Radiosensitization Effect and Mechanism of Xuefu Zhuyutang on Transplanted Esophageal Carcinoma in Nude Mice / 中国实验方剂学杂志

ObjectiveTo explore the radiosensitization and underlying mechanism of Xuefu Zhuyutang on subcutaneous transplanted esophageal carcinoma. MethodThe subcutaneous xenograft model of human esophageal carcinoma ECA-109 in nude mice was induced and the model mice were divided into a model group， an irradiation group， a Xuefu Zhuyutang group， and a combination group， with six nude mice in each group. After the intervention， the transplanted tumors were removed and weighed， and the tumor inhibition rate of each group was calculated according to the formula. The protein expression of hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor A （VEGFA） was detected by immunohistochemistry （IHC）. The protein expression of mammalian target of rapamycin （mTOR）， HIF-1α， VEGFA， and vascular endothelial growth factor receptor 2 （VEGFR2） in transplanted tumors was detected by Western blot. The mRNA expression of mTOR， HIF-1α， and VEGFA in transplanted tumors was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in the model group， the tumor weight decreased in the irradiation group and the Xuefu Zhuyutang group （P<0.05）， as well as the combination group （P<0.01）. Compared with the irradiation group， the combination group showed decreased tumor weight （P<0.05）， with tumor inhibition rate of 57.37%. Compared with the model group， the irradiation group， the Xuefu Zhuyutang group， and the combination group showed decreased protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. Compared with the irradiation group， the combination group showed down-regulated protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can inhibit the growth of transplanted esophageal carcinoma ECA-109 in nude mice and shows an obvious radiosensitization effect in combination with radiotherapy. The mechanism may be related to the inhibition of the mTOR/HIF-1α/VEGFA signaling pathway to improve the hypoxic state of tumors.

Development of a mouse model of arecoline-induced oral mucosal fibrosis

OBJECTIVE@#To develop a BALB/c mouse model of oral submucous fibrosis (OSF) induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes.@*METHODS@#BALB/c mice were randomly assigned to either the control (distilled water) or experimental group (arecoline) (n = 40). Eight mice from each group were sacrificed every 4 weeks since 8 weeks post treatment. Changes in histopathologic features, levels of collagen type I and collagen type III, and angiogenesis were measured.@*RESULTS@#In the 8th week, epithelium atrophy, collagen cumulation and micrangium pathologic changes in the lamina propria were observed in the oral mucosa. In the 20th week, hyaline degeneration of the connective tissues was observed on the tongue and palate mucosa. The angiogenesis and collagen type I changed significantly as the diseases advanced (P < 0.05); however, collagen type III was not statistically different.@*CONCLUSIONS@#An OSF model involving mice can be rapidly induced by drinking a high-dose of arecoline. OSF angiogenic changes in mice primarily decrease and collagen accumulation is mainly collagen type I.

Development of a mouse model of arecoline-induced oral mucosal fibrosis

Objective To develop a BALB/c mouse model of oral submucous fibrosis (OSF) induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes. Methods BALB/c mice were randomly assigned to either the control (distilled water) or experimental group (arecoline) (n = 40). Eight mice from each group were sacrificed every 4 weeks since 8 weeks post treatment. Changes in histopathologic features, levels of collagen type I and collagen type III, and angiogenesis were measured. Results In the 8th week, epithelium atrophy, collagen cumulation and micrangium pathologic changes in the lamina propria were observed in the oral mucosa. In the 20th week, hyaline degeneration of the connective tissues was observed on the tongue and palate mucosa. The angiogenesis and collagen type I changed significantly as the diseases advanced (P < 0.05); however, collagen type III was not statistically different. Conclusions An OSF model involving mice can be rapidly induced by drinking a high-dose of arecoline. OSF angiogenic changes in mice primarily decrease and collagen accumulation is mainly collagen type I.

