OBJECTIVE:To prepare nicotine ethosome and study its transdermal permeability in vitro. METHODS:Injection method was adopted to prepare nicotine ethosome. Single-factor test was conducted to study the effects of the amounts of ethanol and phospholipid on the particle size and encapsulation efficiency of the ethosome. Franz diffusion cell was employed to conduct permeability test on excised rat skin to compare cumulative permeating quantities of the nicotine in nicotine ethosome,nicotine lipo-some and nicotine ethanol solution. Confocal laser scanning electron microscope was applied to observe the penetration depths of rhodamine B-containing nicotine ethosome,nicotine liposome and the solution of nicotine ethanol solution in the in vitro rat skin. RESULTS:When the formulation contained 3%(m/V)phospholipid and 35%(V/V)ethanol,the obtained nicotine ethosome had the smallest particle size [(105 ± 11.5) nm] and the highest encapsulation efficiency [(89.13 ± 6.12)%]. Compared with nicotine ethosome and the nicotine ethanol solution,nicotine ethosome had the largest cumulative permeating quantity in vitro at 12 h. Fur-thermore,the above-mentioned 3 preparations all became saturated in permeability at 12 h with the penetration depths of 80 μm, 156 μm and 175 μm,respectively. CONCLUSIONS:The nicotine ethosome that can increase the transdermal permeability of nico-tine has been prepared successfully.

The purpose of this article is to identify the characteristics and research progress of resting-state EEG microstates in patients with schizophrenia， in order to provide references for clinical research of schizophrenia from the perspective of neuroelectrophysiology. In September 2022， literature was retrieved from CNKI， Wanfang Data Knowledge Service Platform and PubMed database， and 27 studies meeting the requirements were finally included. Previous studies have demonstrated that patients with schizophrenia show increased presence of microstate class C and decreased presence of microstate class D in resting-state recordings， and the two commonly EEG microstate classes have been suggested as a potential endophenotype for schizophrenia. Although the correlation between psychiatric symptoms and resting-state EEG microstate abnormalities in patients with schizophrenia remains unclear， the altered resting-state EEG microstates in patients before and after treatment have undoubtedly validated its clinical significance.

ObjectiveTo determine the contents of four kinds of indole alkaloids （rhynchophylline， isorhynchophylline， corynoxeine， isocorynoxeine） in Uncaria by high-performance liquid chromatography-mass spectrometry-automatic internal standard （HPLC-MS-AIS）. MethodsChromatographic separation was performed using C₁₈ column （3.0 mm×50 mm， 3.3 μm）， and the mobile phase， comprising 0.1% formic acid aqueous solution-acetonitrile （82∶18， V/V）， was eluted at a flow rate of 0.5 mL/min and column temperature of 30℃. Mass spectrometric detection was performed using an electrospray ionization source and positive multiple-reaction monitoring mode at a voltage capillary of 4 000 V. The mass-to-charge ratio （m/z） transition was 385.25/160.10 for rhynchophylline， 385.30/160.10 for isorhynchophylline， 383.25/160.15 for corynoxeine and 383.25/160.15 for isocorynoxeine， respectively. The injection volume was kept constant at 2 μL. ResultsThe linear concentration ranges of rhynchophylline， isorhynchophylline， corynoxeine and isocorynoxeine were 2.30~600.00 ng/mL （r=0.999 3）， 2.30~600.00 ng/mL （r=0.999 2）， 2.47~650.00 ng/mL （r=0.999 4） and 2.47~650.00 ng/mL （r=0.999 2）， respectively. The relative standard deviation （RSD） of precision and stability were all lower than 5.00%， the accuracy ranged from 92.40% to 104.10%， and the average recovery was 95.90%~104.60%. ConclusionHPLC-MS-AIS method is simple and accurate for the determination of four kinds of alkaloids in Uncaria， and can be used as a new method for quality control of Uncaria.

