Objective To investigate the efficacy and mechanism of Salviae Miltiorrhiza and Ligustrazine Hydrochloride Injection (SMLHI). Methods The targets of chemical components of SMLHI were predicted and the compounds-targets (C-T) network was constructed. The key targets were screened through the topology analysis of the C-T network. Also, protein-protein interaction (PPI) network was established, and the Gene ontology and KEGG pathway was enriched and analyzed. The pharmacological action mechanism of SMLHI was predicted, and the mechanism was preliminarily verified by pretreating with SMLHI on the MARK expression of cerebral ischemia rats. Results Fifteen main compounds in SMLHI act on 94 targets and PRSS1, PTGS2, F2, and PTGS1 were key targets in the C-T network. There were 71 targets in the PPI network including several key nodes such as SRC, MAPK-1, MMP-9, MAPK-14, PTGS2, BCL-2, and so on. All the targets were enriched in 26 GO items and six KEGG pathways. Conclusion Results in this study preliminarily verified the action of SMLHI on cerebral infarction and diabetic peripheral neuropathy, thus laying a solid foundation for further study on the mechanism of action.

Animals ; Chronic Disease ; Diet, High-Fat ; Hypoxia ; metabolism ; Lung ; metabolism ; physiopathology ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Rats ; Rats, Sprague-Dawley

AIMTo search for some substituted alpha-amino phosphonates as leading compounds with the vasodilator effects.

METHODSTarget compounds were prepared from benzyl aldehyde, piperazine and diethyl phosphite using alcohol as solvent via Mannich-type reaction. In isolated rat aorta and in isolated guinea pig ileum, the vasodilator effects of compounds were investigated and evaluated whether they activated muscarine receptor.

RESULTSSeven compounds of substituted alpha-amino phosphonates have been synthesized and identified by IR, 1H NMR and elemental analysis. Three of them, compound 2a, 2b and 2c have vasodilator activity and do not activate M receptor.

CONCLUSIONTwo (2b and 2c) of them were found to have the notable vasodilator effect, and the rates of relaxing are (67 +/- 21) % and (82 +/- 18)%, separately. But they did not activate M receptors on ileum.

Animals ; Aorta ; drug effects ; Benzylamines ; chemical synthesis ; chemistry ; pharmacology ; Guinea Pigs ; Ileum ; drug effects ; Molecular Structure ; Muscle Contraction ; drug effects ; Organophosphonates ; chemical synthesis ; chemistry ; pharmacology ; Rats ; Vasodilation ; drug effects ; Vasodilator Agents ; chemical synthesis ; chemistry ; pharmacology

Objective To establish the standard operating procedures on multiple locus variable number tandem repeat analysis and to evaluate the values in identification of Brucella(B.) melitensis and epidemiological trace-back.Methods Sixteen B.melitensis,22 B.abortus,21 B.suis and 10 B.cnais were investigated by Brucella MLVA-16 genotyping scheme.All data were analyzed using BioNumerics version 5.1 software (AppliedMaths,Belgium).Clustering analysis was based on the categorical coefficient and unweighted pair group method using arithmetic averages(UPGMA) method.Polymorphism at each locus was quantified using Nei's diversity index.Resultant genotypes were compared using the web-based Brucella 2010 MLVA database.Results MLVA methods were successfully established and some strains can be clustered.Bruce06,bruce08,bruce11,bruce12,bruce42,bruce43,bruce45 and bruce55 were useful for species identification of Brucella isolates.Bruce04,bruce07,bruce09,bruce16 and bruce 30 afforded a higher discriminatory power for investigation of strain relatedness in regions of endemicity.Conclusions TheMLVAmethod has proved to be highly discriminatory and epidemiological concordance and is easy for Brucellosis surveillance in province-level lab.