The effect of total cholesterol on myocardial infarction in Chinese male hypertension population / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Total cholesterol (TC) is an important risk factor for myocardial infarction (MI), but the effect of TC on MI in Chinese male hypertension population has not been well documented. We conducted a prospective cohort study to determine the incidence and relative risk for MI across a wide range of TC levels in Chinese male hypertension population.</p><p><b>METHODS</b>A cohort of 5298 male employees aged 18-74 years recruited from Capital Steel and Iron Company in Beijing of China in 1974-1980 was followed up for an average of 20.84 years. A total of 122 incident MI cases were identified during the period of follow-up.</p><p><b>RESULTS</b>The incidence of MI among participants with elevated TC and those with desirable TC in male non-hypertension population was 137.20 and 63.81 per 100,000 person-years, respectively; and the corresponding incidence in male hypertension population was 279.80 and 130.96 per 100,000 person-years, respectively. After adjustment for important covariables, 10.38%, 16.71%, and 23.80% of MI cases were attributable to hypertension, elevated TC, and hypertension plus elevated TC, respectively. In male hypertension population, the multivariate adjusted hazard ratios of MI were 1.21, 2.39, 3.38, and 3.95 for participants with TC level of 5.17-5.68, 5.69-6.20, 6.21-6.71, and > or = 6.72 mmol/L, compared with those with TC < 5.17 mmol/L. The corresponding population attributable risks were 2.92%, 9.20%, 8.87%, and 9.84%, respectively.</p><p><b>CONCLUSION</b>Elevated TC is an important independent risk factor of MI both in male non-hypertension and hypertension populations. There is a linear association between TC level and MI incidence in Chinese male hypertension population.</p>

Perilipin gene 1237 T > C polymorphism is not associated with obesity risk in northern Chinese Han adults / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To identify the association between PLIN 1237 polymorphism and obesity in Chinese Han adults.</p><p><b>METHODS</b>A total of 994 adults (157 obese subjects, 322 overweight subjects, and 515 normal controls) were recruited from two rural communities. PLIN 1237 polymorphism was genotyped by polymerase chain reaction-restriction-fragment-length-polymorphism (PCR-RFLP). Association between PLIN polymorphisms and obesity status was estimated by ordinal logistic regression.</p><p><b>RESULTS</b>The three genotypes of PLIN 1237 were detected with a percentage of 54.3%, 37.1%, and 8.6% in TT, TC, and CC genotypes, respectively. For the PLIN 1237 polymorphism locus, the frequency of alleles T and C was 0.73 and 0.27, respectively. The PLIN 1237 polymorphisms were in Hardy-Weinberg equilibrium. PLIN 1237 polymorphism was not associated with obesity. The odds ratio for overweight or obesity for the CC+TC genotype was 0.8 (0.4, 1.4) in women (P = 0.4) and 0.6 (0.3, 1.3) in men (P = 0.2) after adjustment for age, education, household income and alcohol consumption, smoking, and physical activity.</p><p><b>CONCLUSION</b>Chinese Han adults have a lower frequency of variant-allele C in PLIN 1237. PLIN 1237 T > C polymorphism is not significantly associated with obesity in northern Chinese adults.</p>

