Objective To investigate the effect and mechanism of sevoflurane on short-term cognitive function in juvenile rats. Methods Thirty juvenile male SD rats were randomly divided into blank control group (group K), model control group (group C) and the experimental group.Rats of group K were not treated, rats of group C inhaled pure oxygen for 30 min.The rats in the experimental group inhaled 2% sevoflurane for 30 min, and were divided into 4 subgroups: revive 2 h after anesthesia (Sev-2 h group), 12 h (Sev-12 h group), 24 h group (Sev-24 h group) and 72 h group (Sev-72 h group, n=5).The Morris water maze behavior test was carried out at every time point.The expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in plasma of rats were detected by Western blotting. Results There was no statistical difference in the behavior of rats in each group before anesthesia (P>0.05).Compared with the group C and group K, the escape latency and swimming distance after anesthesia was significantly prolonged in group Sev-2 h(P<0.05).Compared with the group Sev-24 h and group Sev-72 h, the escape latency and swimming distance was prolonged in group Sev-2 h(P<0.05).Compared with the group C, the effective regional motion time and effective region motion distance after anesthesia were shortened in group Sev-2 h (P<0.05).Compared with the group sev-24 h and group sev-72 h, the effective regional motion time and effective regional motion distance were significantly shortened in the group sev-2 h (P<0.05).Compared with the group C and group K, expression of PI3K and AKT in group Sev-2 h were markedly down-regulated (P<0.05).Compared with the group Sev-24 h and group Sev-72 h, the expression of PI3K and AKT in group Sev-2 h decreased (P<0.05). Conclusion 2% sevoflurane can cause the short-term learning and memory extraction ability of juvenile rats, the mechanism may be related to the inhibition of PI3K/AKT signaling pathway.
Objective To analyze the inhibitory effect and its mechanism of matrine on the proliferation of cervical cancer HeLa cells in vitro. Methods HeLa cells were treated with matrine in vitro at concentrations of 0.5, 1.0, 1.5 and 2.0 g·L-1, respectively.The inhibition rate of cell proliferation was measured by MTT, the cell cycle distribution was detected by flow cytometry, and the changes of cell cycle-related proteins Wee1, CyclinA, CDC2 and CyclinB were detected by Western boltting. Results Matrine inhibit the proliferation of HeLa cells in a time and concentration dependent manner (P<0.01),and the inhibition rate peaked at 72 h in the concentration of 2.0 g·L-1.Flow cytometric analysis showed that the cell cycle ratio of HeLa cells changed significantly after being treated with 2.0 g·L-1 of matrine (P<0.01).Western boltting showed that after Mat treatment with different concentrations for 72 h, cycl-related proteins Wee1 increased with the concentration, while CyclinA, CDC2 and CyclinB decreased with the concentration.After treatment with 2.0 g·L-1 mat, Wee1 increased significantly, while CyclinA, CDC2 and CyclinB decreased significantly (P<0.05). Conclusion Matrine has obvious inhibitory effect on human cervical cancer HeLa cells in vitro, which may be achieved by inducing apoptosis and blocking cell cycle procession.
Objective To observe the protective effects of epigallocatechin (EGC) on mouse brain slices and HT-22 cells subjected to by oxygen-glucose deprivation (OGD), and further elucidate its mechanism. Methods The brain slices and HT-22 cell lines were randomly assigned to one of the following groups: normal control group, model control group, low dose of EGC group(1 mg·L-1), medium dose of EGC group(3 mg·L-1) , high dose of EGC group(10 mg·L-1).Slices were stained with TTC to determine lactate dehydrogenase (LDH).Viability of HT-22 cells were assessed by a CCK-8 kit, superoxide (SOD) activity in brain slices and HT-22 cells were also assessed. Results The A490 of TTC staining was significant reduced and the LDH release was significant increased in cortical and hippocampal slices after OGD.EGC (1, 3 and 10 mg·L-1) treatment greatly reversed the decreased of A490 of TTC staining (P<0.01) and the increased of LDH release (P<0.01 or P<0.05).Moreover, OGD reduced the activity of SOD in cortical and hippocampal slices and EGC can dose-dependently attenuate the decrease of SOD activity induced by OGD (P<0.01).In addition, EGC can reverse the decrease of cell activity and SOD activity caused by OGD in HT-22 cells. Conclusion EGC exerts a protective effect against OGD induced injury in mouse brain slices and HT-22 cell lines, in part via enhancing the activity of SOD.
