OBJECTIVE: To study the bone-targeting potential and dynamic changing process in vivo of a new type of anti-osteoporosis bisphosphonate drug under research (SC). METHODS: The distribution in rabbits and bone-targeting of SC was observed by isotope tracer technique. 99Tcm-SC was injected into the rabbits, then the SPECT images were collected and analyzed in 12 h. RESULTS: The labeling rate of 99Tcm-SC could be maintained above 90% within 12 h, which proved the good stability of 99Tcm-SC in vitro. The rabbit bone imaging showed that the targeting of SC to bone was equivalent to MDP, a bone imaging agent. CONCLUSION: This study provides valuable data for the non-clinical and clinical studies of SC. SC has a good potential for being developed into a new generation of anti-osteoporosis drug.

Purpose To evaluate the correlations between high resolution CT (HRCT) findings and IASLC/ATS/ERS pathological classification of ground glass nodule (GGN). Materials and Methods 121 patients with confirmed GGN were selected, and divided into benign group (22 cases), PIL group (21 cases), microinvasive carcinoma group (26 cases) and invasive carcinoma group (52 cases), then the imaging, pathology and prognosis data of patients with pulmonary GGN were reviewed, and the differences among GGN of different pathological types were analyzed.Results Maximum diameter, margin, vacuole sign, solid component, shape and blood vessels through of GGN were significantly different among the four groups (χ2=9.945-31.068,P<0.05). Maximum diameter and margin were significantly different between invasive adenocarcinoma and other groups (P<0.008); vacuole sign of the benign group was significantly different with other groups (P<0.008); the existence of solid component and shape were significantly different between invasive adenocarcinoma and minimally invasive adenocarcinoma (P<0.008); there was significant difference of blood vessels through between invasive adenocarcinoma and benign lesions (P<0.008). Among the 121 lesions, no metastasis except one invasive adenocarcinoma case complicated with distant metastasis.Conclusion Maximum diameter of GGN greater than 16.35 mm, with spiculation or lobulation represent invasive adenocarcinoma; vacuole sign within the GGN represent malignancy; with solid component and irregular shape can be used to identify invasive adenocarcinoma from minimally invasive adenocarcinoma; while blood vessels through can be used to identify invasive adenocarcinoma from benign lesions; the prognosis of GGNs is well with only 0.83% probability of distant metastasis.

ObjectiveAnalyze preoperative clinical relevanted factors of acute type A aortic dissection with hypoxemia according to a group clinical data.MethodsFrom January 2011 to June 2011,we have collected 54 preoperative cases of acute type A aortic dissection,including 42 males,12 females,aged 28-73 years old,onset to treatment time is 0.4-14.0 days.General information:age,gender,time of onset,body mass index,hypertension,diabetes mellitus,smoking,drinking,heart ejection fraction,prothrombin time,quantitative fibrinogen,fibrinogen degradation products,D-dimer,C-reactive protein,procalcitonin,ICU time,length of hospital stay.According to the blood gas analysis of quiet state case without oxygen,with PaO2 ＜ ( 100-age ×0.33 ±5) mm Hg is for the hypoxemia group,equal or higher than this is no-hypoxemia group.ResultsNo-hypoxemia group has 14 cases,11 males,3 females,average aged (51.14 ± 14.24) years old,including 12 operation patients ( no death) and 2 no-operation patients(2 cases death).Hypoxemia group has 40 cases,31 males,9 females,average aged (50.53 ± 9.73 ) years old,including 33 operation patients(2 cases death) and 7 no-operation patients(7 cases death).There is no significant difference in age,gender,time of onset,hypertension,diabetes mellitus,smoking,drinking,cardiac ejection fraction,prothrombin time and fibrinogen.There is statistically significant on body mass index,fibrinogen degradation products,D-dimer,C-reactive protein,procalcitonin,ICU time and length of hospital stay time ( P ＜ 0.05 ).ConclusionPreoperative hypoxemia with acute type A aortic dissection is associated with obesity,excessive inflammation and activation of coagulation and fibrinclytic system,and hypoxemia may prolong the time of operative patients with acute type A aortic dissection in ICU and hospital.

