OBJECTIVE To investigate the effects of multiple doses of Shugan jieyu capsules on the pharmacokinetics of voriconazole， rivaroxaban and apixaban in rats. METHODS Male SD rats were randomly divided into voriconazole group （30 mg/kg）， rivaroxaban group （2 mg/kg）， apixaban group （0.5 mg/kg）， Shugan jieyu capsules+voriconazole group （145 mg/kg+30 mg/kg）， Shugan jieyu capsules+rivaroxaban group （145 mg/kg+2 mg/kg）， Shugan jieyu capsules+apixaban group （145 mg/kg+0.5 mg/kg）， with 6 rats in each group. After the rats in each group were consecutively administered solvent （0.5% sodium carboxymethyl cellulose solution） or Shugan jieyu capsules by intragastric gavage for 8 days， they were respectively given voriconazole， rivaroxaban and apixaban solution by intragastric gavage on the 8th day. Blood samples were then collected at different time points （in voriconazole group， rivaroxaban group and corresponding drug combination groups， blood was collected before administration and at 0.17， 0.34， 0.5， 0.75， 1， 1.5， 2， 3， 4， 5， 6， 8， 10 and 12 hours post-administration； in apixaban group and corresponding drug combination group， blood was collected before administration and at 0.08， 0.17， 0.25， 0.34， 0.5， 0.75， 1， 3， 5， 7， 10 and 12 hours post-administration）. Ultra-high performance liquid chromatography-tandem mass spectrometry method was employed to determine the mass concentrations of voriconazole， rivaroxaban and apixaban in rat plasma. The main pharmacokinetic parameters of these drugs were calculated using a non-compartmental model， and the comparisons were made between groups. RESULTS Compared with single drug group， after multiple administrations of Shugan jieyu capsules， AUC0－t， AUC0－∞ and cmax of voriconazole were significantly decreased， while CLz/F was significantly increased， and tmax was also significantly prolonged （P＜0.05）. For rivaroxaban and apixaban， their tmax values were both significantly prolonged （P＜0.05）. However， there were no statistically significant differences in the other pharmacokinetic parameters between the two groups （P＞0.05）. CONCLUSIONS The combination of Shugan jieyu capsules can decrease the exposure， increase the clearance， and delay the peak concentration of oral voriconazole. However， it does not affect the exposure levels of rivaroxaban and apixaban， but it does delay the time to reach peak concentration for both drugs.

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with al-terations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,trans-mission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assess-ment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

AIM: To explore the pharmacokinetic interactions between sorafenib and dapagliflozin in rats and to provide some theoretical basis for the rational clinical use of the two drugs. METHODS: An ultra -performance liquid chromatography-tandem mass spectrometry (UPLC / MS / MS) method was developed for the simultaneous determination of sorafenib and dapagliflozin. Male SD rats were randomly divided into 5 groups (6 rats in each group), including 100 mg / kg sorafenib group, 0.5 mg / kg dapagliflozin group, 1 mg / kg dapagliflozin group, and 100 mg/kg sorafenib combined with 0.5 mg/kg dapagliflozin group and 100 mg/kg sorafenib combined with 1 mg / kg dapagliflozin group, for sorafenib and dapagliflozin drug interaction study. All samples were analyzed using a validated UPLC/ MS/MS method, and the main pharmacokinetic parameters were calculated by compartment model. RESULTS: 1 mg/kg dapagliflozin increased the C

