Anti-Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous lesions

AIM： To evaluate whether celecoxib, a selective cyclooxygenase 2 （COX-2） inhibitor, could reduce the severity of gastric precancerous lesions following Hel/cobacter pylori （H pylorl） eradication. METHODS： H pylori-eradicated patients with gastric precancerous lesions randomly received either celecoxib （n = 30） or placebo （n = 30） for up to 3 mo. COX-2 expression and activity was determined by immunostaining and prostaglandin E2 （PGE2） assay, cell proliferation by Ki-67 immunostaining, apoptosis by TUNEL staining and angiogenesis by microvascular density （MVD） assay using CD31 staining.RESULTS： COX-2 protein expression was significantly increased in gastric precancerous lesions （atrophy, intestinal metaplasia and dysplasia, respectively） compared with chronic gastritis, and was concomitant with an increase in cell proliferation and angiogenesis. A significant improvement in precancerous lesions was observed in patients who received celecoxib compared with those who received placebo （P 〈 0.001）. Of these three changes, 84.6% of sites with dysplasia regressed in patients treated with celecoxib （P = 0.002） compared with 60% in the placebo group, suggesting that celecoxib was effective on the regression of dysplasia. COX-2 protein expression （P 〈 0.001） and COX-2 activity （P 〈 0.001） in the gastric tissues were consistently lower in celecoxib-treated patients compared with the placebo-treated subjects. Moreover, it was also shown that celecoxib suppressed cell proliferation （P 〈 0.01）, induced cell apoptosis （P 〈 0.01） and inhibited angiogenesis with decreased MVD （P 〈 0.001）. However, all of these effects were not seen in placebo-treated subjects. Furthermore, COX-2 inhibition resulted in the up-regulation of PPARy expression, a protective molecule with anti-neoplastic effects. CONCLUSION： H pylori eradication therapy followed by celecoxib treatment improves gastric precancerous lesions by inhibiting COX-2 activity, inducing apoptosis, and suppressing cell proliferation and angiogenesis.

Evidence-based optimization of integrated traditional Chinese and Western medicine therapies for prevention and treatment of coronary heart disease： design and implementation

As a chronic disease that seriously endangers public health, the number of coronary heart disease （CHD） patients in China has increased in recent years. There is great potentiality to integrate traditional Chinese and Western medicine therapies to prevent and treat CHD in clinical practice. However, most of the current integrated therapies still lack sufficient high-quality evidence, and the key links in how to apply are unclear. It is urgent to optimize them through evidence-based research to further improve the effectiveness. Therefore, we propose strategies to conduct evidence-based optimization of integrated traditional Chinese and Western medicine therapies in prevention and treatment of progressive cardiovascular diseases. These are integrated clinical trial design, attention to the key links of taking effect, combination of clinical and basic research. Based on the strategies, we started the national key research and development project ＂Evidence-based optimization research of TCM therapies in prevention and treatment of CHD （angina pectoris - myocardial infarction - heart failure）＂, which is expected to be a new paradigm in the field.

Efficacy of one-day quadruple therapy for H pylori infection in Chinese patients

AIM： TO compare the efficacies of one-day quadruple therapy and seven-day triple therapy in Chinese patients. METHODS： Sixty consecutive patients with nonulcer dyspepsia and confirmed H pylori infection were randomized to receive either omeprazole 40 mg, amoxycillin 1 g, and furazolidone 100 mg, all twice a day for 7 d or omeprazole 20 mg （at breakfast and dinner）, amoxicillin 1 g, furazolidone 200 mg, and colloidal bismuth subcitrate 220 mg four times for only one day. H pylori status was determined before and at least 5 weeks after therapy by endoscopy with antral and corpus biopsies for rapid urease test and histology. RESULTS： Hpyloi eradication was successful in 66.67% （20/30） patients in the 7-d group and in 36.67% （11/30） patients in the 1-day group （P = 0.037）. Side effects were induced by the treatment in 13.3% （4/30） patients of each group, but these were all self-limiting, shortlasting, and did not require any specific treatment. CONCLUSION： The one-day quadruple therapy is less effective than the one-week regimen in curing H pylori infection in Chinese patients.