Objective To investigate the spectrum effect relationship of nutmeg volatile oil on relieving chronic inflammatory pain. Methods The fingerprints of 19 species of volatile oil obtained from nutmeg were established by GC-MS;Complete Freund's Adjuvant was used to establish chronic inflammatory pain model of Wistar rats.132 rats were randomly divided into blank control group, model control group, diclofenac sodium (positive control) group and nutmeg volatile oil group(19 groups:S1-S19,30 mg·kg-1).The blank control group and model control group were given equal volume of 0.9% sodium chloride solution, diclofenac sodium group was given corresponding dose of diclofenac sodium, and nutmeg volatile oil group was given corresponding dose of nutmeg volatile oil.Joint swelling degree, thermal pain threshold, expression of NK-1R and COX-2 in the fifth lumbar dorsal root ganglion and substance P in blood were detected to study the pharmacodynamics of nutmeg volatile oil on relieving chronic inflammatory pain.GC-MS fingerprints of nutmeg volatile oil with the efficacy evaluation indicators and total drug efficacy were analyzed by grey relational analysis. Results The nutmeg volatile oil had the effect of relieving chronic inflammatory pain .All of the correlations of 26 common peaks were greater than 0.6.Among them, the top five peaks with the highest correlation degree were No.6 > No.8 > No.9 > No.5 > No.12. Conclusion The effect of nutmeg volatile oil on relieving chronic inflammatory pain is the result of the joint action of its active ingredient group -- the chemical components represented by the common peaks of 26 characteristics, which provides a reference basis for the establishment of quality control standards of Chinese medicinal materials based on active ingredients.
Objective To investigate the effect of aqueous extract of Rubia Cordifolia’s aerial part (AERCA) on dextran sodium salt (DSS)-induced ulcerative colitis (UC) model. Methods Totally 24 C57BL/6 mice were randomly divided into blank control group (n=6), model control group (n=6), high-dose (4.8 g·kg-1) and low-dose (1.2 g·kg-1) of AERCA-treatment groups.After 3 days of prophylactic administration of AERCA (same volume of water in blank control group and model control group), the model control group and AERCA-treatment groups were treated with 3% of DSS solution for 7 consecutive days;Meanwhile, mice of normal control group were given the same amount of water. The body mass, stool consistency and blood in the stool were monitored every day to calculate the disease activity index (DAI). Hematoxylin and eosin (HE) staining was used to observe the pathological changes of colon and the histopathological scores were recorded;Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of interleukin-1β (IL-1β) in serum, and the tumor necrosis factor-α (TNF-α ), interferon-γ (IFN-γ) in the tissue of mice.Immunohistochemistry (IHC) was used to detect the levels of TLR4 and MYD88 in colon tissues. Results DAI was decreased in the blank control group and AERCA-treatment groups when compared with the model control group (P<0.05). HE staining of colon tissue showed that the degree of inflammatory injury in the model control group was significantly worse than that in the blank control group.The histopathological injury of the colon in AERCA-treatment groups were significantly improved, the histopathological score in AERCA-treatment groups were significantly lower than that in the model control group (P<0.01).The levels of IL-1β and TNF-α in the model control group were significantly higher than that in the blank control group (P<0.05), the levels of IL-1β in AERCA-treatment groups were significantly lower than that in the model control group (P<0.05), and the levels of TNF-α in the high-dose of AERCA-treatment group was significantly lower than that in the model control group (P<0.05).The level of IFN-γ in the model control group was higher than that in the blank control group (P>0.05), the levels of IFN-γ in AERCA-treatment groups were lower than that in the model control group (P>0.05).IHC results showed that TLR4 expression of model control group was higher than that in the blank control group, and the TLR4 expression of AERCA-treatment groups were lower than that in the model control group.MYD88 was lower expressed in the blank control group and model control group, the expressions of MYD88 in AERCA-treatment groups were increased when compared with the model control group. Conclusion AERCA-treatment can inhibit DSS-induced colitis in mice.
