Objective To investigate the clinical efficacy of Chailian Lvping Granules(mainly composed of Bupleuri Radix,Coptidis Rhizoma,Paeoniae Radix Alba,Angelicae Sinensis Radix,Salviae Miltiorrhizae Radix et Rhizoma,Citri Sarcodactylis Fructus,and Ziziphi Spinosae Semen)in treating post-stroke anxiety and to observe their effect on serum neurotransmitters and oxidative stress.Methods A total of 104 patients with post-stroke anxiety of liver-qi stagnation and heart-fire exuberance type were randomly divided into an observation group and a control group,52 cases in each group.The control group was treated with conventional western medicine of Paroxetine,and the observation group was treated with Chailian Lvping Granules on the basis of treatment for the control group.The course of treatment lasted for eight weeks.The two groups were observed in the changes of Hospital Anxiety and Depression Scale(HADS)score,Hamilton Anxiety Scale(HAMA)score,serum neurotransmitter parameters of brain-derived neurotrophic factor(BDNF),dopamine(DA),5-hydroxytryptamine(5-HT)and norepinephrine(NE),and oxidative stress indicators of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)before and after treatment.Moreover,the clinical efficacy and total incidence of adverse reactions were compared between the two groups.Results(1)After eight weeks of treatment,the total effective rate of the observation group was 94.23％(49/52),and that of the control group was 76.92％(40/52).The intergroup comparison(tested by chi-square test)showed that the curative effect of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the HADS score and HAMA score for the axienty degree in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of HADS score and HAMA score in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the serum level of neurotransmitter BDNF in the two groups was increased while the serum levels of DA,5-HT and NE were decreased compared with those before treatment(P＜0.05).The increase of serum BDNF level and the decrease of serum DA,5-HT and NE levels in the observation group were significantly superior to those in the control group(P＜0.01).(4)After treatment,the serum level of oxidative stress indicator MDA in the two groups was decreased while the serum levels of SOD and GSH-Px were increased compared with those before treatment(P＜0.05).The decrease of serum MDA level and the increase of serum SOD and GSH-Px levels in the observation group were significantly superior to those in the control group(P＜0.05 or P＜0.01).(5)The total incidence of adverse reactions in the observation group was 5.77％(3/52),and that in the control group was 9.62％(5/52).There was no significant difference between the two groups(P＞0.05).Conclusion On the basis of conventional western medicine treatment,Chailian Lvping Granules exert certain effect in the treatment of patients with post-stroke anxiety of liver-qi stagnation and heart-fire exuberance type.The combined therapy is effective and safe on alleviating the anxiety symptoms of patients,decreasing the degree of neurological impairment and stress response level,and has few adverse reactions.

Objective:To investigate the clinical features of patients with epilepsy in Neurosurgery Outpatient and influencing factors for their seizure control.Methods:Six hundred and seventy-three epilepsy patients admitted to Neurosurgery Outpatient of 6 hospitals including Fifth Affiliated Hospital of Zhengzhou University from September 2017 to December 2022 were chosen. Clinical data (including general demographic data, education level, onset age, onset cycle and duration, course of onset, family annual income and seizure control) were collected using a questionnaire prepared by He'nan Epilepsy Systematic Diagnosis and Treatment Center to summarize the clinical features. Univariate and multivariate Logistic regressions were used to analyze the influencing factors for their seizure control.Results:(1) In these 673 epilepsy patients, 50 (7.4%), 78 (11.6%), 192 (28.5%), 100 (14.9%), 68 (10.1%), 72 (10.7%) and 113 (16.8%), respectively, were <1 year old (infant stage), 1-2 years old (children stage), 3-5 years old (preschool stage), 6-16 years old (juvenile stage), 17-39 years old (young stage), 40-64 years old (middle-aged stage) and ≥65 years old (elderly stage). In the past medical treatment history, 23.0% (155/673) patients did not receive intervention, 72.4% (487/673) received medication, and 4.6% (31/673) received surgical treatment; 55.9% (376/673) had good seizure control and 44.1% (297/673) had poor seizure control. (2) Secondary education ( OR=2.199, 95% CI: 1.037-15.221, P=0.033), primary education or below ( OR=3.544, 95% CI: 2.101-21.343, P=0.012), daily seizures ( OR=4.788, 95% CI: 1.369-33.103, P=0.011), each seizure lasted ≥3 min ( OR=4.179, 95% CI: 3.338-18.550, P=0.003), course of disease≥3 years ( OR=0.199, 95% CI: 0.077-0.602, P=0.001), course of disease for 1-3 years ( OR=0.379, 95% CI: 0.108-0.882, P=0.031), and currently taken antiepileptic drugs for 3 or more ( OR=6.237, 95% CI: 2.195-17.837, P=0.001) were independent risk factors for poor seizure control in epilepsy patients. Conclusion:In Neurosurgery Outpatient, children with diseases before childhood enjoy the largest proportion; drug therapy remains the main treatment; low education level, short seizure cycle, long duration of attack, long course of disease, and multiple drugs used in these patients imply poor anti-epileptic effecacy.