Comparing the effects of depression,anxiety,and comorbidity on quality-of-life,adverse outcomes,and medical expenditure in Chinese patients with acute coronary syndrome

Background:Depression and anxiety have been correlated with elevated risks for quality-of-life (QOL),adverse outcomes,and medical expenditure in patients with acute coronary syndrome (ACS).However,the relevant data are lacking for Chinese ACS populations,especially regarding different effects of major depression,anxiety,and comorbidity.The objective of this study was to evaluate the dynamic changes of depression and/or anxiety over 12 months and examine the effects of depression,anxiety,and comorbidity on QOL,adverse outcomes,and medical expenditure in Chinese patients with ACS.Methods:For this prospective longitudinal study,a total of 647 patients with ACS were recruited from North China between January 2013 and June 2015.Among them,531 patients (82.1%) completed 12-month follow-ups.Logistic regression model was utilized for analyzing the association of baseline major depression,anxiety,and comorbidity with 12-month all-cause mortality,cardiovascular events,QOL,and health expenditure.Results:During a follow-up period of 12 months,7.3% experienced non-fatal myocardial infarction (MI) and 35.8% cardiac rehospitalization.Baseline comorbidity,rather than major depression/anxiety,strongly predicted poor 12-month QOL as measured by short-form health survey-12 (odds ratio [OR]:1.77,95% confidence interval [CI]:1.22–2.52,P = 0.003).Regarding 12-month non-fatal MI and cardiac re-hospitalization,baseline anxiety (OR:2.83,95% CI:1.33–5.89,P<0.01;OR:4.47,95% CI:1.50–13.00,P<0.01),major depression (OR:2.58,95% CI:1.02–6.15,P<0.05;OR:5.22,95% CI:1.42–17.57,P<0.03),and comorbidity (OR:6.33,95% CI:2.96–13.79,P<0.0001,OR:14.08,95% CI:4.99–41.66,P<0.0001) were all independent predictors,and comorbidity had the highest predictive value.Number of re-hospitalization stay,admission frequency within 12 months and medical expenditure within 2 months were the highest in patients with ACS with comorbidity.Conclusions:Major depression and anxiety may predict 12-month non-fatal MI and cardiac re-hospitalization.However,comorbidity has the highest predictive value with greater medical expenditure and worse QOL in Chinese patients with ACS.And depression with comorbid anxiety may be a new target of mood status in patients with ACS.

生理条件下分子内环化自降解聚(4-羟基丁酸)衍生物

通过水溶低聚乙二醇异腈(OEG-NC)与(E)-4-氧杂-2-丁烯酸的Passerini多组分聚合反应以及聚合物的氢化反应制备了两种新型的水溶性聚(4-羟基丁酸)衍生物.利用核磁共振(NMR)和凝胶渗透色谱详细研究了这两种聚合物在水溶液中的降解行为,结果表明,在37℃的磷酸缓冲溶液中(pD 7.4),聚合物的分子量随时间延长逐步下降,同时生成唯一的γ-丁内酯衍生物,其数量逐渐增加, 1 d后降解达到85%.进一步比较了它们在磷酸缓冲溶液(pD 6.8)及混合溶液(pD 7.4缓冲溶液/丙酮)中的降解行为,发现γ-丁内酯衍生物仍是唯一的降解产物,但由于降解环境pH或极性的降低,降解速度明显减慢.模拟聚合物的重复单元、端基以及降解产物结构,设计合成了三种模型小分子化合物,详细研究了它们在相同条件下的水解行为,证明实验条件下酯键不会发生无规水解断裂,确定了这类聚合物在磷酸缓冲溶液中的降解机理,聚合物首先以从头到尾内环化的方式快速解聚合为γ-丁内酯衍生物,随后该内酯化合物缓慢水解开环生成4-羟基丁酸盐类化合物.