Objective To evaluate the efficacy and safety of vilazodone agents against major depressive disorder. Methods The randomized controlled clinical trial (RCT) of verazodone in the treatment of major depressive disorder was searched by computer in Chinese and English databases, with a time limit from the establishment of the database to June 2018.Two researchers independently review the literature, performed screening and quality evaluation.RevMan 5.0 software was used to analysis the effect. Results Four RCT were included, and literature quality evaluation showed low risk of bias.Total of 1976 patients with major depressive disorder were included, including 989 in test group(vilazodone)and 987 in control group(placebo).Meta-analysis results showed that, at the end of the treatment period, there were statistically significant differences in MADRS score, HAMA score, CGI-S score and CGI-I score between the two groups(P<0.05).In terms of safety, there were statistically significant differences in the incidence of diarrhea, nausea, dizziness, insomnia, vomiting and lethargy between the two groups(P<0.05), There was no significant difference in the incidence of headache, upper respiratory tract infection, nasopharyngitis, dry mouth and fatigue(P>0.05). Conclusion Vliazodone(40 mg·d-1)can significantly improve the clinical symptoms of patients with severe depression, with a low incidence of adverse reaction.Gastrointestinal and central nervous system symptoms are common, which can be tolerated by patients, and it is a relatively safe and effective antidepressant drug.However, the possible risk of serious adverse reactions (death) can't be ruled out, which still needs to be verified by long-term, multi-center and rigorously designed clinical trials.
Objective To explore the efficacy and safety of agomelatine combined with zolpidem on patients with insomnia. Methods A total of 90 patients with insomnia were randomly divided into treatment group (n=45) and control group (n=45).Patients of treatment group were given 25-50 mg·d-1 of agomelatine and 5-10 mg·d-1 of zolpidem, patients of control group were given 5-10 mg·d-1 of zolpidem, the duration lasted for 4 weeks.The Pittsburgh Sleep Quality Index (PSQI) and Hamilton Rating Scale for Anxiety (HAMA) were used to assess the treatment efficacy, while the treatment emergent symptom scale (TESS) and Biochemical index were chosen to assess the safety of treatment. Results The scores of PSQI and HAMA were significantly lower than before treatment in both group.The scores of PSQI and HAMA in treatment group were lower than that of control group at the 2nd and 4th weeks (P<0.05).The total efficiency of the treatment group was 95.6%, which higher than the control group(82.2%), but the hepatic dysfunction was higher than the control group (P<0.05). Conclusion Agomelatine combined with zolpidem can improve the clinical efficacy in insomnia,but it would be more likely to have advise reactions as hepatic dysfunction.
Objective To study intestinal absorption and absorption kinetics of buprespirone hydrochloride in rats. Methods Intestinal absorption of buspirone hydrochloride in rats was investigated under different intestinal segments, different drug concentrations and different pH values of media.High performance liquid chromatography (HPLC) was used to determine the concentration of buspirone hydrochloride in circulating irrigation solution and its absorption kinetic parameters. Results The order of absorption rate of buspirone hydrochloride in each intestinal segments of the rats was duodenum > jejunum > ileum > colon.The absorption rate constants were(0.164±0.012),(0.146±0.017),(0.094±0.014),(0.070±0.008) h-1, respectively;There was no statistically significant difference in intestinal absorption parameters of buspirone hydrochloride at different concentrations and pH values.and there was no statistically significant difference difference between intestinal absorption rate constant of buspirone hydrochloride at different concentrations and pH conditions. Conclusion The absorption of buspirone hydrochloride in the intestine of rats complies with first-order kinetics process, and the absorption was dominated by passive diffusion.Its absorption in the intestine of rats is not affected by the concentration and pH.Buspirone hydrochloride can be absorbed throughout the intestine.