Pruni Semen,the seed of several unique Prunus plants,is a traditional purgative herbal material.To determine the authentic sources of Pruni Semen,46 samples from four species were collected and analyzed.Ten compounds including multiflorin A(Mul A),a notable purative compound,were isolated and identified by chemical separation and nuclear magnetic resonance spectroscopy.Seventy-six communal components were identified by ultra-high performance liquid chromatography with linear ion trap-quadrupole Orbitrap mass spectrometry,and acetyl flavonoid glycosides were recognized as characteristic constituents.The flavonoids were distributed in the seed coat and cyanogenic glycosides in the kernel.Based on this,methods for identifying Pruni Semen from different sources were established using chemical fingerprinting,quantitative analysis of the eight principal compounds,hierarchical cluster analysis,principal component analysis,and orthogonal partial least squares discriminant analysis.The results showed that the samples were divided into two categories:one is the small seeds from Prunus humilis(Ph)and Prunus japonica(Pj),and the other is the big seeds from Prunus pedunculata(Pp)and Prunus triloba(Pt).The average content of Mul A was 3.02.6.93,0.40,and 0.29 mg/g,while the average content of amygdalin was 18.5,17.7,31.5,and 30.9 mg/g in Ph,Pj,Pp,and Pt,respectively.All the above information suggests that small seeds might be superior sources of Pruni Semen.This is the first comprehensive report on the identification of chemical components in Pruni Semen from different species.

OBJECTIVE:To establish the method for simultaneous determination of tenacissoside A,tenacissoside H and tenacissoside I in Marsdenia tenacissima. METHODS:UPLC-MS/MS method was adopted. The determination was performed on a Phenomenex Kinetex XB-C18column with mobile phase consisted of 0.1% formic acid solution-acetonitrile(gradient elution)at the flow rate of 0.2 mL/min. The column temperature was set at 40 ℃,and sample size was 5 μ L. Multiple reaction monitoring (MRM)mode was adopted with electrospray ion source as ion source,using positive ion scanning. Source jet voltage was 5 500 V,nebulizer pressure was 60 psi,heating pressure was 60 psi,curtain pressure was 20 psi and cone temp was set at 600 ℃. RESULTS:The linear ranges of tenacissoside A,tenacissoside H and tenacissoside I were 0.1-10 ng/mL(r=0.999 7),0.025-10 ng/mL(r=0.999 5),0.025-10 ng/mL(r=0.998 9),respectively;limited of quantation were 0.1,0.025,0.025 ng/mL,limited of detection were 0.05,0.012 5,0.012 5 ng/mL,respectively;RSDs of precision,stability and reproducibility tests were<4.0%. The recoveries were 97.67%-99.00%(RSD=0.47%,n=6),95.00%-101.67%(RSD=2.59%,n=6),96.67%-103.33%(RSD=2.83%, n=6). CONCLUSIONS:The method is simple,precise,stable and reproducible,and can be used for simultaneous determination of tenacissoside A,tenacissoside H and tenacissoside I in M.tenacissima.

Objective Objective To evaluate the effects and safety of total glucosides of paeony (TGP) in the treatment of patients with Sjogren syndrome.Methods The Cochrane Library,PubMed,EMBASE,CBM,VIP,CNKI,Wanfang databases were searched from their establishments up to September 30,2015.We used the method recommended by the Cochrane collaboration to perform a meta-analysis of randomized controlled trails (RCTs) of total glucosides of peony in the treatment of patients with Sjogren syndrome.Two reviewers analyzed these data independently.The Cochrane Collaboration's software RevMan 5.3 was used for meta-analysis.Results A total of 573 patients in 10 studies were finally included,and were divided into different subgroups.The results of subgroup-analysis showed that:①Schimer test:TGP group had a higher effective rate than the blank control group [MD=2.41,95%CI (0.08,4.74)],lower effective rate than Chinese herbal medicine [MD=-2.55,95%CI (-3.88,-1.22);②Salivary flow:TGP group had a lower effective rate than the control group [SMD=-0.87,95%CI (-1.20,-0.54)].③Rheumatic factors (RF):TGP group had a higher effective rate than Chinese herbal medicine [SMD=0.44,95%CI (0.06,0.82)] and Chinese patent drug [SMD=0.74,95%CI (0.36,1.12)],lower effective rate than the blank control group [SMD=2.23,95%CI (-2.79,-1.67);④ C-reactive protein (CRP):TGP group had a higher effective rate than the control group [MD=4.51,95%CI (1.75,7.26)];⑤IgG:TGP group had a higher effective rate than Chinese patent drug group [MD=2.73,95%CI (1.63,3.84)],lower effective rate than the blank control group [MD=-3.90,95%CI (-5.67,-2.13),but no statistical difference was noted when compared with Chinese herbal medicine and Western medicine groups;⑥ESR:TGP group had a higher effective rate than Chinese herbal medicine group [MD=12.73,95%CI (3.62,21.84)] and Chinese patent drug group [MD=7.82,95%CI (5.39,10.24)],lower effective rate than the blank control group [MD=-7.13,95%CI (-12.70,-1.56) and Western medicine group [MD=-12.19,95%CI (-24.19,-0.19)];⑦Safety:8 studies reported adverse effects in 41 patients.TGP group had a higher adverse reaction rate than the control group [OR=3.23,95%CI (1.60,6.50)].Conclusion Current evidence demonstrates that TGP can effectively improve CRP,but its effects on Salivary flow,Schimer test,IgG,ESR,RF were not significant.However,the heterogeneity and high risk of bias in the reports involved in this study limits the reliability of this conclusion.

