Comparison of efficacy and safety of different chemotherapy regimens for progressive patients with brain metastasis of small cell lung cancer after radiotherapy / 肿瘤研究与临床

Objective To analyze the efficacy and safety of different chemotherapy regimens for treatment of progressive patients with small cell lung cancer (SCLC) brain metastasis after radiotherapy. Methods 96 SCLC brain metastasis patients with progressive intracranial lesions after radiotherapy were divided into four groups: carmustine group (Group A, 28 cases), temozolomide group (Group B, 19 cases), topotecan group (Group C, 24 cases) and no chemotherapy group (Group D, 25 cases). Results In terms of brain metastases, there were no complete response cases in the whole groups. The rates of partial remission (PR), stable disease (SD) and progression of disease (PD) in Group A were 17.8%(5/28), 53.6%(15/28) and 28.6 % (8/28), respectively, the response rate (RR) of intracranial lesions was 17.9 % (5/28), and disease control (CR+PR+SD) rate was 71.4%(20/28). The rates of PR, SD and PD in Group B were 15.8%(3/19), 63.2 % (12/19) and 21.1 % (4/19), respectively, the RR of intracranial lesions was 15.8 % (3/19), and disease control rate was 78.9 % (15/19). The rates of PR, SD and PD in Group D were 8.3 % (2/24), 54.2 %(13/24) and 37.5 % (9/24), respectively, the RR rate of intracranial lesions was 8.3 % (2/24), and disease control rate was 62.5 % (15/24). In Group D, there was no response case, and 20 patients with PD (80.0 %) were found. The median progression-free survivals (PFSs) were (3.64 ±0.43) months, (4.68 ±0.49) months,(3.58 ±0.50) months, (2.60 ±0.31) months in Group A, B, C and D, respectively, and the median overall survivals (OSs) were (18.80±1.74) months, (18.76±1.85) months, (19.10±1.64) months and (9.64±0.84) months, respectively. The median OS of Group A, B or C was longer than that of Group D (P=0.002). The differences of grade Ⅲ-Ⅳhematologic toxicities among the four subgroups were not statistically different. Patients in Group B had better tolerance to nausea and vomit. In Group D, the central nervous system symptoms such as fatigue and headache occurred frequently. Conclusions The response rate and OS of SCLC brain metastasis patients with progressive intracranial lesions after radiotherapy are improved after chemotherapy, however, PFS is not significantly prolonged. The efficacies of carmustine, temozolomide and topotecan are similar in short and long term, besides, temozolomide shows less adverse events and a higher disease control rate. The application of chemotherapy that could penetrate the blood-brain barrier can improve the efficacy on SCLC brain metastasis patients with progressive intracranial lesions after radiotherapy with well tolerance.

Association of plasma dys-acyl ghrelin with different stages of chronic kidney disease / 实用医学杂志

Objectives To assess the plasma levels of acyl ghrelin (AG) and dys-acyl ghrelin (DG) in chronic kidney disease (CKD) and hemodialysis (HD) patients and analyze their relationships with different stages of CKD and hemodialysis. Methods Forty-six CKD stage 1-5 patients and 15 hemodialysis patients were enrolled into the study. Body weight, height, hemoglobin, biochemical parameters, inflammatory parameters, preprandial, postprandial and 3 hours after hemodialysis plasma AG and DG levels were measured. Appetite and food intake were assessed. Body mass index (BMI), and estimated glomerular filtration rate (eGFR) were calculated. Results There were no significant differences in BMI, SGA, appetite, food intake and malnutrition among CKD patients of different stages. eGFR was declining with the progression of CKD stages and patients received a three-week hemodi-alysis. Compared with that in CKD stage 1-2 patients, the level of preprandial and postprandial DG was remarkably increased in stage 3-5 patients (P 0.05);levels of DG decreased slightly postprandially and were markedly decreased by hemodialysis (P<0.01), even lower than those seen postprandially in CKD stage 1-2;Both preprandial and postprandial DG were negatively correlated with serum albumin levels (r=-0.64, P < 0.05; r=-0.59, P < 0.05), while there was no correlation between AG and serum albumin levels. Conclusions There is a strong and independent correlation of DG with CKD stage. Postprandial suppression of ghrelin is impaired with reduced renal function. Hemodialysis removes DG but not AG.