Objective:To determine the contents of inorganic arsenic（iAs），monomethylarsonic acid（MMA） and dimethylarsinic acid（DMA） in brain tissues and blood by using hydride generation-cold trap-atomic absorptionspectrometry（HG-CT-AAS）， and to explore the toxic effects of Realgar on central nervous system of rats. Method:The 96 Wistar rats were randomly divided into 4 groups：normal control group，0.3，0.9 and 2.7 g·kg^-1 Realgar groups. They then received intragastric administration for 14，28 and 42 days respectively， so a total of 12 groups were formed， with 8 animals in each group. The normal group was given the same dose of sodium carboxymethyl cellulose （CMC-Na） by gavage. The contents of iAs，MMA and DMA in blood and brain tissues were determined by HG-CT-AAS. The novel object recognition test was conducted to observe the learning and memory ability of rats. The changes of hippocampal neuron ultrastructure were observed by transmission electron microscopy. Result:There was no difference in the growth，weight and hippocampal coefficient of the experimental animals. The method of HG-CT-AAS showed a good linearity，precision，accuracy and recovery in content determination of arsenic （at various forms） in rat brain and blood. MMA and DMA were detected in the brain of realgar groups at time-dose-effect relationship. iAs，MMA and DMA were detected in the blood of Realgar groups. The nuclear membrane， mitochondria and endoplasmic reticulum in hippocampus neurons of rats were gradually damaged with the increase of Rhubarb exposure dose and time. After 14 days of exposure to Realgar，compared with the normal control group，there was no significant difference in the novel object recognition index among Realgar groups. After 28 days of exposure，only 2.7 g·kg^-1 Realgar group showed statistically significant difference with the control group （P<0.05）. After 42 days of exposure， the novel object recognition index of 0.9 and 2.7 g·kg^-1 Realgar groups was significantly lower than that in normal control group（P<0.05）. Conclusion:The metabolites of Realgar in rats are iAs，MMA and DMA. MMA and DMA can be accumulated in the brain tissue through the blood-brain barrier，causing the decline of the ability of learning and memory and leading to damage of hippocampal neurons.

AIM To investigate the pharmacokinetic behaviors of four constituents in sugar-free Xinnaosu Granules in rat plasma.METHODS Rats intragastrically administered with the 0.5％ CMC-Na suspension of this drug (3 g/kg) had their blood collected for the determination of plasma concentration by UHPLC-MS/MS,after which pharmacokinetic parameters were calculated by DAS2.0 software.RESULTS The plasma concentrationtime curves for tanshinone Ⅱ A,salvianolic acid B,ginsenoside Rg1,notoginsenoside R1 accorded with two compartment model,with the t1/2values of (1.68 ±0.56),(4.13 ±0.87),(3.62 ±0.87),(9.77 ±3.12) h,Tmax values of (0.51 ±0.19),(1 ±0),(6 ±0),(4.00 ±1.09) h,Cmax values of (0.42 ±0.08),(0.17 ±0.02),(0.46±0.11),(0.41 ±0.12) mg/L,respectively.CONCLUSION All the four constituents in sugar-free Xinnaosu Granules demonstrate high bioavailabilities.

