting.Results Within the four functional phenotypes of Vδ1 as well as Vδ2 γδT cells,CD27~+cells(including CD27~+CD45RA~+and CD27~+CD45RA~-subsets)expressed lymphoid tissue homing receptor CCR7,whereas CD27~-cells(including CD27~-CD45RA~+and CD27~-CD45RA~-subsets)had the peripheral tissue homing potential.All the studied γδT functional subsets showed the expression of activity related receptors,and the ability of a rapid production of various amount of cytotoxicity related effectors following mitogen stimulation.Although IL-2 at high concentration suppressed the proliferation of CD4 T cells,it may promote the proliferation of γδT cells.The proliferated γδT cells were mainly CD27~-CD45RA~-effector cells.Conclusion IL-2 of the clinical dose range may promote proliferation of human peripheral blood γδT cells,which might have important biological significance in IL-2 based anti-tumor therapy.

Objective To investigate the effect of at-RA in macrophage accumulation in tubulointerstitium of rats with renal tubulointerstitial fibrosis.Methods Unilateral ureteral obstructive(UUO) rat animal models were used for the study.40 SD rats were randomly divided into 5 groups: sham group,UUO group,benazepril group,low-dose at-RA groups and high-dose at-RA groups.The rats were under intragastric administration by benazepril(10mg/(kg?d)) in benazepril group,and by(at-RA)(10mg/(kg?d)) in low-dose at-RA group and 20mg/(kg?d) in high-dose at-RA group and by sodium chloride in tales doses in sham group and UUO group from the day before the operation to 14 day after operation.Immunohistochemistry staining of CD68 and Col Ⅲ was used to define the macrophage accumulation and expression of interstitial Col Ⅲ.The degree of tubulointerstitial damage was scored by HE and Masson staining.Results Tubulointerstitial macrophage infiltration were all significantly reduced by(at-RA) or benazepril treatment.They also improved the histological changes of UUO rats and inhibited interstitial colⅢ deposition.Conclusion Reduction of interstitial macrophage infiltration may be an important event by which(at-RA) or benazepril prevents renal injury caused by UUO.

Objective To established cardiac-specific transgenic mice of the cTnC D145E and cTnCG159D and compare the HCM and the DCM.Methods The cTnCD145E and cTnCG159D were generated by site-directed mutagenesis and the transgenic plasmids were constructed by insertion of the mutant genes under the control of α-MHC, which is a myocardium specific promoter.The transgenic mice were generated by microinjection and were all maintained on a C57BL/6J genetic backgroud .The cardiac structure and function of the transgenic mice were compared and analysized by echocardiographic and pathological observation at different ages .Results The cTnCD145E and cTnCG159D transgenic mice were established and developed to HCM and DCM, respectively, with aging.The left ventricular end-systolic volume (ESV) and left ventricular end-diastolic volume ( EDV) decreased and ejection fraction ( EF) and left ventricular end-systolic posterior wall thickness (ESPWT) increased in the cTnCD145E transgenic mice, while EDV and ESV increased and EF and ESPWT decreased in the cTnCG159D transgenic mice at 12 months of age.Conclusions Cardiac-specific human cTnCD145E transgenic mice showed HCM phenotypes , and cardiac-specific human cTnC G159D transgenic mice showed DCM phenotypes , which can be used as different models for comparative study of the pathogenesis of cardiomyopathy .

Objective To comparatively analyze the domestic and foreign sicentific product, academic impact and cooperation in toxicology from 1980 to 2015.Methods The countries, Chinese scientific research institutions and authors engaged in research of toxicology were analyzed according to the InCites-covered number of published pa-pers, cited papers and collaborations .The highly cited papers covered in Web of Sciene were analyzed by biblio-metric analysis.Results The number of papers on toxicology published by USA, Britian and Japan was greater than that published by other countries.The number of papers on toxicology published by China increased significantly and their academic level was notebly improved.Conclusion China should strengthen the subject system construc-tion, attach importance to frontier and retrospective analysis and international cooperation, speed up the develop-ment of toxicology and improve the academic level of its scientific achievements .

