Objective:To develope a method for the separation and preparation ginkgolic acid ? 1. Methods: Ginkgolic acids were extracted by alcohol, and adsorbed by silica gel to remove most of the polar impurities. It was preparated with RP HPLC. Results: The extraction ratio of ginkgolic acid ? 1 by this extraction process was above 84%, and the purity of ginkgolic acid ? 1 reached 98%. Conclusion: This procedure is simple and relatively effective.

Objective To investigate the clinical effect and safety of EEG biofeedback therapy combined with mirtazapine in the treatment of depressive disorder.Methods 124 patients with depressive disorder were selected and randomly divided into the observation group and the control group,62 cases in each group.The control group was given mirtazapine treatment,while the observation group was given EEG biofeedback therapy combined with mirtazapine.All the two groups were treated for 8 weeks.Before and 2,4,8 weeks after treatment,the clinical effects in the two groups were evaluated by Hamilton depression scale (HAMD),Montgomerie depression rating scale (MADRS) and the clinical global impression scale (CGI).The side effects scale(TESS) assessment was used to assess the side effects.And the serum norepinephrine (NE),5-hydroxytryptamine (5-HT) and dopamine (DA) levels were measured before and 8 weeks after treatment.Results The total effective rate of the observation group was 87.5％,which was significantly higher than 66.1％ in the control group (x2 =7.213,P ＜ 0.05).In the two groups,2,4,8 weeks after treatment,the HAMD scores were significantly lower than those before treatment (t =9.391,19.349,26.349,5.026,12.610,19.518,all P ＜ 0.05),the M ADRS scores were significantly lower than those before treatment (t =8.646,22.190,33.101,4.986,13.185,25.959,all P ＜ 0.05),and the CGI scores were significantly lower than those before treatment(t =17.471,29.482,42.256,13.136,28.358,35.661,all P ＜ 0.05).In the observation group,after treatment for 2,4,8 weeks,the HAMD scores were significantly lower than those in the control group(t =4.093,4.537,5.655,all P ＜ 0.05),and the MADRS scores were significantly lower than those in the control group (t =3.622,9.740,7.490,all P ＜ 0.05),while the CGI scores were significantly lower than those in the control group(t =8.608,11.024,12.598,all P ＜ 0.05).After treatment,the levels of 5-HT,NE and DA were (148.5 ± 4.9) ng/mL,(60.6 ± 4.2) ng/L and (78.0 ± 4.1) ng/L in the observation group,which were significantly higher than before treatment [(79.8 ± 4.3) ng/mL,(30.3 ± 4.0) ng/L and (43.5 ± 4.0) ng/L,t =82.977,41.134,46.837,all P ＜ 0.05].In the control group after treatment,the levels of 5-HT,NE and DA were (125.4 ± 4.1) ng/mL,(40.2 ± 4.0)ng/L and (50.3 ± 4.3)nig/L,which were significantly higher than those before treatment [(79.2 ± 3.9)ng/mL,(30.5 ±4.1)ng/L and (43.2 ±3.6)ng/L,t =64.287,13.334,9.969,all P ＜0.05],but which those in the observation group increased more significantly (t =28.469,27.695,36.286,all P ＜ 0.05).4 weeks and 8 weeks after treatment,the TESS scores in the observation group were (3.0 ± 1.0) points and (4.3 ± 1.2) points,which in the control group were (2.8 ± 1.2) points and (4.1 ± 1.3) points,there were no significant differences in terms of TESS scores (t =1.150,0.846,all P ＞ 0.05).Conclusion EEG biofeedback therapy combined with mirtazapine in the treatment of depression is better,the adverse reactions is not significantly increased,and it also has higher clinical safety compared with mirtazapine alone.

