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.

Background: Right upper lobectomy (RUL) for lung cancer with different dissecting orders involves the most vari-able anatomical structures, but no studies have analyzed its effects on postoperative recovery. This study compared the conventional surgical approach, VAB (dissecting pulmonary vessels first, followed by the bronchus), and the alter-native surgical approach, aBVA (dissecting the posterior ascending arterial branch first, followed by the bronchus and vessels) on improving surgical feasibility and postoperative recovery for lung cancer patients. Methods: According to the surgical approach, consecutive lung cancer patients undergoing RUL were grouped into aBVA and VAB cohorts. Their clinical, pathologic, and perioperative characteristics were collected to compare periop-erative outcomes. Results: Three hundred one patients were selected (109 in the aBVA cohort and 192 in the VAB cohort). The mean operation time was shorter in the aBVA cohort than in the VAB cohort (164 vs. 221 min, P < 0.001), and less blood loss occurred in the aBVA cohort (92 vs. 141 mL, P < 0.001). The rate of conversion to thoracotomy was lower in the aBVA cohort than in the VAB cohort (0% vs. 11.5%, P < 0.001). The mean duration of postoperative chest drainage was shorter in the aBVA cohort than in the VAB cohort (3.6 vs. 4.5 days, P = 0.001). The rates of postoperative complica-tions were comparable (P = 0.629). The median overall survival was not arrived in both cohorts (P > 0.05). The median disease-free survival was comparable for all patients in the two cohorts (not arrived vs. 41.97 months) and for patients with disease recurrences (13.25 vs. 9.44 months) (both P > 0.05). The recurrence models in two cohorts were also comparable for patients with local recurrences (6.4% vs. 7.8%), distant metastases (10.1% vs. 8.3%), and both (1.8% vs. 1.6%) (all P > 0.05). Conclusions: Dissecting the right upper bronchus before turning over the lobe repeatedly and dissecting veins via the aBVA approach during RUL would promote surgical feasibility and achieve comparable postoperative recovery for lung cancer patients.

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.

Background:Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course,and available treatments for delaying the progression to end-stage renal disease are limited.This study aimed to assess the efficacy and safety of the traditional Chinese medicine,Niaoduqing particles,for delaying renal dysfunction in patients with stage 3b-4 CKD.Methods:The present study was a prospective,randomized,double-blind,placebo-controlled,multicenter clinical trial.From May 2013 to December 2013,300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml,min-1· 1.73 m-2,aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces.Patients were randomized in a 1∶1 ratio to either a test group,which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks,or a control group,which was administered a placebo using the same methods.The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment.The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test.The present study reported results based on an intention-to-treat (ITT) analysis.Results:A total of 292 participants underwent the ITT analysis.At 24 weeks,the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the test and control groups,respectively (Z =2.642,P =0.008),and the median change in eGFR was-0.2 (-4.3-2.7) and-2.2 (-5.7-0.8) ml·min-1.1.73 m-2,respectively (Z =-2.408,P =0.016).There were no significant differences in adverse events between the groups.Conclusions:Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD.This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction.

Rare diseases have a significant and profound impact on society, the economy, and the healthcare system. The path to developing drugs for rare diseases is particularly arduous. Due to the small number of patients and limited market demand, pharmaceutical companies don′t have enough incentives and resources to invest in drug research and development. Additionally, the long development cycles, high costs, and high risks have led to a number of potential therapeutic drug failures at the early stages of development. This article summarizes a series of encouraging policies adopted by the National Medical Products Administration for rare diseases, which is an important public health issue, as well as the achievements in the review and approval of rare disease drugs in recent years. These policies have accelerated the approval process. Meanwhile, the policies ensure the safety and effectiveness of drugs and offer more treatment options and hopes to patients with rare diseases. With the continuous effort at optimizing the policy environment and the advancement of research and development technologies, China′s drug regulatory authorities will continue to focus on the clinical needs of rare diseases, to implement " patient-centered " approach to drug development, inject new vitality into the research and development of drugs of rare diseases, and offer more precise and effective treatment choices for patients with rare diseases.