AIM: The effective antisense sequences targeted VEGF mRNA with computer software would be screened and designed, and effect of them on growth K562 cells and protein expression of VEGF were studied with experiments. METHODS: Seven antisense sequences were selected and synthesized, which consisted of 18-20 deoxynucleotide acid and were modified with phosphorothioate, according to principle of low free energy of overall △G 37 Overall. Cell growth was assayed by trypan blue dye exclusion assay and level of VEGF protien in the media was determined by ELISA. RESULTS: Six of seven sequences were capable of inhibing growth of K562 cells and downregulating the VEGF protein expression significantly, compared with Scrambed control group. It was found that there was a close correlation between low level of overall △G 37 and antisense effectiveness ( r =0 887, P

AIM: To investigate inhibition of K562 cell growth by antisense drug targeted VEGF mRNA. METHODS: X7, 20-mer antisense sequences were selected, synthesized and modified with phosphorothioate. The drug was transfected into K562 cells in the present of lipofection. Cell growth was assayed by trypan blue dye exclusion assay and MTT. The level of VEGF protein in the media was determined by ELISA. The morphology of apoptotic cells were observed by Giemsa staining, and the propotion of apoptotic cells was detected by flow cytometry. RESULTS: The antisense drug inhibited growth of K562 and downregulated expression of VEGF protein significantly, compared with Scrambed control group and showed dose-dependent relation. Signs of apoptosis of K562 cells were not observed. CONCLUSION: Inhibition of K562 cell proliferation, but not cells apoptosis induction is the mechanism of inhibing growth of K562 cells by antisense drug targeted VEGF mRNA. At same time, VEGF has function of promoting K562 cell proliferation, and VEGF mRNA may be a new target attached by drugs. [

Aim To determine the effects of Qiliqian-gxin injected into lateral ventricle on Cardiac function, angiotensin Ⅱ( Ang Ⅱ) , angiotensin converting en-zyme(ACE), angiotensin type 1 receptor(AT1R) and the sympathetic nervous system in the hypothalamic pa-raventricular nucleus of rats with chronic heart failure. Methods Rat model of heart failure was prepared by acute myocardial infarction that was induced by ligation of the left anterior descending coronary artery. Four weeks after heart failure, Qiliqiangxin and Losartan were continuously administered via a syringe pump in-jector connected to lateral ventricle. After four weeks, echocardiogram was used to evaluate the cardiac func-tion and HE was used to observe myocardial tissue morphology, and enzyme linked immunosorbent assay was used to measure plasma norepinephrine( NE) , ser-um NT-proBNP and Ang Ⅱ in the paraventricular nu-cleus. The expression of ACE and AT1 R at mRNA and protein levels in the paraventricular nucleus was deter-mined by Real-time PCR and Western blot, and the RSNA was measured by PowerLab in anesthetized rats. Results Compared with the sham control, the cardiac function was significantly lower while the AngII, ACE, AT1 R expression in the paraventricular nucleus and RSNA were significantly increased in rats with heart failure. Compared with heart failure control, Qiliqian-gxin and Losartan decreased the RSNA and the AngII, ACE, AT1 R expression in the paraventricular nucleus. Conclusion Giving traditional Chinese medicine to the lateral ventricles can decrease the activation of the RAS system, reduce the renal sympathetic nerve activi-ty and improve cardiac function.

Data mining, as known as knowledge discovery in databases, is a non-trivial process of revealing the implied, previously unknown and potentially useful information from the massive data. In recently years, the applications of data mining in the field of pharmaceutical research of traditional Chinese medicine have widespread. Especially in the field of the heritage of experiences of na-tional medical masters, data mining plays an important role. In this study, we would expound of the use of methods of data mining in the heritage of experiences of national medical masters, and analyze their advantages and disadvantages, such as association rules, Bayesian networks, neural networks, and decision trees.
Data Mining ; Databases, Pharmaceutical ; Medicine, Chinese Traditional ; Neural Networks (Computer)