To discover novel antitumor fluoroquinolone lead compounds from a rational modification for antibacterial fluoroquinolones, a fused heterocyclic ketone corresponding to thiazolo[2,3- b][1,2,4]triazolone used as a bioisosteric replacement of the C-3 carboxylic acid group of ciprofloxacin 1, and further modification by a Claisen condensation reaction with substituted benzaldehydes formed novel fluoroquinolone C-3 fuse heterocyclic α, β-unsaturated ketones as the title compounds (6a-6r), separately. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS, and the in vitro anti-proliferative activity against human hepatoma Hep-3B cells, pancreatic Capan-1 cells and leukemia HL60 cells was evaluated by a MTT assay. The preliminary results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. In particular, compounds carrying an electron-withdrawing carboxyl (6k, 6m) or sulfonamide substituent (6q, 6r) attached to benzene ring were comparable to or better than constractive drug doxorubicin against Capan-1 cells. As such, it suggests that it is favorable for a fused heterocyclic α, β-unsaturated ketone scaffold instead of the C-3 carboxylic acid group to improve the antitumor activity of fluoroquinolones.

Objective:To explore the relationship between smoking and the effect of antipsychotics in schizophrenics.Methods:From July 2017 to July 2019, 142 schizophrenics in the mental health center were treated with olanzapine, and the serum drug concentration and concentration/dose ratio (C/D) were calculated.The age, sex, liver function, smoking, combined medication and other clinical data of the two groups were collected, and the influencing factors of serum olanzapine concentration in schizophrenic patients were analyzed by multivariate logistic regression.Results:Forty-four patients were in the non-compliance group(serum olanzapine concentration <20ng/mL), and 98 patients were in the compliance group(serum olanzapine concentration 20-80ng/mL). In the non-compliance group, males accounted for 72.2%, the average age was (61.6±10.5)years old, smoking history accounted for 90.1%, and serum C/D was (2.5±1.1)ng·mL -1·mg -1·d -1, and in the compliance group, males accounted for 51.0%, the average age was (57.9±9.6)years old, smoking history accounted for 41.8%, and serum C/D was (3.2±1.8)ng·mL -1·mg -1·d -1, and there were statistically significant differences in sex, age, smoking history and serum C/D between the two groups ( t=5.86, χ 2=2.06, χ 2=5.43, t=2.38, all P<0.05). Multivariate logistic regression analysis showed that smoking and CYP1A2 genes were independently related to whether the plasma concentration of olanzapine was up to standard in schizophrenic patients.Compared with non-smokers, previous smoking increased the probability of blood concentration non-compliance by 11% and current smoking by 15% respectively( OR=1.15, P=0.001). And compared with CYP1A2 gene AA, CYP1A2 gene AC reduced the probability of blood concentration non-compliance by 15% and CYP1A2 gene CC by 13%( OR=0.87, P=0.002). Conclusion:There is an independent correlation between smoking and serum C/D value of olanzapine in schizophrenics.Quitting smoking can reduce the probability of substandard blood concentration.

Objective:To investigate the clinical effect of oxcarbazepine combined with ziprasidone in the treatment of acute excitatory agitation in patients with schizophrenia.Methods:From January 2016 to January 2019, a total of 110 patients with acute excitatory schizophrenia who admitted in the Third Hospital of Quzhou were enrolled, and they were divided into observation group and control group according to the random digital table method, with 55 cases in each group.The control group was given ziprasidone capsule, and the observation group was given oxcarbazepine combined with ziprasidone capsule treatment for 4 weeks.The PANSS excitatory agitation factor(PANSS-EC), explicit aggressive behavior scale(MOAS), clinical efficacy rating scale(CGI-SI) score, serum neurocytokines[brain-derived nutritional factors(BDNF), nerve growth factor(NGF), glial-derived neurotrophic factor(GDNF)], homocysteine (Hcy), inflammatory factors[interleukin 1β(IL-1β), interleukin 6(IL-6), interleukin 12(IL-12), tumor necrosis factor α(TNF-α)] before and after treatment and the incidence of adverse reactions were compared between the two groups.Results:After treatment, the PANSS-EC, MOAS, CGI-SI scores, Hcy, IL-1β and TNF-α levels were decreased in the two groups( t=7.829, 14.952, 3.417, 15.511, 18.948, 7.193, 18.453, 24.161, 1.995, 3.378, 3.968, 6.820, all P<0.05), which of the observation group were lower than those of the control group[(15.34±3.56)points vs.(11.08±3.17)points, (5.36±1.68)points vs.(4.15±1.46)points, (5.56±1.21)points vs.(4.18±1.35)points, (14.29±2.42)μmol/L vs.(10.63±2.24)μmol/L, (48.15±15.63)ng/L vs.(42.18±10.51)ng/L, (29.57±8.76)ng/L vs.(23.48±6.76)ng/L]( t=6.628, 4.032, 5.645, 8.231, 2.351, 4.082, all P<0.05), while the BDNF, NGF, GDNF levels were increased( t=6.253, 6.346, 3.513, 13.906, 15.874, 7.507, all P<0.05), which of the observation group were higher than those of the control group[(9.34±1.23)μg/L vs.(11.35±1.34)μg/L, (21.37±2.85)μg/L vs.(26.87±3.21)μg/L, (439.51±56.42)ng/L vs.(489.63±58.15)ng/L], the differences were statistically significant( t=2.351, 3.523, 3.204, all P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups[25.45%(14/55) vs.12.73%(7/55), χ 2=2.884, P=0.089]. Conclusion:Oxcarbazepine combined with ziprasidone in the treatment of acute excitatory patients with schizophrenia can control the clinical symptoms, improve the serum levels of cytokines, Hcy and inflammatory factors, and has high safety.