To obtain water-soluble holothurian glycosides with high tumor suppressing activities from Apostichopus japonicus, macroporous resin, silica gel and gel-filtration column chromatograghy were used to purify the water-soluble holothurian glycosides, and their tumor suppressing activity and inducing apoptosis of tumor cells were examined in this study. The 70% ethanol fraction of macroporous resin column, the pSC-2 and pSC-3 fractions from silica gel column showed very strong tumor suppressing activity towards HeLa cells, A-549 lung cancer cells, SGC-7901 stomach cancer cells and Bel-7402 liver cancer cells. SC-2 and SC-3 fraction purified from Sephadex LH-20 gel-filtration column chromatography, with a purity above 99.6%, all had the properties of triterpenoid glycosides. Purified SC-2 fraction had remarkable tumor suppressing activity on HeLa cells in a dose- and time-dependent manner, and had prominent tumor suppressing activity to mouse S180 solid tumors in a dose-dependent manner. Besides, the SC-2 fraction also had remarkable ability in elevating mouse thymus index and spleen index. The purified SC-2 fraction could induce apoptosis of HeLa cells in a dose-dependent manner, and DNA fragmentation of HeLa cells occurred after treated 12 h with 10 mg x L(-1) and 50 mg x L(-1) of SC-2 fractions. From the results, it can be concluded that the purified SC-2 fraction of water-soluble holothurian glycosides has extremely strong tumor suppressing activity, and the suppression is realized by inducing tumor cells to undergo apoptosis. This study lays solid foundation for development of highly effective new natural anticancer agents from sea cucumbers.
Animals ; Antineoplastic Agents ; isolation & purification ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Glycosides ; isolation & purification ; pharmacology ; HeLa Cells ; Humans ; Inhibitory Concentration 50 ; Mice ; Neoplasm Transplantation ; Random Allocation ; Sarcoma 180 ; pathology ; Stichopus ; chemistry ; Tumor Burden ; drug effects

The present study was aimed to investigate the effect of different altitudes on telomere length of rat peripheral blood leukocyte and possible mechanism. Sixty male rats were randomly divided into three groups, lower altitude control group (10 m), moderate altitude group (2 260 m) and very high altitude group (simulated 5 000 m). The moderate altitude group and very high altitude group rats were transported to Xining and hypobaric chamber in Qinghai University, respectively. The peripheral blood specimens were extracted 30 d after the transportation. By means of real-time PCR, automatic blood cell analyzer, ELISA, TBA and WST-1 methods, the telomere lengths of blood leukocyte, the hemoglobin (Hb) contents, the plasma levels of telomerase reverse transcriptase (TERT) and hypoxia-inducible factor 1α (HIF-1α), the plasma content of malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured, respectively. The results showed that the telomere lengths of peripheral blood leukocyte in moderate altitude group were longer than those in control group and very high altitude group. The changes of TERT were compatible with the telomere length of peripheral blood leukocyte under different altitudes. The levels of HIF-1α in moderate altitude group and very high altitude group were higher than that of control group. The very high altitude group showed decreased SOD activities and increased level of MDA, compared with the other two groups. These results suggest that the telomere lengths of rat peripheral blood leukocyte in moderate altitude are elongated, and that the telomere-elongating effect is lost under very high altitude. The changes of HIF-1α, TERT and oxidative stress damage are the main mechanisms of telomere length changes. Moderate altitude living might be beneficial to increasing the life span in mammals.
Altitude ; Animals ; Hemoglobins ; metabolism ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit ; blood ; Leukocytes ; physiology ; Male ; Malondialdehyde ; blood ; Oxidative Stress ; Rats ; Superoxide Dismutase ; metabolism ; Telomerase ; blood ; Telomere ; physiology

Objective To investigate the efficacy and safety of standard access assisted minimally access percutaneous nephrolithotomy (MPCNL) combined with EMS lithotripsy system in treatment of staghorn caculi accompanied with pyonephrosis. Methods From October 2015 to May 2017, we retrospectively analyzed the clinical data of 53 patients of staghorn calculi accompanied with pyonephrosis (55 sides, 2 patients with bilateral) were treated with using the special urology ultrasound, kidney dome puncture path method method to do standard channel assisted MPCNL combined with EMS. To summarize the operation time, stone clearance rate, postoperative hospital stay, postoperative blood transfusion rate and complications. Results 53 patients had a total of 55 kidneys had been established first-staged F24 channels,and successfully gravel stone. The operation time was (82.3 ± 22.5) min; 72.7% of the renal had been established first-staged F24 channels assisted F16/18 dual channel;18.2% for the first phase F24 and secondary phase F16/18 of the dual or multi-channel; 9.1% PCNL combined with retrograde flexible ureteroscope; 4 cases of extracorporeal shock wave lithotripsy. The initial stone-free rate was 70.9% (39/55), total stone-free rate was 89.1% (49/55). 2 patients with postoperative blood transfusion, 1 case of super-selective renal artery embolization to stop bleeding, 3 patients had postoperative fever, 1 case of septic shock, 2 cases of conservative treatment of a small amount of liquid chest, 1 case of apparent low back pain due to urine extravasation, given pain medication.no other serious complications. Conclusions By special urology ultrasound probe guide, use the kidney dome puncture path method to do standard channel assisted MPCNL combined with EMS for the treatment of staghorn calculi accompanied with pyonephrosis, its benefits in high stone-free rate, low renal pelvis pressure, high security rate, low complication rate and so on. Therefore, it is worthy of clinical application.