Effects of Jiji decoction on the cognitive function and oxidative stress in mice with vascular dementia induced by cerebral ischemia/reperfusion / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To determine the effects of Jiji decoction (Traditional Chinese Medicine) on the cognitive function and oxidative stress in mice with vascular dementia (VD) induced by cerebral ischemia/reperfusion.</p><p><b>METHODS</b>Thirty-two mice were randomly divided into nonnal group (n = 8), sham group (operation, but no cerebral ischemia/reperfusi6n, n = 8), model group (vascular dementia model induced by cerebral ischemia/reperfusion, n = 8), and Jiji decoction-treated group (vascular dementia model plus treatment with Jiji decoction, n = 8). Fourteen days of treatment after operation, the cognitive behavior was measured in step-through test, spatial probe test and platform test. Afterwards, to assess the levels of oxidative stress, the activity of superoxide dismutase(SOD) and content of malonaldehyde (MDA) in brain of these mice were measured.</p><p><b>RESULTS</b>Data from step-through test indicated that the escaping latency of Jiji decoction-treated group was prolonged and the error counts were decreased significantly ( P <0.01) compared with those of model group. Data from spatial probe test indicated that the time of entering darkroom, the time of climbing height and the time of entering bright room in Jiji decoction-treated group were shortened and the counts of climbing height were increased (P < 0.05-0.01) significantly compared with those of model group. Data from platform test showed that the escaping latency of Jiji decoction-treated group was prolonged significantly (P < 0.01) compared with that of model group. Compared with normal and sham group, the activity of SOD was decreased and the content of MDA was increased in model group significantly (P < 0.01). Compared with those of model group, the levels of SOD and MDA in Jiji decoction-treated group were improved significantly (P < 0.01).</p><p><b>CONCLUSION</b>Jiji decoction could improve cognitive function of VD mice. Its mechanism might be related with the inhibition of oxidative stiess in the brain.</p>

Effect of amygdalin on end-plate chondrocytes apoptosis induced by IL-1βderived from rat intervertebral discs / 中国药理学通报

Aim To observe the anti-apoptotic effect of different concentrations of amygdalin on the endplate chondrocytes induced by IL-1 βderived from rat inter-vertebral discs and explore the possible mechanism fur-ther.Methods Chondrocytes were obtained from endplate of one-month SD rat intervertebral discs and cultured primary chondrocytes.After identifying,they were divided into normal group,induced group and A-mygdalin 1 0 -2 mol·L -1 ,1 0 -3 mol·L -1 ,1 0 -4 mol· L -1 ,1 0 -5 mol · L -1 administration group.Then the apoptosis was detected by flow cytometry (FCM).Re-al-Time PCR was adopted to detect the mRNA expres-sion of Bax and Bcl-2.The protein expression of Bax and Bcl-2 was detected by Western blot.Results The apoptosis of the endplate chondrocytes induced by IL-1 βderived from rat intervertebral discs could be inhib-ited by amygdalin with different concentrations.Amyg-dalin could reduce the apoptotic rate analysed by FCM,down-regulate the Bax mRNA expression of Bax and up-regulate the Bcl-2 mRNA assayed by RT-PCR;compared with the induced group the differences were statistically significant (P <0.05).Besides,observa-tion of the protein expression of Bax and Bcl-2 by Western blot found that amygdalin 1 0 -4 mol · L -1 could inhibit the effect of IL-1 β,which could increase the protein expression of Bax and reduce the protein expression of Bcl-2.Conclusion Amygdalin has an effect on anti-apoptosis of the end-plate chondrocytes induced by IL-1 βderived from rat intervertebral discs and improve the degeneration of intervertebral discs.

The synergistic effect of amygdalin and HSYA on the IL-1beta induced endplate chondrocytes of rat intervertebral discs / 药学学报

The effect of amygdalin joint hydroxysafflor yellow A (HSYA) on the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and the possible mechanism were studied and explored. Chondrocytes were obtained from endplate of one-month SD rat intervertebral discs and cultured primary endplate chondrocytes. After identification, they were divided into normal group, induced group, amygdalin group, HSYA group and combined group. CCK-8 kit was adopted to detect the proliferation of the endplate chondrocytes. FCM was measured to detect the apoptosis. Real-time PCR method was adopted to observe the mRNA expression of Aggrecan, Col 2 alpha1, Col 10 alpha1, MMP-13 and the inflammatory cytokines IL-1beta. The protein expression of Col II, Col X was tested through immunofluorescence. Compared with the normal group, the proliferation of the endplate chondrocytes decreased while the apoptosis increased (P < 0.05). With down regulation of the mRNA expressions of Aggrecan, Col 2 alpha1 and up regulation of the mRNA expressions of Col 10 alpha1, MMP-13, IL-1beta (P < 0.05), the protein expression of Col II decreased while the protein expression of Col X increased. Compared with the induced group, amygdalin group, HSYA group, the combined group could inhibit the apoptosis and promote the proliferation (P < 0.05). They could increase the mRNA expressions of Aggrecan and Col 2 alpha1 while decrease the mRNA expressions of Col 10 alpha1, MMP-13 and IL-1beta (P < 0.05). They could also enhance the protein expression of Col II while reduce the protein expression of Col X. The effect of the combined group was significantly better than that of amygdalin and HSYA. Amygdalin joint HSYA could inhibit the degeneration of the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and better than the single use of amygdalin or HSYA.