Objective: To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance time in patients with COVID-19. Methods: A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, School of Medicine, Zhejiang University were recruited. All patients received oral abidol and/or combined lopinavir/ritonavir, darunavir antiviral, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg^-1·d^-1) (glucocorticoid treatment group), and 21 patients who did not use glucocorticoid were the control group. The time of stable virologic conversion insputumand the time of radiologic recovery in lungsince onset were compared between the two groups and among the normal patients.The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results: The median ages of the glucocorticoid group and the control group were 52 [interquartile range (IQR):45, 62] years and 46 (IQR: 32, 56)years, and the differences were significant (P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). There were 52.0% critical ill patients in the glucocorticoid treatment group, compared to that of 71.4% normal patients in the control group. The median times from the onset tostable virologic conversion to negative in the two groups were 15 (IQR:13,20) days and 14 (IQR:12,20) days (P>0.05), and the difference was no statistically significant. The median times from onset to radiologic recovery were 13 (IQR: 11,15) days and 13 (IQR:12,17) days in the two groups, and there was no difference (P>0.05). In ordinary patients, the median timesfrom the onset tostable virologic conversion insputum were no difference (P>0.05), with 13 (IQR:11,18) days in the glucocorticoid group and 13 (IQR:12,15) days in the control group; The median times from onset to radiologic recovery in lungwere also no difference (P>0.05), with 12 (IQR: 10,15)days in the glucocorticoid group and 13 (IQR: 12,17) days inthe control group. Conclusions Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19. The glucocorticoid is not recommended since no effectiveness on accelerating the improvement of radiologic recovery in lung has been observed.

Objective:To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19.Methods:A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg -1·d -1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results:The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years ( χ2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups ( P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days ( P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups ( P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group ( P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively ( P>0.05). Conclusions:Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.

The EtOH extracts of the whole plants of afforded 17 new jatrophane diterpenoid esters, helioscopianoids A-Q (-), along with eight known compounds (-). Their structures were elucidated by extensive spectroscopic methods and Mo(OAc)-induced ECD analysis, and the structures of compounds , , and were confirmed by X-ray crystallography. Compounds - were evaluated for inhibitory effects on P-glycoprotein (P-gp) in an adriamycin (ADM)-resistant human breast adenocarcinoma cell line (MCF-7/ADR) and neuroprotective effects against serum deprivation-induced and rotenone-induced PC12 cell damage. Compounds and increased the accumulation of ADM in MCF-7/ADR cells by approximately 3-fold at a concentration of 20 μmol/L. Compound could attenuate rotenone-induced PC12 cell damage, and compounds , , and showed neuroprotective activities against serum deprivation-induced PC12 cell damage.