Objective To explore the factors influencing serum trough concentration of vancomycin in pediatric patients with severe gram-positive cocci pneumonia. Methods The general information, the biochemical test results, and plasma concentration of vancomycin were collected from 93 pediatric patients with severe gram-positive cocci pneumonia. The relative factors influencing trough concentration of vancomycin were analyzed retrospectively. Results With the dosage of 40-60 mg/(kg·d), serum trough concentration of vancomycin were between 10-20 mg/L in 26 patients, <10 mg/L in 54 cases, ≥20 mg/L in 13 cases. The ALT, AST, GFR, and γ-GT were significantly different among three groups (P<0.05); the 10-20 mg/L group had the highest levels of AST and γ-GT, the ≥20 mg/L group had the highest level of ALT and the lowest level of GFR. Multiple linear regression analysis showed that GFR was negatively linearly correlated with the serum trough concentration of vancomycin (R2=0.039, P<0.05). The median serum trough concentration of vancomycin in pediatric patients with GFR≥90, 60–90, 30–60 mL/(min·1.73m2) were 8.66, 18.21, 8.45 mg/L respectively, and the difference is statistically significant (P<0.05). Conclusions The serum trough concentration of vancomycin is negatively linearly correlated with GFR in pediatric patients with severe gram-positive cocci pneumonia. The patients with impaired renal function are easier to reach the target serum trough concentration of vancomycin. Clinical use of vancomycin should follow the low doses in the range the guideline recommended, and the serum trough concentration should be closely monitored.

To explore dose-effect or time-effect of vascular endothelial growth factor (VEGF) antisense phosphorothioate oligodeoxynucleotides (AS PS-ODN) on growth of HL-60 cells, and to study the effect mechanism so as to find new role of VEGF, A7, which was the most effective one of AS PS-ODN selected with computer-aided design and experimental assay, contains 20-DNA modified with phosphorothioate and was tranferred into cells mediated with lipofectin. After culture for 72 hours, inhibitive rate of cell growth was detected with MTT methods, viable cells were counted with trypan blue exclusion each 24 hour, cell configuration and apoptosis were observed with Geimsa staining and flow cytometry respectively, level of VEGF protein was detected with VEGF ELISA kit. The results showed that A7 is able to inhibit cell growth of HL-60 in dose-depending manner of AS PS-ODN, to down-regulate VEGF protein expression significantly, and not to induce apoptosis of HL-60 cells. It is concluded that there is possibility that the inhibition effect of VEGF AS PS-ODN on HL-60 cell growth is to restrain cell proliferation without inducing apoptosis of HL-60 cell, which would interpret that endogenous VEGF proteins have a capacity of promoting proliferation of HL-60 cell.
Cell Proliferation ; drug effects ; Flow Cytometry ; HL-60 Cells ; Humans ; Oligonucleotides, Antisense ; pharmacology ; Thionucleotides ; pharmacology ; Vascular Endothelial Growth Factor A ; analysis ; physiology

Objective To explore the alteration of brain pain functional areas in patients with functional dyspepsia (FD) irritable bowel syndrome (IBS) overlap by rectal balloon volume stimulation and magnetic resonance imaging (MRI) and the differences with IBS alone patients and healthy individuals were compared.Methods A total of 11 IBS alone patients,16 IBS overlapped with FD patients (IBS-FD) and 10 healthy controls were recruited.Sensory thresholds and visual analogue scale (VAS) were recorded during the rectal balloon air injection process. The changes of brain activated areas were analyzed by functional MRI (fMRI) when the rectum was stimulated at the volume of 50,100 and 150 ml.The data were analyzed by least significant difference (LSD) test.Results Under rectal volumetric stimulation,the sensory thresholds of IBS-FD group and IBS alone group were (53.14 ± 16.05) ml and (59.20 ± 20.55) ml and the difference was not statistically significant (LSD test,P＞0.05).There was no significant difference in VAS score between IBS alone group and IBS-FD group (LSD test,P＞0.05).Rectal stimulated under different volume,the results of fMRI indicated the activation of anterior cingulated cortex, dorsolateral prefrontal cortex,postporietal cortex,thalamus and insular cortex in both IBS alone group and IBS-FD group.And there was no significant difference in activated areas and intensity between IBS alone group and IBS-FD group (LSD test,P＞0.05).Conclusions There was no significant difference in activations of brain areas between IBS alone and IBS-FD patients under rectal volumetric stimulation. Under rectal volumetric stimulation,although symptoms overlapped,there was no evidence of the overlap of braingut axis and visceral hypersensitivity between IBS alone and IBS-FD.