Construction of plasmid vector pAFP-HSVtk-IRES2-EGFP and its effect on the cytotoxicity of ganciclovir to hepatocellular carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Herpes simplex virus thymidine kinase phosphorylates ganciclovir to ganciclovir monophosphate, which is then converted to ganciclovir triphosphate by endogenous cellular nucleoside kinases. The ganciclovir triphosphate acts as a DNA chain terminator due to the lack of a functional 3'-OH group and terminates the process of DNA replication, hence leading to cell apoptosis. At present, HSVtk gene usually acts as suicide gene to kill tumor cells. The aim of this study was to investigate the selective cytotoxicity of the herpes simplex virus thymidine kinase/ganciclovir (HSVtK/GCV) suicide gene system controlled by the a-fetoprotein (AFP) promoter on hepatocellular carcinoma (HCC) cells in vitro.</p><p><b>METHODS</b>pAFP-HSVtk-IRES2-EGFP recombinant plasmid vectors driven by the AFP promoter were constructed. HL-7702 liver cells, HUH-7 HCC, and HepG2 HCC were transfected with the recombinant plasmids. HSVtK gene expression was detected using Western blotting analysis. HepG2 cells line stably expressing HSVtk gene was selected by G418 reagent. The cytotoxicity of HSVtK/GCV suicide gene system on hepatoma cells was measured by CCK-8 reagents when different doses of ganciclovir were added.</p><p><b>RESULTS</b>Plasmid pAFP-TK-IRES2-EGFP-expressed HSVtk gene was constructed successfully. HSVtk gene expression level was significantly higher in AFP-positive hepatoma cells than in AFP-negative liver cells. After G418 selection, a HepG2 cells line stably expressing HSVtk gene was acquired. With the increase of the dose of ganciclovir the optical density at 450 nm of HepG2 cells stably expressing HSVtk gene gradually decreased (P < 0.05).</p><p><b>CONCLUSION</b>The HSVtK gene-specific expression in hepatoma cells as well as the cytotoxicity of the suicide gene system in HepG2 cells provided the basis for the targeted gene therapy of HCC.</p>

The synergistic effect of amygdalin and HSYA on the IL-1beta induced endplate chondrocytes of rat intervertebral discs / 药学学报

The effect of amygdalin joint hydroxysafflor yellow A (HSYA) on the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and the possible mechanism were studied and explored. Chondrocytes were obtained from endplate of one-month SD rat intervertebral discs and cultured primary endplate chondrocytes. After identification, they were divided into normal group, induced group, amygdalin group, HSYA group and combined group. CCK-8 kit was adopted to detect the proliferation of the endplate chondrocytes. FCM was measured to detect the apoptosis. Real-time PCR method was adopted to observe the mRNA expression of Aggrecan, Col 2 alpha1, Col 10 alpha1, MMP-13 and the inflammatory cytokines IL-1beta. The protein expression of Col II, Col X was tested through immunofluorescence. Compared with the normal group, the proliferation of the endplate chondrocytes decreased while the apoptosis increased (P < 0.05). With down regulation of the mRNA expressions of Aggrecan, Col 2 alpha1 and up regulation of the mRNA expressions of Col 10 alpha1, MMP-13, IL-1beta (P < 0.05), the protein expression of Col II decreased while the protein expression of Col X increased. Compared with the induced group, amygdalin group, HSYA group, the combined group could inhibit the apoptosis and promote the proliferation (P < 0.05). They could increase the mRNA expressions of Aggrecan and Col 2 alpha1 while decrease the mRNA expressions of Col 10 alpha1, MMP-13 and IL-1beta (P < 0.05). They could also enhance the protein expression of Col II while reduce the protein expression of Col X. The effect of the combined group was significantly better than that of amygdalin and HSYA. Amygdalin joint HSYA could inhibit the degeneration of the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and better than the single use of amygdalin or HSYA.

Experimental study on lumbar intervetebral disc degeneration model with kidney deficiency by ovariectomizing / 中国骨伤