Objective To evaluate the clinical efficacy and safety of arsenic trioxide combined with vitamin C in the treatment of relapsed refractory multiple myeloma (MM) in the elderly patients. Methods The clinical data of 33 patients with recurrent/refractory MM treated with arsenic trioxide combined with vitamin C from June 2012 to May 2016 were summarized, and the therapeutic effect and adverse reactions were analyzed. Results ①72.7% of patients in Durie-Salmon (DS) stage Ⅲ, 34.8% of patients in revised international staging system (R-ISS) stage Ⅲ, and 47.8% of patients harbored at least one of the high-risk cytogenetic abnormalities.②The overall remission rate (ORR) of the chemotherapy patients was 63.7%, of which the complete remission rate (CR) was 6.1%, the very good partial remission rate (VGPR) was 18.2%, the partial remission rate (PR) was 39.4%, and the small remission rate (MR) was 15.2%.Total clinical benefit rate was 78.9%.Patients with R-ISS stage Ⅲ disease showed significantly lower ORR.③ Kaplan-Meier statistical analysis showed the median progression free survival(PFS) and the median1 duration of response(DOR) were 11 months and 2 months, respectively.Univariate prognostic analysis showed that abnormal karyotype and R-ISS stage Ⅲ were negative prognostic factors for PFS.④The most common adverse events (AEs) were weak,leukopenia, and gastrointestinal reactions. Conclusion Arsenic trioxide and vitamin C based chemotherapy regiments are effective and generally well tolerated in elderly patients with relapsed/refractory MM.Prognostic factors analysis shows that in this patient population abnormal chromosome karyotype and R - ISS stage Ⅲ are independent factors of poor prognosis.
Objective To establish the method of determining rnannitol in pazufloxacin mesylate injections by HPLC-ELSD. Methods The chromatographic analysis was carried on the NH2 column(4.6 mm×200 mm, 5 μm)with the column temperature at 30 ℃, the mobile phase consisted of acetonitrile-water(90:10), the flow rate was 1 mL·min-1, ELSD was used to determine mannitol.Drift tube temperature was 90 ℃, gas flow rate was 2.0 L·min-1. Results Mannitol showed a good linear relationship within the range from 0.792 μg to 7.916 μg(r=0.999 5).The average recovery of the method was 101.2% and RSD was 2.1%(n=9). Conclusion The method is simple, sensitive, accurate, and repeatable, which was suitable for the determining of mannitol in pazufloxacin mesylate.
Objective To establish a high performance liquid chromatography (HPLC) method for content determination of gypenoside A in Gypenoside dispersible tablets. Methods An Alltima C18 column (150 mm× 4.6 mm,5 μm) was used for the separation with mobile phase of acetonitrile-purified water (31:69) at a flow rate of 1.0 mL·min-1.The detection wavelength was 210 nm and the injection volume was 20 μL. Results The excipients did not interfere with the determination of gypenoside A.The linear range of gypenoside A was 32.69-163.46 μg·mL-1 with 1.000 0 as the correlation coefficient.The precision and stability were satisfactory with the relative standard deviations (RSDs) below 1.0%.The average spiked recovery of gypenoside A was 97.2% (n = 6).The determination results of three batches of gypenoside dispersible tablets were 4.05, 3.88 and 3.21 mg·g-1. Conclusion The established method is accurate and simple with high specificity, and suitable for determination of gypenoside A in gypenoside dispersible tablets.