To analyze the composition regularity of prescriptions containing Scutellaria baicalensis in Drug Standard of Ministry of Public Health of the Peoples Republic of China--Chinese Patent Medicines and Preparations on the basis of the traditional Chinese medicine inheritance support system (TCMISS), in order to provide reference for new drug R&D. the platform's software V2.0 was applied to establish a database of prescriptions containing S. baicalensis. The software's statistical statement module, association rules and improved mutual information method and other data mining technologies were adopted to analyze commonly used drugs, combination rules and core combination of S. baicalensis prescriptions. Having analyzed 477 prescriptions containing S. baicalensis, the researchers summarized 45 most commonly used drug combinations, whose ingredients mostly had functions of heat-clearing and damp-drying, purging fire for removing toxin and hemostasis. Drugs adopted in core combinations were relatively concentrated and selected according to definite composition methods. There were 23 diseases that S. baicalensis were most frequently applied in the treatment. Having compared three highly frequent diseases--cold, cough and dizziness, the researchers concluded that S. baicalensis could show different therapeutic effects through different combination ratios. Therefore, TCMISS (V2.0) is an important tool in analyzing the composition regularity of traditional Chinese medicines. The longitudinal and parallel comparison method is an effective method for studying the clinical composition regularity of S. baicalensis, while providing reference for new drug R&D.
China ; Drug Compounding ; statistics & numerical data ; Drug Therapy ; statistics & numerical data ; Humans ; Plant Extracts ; analysis ; therapeutic use ; Scutellaria baicalensis ; chemistry

OBJECTIVETo explore action mechanism of electroacupuncture (EA) at "Fenglong" (ST 40) for treatment of hyperlipidemia.

METHODSForty SPF-grade SD rats were randomly divided into a normal group (group A), a model group (group B), a model diet-control group (group C), a model + EA group (group D) and model diet-control + EA group (group E), 8 cases in each one. The rats in group A were fed with normal diet continuously while those in the rest 4 groups were fed with high-fat diet to establish hyperlipidemia model. Afterwards, the rats in group C and group E were fed with normal diet, while EA at "Fenglong" (ST 40) was applied in group D and group E, 30 min per time, once a day. After 28 days of treatment, macrophage was collected in each group. Oil red O-staining was applied to detect the formation of foam cells, and enzyme-linked immunosorbent assay (ELISE) was adopted to measure the contents of total cholesterol (TC) in macrophage and analyze the rate of cholesterol efflux.

RESULTSThe counts of positive cells of oil red O-staining and the contents of TC in the group B, group C and group D were significantly increased compared with those in the group A (all P < 0.01). The counts of positive cells and contents of TC in the group C, group D and group E were significantly clecreased compared with those in the group B (all P < 0.01), and the decline in group D was more obvious than that in the group C (all P < 0.01). Compared with group C and group D, the counts of positive cells and contents of TC in the group E was obviously decreased (all P < 0.01), which was not statistically different from group A (P > 0.05). In the meantime, compared with group C, the rate of cholesterol efflux in group D and group E was significantly increased (both P < 0.01), and the rise in group E was more obvious than that in the group D.

CONCLUSIONThe electroacupuncture at "Fenglong" (ST 40) could significantly prohibit the transformation of macrophage into foam cell and increase rate of cholesterol efflux in macrophage, which could prevent and reverse the formation of foam cell and play an essential role in treating hyperlipidemia and stopping it from developing into a further level.

Acupuncture Points ; Animals ; Biological Transport ; Cells, Cultured ; Cholesterol ; metabolism ; Electroacupuncture ; Foam Cells ; metabolism ; Humans ; Hyperlipidemias ; metabolism ; therapy ; Macrophages ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley

In this article we built formula database of health food containing Gardeniae Fructus with Traditional Chinese Medicine Inheritance Support System (V2.0). And on this basis, use data mining method such as association rules of the software, to analyze commonly used formula raw materials or materials combination of formula containing Gardeniae Fructus and raw material application having assisted function formula to protect chemical liver injury. The result shows that of the 71 health food formulas containing Gardeniae Fructus, most used materials are Gardeniae Fructus, Lycii Fructus, Angelica Sinensis Radix, Poria and so on. Commonly used materials combination mostly are Gardeniae Fructus and Lycii Fructus, Gardeniae Fructus and Angelica Sinensis Radix, Gardeniae Fructus and Poria, Gardeniae Fructus and Paeonia. There are nearly 18 healthcare functions of the health food containing Gardeniae Fructus, and most of these are assisted functions to protect chemical liver injury, and then immune modulating function. Of 23 formulas containing Gardeniae Fructus having assisted function formula to protect chemical liver injury, Gardeniae Fructus usually combined with traditional Chinese medicine which nourishs blood and liver such as Pueraria, Lycii Fructus, Hawthorn, Paeonia and Turnjujube. Analyzing formula raw materials application of health food containing Gardeniae Fructus contributes a lot to the further development and utilization.
Chemical and Drug Induced Liver Injury ; drug therapy ; Data Mining ; methods ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Food, Organic ; Fruit ; chemistry ; Gardenia ; chemistry ; Medicine, Chinese Traditional ; methods