<p><b>OBJECTIVE</b>To observe effects of removing arms and ovarian on lumbar intervertebral disc and vertebral bone mineral density (BMD) by establishing rat model of lumbar intervetebral disc degeneration (IDD) with kidney deficiency, and to explore internal mechanism of disc degeneration, relationship between disc degeneration and osteoporosis.</p><p><b>METHODS</b>Thirty Sprague-Dawley female rats aged one month were randomly divided into control group, lumbar IDD group and lumbar IDD with kidney deficiency group (combined group), 10 rats in each group. Lumbar IDD group removed double arms, lumbar IDD with kidney deficiency group removed double arms after 3 months, both ovaries were removed. Vertebral bone mineral density were observed by Micro-CT scan; morphological changes were tested by safranine O-fast green staining; II, X collagen protein expression in the intervertebral disc were obsevered by immunohistochemistry; extracellular matrix gene expression were obsevered by real-time polymerase chain reaction (RT-PCR), in order to evaluate the effects of removed of forelimbs and double ovarian on degeneration and vertebral bone mineral density of intervertebral disc.</p><p><b>RESULTS</b>Micro-CT scan showed osteoporosis in kidney deficiency group was obviously worse than other two groups; safranine O-fast green staining showed that intervertebral space became narrowed, intervertebral disc tissue degenerated obviously, chondral palte was underdeveloped in kidney deficiency group; immunohistochemistry showed that X collagen expression increased, type II collagen expression decreased in kidney deficiency group; RT-PCR showed that type II collagen expression in lumbar IDD group and kidney deficiency group was lower than control group, and had statistical meaning among three groups (P=0.000, P=0.000); Age 1 in lumbar IDD group and kidney deficiency group was lower than control group, and had statistical meaning among three groups (P=0.000, P= 0.000); while type X collagen expression was higher than control group, but no significant meaning; MMP-13 in lumbar IDD group and kidney deficiency group was higher than control group, with significant meaning compared among three groups (P= 0.000, P=0.000); aggrecanase-2 in lumbar IDD group and kidney deficiency group was higher than control group, with significant meaning compared among three groups (P=0.006, P=0.008).</p><p><b>CONCLUSION</b>Rats model of lumbar disc degeneration established by removed forelimbs and ovariectomized can occure "bone like"--osteoporosis, which is similar with clinical kidney lumbar disc degeneration in tissue morphology, molecular cell biology expression.</p>

Clinical significance of CD4+CD25hiCD127low regulatory T cells in the peripheral blood of patients with cardiac cancer / 肿瘤研究与临床

Objective To analyse the dysfunction of immunity and clinical significance in patients with cardiac cancer.Methods The level of CD4+ CD25hi CD127low Treg cells were detected by flow cytometry (FCM),and serum IL-10 and TGF-β1 levels were determined by enzyme linked immunosorbent assay (ELISA) kit in 56 patients with cardiac cancer.15 healthy volunteers were tested as normal controls.The clinical data of each patient were collected and analyzed. Results There was a significantly higher percentage of CD4+ CD25hi CD127low Treg cells in patients with cardiac cancer (5.73±1.56)% than that (4.45±1.06)% of healthy volunteers (P<0.01).The IL-10 and TGF-β1 levels in the serum of patients with cardiac cancer were also significantly higher than that of healthy volunteers (P<0.05).There was a positive correlation between levels of IL-10.TGF-β1 and the levels of CD4+ CD25hi CD127low Treg cells.The number of CD4+ CD25hi CD127low regulatory T cells in the peripheral blood of cardiac cancer patients were significantly correlated with clinical stages and metastasis lymph node.Conclusion The CD4+ CD25hi CD127low Treg cells in the peripheral blood of cardiac cancer patients is significantly increased in comparison with that in healthy volunteers,and was also correlated with different stages.The abnormal levels of CD4+ CD25hi CD127low Treg cells may be related to tumor progression in patients with cardiac cancer.

Clinical significance of level of CD4+CD25HiCD127Low regulatory T cells in the peripheral blood of patients with esophageal cancers / 肿瘤研究与临床

Objective To detect the levels of CD4+CD25HiCD127Low regulatory T cells (Treg) in the peripheral blood and its clinical significance in patients with esophageal cancer. Methods The levels of Treg in the peripheral blood were detected by three-color flow cytometry (FCM) in 80 patients with esophageal cancer and 20 healthy controls. Among the 80 patients, 30 patients were also further studied for preoperative and postoperative comparison after operation. The clinical and pathological data of each patient were collected and analyzed for the correlation with the Treg levels. Results The level of Treg in the peripheral blood of the control group was lower than that of the esophageal cancer patients [(3.36±1.14) % and (5.70±1.96) %, respectively], with significant difference (P <0.01). The levels of Treg in the peripheral blood was higher in the patients with metastasis of lymph node (n=40) than that in the patients without metastasis of lymph node (5.96±1.36) % and (4.23±1.18) %, respectively] (n=30), with significant difference (P <0.01). The levels of Treg in the peripheral blood of the patients were negatively correlated with their TNM classification. As the TNM classification advanced, the level of the Treg in the peripheral blood increased. Conclusion The levels of Treg in the peripheral blood of the patients with esophageal cancer are significantly higher than that of the healthy subjects, which is correlated with the clinical and pathological conditions. The development of esophageal cancer may relate with suppression of immune function.