Objective To evaluate the uncertainty for the determination of hydronidone concentration in human plasma by LC-MS/MS. Methods The uncertainty caused by various factors in the whole process of determination of hydronidone in human plasma by LC-MS/MS, including weighting, preparation of standard solutions, drug-spiked sample preparation, protein precipitation, calibration curve fitting, equipment error, matrix effect and repeatability was analyzed.The uncertainty of each source component, as well as the combined uncertainty and combined uncertainty were calculated. Results The expanded uncertainty for low (6.0 ng·mL-1), medium (60.0 ng·mL-1) and high (300.0 ng·mL-1) level of hydronidone was 0.63, 5.46, 33.40 ng·mL-1, respectively (k=2, P=95%). Conclusion The uncertainty for the determination of hydronidone in human plasma by LC-MS/MS is mainly caused by matrix effect, equipment error, pretreatment of plasma samples, repeatability, and calibration curve fitting (especially for the low concentration).
Objective To establish a LC-MS/MS method for the determination of mycophenolic acid (MPA) and further applied in investigating pharmacokinetic study and therapeutic drug monitoring in heart transplant patients. Methods The internal standard MPA-d3 (20 μL,2 μg·mL-1) was added into 200 μL of plasma, and precipitated with acetonitrile.The supernatant was collected for injection.High-performance liquid chromatographic separation was performed on an Agilent ZORBAX SB-C18 (2.1 mm×50 mm, 3.5 μm) column with 5 mmol ammonium acetate in 0.25% formic acid and acetonitrile as the mobile phases in a gradient manner.The flow rate was set at 0.2 mL·min-1.Multiple reactions monitoring mode (MRM) was adopted, and electrospray ionization (ESI) was a negative-ion.The precursor ion→product ion transitions m/z was 319.1→191.0 for MPA and m/z 322.1→191.1 for MPA-d3, respectively.Six heart transplant patients treated with triple immunotherapy including mycophenolate mofetil (MMF) were enrolled in this study.MPA concentrations were determined within 0-12 h after the first dose and pharmacokinetic parameters were calculated.Thirty patients were at the dose of 0.5 g twice daily, concentrations of MPA at steady state were also determined. Results MPA was in a good linearity within 0.1-40 μg·mL-1.Inter- and intra-day imprecision were less than 10%, with recovery from 96.3% to 97.9%, and matrix effect from 99.7% to 106.5%.The main pharmacokinetic parameters of the 6 patients after a dose of 1 g of MMF were as follows: Cmax was (7.58±5.09) μg·mL-1, tmax was (1.83±1.13) h, AUC0-12 was (26.58±7.23) μg·mL-1·h, AUC0-∞ was (37.41±14.42) μg·mL-1·h, t1/2was (7.53±8.01) h, CL/F was (29.36±7.78) L·h-1, Vd was (258.80±177.96) L.The trough concentration of MPA at steady state ranged from 0.37 to 3.832 μg·mL-1 in 30 patients, with inter-individual variation up to 59.2%. Conclusion The established method is simple, accurate, sensitive and specific, and is proved to be suitable for determination of MPA in human plasma and pharmacokinetic study in heart transplant patients.
Objective The stability of the compatibility of magnesium isoxalate injection with cyclic adenosine glucamine for injection in different solvents was investigated to provide a preliminary theoretical basis for clinical administration. Methods According to the concentration of clinical compatibility, 200 mg of magnesium isoglycyrrhizinate injection and 180 mg of meglumine adenosine cyclophosphate for injection were dissolved in 250 mL of five kinds of solvents, and the changes of appearance, pH,content and insoluble particles within 24 hours under storage conditions of 25 ℃ and 4 ℃ were examined. Results There were no significant changes in the appearance and pH of the five compatible solutions within 24 hours under storage conditions of 25 ℃and 4 ℃.The change of drug content was determined by HPLC with (100±5)% and the number of insoluble particles in accordance with the relevant provisions of the Chinese Pharmacopoeia with storage time increasing. Conclusion The stability of this clinical application compatibility program is good within 24 h and can be used clinically.