Isolation and Expression Analysis of Two Cold-Inducible Genes Encoding Putative CBF Transcription Factors from Chinese Cabbage （Brassica pekinensis Rupr）

Two homologous genes of the Arabidopsis C-repeat/dehydration-responsive element binding factors （CBF/ DREB1） transcriptional activator were isolated by RT-PCR from Chinese cabbage （Brassica pekinensis Rupr. cv. Qinbai 5） and were designated as BcCBF1 and BcCBF2. Each encodes a putative CBF/DREB1 protein with an AP2 （Apetal2） DNA-bindlng domain, a putative nuclear localization signal, and a possible acidic activation domain. Deduced amino acid sequences show that BcCBF1 is very similar to the Arabidopsis CBF1, whereas BcCBF2 Is different in that it contains two extra regions of 24 and 20 amino acids in the acidic domain. The mRNA accumulation profiles indicated that the expression of BcCBF1 and BcCBF2 is strongly induced by cold treatment, but does not respond similarly to dehydration or abscisic acid （ABA） treatment. However, the cold-induced accumulation of BcCBF2 mRNA was rapid but short-lived compared with that of BcCBFI. The mRNA levels of both BcCBF1 and BcCBF2 were higher in leaves than in roots when plants were exposed to cold, whereas, salt stress caused higher accumulation of BcCBF2 mRNA in roots than in leaves, suggesting that the organ specificity of the gene expression of the BcCBFs is probably stress dependent. In addition, the accumulation of BcCBF1 and BcCBF2 mRNAs was greatly enhanced by light compared with darkness when seedlings were exposed to cold. It is concluded that the two BcCBF proteins may be involved in the process of plant response to cold stress through an ABA-independent pathway and that there is also a cross-talk between the light signaling conduction pathway and the cold response pathway in B. pekinensis as in Arabidopsis.

Mechanical alloying behavior of Nb–Ti–Si-based alloy made from elemental powders by ball milling process

Nb-Ti-Si-based alloy powders were prepared by mechanical alloying （MA） of elemental particles.The evolutions of morphology,size,phase constituents,crystallite size,lattice strain,composition and internal microstructure,etc.,of the alloy powders were analyzed by X-ray diffraction （XRD）,scanning electron microscopy （SEM）,energy-dispersive spectroscopy （EDS）,laser particle size analyzer and transmission electron microscope （TEM） analyses.The alloy particles are gradually refined and their shapes become globular with the increase in milling time.The diffraction peaks of Nb solid solution （Nbss） phase shift toward lower 2θ angles during ball milling from 2 to 5 h,and after that Nbss diffraction peaks shift toward higher 2θ angles with the increase in milling time from 5 to 70 h,which is mainly attributed to the alteration of the lattice parameter of Nbss powders due to the solution of the alloying element atoms into Nb lattice to form Nbss.During ball milling process,the decrease in crystallite size and increase in lattice strain of Nbss powders lead to continuous broadening of their diffraction peaks.A typical lamellar microstructure is formed inside the powder particles after ball milling for 5 h and becomes more refined and homogenized with the increase in milling time.After 40-h-ball milling,the typical lamellar microstructure disappears and a very homogeneous microstructure is formed instead.This homogeneous microstmcture is proved to be composed of only supersaturated Nbss phase.

Synthesis and in vitro cytotoxic activities of sorafenib derivatives

A series of novel sorafenib derivatives have been designed and synthesized.The cytotoxic activities of these compounds were tested in three tumor cell lines.Most of the compounds showed potent antiproliferative activity against the tested cell lines with IC50= 0–20 mmol/L.Some compounds demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines.Among them,compound 5g demonstrated significant inhibitory activity against A549,ACHN and MDAMB-231 cell lines with IC50values of 1.29,1.99,3.11 mmol/L,respectively.