Objective To investigate the morbidity,clinical manifestations,and imageology characteristics,and the influencing factors of severe cyclosporine A(CsA)-related neurotoxicity(SNCT)in the patients after allogenic hematopoietic stem cell transplantation(allo-HSCT).Methods Finding of SNCT was carried out in 164 allo-HSCT recipients from January 2003 to June 2006.Clinical characteristics were analysed,including precursory symptoms and clinical manifestations.Associations between the onset of SNCT with blood CsA levels,age,transplant types,human leucocyte antigen(HIJA)matching,conditioning regimens,antihuman thymocyte globulin(ATG)used in the prevention and treatment for graft-versus-host disease(GVHD)and intravenous corticosteroid used for acute GVHD were analyzed.Statistical analysis was performed with Binary Logistic Regression using SPSS/PC version 11.0.Results Thirteen patients(7.93%)were identified to have SNCT,including seizures(n=8,4.88%),paralysis(n=6,3.66%),coma(n:2,1.22%),cerebllar ataxia(n=3,1.83%)and chondrioid encephalomyopathy (n=1,0.61%).All the patients had precursory symptoms prior SNCT including headache(n=8),agitation(n=4)and hypertension(n=6).Magnetic resonance imaging(MRI)performed in twelve patients after SNCT showed that eleven patients had signal abnormalities in cerebral cortex and cerebral white matter.Six patients examined with computerized tomography(CT)had no abnormal findings.After extenuation or withdrawal of CsA.ten patients had complete recovery.two had partial recovery and one died of SNCT.Simple effect analysis of Binary Logistic Regression showed that the associations between the onset of SNCT with blood CsA levels.transplanta types.HLA matching.ATG used in the prevention and treatment for GVHD and intravenous corticosteroid used for acute GVHD were of statistical significance.The multiple effect analysis of Binary Logistic Regression showed that the associations of the onset of SNCT with blood CsA levels and ATG used had statistical significance and the odds ratio(OR)was 1.007(P=0.006) and 6.727(P=0.030),respectively.Conclusions 91.67%of the allo-HSCT recipients with SNCT have MRI abnormalities.High blood CsA levels and the use of ATG Call elevate the risk of the occurrence of SNCT.

Objective To investigate the effects of TLR7 on imiquimod induced apoptosis of THP-1 derived macrophages.Methods Three cell lines ( THP-1 derived macrophages, MDCK cell line and HUVEC cell line) with different capabilities of expressing TLR7 were selected.The survival rates of cells af-ter the treatment with different concentrations of imiquimod were detected by MTT assay.The levels of IL-6 in the supernatants of TLR7 inhibitor chloroquine or TLR7-siRNA treated cells were detected by enzyme-linked immunosorbent assay.The apoptosis of cells was detected by flow cytometry after inhibiting the ex-pression of TLR7.Results Imiquimod induced the apoptosis of THP-1 derived macrophages, MDCK cell lines and HUVEC cell lines.The levels of IL-6 were significantly decreased as the expression of TLR7 was inhibited by treating THP-1 derived macrophages with chloroquine or TLR7-siRNA.Treating THP-1 derived macrophages with chloroquine or TLR7-siRNA did not affect the cell apoptosis induced by imiquimod.Con-clusion Imiquimod could induce the apoptosis of THP-1 derived macrophages through TLR7 independent pathway.

Background Glial cells perform specialized function in many aspects of the development,homeostasis,and function of neurons.Retinal ganglion cells (RGCs)and glia interactions are critically important in glaucomatous neurodegeneration.However,the precise mechanisms of glial activation and ganglion cells damage are still remained unclear. Objective This study was to assess the early responses of glial cells in the retina,optic nerve and optic chiasm in rat models of acute high intraocular pressure (IOP),and to examine the expression of nestin,a neuronal progenitor marker,in the reactive glias. Methods Acute high IOP of 110 mmHg was induced in the right eyes of 6 clean adult female Wistar rats by infusing normal saline solution into the anterior chamber for 60 minutes.Three normal matched Wistar rats were used as controls.The rats were sacrificed by overanaesthesia and sections of retina,optic nerve and optic chiasm were collected on 3 days and 7 days after the injection.Rat retina was examined by Nissl staining to illustrate the gross structure changes.Loss of axons of RGCs in the optic nerve was assessed by immunostaining of β Ⅲ-tubulin.Double labeling of glia] fibrillary acidic protein (GFAP) and nestin was performed in sections of retina,optic nerve and optic chiasm to evaluate the glial responses.The use of the animals complied with Statement of Animal Ethic Committee of Peking University Third Hospital. Results In control rats,GFAP-positive glial cells were observed in the retina,optic nerve and optic chiasm,where only weak positive response for nestin was noticed.Three days after acute IOP elevation,thickness of inner plexus form layer was significantlydecreased in comparison with the control rats.A loss of 46％ RGCs was found in the rats with ocular hypertension.Obvious increase of GFAP expression was displayed in the retina,and processes of GFAP-positive glia cells extended into outer retina accompanied with significant up regulation of nestin.Axons in the optic nerve demonstrated a tendency of degeneration.Nestin expression increased significantly in the GFAP-positive glias in the optic nerve.Cross-sectional area of optic chiasm corresponding to the injured retina decreased relative to its countcrpart.Astrocyte like GFAP and nestin-colabeled glials were observed in this part of optic chiasm.The pathological changes of the retina,optic nerve and optic chiasm in hypertensive eyes aggravated on 7 days. Conclusions Acute ocular hypertension induce early onset of RGCs loss and axon degeneration.Neuronal injury is accompanied with glial reaction.Reactive glial cells express neuronal progenitor markers.The structural changes of the optic nerve and optic chiasm occur simultaneously with the high IOP.