Objective To analyze the risk factors and pathogenic bacteria of ventilator-associated pneumonia (VAP) caused by multi drug resistant bacteria in intensive care unit(ICU), so as to conduct risk assessment management and guide rational drug use. Methods A retrospective cohort study of VAP patients in ICU from September 2016 to March 2018 was conducted.Single factor and logistic regression analysis were used to screen the risk factors of VAP caused by multidrug resistance (MDR), and the pathogenic characteristics of VAP patients in ICU were analyzed. Results From September 2016 to March 2018, 78 cases of VAP occurred in ICU, among which 41 cases (52.56%) were caused by MDR.7 variables were analyzed by single factor analysis and logistic multifactor analysis.The results showed that there were 4 independent risk factors of MDR-HAP,including direct transfer from other medical institutions(OR=36.50), the treatment of the 3rd and 4th generation cephalosporins as well as complex preparations containing enzyme inhibitors and carbapenems in the past 90 days (OR=24.55), severe combined infectious shock (OR=12.32), and length of stay in ICU more than 5 days (OR=12.22).A total of 121 strains of pathogenic bacteria and 84 strains of multidrug-resistant bacteria were isolated from 78 patients with VAP, accounting for 69.42%. Among the main pathogens causing VAP, acinetobacter baumannii was mainly drug-resistant, while Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus were drug-resistant and non-drug-resistant, and Stenotrophomonas maltophobia was mainly non-drug-resistant. Conclusion The main pathogenic bacteria of VAP in ICU include Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. Empirical drug resistance to pathogenic bacteria should be evaluated according to risk factors, and the corresponding prevention and control strategies should be developed, based on which initial empirical anti-infection treatment should be standardized.
Prolonged the course of prophylactic use of antibiotics after surgery was not recommend by WHO and the US Centers for Disease Control and Prevention.But a long course of antibiotic treatment to prevent surgical site infection after surgery is a common problem. In particular, the prophylactic use of antibacterials beyond the course of postoperative treatment is more common in the operation with great difficulty and high risk of postoperative complications.Taking esophageal cancer surgery as an example, based on our national conditions, this paper applied the evidence-based concept to deeply study the existing evidence of antimicrobial use in perioperative period of esophageal cancer, and analyze the feasibility and difficulties.Evidence analysis shows that there is no evidence that prolonged use of antibiotics after esophageal cancer surgery could reduce the incidence of postoperative infection.Preventing surgical site infections requires a multi-pronged approach and should not be overly dependent on on antibiotics.
Objective To investigates drug consultation process and thought pattern of safe medication in lactation,so as to ensure safe medication to nursing mothers and infants. Methods Analysis was made by integrating clinical pharmacists' careful enquiring on medical history including previous medication, present illness and allergies to medications or food and drug properties, factors of nursing mother and infant, package insert, consensus, guidebook, lactation drug risk rating, database and literatures. Results Through comprehensive analysis, advices were given in terms of time of taking medicine and breast-feeding. Conclusion There can be concluded that breast-feeding will not be impacted with rational drug use. Drug consultation for nursing mothers can help pharmacists to find the new entry point of clinical practice and upgrade their capabilities, which is a valuable and practicable prejudgment for safe medication in lactation.
Objective To explore the anti-infective treatment strategies for type 2 diabetes patients with liver abscess, and provide reference for clinical rational drug use. Methods Clinical pharmacists participated in the drug treatment of a case of type 2 diabetes mellitus patient companied with liver abscess, and analyzed drug variety, efficacy, and adverse reaction, then assisted the doctors to formulate individualized anti-infective regimen and provide pharmaceutical acre. Results Clinical pharmacists adjusted the anti-infective regimen according to drug susceptibility test result and pharmacodynamic characteristics of antimicrobial agents.The infection of the patient was effectively controlled. Conclusion Clinical pharmacists give full play to their professional expertise, play an active role in the optimization of treatment plan, and provide guarantee for the safety and rational clinical use of drugs for patients.
Since the beginning of this century, China has encouraged the cluster development of bio-pharmaceutical industry.Represented by biomedical industrial parks all over the country, the agglomeration effect is gradually evident. The existing research advocates that the labor shall be divided according to industry chain and new drug R&D chain in clusters, but lack of systematic research on the division of labor among different clusters.This paper was devoted to summarizing the research status of regional industrial division and regional biomedical industry division in China.