Objective To investigate the expression changes of victims suffering from sudden cardiac death(SCD), eurological calcium adhesion proteins (N-Cadherin) and Bax and explore their significance in forensic medicine. Methods Separately select 33 samples of myocardial tissue suffering from sudden cardiac death and 29 samples of myocardial tissue from the cases which were diagnosed not dying of heart disease as SCD and controls. Histological methods were used to examine the morphologic changes in myocardial tissue, examining the expression changes of N-Cadherin and Bax and analyzing them in a statistic way. Results N-Cadherin was weakly positively expressed in myocardial tissue of group SCD and the cells shew disordered arrangement, which is obviously lower than the controls. The cells exhibited obvious features ordered arrangement in control group. The positive expression of Bax was detected in myocardial tissue of group SCD, which is obviously higher than the controls. Conclusion The expression changes observation of N-Cadherin and Bax will make a difference to the sudden cardiac death.

Objective To investigate the detection results of liver function enzymologic indexes,blood glucose and blood lipid in the patients with fatty live and their clinical significance.Methods Thirty-three patients with fatty liver in the hospital from Augustlst,2015 to August lst,2016 served as the observation group of this study,and contemporaneous 33 people undergoing physical examination in the hospital were selected as the control group.The liver function enzymologic indexes,blood glucose and blood lipid in all subjects were detected.Their clinical significance in the two groups were observed.Results The blood detection in the two groups found that the fasting blood glucose,total cholesterol,triglyceride and high density lipoprotein cholesterol in the control group were significantly lower than those in the observation group,the difference was statistically significant (P<0.05);total cholesterol,triglyceride,high density lipoprotein cholesterol detection in the observation group had statistical difference among mild,mild to moderate,above moderate fatty liver (P<0.05).The multivariate Logistic regression analysis results did not find the independent risk factors of fatty liver;total cholesterol and high density lipoprotein cholesterol showed high correlation in the control group (r=0.871,P<0.05),blood glucose and total cholesterol in fatty liver and its subgroups showed a low correlation (r=0.341,P<0.05).Conclusion The occurrence of fatty liver has close link with blood lipid,blood sugar and liver function enzymology.Conducting the enzymologic indexes,blood glucose and blood lipid detection has very important value for the patients with fatty liver.

Objective To assess the abstracts on randomized controlled trials ( RCT) in non-small cell lung cancer ( NSCLC) published in Chinese and their influencing factors.Methods RCT in NSCLC published in Chinese were included according to the CONSORT statement and their influencing factors were analyzed by RevMan 5.3 soft-ware.Results The titles were identified as random, randomization, blinding, statistical method, recruited partici-pants, trial registry and fund-supported, respectively, in 20%of the 2677 abstracts included in this study.Con-clusion The titles are identified as random, randomization, blinding, statistical method, recruited participants, trial registry and fund-supported in RCT published in Chinese.Although the abstracts are improved after the publication of CONSORT, they need to be further brushed up.