The 'ECU-1'environmental control units are applied to severely disabld individuals for operating home electrical equipments without other's help.They can freely turn on (off)lights,switch on (off)fan,watch on TV and give alarm for help,The function,principle and clinical application of 'ECU-1'is described in this paper.

OBJECTIVETo observe the clinical effect of Guilu Erxian Glue Cataplasm (GEGC) on carcinoma of the large intestine patients with myelosuppression after chemotherapy, and further to confirm its efficiency and safety.

METHODSTotally 60 patients with carcinoma of the large intestine were randomly assigned to two groups. Meanwhile, they all accepted FOLFIRI chemotherapy. Patients in the treatment group were additionally applied at Shenque (RN8), exchanging once per every other day, for 14 successive days. Patients in the control group took placebos with the same dose and dosage as the treatment group. The blood cell counts (WBC, NE, and PLT) were detected before chemotherapy, at day 7, 10, and 14. The TCM symptoms integrals, Karnofsky performance score (KPS), liver and kidney functions were observed before chemotherapy, at day 7 and day 14. Adverse skin reactions were observed each day. And the usage of hematopoietic growth factors was recorded.

RESULTS(1) The KPS score at day 7 was more stable in the treatment group than in the control group; the WBC and NE counts in the peripheral blood at day 14 were higher in the treatment group than in the control group; and TCM symptoms integrals at day 14 was lower in the treatment group than in the control group, all with statistical difference (P < 0.05). (2) Compared with the control group, the PLT count was higher in the treatment group than in the control group, the usage of rhG-CSF and antibiotics was less in the treatment group than in the control group, all with no statistical difference (P > 0.05). (3) No obvious adverse reactions such as liver injury, renal injury, or skin allergy were observed.

CONCLUSIONSAdjuvant treatment of GEGC could improve carcinoma of the large intestine patients with myelosuppression to some extent. No relevant adverse reactions were found.

Adjuvants, Immunologic ; therapeutic use ; Adult ; Aged ; Bone Marrow Diseases ; chemically induced ; drug therapy ; Colorectal Neoplasms ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged

OBJECTIVETo study the effects and mechanisms of Zuoguiyin (ZGY) on the ovarian nitric oxide (NO) production in peri-menopausal rats.

METHODSThe peri-menopausal model rats were respectively administered with low (13.78 g/kg), middle (20.67 g/kg), and high (31.00 g/kg) dose ZGY, and nilestriol for 8 weeks. Normal saline was given by gastrogavage to rats in the model group and the young control group (as the control group). The ovarian NO content and the activity of total nitric oxide synthase (NOS) were detected using nitrate reductase method and chemical colorimetry respectively. The mRNA and protein expressions of inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS) were detected using RT-PCR and immunohistochemical assay.

RESULTS(1) Compared with that in the control group, the ovarian NO content and the activity of total NOS in peri-menopausal rats were significantly lower (P < 0.01). Middle and high dose ZGY could obviously up-regulate them (P < 0.01, P < 0.05). (2) The three kinds of NOS expression levels in perimenopausal rats were obviously lower when compared with those of the control group (P < 0.01). Middle dose ZGY could significantly promote all the three kinds of NOS expression levels of pre-senile rats (P < 0.01). High dose ZGY could up-regulate the expressions of iNOS and eNOS, while low dose ZGY could only enhance the iNOS expression (P < 0.01).

CONCLUSIONSThe down-regulated expressions of eNOS, iNOS, and nNOS in local ovaries resulted in decreased NOS activity and NO production, which were closely correlated with damaged microcirculatory vascular functions of ovaries in peri-menopausal rats. ZGY could protect rats' ovarian microcirculation by up-regulating the expressions of eNOS, iNOS, and nNOS, and enhancing the ovarian NOS activity and NO production.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Female ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Ovary ; drug effects ; metabolism ; Perimenopause ; Rats