Purpose:This report evaluate whether the single-agent therapy with vinorelbine (V group) may obtain a high response rate, with acceptable toxicity and improvement in survival and quality of life, comparing with the therapy with Kanglaite (a traditional Chinese medicine) (K group) and other supportive care among elderly patients.Methods:Forty patients with advanced NSCLC were included,20 of whom were allocated to receive continual infusional NVB 7.5mg/m 2 /24hr delivered via a central venous line on days 1-5, and NVB 7.5mg /m 2 was given as a 20 min intravenous infusion on days 1 every 3 weeks; 20 of whom were allocated to receive infusional Kanglaite 200 ml on days 1-20 every month. Patients received a minimum of two courses unless progressive disease was detected. Results:V group: CR 0,PR 7,CR+PR 35%(7/20), median survival time was 7.2 months and projected 1-year survival was 25%; K group:CR 0,PR2,CR+PR 10%(2/20),median survival time was 4.8 months and projected 1-year survival was 5%. Conclusions:In elderly patients with NSCLC, single-agent vinorelbine treatment is associated with better effective,better survival and improved quality of life than Kanglaite .Its toxicity is mild and acceptable.

BACKGROUND: Researches indicated that bone marrow stem cells (BMSCs) could differentiated into neural stem cells in vitro, but what was the role of neural stem cells(NSCs) in the recovery of cortical injury,whether the NSC is capable of growing and migration in injured still remained unknown.OBJECTIVE: To explore the growing state of autograft NSC derived from crab-eating macaque BMSC transplanted in brain.DESIGN: Prospective case control study based on experimental animals.SETTING: Department of neurosurgery in a hospital of a military medical university.MATERIALS: This study was carried out at Center Laboratory of Neurological Research Institute, Zhujiang Hospital affiliated to the First Military Medical University of Chinese PLA. Six healthy adult crab-eating macaques were purchased from the South China Primate Animal Center.INTERVENTIONS: BMSCs harvested from six crab-eating macaques were cultured in vitro and induced to differentiate into neural stem cells, which then labeled by bromodeoxyuridine(BrdU) and autografted into brains.MAIN OUTCOME MEASURES: Brain tissues underwent hematoxylin and eosin(HE) staining and immunohistochemical staining before observed under optical microscope.RESULTS: The results of HE staining showed that the cell number in injured brain vas obviously higher in both instant and delayed transplanting groups than sham-transplanting group; moreover cells were proved reacting to BrdU by immunohistochemical staining in cortical injuries of both groups at 1-6 months following stem cells autograft, as well as at neighboring white matters at half year later, but no BrdU positive cells could be found in traumatic controls, sham-transplanting group and normal brains.CONCLUSION: NSCs derived from in vitro cultured BMSCs were proved capable of surviving, proliferating, differentiating and migrating in cortex after autograft, so that BMSCs is considered as replacing cells or the source of NSCs; moreover autograft stem cells could survive, proliferate and migrate in old cortical traumatic focus.

Objective To study the expression of matrix metalloproteinase(MMP)-2,9 and tissue inhibitor of metalloproteinase(TIMP)-1,2 protein in human endometrial carcinoma tissue and its relation to the invasion and metastasis of endometrial carcinoma. Methods Immunocytochemistry and zymography techniques were used to measure the MMP-2,MMP-9,TIMP-1,TIMP-2 protein levels and activities in endometrial carcinoma tissue of 37 patients and control group composed of 7 normal postmenstrual endometrial samples. Results The MMP-2,MMP-9,TIMP-1 and TIMP-2 proteins mainly expressed in endometrial carcinoma cells, glandular cells and endothelial cells. The strongly positive expression proportions of MMP-2,9 and TIMP-1 proteins in grade Ⅲ carcinoma cells were respectively 73%, 20% and 67%, which were higher than those in gradeⅡ (13%, 0, 27%) and gradeⅠ (0) ones ( P

Objective To investigate the value of medical thoracoscopy in diagnosis of pleural effusion of unknown aetiology in aged people.Methods The patients aged 65 years and over,with exudative pleural effusion of unknown aetiology,were enrolled in this study.And they underwent medical thoracoscopy for diagnosis.Results The 49 patients,33 males and 16 females,aged 65-82years (at average age of 70.5 yeas),were enrolled.The 83.7% (41 cases) of pleural effusion was unilateral,and 16.3% (8 cases) was bilateral.The 28.6% (14 cases) of them suffered from tuberculosis,16.3 % (8 cases) malignant tumor.The pathology results of 16 cases showed nonspecific inflammation and normal pleural tissue.The other 10 patients showed a normal pleuracy or abnormal pleuracy undergoing a failure biopsy.Considering the clinical data of the 27 cases,8 cases (16.3 %)had infectious disease,18 cases (38.8%) remained unknown.Diagnostic accuracy of medical thoracoscopy was 61.2%.Complications of these patients undergoing medical thoracoscopy were fever (n=8,16.3%) and subcutaneous emphysema (n=7,14.3%).Conclusions Medical thoracoscopy is a standard option for diagnosing pleural effusion.It could be easily managed by physicians.The complications appear more often in aged people.