Antiangiogenic and antitumor effects of vascular endothelial growth factor small interfering RNA on Tca8113 human tongue squamous cell carcinoma xenografts in vivo / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To examine the antiangiogenic and antitumor effects of vector-based small interfering RNA (siRNA) targeting vascular endothelial growth factor (VEGF) on human tongue squamous cell carcinoma xenografts in vivo.</p><p><b>METHODS</b>Tca8113 human tongue cancer nude mice xenograft model was established, and subsequently divided into four groups randomly (5/group). Two siRNA targeting VEGF constructed in eukaryotic expression vector (PU-VEGF-siRNA1, PU-VEGF-siRNA2) were injected intratumor and peritumor with lipofectamine 2000, respectively. No siRNA vector injected and non-injected tumors were used as experimented and negative controlled, respectively. Animals were injected one time every 3 days for a total of 10 times. Three days after the last injection, the weigh and volume of tumors, and intratumor microvessel density (MVD) were measured. The expression of VEGF in xenograft tumors was detected by reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry. The cell apoptosis and cell cycle analysis of tumors were detected by Tunel and Flow cytometry, respectively.</p><p><b>RESULTS</b>Compared to the experimental and negative controls, the percentage of cells in the G(1) phase increased (P < 0.05), the expression of VEGF on both mRNA and protein level, the tumor weigh and volume, and MVD decreased in the PU-VEGF-siRNA2 group (P < 0.05), and more apoptosis was induced (P < 0.01). But significant differences were not noted between PU-VEGF-siRNA1 group and two controls (P > 0.05).</p><p><b>CONCLUSIONS</b>VEGF-siRNA can reduce VEGF expression, inhibit tumor growth and angiogenesis, and induce apoptosis in Tca8113 cell carcinoma in vivo. Different VEGF-siRNA may have different effect in vivo.</p>

Suppression of vascular endothelial growth factor expression by vector-based small interfering RNA in human tongue squamous carcinoma cell line Tca8113 / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To assess suppression effects of vector-based small interfering RNA (siRNA) on vascular endothelial growth factor (VEGF) expression of human tongue squamous carcinoma cell line (Tca8113) in vitro.</p><p><b>METHODS</b>Two siRNA targeting VEGF constructed in eukaryotic expression vector (Pu-VEGF-siRNA1, Pu-VEGF-siRNA2), eukaryotic expression vector as the experiment control, all of which were transfected into Tca8113 cells with Lipofectamine 2000. Non-transfection cell was used as negative control. VEGF mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and enzyme linked immunosorbent assay (ELISA), respectively.</p><p><b>RESULTS</b>Compared to the experimental and negative controls, the expression of VEGF mRNA and protein were significantly decreased in the Pu-VEGF-siRNA1 group and Pu-VEGF-siRNA2 group. But there were no significant differences between two controls (P > 0.05).</p><p><b>CONCLUSION</b>Vector-based siRNAs targeting VEGF are efficient in down-regulating VEGF expression in Tca8113 cells.</p>

Effect of SH2A gene in cell signal transduction and its subcellular locolization / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To examine the effect of SH2A gene in cell signal transduction and its subcellular localization.</p><p><b>METHODS</b>RT-PCR method was used to amplify the coding sequence of SH2A gene. Eukaryotic recombined expression vector pcDNA 3.1-SH2A was constructed, and then Bel7402 cell and COS7 cell transfected by liposome. Multiple kinase assay was performed to examine the activity of protein kinase (PKC), mitogen activated protein kinase (MAPK), tyrosine protein kinase (TPK) in the transfected cells. Meantime, pEGFP-SH2A vector was also constructed and the cells transfected with it were examined by fluorescent microscopy.</p><p><b>RESULTS</b>Recombined expression vector pcDNA3.2-SH2A and pEGFP-SH2A contained the coding sequence of SH2A cDNA. In both cell lines expressing SH2A gene, the cytoplasm PKC activity decreased by 40% or so, but no apparent alteration was found in MAPK and TPK activity. SH2A gene was found localized in the cytoplasm of transfected cells under fluorescent microscope.</p><p><b>CONCLUSION</b>SH2A gene may act as an inhibiting factor in PKC signal transduction, and it is localized in cytoplasm.</p>

Pharmacokinetics of rebamipide in the patients with peptic ulcer / 中国临床药理学与治疗学

0.05).Cmax of domestic and imported rebamipide tablet were (0.56?0.24) and (0.59?0.29)mg?L-1, with that tmax were (1.75?0.92) and (1.98?1.05)h,t1/2(?) were (1.86?1.38) and (1.93?1.45)h,AUC0～∞ were (2.48?1.06) and (2.62?1.35)mg?h?L-1. Conclusion The pharmacokinetics of the two products are similar.