Objective To evaluate the detection of alpha 5 (Ⅳ) collagen chain of skin basement membrane in diagnosis of Alport syndrome among suspected patients. Methods Data of suspected patients with the detection of alpha 5 (Ⅳ) collagen chain of skin basement membrane were retrospectively collected and analyzed from January 2007 to March 2008. Results A total of 254 suspected patients ranged from 1 to 71 years old with an average age of (25.85±17.03) years old were enrolled (male/female ratio, 0.76). There was no significant difference in average age between male and female. Abnormal alpha 5 (Ⅳ) collagen chain expression of skin basement membrane was found by indirect immunofluorescense in 19 patients among whom 12 cases were negative and 7 cases were diseontinous deposit. These 19 patients were diagnosed as Alport syndrome and the diagnostic rate was 7.5%. Conclusions The diagnostic rate of Alport syndrome by detection of alpha 5 (Ⅳ) collagen chain in skin basement membrane is significant and helpful for early and differential diagnosis of Alport syndrome.

Objective To observe the expression of stromal cell-derived factor-1α(SDF-1α)and glial cell line-derived neurotrophic factor(GDNF)genes in bone marrow stromal cells(BMSCs)of rhesus monkey. Methods With gene recombination technique,SDF-1α and GDNF genes obtained from cDNA were subcloned into pBudce4.1 vector to get pBudCE4.1-SDF-1-GDNF, evaluated by restriction enzyme analysis and sequencing analysis.The pBudCE4.1-SDF-1α-GDNF was transfected into BMSCs with lipofectamine2000.After 48 h,the expression of SDF-1α and GDNF was measured by RT-PCIL,Western blotting and immunohistochemistry. Results Correct construction of pBudCE4.1-SDF-1α-GDNF was identified by enzyme restriction analysis and sequencing analysis.Western blotting and immunohistochemistry confirmed the expressions Of SDF-1α and GDNF genes in the transfected cells.The protein expressions of GDNF and SDF-1α in the GDNF and SDF-1α transfected BMSCs were 6 times higher than those in the negative control cells. Conclusion The pBudCE4.1-SDF-1α-GDNF can successfully express SDF-1α and GDNF in BMSCs of rhesus monkey,which may be used in gene therapy for Parkinson's disease.

Objective To study the dynamic changes of Omi/HtrA2 in the cytoplasm of cerebral parietal cortex in neonatal rats with hypoxic-ischemic brain damage (HIBD),and explore the role of Omi/HtrA2 in HIBD.Methods Seven-day-old SD rats were randomly assigned to sham-operated group and vehicle group; and HIBD models were established by the Rice and CHEN Hui-jin methods.Each group was further divided into 4 subgroups (n=8) according to the observation time points (6,12,24and 72 h).In each subgroup,the turnover ability and dextrorotatory ability when their tails were gripped were observed before the experiment and 1 h after hypoxic-ischemia (HI).The appearance of the brain was observed,and the protein levels of Omi/HtrA2 in the brain tissues or homogenates were examined by immunohistochemistry and Western blotting.Results (1) Changes of behavior of the rats:before the experiment,all rats were healthy; 1 h after HI,the rats in sham-operated group were still healthy,while out of 32 rats which bared HI injury,18 could not turn themselves over,20 became dextrorotatory when their tails were gripped and 14 exhibited both behavior problems.(2) General examination of the brain:the ligated brain hemisphere in the vehicle group showed obvious pallor and edema at 24 h; the two brain hemispheres in sham-operated group showed no pathological change.(3) Western blotting results showedthat the protein levels of Omi/HtrA2 in the vehicle group were significantly higher than those in the sham-operated group at each observation time points (P＜0.05); the expressions of Omi/HtrA2 in the vehicle group began to increase at 6 h,peaked at 24 h after HI insult and decreased thereafter.(4) By immunohistochemistry,it showed that the Omi/HtrA2 positive cells in cytoplasm and membrane of cerebral cortex in the vehicle group peaked at 24 h after HI insult and decreased thereafter; the quantity of positive cells in the vehicle group was larger than that in the sham-operated group (P＜0.05).Conclusion The levels of Omi/HtrA2 in the cerebral cortex increase after HI insult in neonatal rats,showing time-difference expression,which may play important roles in cell apoptosis induced by HIBD.