Objective To study the pharmacokinetic features of reactive sulfide in rats after oral administration of Cinnabaris. Methods An HPLC coupled with precolumn derivatization method was developed for the pharmacokinetic features study on reactive sulfide in rats after oral administration of Cinnabaris. Results Good linearity (r>0.99) was found for reactive sulfide in plasma in the concentration range of 0.25–15 μmol/L (r>0.99). The LOQ and LOD of the method were 0.1 μmol/L and 0.02 μmol/L, respectively. The intra- and inter-day precision was less than 4.4% and 3.5% respectively, and the accuracy was -9.9%–6.0%. The average recovery rate was 74.9%. 0.6 g/kg Cinnabaris was given the rats for gavage, and the time-course pharmacokinetics parameters were as follows:Cmax(1.33±0.13) μmol/L, tmax(150±34) min, t1/2(323±62) min, AUC0-∞ (5743±297) ng/mL?h. Conclusion A sensitive, robust and accurate precolumn derivatization-HPLC method for the determination of plasma reactive sulfide is developed and validated. The method is successfully applied in the pharmacokinetic features study on reactive sulfide in plasma of rats after administration of Cinnabaris.

This experiment was aimed to screen the absorption enhancer for intranasal administration preparations of paeoniflorin. In this study, HPLC method for determination of paeoniflorin in perfusion liquid was established and the improved model of nasal perfusion in rats was used to screen out the species and amounts of absorption enhancer. In order to avoid the influence of the secretion and absorption of nasal cavity on the volume of perfusion fluid, the residual dose was calculated by using the volume correction method. Linear regression was carried out between the logarithm to the percentage of the residual dose and the corresponding time, and the slope of the regression line was exactly the absorption rate constant. Experimental results showed that hydroxypropyl-β-cyclodextrin and water-soluble azone can significantly improve the nasal absorption of paeoniflorin. Furthermore, water-soluble azone had the highest absorption rate constant and the best promoting penetration effect on intranasal administration preparations of paeoniflorin. It was also found that when the mass concentration of water-soluble azone in the perfusion liquid increased from 5 g•L⁻¹ to 20 g•L⁻¹, the absorption rate constant was gradually increased and peaked at 20 g•L⁻¹. When the mass concentration was increased to 30 g•L⁻¹, the absorption rate constant was decreased, indicating that the best mass concentration of water-soluble azone was 20 g•L⁻¹.

In this experiment, rat nasal mucosa absorption characteristics of prim-O-glucosylcimifugin and 5-O-methylvisammioside were studied to provide a basis for drug delivery of Toutongning nasal spray. The nasal mucosa absorption test in rats was conducted with in situ nasal perfusion method after pH 6 buffer solution was used to prepare high, medium and low concentrations of prim-O-glucosylcimifugin, 5-O-methylvisammioside mixed solution as liquid circulation in nasal cavity. Then the concentrations of the circulating liquid compositions to be measured were determined by HPLC, and the absorption rates of prim-O-glucosylcimifugin and 5-O-methylvisammioside under different pH conditions were also investigated. According to the results, the absorption rate constant was (0.588±0.041)×10⁻³, (0.547±0.023)×10⁻³, (0.592±0.063)×10⁻³ min⁻¹ for prim-O-glucosylcimifugin high, middle and low concentrations, and (0.438±0.041)×10⁻³, (0.407±0.023)×10⁻³, and (0.412±0.063)×10⁻³ min⁻¹ for 5-O-methylvisammioside high, middle and low concentrations. There was no significant difference among high, middle and low concentration groups, and the absorption under pH 6 was better than that under other pH conditions. Therefore, we can get the conclusion that the main active ingredient of Toutongning nasal sprays can be absorbed through the nasal mucosa, and it is feasible to make nasal spray; in addition, pH 6 of nasal spray is scientific and reasonable.