Objective To evaluate the value of quantitative analysis of contrast‐enhanced ultrasonography (CEUS) in differentiating acute rejection(AR) from acute tubular necrosis(ATN) of transplant kidney. Methods Total of 67 kidney recipients were examined with conventional US and CEUS. Biopsies were performed in 37 patients, 26 patients were with AR, 11 with ATN, 30 patients as control group. The hemodynamic parameters (PSV and RI) were measured on infrarenal artery with conventional US, while CEUS quantitative analysis was performed on the cortex, pyramid and interlobar artery by time‐intensity curve (TIC). TIC parameters including rise time (RT ), time to peak (TTP), mean transit time (mTT ) were compared among three groups. In addition, the reproducibility of TIC parameters was evaluated. Results The RI in AR group was significantly higher than that in control group, but there were no significant differences of RI between AR and ATN groups. TIC parameters including RT, TTP were with high reproducibility (ICC> 0 7.5). Compared to the other two groups, the RT and TTP of the pyramid, ΔRTm‐c, and ΔTTPm‐c were significantly longer in AR group, the receiver operating curves (ROC) analysis demonstrated that ΔRTm‐c had the highest accuracy and RI had the lowest accuracy for detecting AR(areas under the curve were 0 7.86, 0 7.56, 0 7.49, 0 7.36 and 0 4.98, respectively). High sensitivity and specificity(78 3.% and 73 5.%, respectively) were shown when using 4 6.2 s as a cutoff point of ΔRTm‐c to diagnose AR. Conclusions Quantitative analysis of CEUS could detected the changes of the microcirculation perfusion in kidney grafts with AR and ATN, which might be superior in the diagnosis of AR compared with conventional US.

Background and purpose: The previous work of this study has showed that the treatment of liver cancer cells with emodin could induce endoplasmic reticulum (ER) stress and apoptosis. Given the cross-talk between ER stress and autophagy, this study aimed to investigate whether blockage of autophagy, a defense mechanism against environmental stress, could improve the killing effect of emodin on liver cancer cells. Methods: The CYTO-ID auto-phagy detection kit and Western blot were used to determine autophagy in liver cancer cells. After combined treatment with chloroquine (CQ) and emodin, cancer cell survival was analyzed by ATPlite assay and clonogenic assay. Apoptosis was detected by both flow cytometry analysis and Western blot. Results: Autophagy could be induced in liver cancer cells after treatment with emodin. Inhibition of autophagy significantly increased growth-inhibitory effect of emodin on both HepG2 and Huh7 cancer cells. The combination treatment with CQ and emodin promoted remarkable apoptosis in liver cancer cells, evidenced by the increase in the percentage of cells in sub-G1 phase and the higher expression lever of cleaved caspase-3. Conclusion: Therapeutically targeting autophagy is capable of enhancing cytotoxicity of emodin in liver cancer cell lines.

BACKGROUND: Bone marrow mesenchymal cells, multiple-potential non-hematopoiefic stem cells adhering to the wall in vitro culture, can be induced to proliferate and differentiate towards neurons and glia cells.OBJECTIVE: To investigate the growth state of cat bone marrow mesenchymal cells in vitro culture, as well as the capability to differentiate towards neural stem cells.DESIGN: A randomized sampling study.SETTING: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University.MATERIALS: This study was carried out at the Central Laboratory of the General Military Neurological Research Institute, Zhujiang Hospital, Southern Medical University between January and December 2002. Twenty healthy home-raised cats, aged 1.0 - 2.0 years and weighing 2. 5 - 4.0 kg, male and female in half, were provided by the Animal Center of the First Military Medical University of Chinese PLA.INTERVENTIONS: Bone marrows were randomly aspirated from the left or right hindlimbs in order to separate bone marrow mesenchymal cells, then the bone marrow mesenchymal cells single cell suspension was co-cultured with neural stem cell culture media in vitro so as to induce differentiation to neural stem cells with tretinoin. CK2 type inverted optical microscope(Olympus,Japan) was used to observe the growth of bone marrow mesenchymal cells in vitro culture, as well as 4, 12, 24, 48 hours of induction upon eliminating or not eliminating the wall-adhering cells. Bone marrow mesenchymal cells in stem cell stage were identified under Olympus optical microscope with modified immunohistochemical staining.MAIN OUTCOME MEASURES: The growth state and the immunocytochemical staining of living bone marrow mesenchymal cells exposed to experimental intervention were observed under the Olympus inverted optical microscope.RESULTS: Data from the 20 cats were analyzed without loss. Reversed microscopic observation revealed that cat bone marrow mesenchymal cells becrame larger when cultured in vitro, which were rich in plasmic granules with prominence projecting, adhering to the wall and forming cell clones. These cells were then successively cultured, and imnunohistochemical staining analysis suggested that the passaged bone marrow mesenchymal cells could express neural stem cells-specific antigen Nestin and differentiate towards glia-like cells and neuron-like cells.CONCLUSION: Cat bone marrow mesenchymal cells possess the characteristics of stem cells; they can be amplified into cell clones and induced to express the property of neural glia cells and neuron-like cells under proper condition.