This study was purposed to investigate the biological effect of vinblastine (VLS), usually known as inductor of mitotic arrest, on MOLT-4 of ALL cells and to evaluate its significance. The cell arrest in M phase and/or cell apoptosis were induced by treatment of MOLT-4 cells with 0.05 microg/ml VLS for 0 - 12 hours; the DNA histogram was detected by flow cytometry; the morphological changes of cells were observed by confocal microscopy; the cell cycle distribution, cell apoptosis and morphological changes of cells before and after arrest were analyzed by using arrest increasing rate (AIR), arrest efficiency (AE), apoptosis rate (AR) and morphologic parameters respectively. The results indicated that the cell arrest did not accompanied by significant increase of apoptosis rate; the DNA histogram of cell arrest showed dynamic change of cell cycle in time-dependent manner; the arrest efficiency could be quantified. The cell arrest at M phase was accompanied by cell stack in S phase, the cell proliferation rate dropped after cell arrest occurred. The cells arrested at M phase possessed of characteristic morphologic features in cell mitosis. It is concluded that the vinblastine can solely induce arrest of MOLT-4 cells at M phase. This study provides experimental basis for further investigating the relation of cell cycle arrest to apoptosis, mechanism of checkpoint and development of new anticancer drugs.
Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Division ; drug effects ; Flow Cytometry ; Humans ; Tumor Cells, Cultured ; Vinblastine ; pharmacology

OBJECTIVETo explore the intrinsic connection between activation of classical nuclear factor-κB (NF-κB) pathway and gefitinib resistance in human lung adenocarcinoma H1650 cells.

METHODSHuman lung adenocarcinoma H1650 cells were exposed to gefitinib continuously for 60 days to obtain resistant H1650 cells. The expressions of P-IκBα, P-p50 and P-p65 in the cytoplasm or nuclei were detected using Western blotting in human lung adenocarcinoma HCC827 cells, parental H1650 cells and gefitinib-resistant H1650 cells. The effects of gefitinib alone or in combination with PDTC on the survival rate and expressions of NF-κB P-p50 and P-p65 were compared among the 3 cell lines.

RESULTSGefitinib-resistant H1650 cells showed increased cytoplasmic and nuclear P-IκBα expressions. The expressions of P-p50 and P-p65 differed significantly among the 3 cell line, decreasing in the order of resistant H1650 cells, parental H1650 cells, and gefitinib sensitive HCC827 cell lines (P<0.05 or 0.01). Treatment with gefitinib alone resulted in a significantly lower cell inhibition rate in resistant H1650 cells than in the parental H1650 cells (P<0.05) and HCC827 cells (P<0.01). The resistant H1650 cells had a significantly higher expression of P-p50 and P-p65 than other two cell lines (P<0.05). In both the resistant and parental H1650 cells, gefitinib significantly lowered P-p50 and P-p65 expressions (P<0.05 or 0.01), and the combined treatment with gefitinib and PDTC significantly decreased the cell survival rate and further lowered the cytoplasmic and nuclear expressions of P-p50 and P-p65 (P<0.01 or 0.01).

CONCLUSIONThe activation of classical NF-κB pathway is a key factor contributing to transformation of the parental H1650 cells into gefitinib-resistant cells. Gefitinib combined with PDTC can inhibit P-IκBα production and NF-κB P-p50 and P-p65 activation to suppress the survival of residual H1650 cells and the generation of gefitinib-resistant cells.

Objective To better understand the prevalence and geographic distribution of genotypes/subtypes on HCV and the relationship between HCV genotypes/subtypes and HIV infection disease progression in the HIV-1/HCV co-infected individuals living in high HIV-1 prevalent areas in China. Methods 186 plasma samples were collected from HIV-1 seropositive individuals infected through paid blood donors (PBD), injecting drug users (IDUs) or sexual contact, living in most severely affected provinces, Henan, Yunnan, Xinjiang, Jilin and Liaoning provinces. Samples with HCV viral load >1000 cop/ml were amplified by RT-nested PCR, sequenced and phylogenetically analyzed for genotyping/subtyping of HCV. HIV-1, HCV viral loads and CD4 T lymphocytes were measured for all subjects. Results (1) HCV were identified as 1 a (1.7%), 1 b (39.9%), 2a (17.9%), 3a (10.4%), 3b (15.6%), 6a (1.2%), 6n (6.4%), and a newly unclassified subtype (7.5%). HCV 2a and lb subtypes predominated in PBD in Henan, 3a and 3b in IDUs in Xinjiang and Yunnan, and 6 genotype/subtypes in IDU in Yunnan. (2) There were no significant differences in CD4 T cell counts among the different HCV subtypes. (3) The viral load of HCV RNA in lb subtype was higher than that of non-1b subtype, however, no significant differences in HIV-1 viral loads and CD4 T cell counts were found between Ib and non-1b subtype. Both HIV and HCV viral loads were lower in 2a than non-2a subtype. Conclusion The prevalence of HCV genotype/subtype in HIV-1/FICV co-infected individuals was associated with geographic areas and transmission routes. HCV subtypes had no direct correlation with HIV infection disease progression.