With Sangtang Yin granule as model drug,and based on the strategy of " unification of medicines and excipients",the feasibility of preparing high drug loading granules with traditional Chinese medicine( TCM) raw powder as carrier was explored. The powder yield,particle size and particle size distribution,fillibility,flowability,hygroscopicity,reconstituability and other key physical properties relating to preparations of 8 herbs( Dioscoreae Rhizoma,Euryales Semen,Atractylodis Macrocephalae Rhizoma,Coicis semen,Poria,Puerariae Lobatae Radix,Puerariae Thomsonii Radix and Coicis Semen by stir-frying with bran) were studied after being smashed,and the feasibility of taking them as excipients of TCM granules was evaluated by co-spray drying,dry granulation and other preparation techniques. According to the results of the physical properties of raw powders,raw powders of Dioscoreae Rhizoma,Euryales Semen and Puerariae Thomsonii Radix had a high powder yield,uniform particle size distribution,good fillibility,poor hygroscopicity and good reconstitutability,with the feature of assisting granule forming. Compared with the prescription of spray dry powder Sangtang Yin without any excipient,the co-sprayed powder had a high yield,good fillibility and compressibility. The yield of dry granules prepared by co-spraying dry powder was increased by more than 10%,and the particles had a uniform color,good fluidity and dissolubility with the drug-loading rate up to 100%. Based on the physical characteristics of TCM raw powder combined with the analysis of the preparation process,Dioscoreae Rhizoma and Puerariae Thomsonii Radix raw powder were selected as the carriers of granule preparations,and Sangtang Yin granule without any excipient was successfully prepared. The findings provide a feasible idea for the preparation of TCM granules with a high drug loading capacity.
Excipients ; Medicine, Chinese Traditional ; Particle Size ; Powders ; Pueraria ; Rhizome

The incidence of each of the rare disease is very low. The complexity and diagnosis difficulty of the rare disease lead to the difficulties in the clinical research and development (R&D) of drugs for rare diseases. There is an urgent clinical need for the drug development of rare diseases in China. Encouraging R&D of new drugs, particularly the innovative drugs with China's own independent intellectural property is the basis for solving the predicament in drug shortage in China.. In order to further improve the efficiency of clinical R&D of drugs for rare diseases, the National Medical Products Administration (NMPA), Center for Drug Evaluation (CDE) issued Technical Guidance for Clinical Research and Development of Drugs for Rare Diseases. This is the first guidance for rare diseases in China that is drafted from the standpoint of the clinical technology research and development.The guidance is the scientifitc thinking and framework for the drug developing enterprises to research and develop drugs for rare disease efficiently and appropriately by following drug developing protocols and relating to the special features of rare disease.This paper presents the concepts and rationale in the guidance for the appraisal of rare disease drug research and development.

To explore the relationship between the variations of the physiochemical properties of traditional Chinese medicine(TCM) decoction before or after precipitation in alcohol and the wall stickiness in spray drying. In this study, widely used TCMs in clinic were selected to determine the physiochemical properties of TCM decoction before or after precipitation in alcohol separately.Afterwards, the principle component analysis(PCA),Hierarchical cluster analysis(HCA),and orthogonal partial least squares-discriminate analysis(OPLS-DA) were used to evaluate the relationship between the variations of those liquid before or after precipitation in alcohol and hot-melt stickiness in spray drying.Three types of statistical analysis methods all indicated that ethanol precipitation affected physiochemical properties of TCM decoction, and the variations of physical properties showed significant association with hot-melt stickiness in spray drying.The results of PCA-X and HCA suggested that the dynamic surface tension(DST) was impacted most by the alcohol deposition treatment,at the same time,the other 5 physiochemical properties were also affected.OPLS-DA verified that PCA-X and HCA results, and revealed that DST,equilibrium surface tension(EST) and pH were significantly affected by alcohol deposition treatment,and the order of the affecting factors from high to low was DST,EST and pH.Therefore,the downward trend of DST and pH were the important factors that directly affected the hot-melt stickiness of TCM after precipitation in alcohol,which would be probably caused by losing macromolecules alcoholic insoluble components and increasing relative proportions of organic acid and small molecule sugar.
Cluster Analysis ; Desiccation/methods* ; Drugs, Chinese Herbal/chemistry* ; Ethanol/chemistry* ; Hot Temperature ; Least-Squares Analysis ; Medicine, Chinese Traditional ; Principal Component Analysis