Objective To evaluate the diagnostic value of virtual touch tissue quantification (VTQ) in the diagnosis of renal allograft fibrosis.Methods The renal allografts of 82 patients with biopsies or nephrectomy were assessed by virtual touch quantification.The renal allograft fibrosis was categorized according to the 2005 updated Banff criteria for a G0～G3 grade.All the results were compared among four groups.Results The mean SWV values in G0～G3 were (2.39 ± 0.31)m/s,(2.45 ± 0.34)m/s,(2.58 ± 0.18) m/s,(3.11 ± 0.40)m/s,respectively.There were no significant differences in the mean SWV value between G0 and G1 group,or between G1 and G2 group(P ＞0.05).There were significant differences in the mean SWV value between G0～G2 and G3 group,or between G0 and G2 group(P ＜0.05).Stiffness of renal allograft was significantly correlated to the mean SWV value (Spearman r =0.671,P ＜0.001).According to the area under the ROC curve,the sensitivity and specificity of SWV (area under ROC curve =0.847,cut-off=2.64 m/s) for grade ≥G2 was 78.9％ and 79.5％ respectively.Conclusions Stiffness measured by VTQ reflects the interstitial fibrosis in renal allograft.VTQ technique might be a new tool to identify patients with chronic allograft injury.

The antibody against AT1-EC2 plays a role in some kinds of inflammatory vascular diseases including malignant hypertension, preeclampsia, and renal-allograft rejection, but the detailed mechanisms remain unclear. In order to investigate the changes of NADPH oxidase and reactive oxygen species in the aorta in a mouse model which can produce AT1-EC2 antibody by active immunization with AT1-EC2 peptide, 15 mice were divided into three groups: control group, AT1-EC2-immunized group, and AT1-EC2-immunized and valsartan-treated group. In AT1-EC2-immunized group and AT1-EC2-immunized and valsartan-treated group, the mice were immunized by 50 μg peptide subcutaneously at multiple points for 4 times: 0, 5, 10, and 15 days after the experiment. In AT1-EC2-immunized and valsartan-treated group, valsartan was given at a dose of 100 mg/kg every day for 20 days. After the experiment, the mice were sacrificed under anesthesia and the aortas were obtained and frozen in liquid nitrogen for the preparation of frozen section slides and other experiments. The titer of AT1-EC2 was assayed by using ELISA. The level of NOX1 mRNA in the aorta was determined by using RT-PCR. The expression of NOX1 was detected by using Western blotting. Confocal scanning microscopy was used to assay the α-actin and NOX1 expression in the aortic tissue. The O(2)∸ production was detected in situ after DHE staining. The mice produced high level antibody against AT1-EC2 in AT1-EC2-immunized group and AT1-EC2-immunized and valsartan-treated group, and the level of NOX1 mRNA in the aortic tissues was 1.6±0.4 times higher and the NOX1 protein expression was higher in AT1-EC2-immunized group than in control group. There were no significant differences in the level of NOX1 mRNA and protein expression between control group and AT1-EC2-immunized and valsartan-treated group. The expression and co-localization of α-actin and NOX1 in AT1-EC2-immunized group increased significantly as compared with those in control group, and the O(2)∸ production increased about 2.7 times as compared with control group. There were no significant differences between control group and AT1-EC2-immunized and valsartan-treated group. It is concluded that active immunization with AT1-EC2 can activate NOX1-ROS, and increase vascular inflammation, which can be inhibited by AT1 receptor blocker valsartan. This may partially explain the mechanism of the pathogenesis of inflammatory vascular diseases related to antibody against AT1-EC2.

Based on the structure of combretastatin A-4 (CA-4), a microtubulin inhibitor, eight novel compounds were designed and synthesized by introducing different substituents into the benzimidazole backbone which substituted B ring of CA-4, and the structures were characterized by NMR and HRMS. Proliferation inhibition of six tumor cells including A549, HepG2, HCT-116, MCF-7, PC-3 and Siha was measured by MTT method.The effect of active compound on cell migration was evaluated by scratch test.Molecular docking technique was applied to investigate the interaction between the most active compound with the tubulin and PI3K kinases respectively.Compound 4e showed prominent inhibition against six strains of tumor cells, especially with the strongest inhibitory effect on Siha cells (IC50 = 12.18 ± 1.17 μmol/L).Moreover, compound 4e could effectively inhibit cell migration, which deserves further study.Molecular docking study showed that the binding energy to the tubulin of compound 4e was stronger than that of CA-4, and the affinity with PI3Ks displayed that the PI3Kδ subtype kinase was the strongest; its binding energy was -37.2 kJ/mol.This study lays a foundation for the development of anti-tumor drug based on PI3K and microtubulin.