ObjectiveTo study a therapeutic reference range and laboratory alert level of amisulpride in the clinical treatment of schizophrenia. MethodsPatients who met the diagnostic criteria for schizophrenia in the International Classification of Diseases， tenth edition （ICD-10） were enrolled， and all patients received amisulpride treatment. Data including age， gender， duration of treatment， single daily dose， clinical diagnosis， amisulpride concentration， the scores of the Scale for the Assessment of Positive Symptoms （SAPS）， Scale for the Assessment of Negative Symptoms （SANS） and Positive and Negative Syndrome Scale （PANSS）， the adverse reaction rate and multitherapy were collected. The concentration of amisulpride was compared within different efficacy groups and different dosage groups， meantime， the incidence rate of adverse reactions was compared within different amisulpride concentration groups， and between monotherapy and multitherapy groups. Thereafter， the therapeutic reference range and laboratory alert level of amisulpride in the clinical treatment of schizophrenia were explored via estimating the negative and positive predictive values. ResultsThe amisulpride concentration yielded no statistical difference within different dosage groups and different efficacy groups （F=0.745， 1.343， P>0.05）. The single daily dose among patients in different efficacy groups demonstrated no significant difference （F=0.902， P>0.05）. The correlation between amisulpride treatment efficacy and its concentration denoted no statistical significance （r=0.023， P=0.744）. The clinical efficacy and adverse reaction rate showed no significant difference between monotherapy group and multitherapy group （F=2.198， 0.095， P>0.05）. The concentration of amisulpride was not linearly correlated with the adverse reaction rates ［y=100x/（78.13+x）， r=0.960］. When amisulpride concentrations ranged from 100 to 600 ng/mL， the mean reduction rate was equal to or above 42%， the effective detection rate of the reference cut-off value was equal to or above 1.485， and the incidence of adverse reactions was equal to or below 85%. When amisulpride concentrations ranged from 1400 to 1800 ng/mL， there was a decreasing trend in reduction rate （all<42%） and an increasing trend in adverse reaction rate （all>85%） as the concentration of amisulpride increased. ConclusionA reference range of 100~600 ng/mL and an alert level of 1400 ng/mL are recommended for the clinical safety of amisulpride.

ObjectiveTo develop a two-dimensional high-performance liquid chromatography （2D-HPLC） for simultaneous determination of the contents of four kinds of Uncaria alkaloids： rhynchophylline， isorhynchophylline， corynoxeine and isocorynoxeine. MethodsThe 2D-HPLC apparatus was comprised of a first chromatographic column in version Aston SC2 （3.5 mm×25 mm， 5 μm）， an intermediate column in version Aston SH C₁₈ （3.5 mm×10 mm， 5 μm）， and an analytical column in version Aston SCB （4.6 mm×125 mm， 5 μm）. The mobile phase of the first and second liquid chromatography system were CAA-1 and mixed mobile phase （V _{BPI-1 basic mobile phase} ∶ V _{MPI-1 mobile phase} ∶ V _{OPI-1 organic mobile phase} = 45∶14∶41）. The chromatographic parameters included a flow rate of 1.0 mL/min， a column temperature of 40℃， a wavelength of 254 nm， an injection volume of 500 μL and a detection time of 9.5 min. ResultsThe linear ranges of rhynchophylline， isorhynchophylline， corynoxeine and isocorynoxeine were 9.77~10 000.00 ng/mL （r=0.999 6）， 10.74~11 000.00 ng/mL （r=0.999 7）， 10.74~11 000.00 ng/mL （r=0.999 7）， 10.74~11 000.00 ng/mL（r=0.999 6）， respectively. The relative standard deviation （RSD） of precision， stability and repeatability were all less than 5.00%. The accuracy was 95.20%~104.01%， and the recovery rate was 93.63%~101.38%. ConclusionThe 2D-HPLC developed for simultaneous determination of four kinds of alkaloids in Uncaria is simple and accurate， which can be used as a new method for quality control of Uncaria.

ObjectiveTo resolve the problems related to the abnormal interpretations of real-time fluorescence polymerase chain reaction （PCR） results for tri-allele， to formulate the interpretation methods of real-time fluorescence PCR by referring to multiplex PCR fragment analysis， so as to obtain an accurate， simple and cheap detection method for ABCB1 tri-allele. MethodsA total of 2 794 DNA samples were collected from Xi'an Mental Health Center from March 2020 to March 2021， and 5% of which were selected as experiments. Real-time fluorescence PCR method and multiplex PCR fragment analysis method were performed respectively. According to the comparison of Ct values of PCR curves and the comparison of base peak intensity in multiplex PCR fragment analysis， comparison and analysis were conducted on the interpretation results of the two methods， and samples with different interpretation results were verified， thereafter， PCR interpretation method was formulated. ResultsA total of 139 samples were collected， of which 120 alleles and 19 tri-allele were detected. The results of allele detection by two methods were absolutely consistent. In combination with the results of multiplex PCR fragment analysis， a method for the interpretation of real-time fluorescence PCR for 19 cases of tri-allele was developed as follows： when ∣∣Ct._G－Ct._T∣－∣Ct._G－Ct._A∣∣ in amplification curve was less than 3， the interpretation results were the combination of the base pairs with small Ct values； when ∣∣Ct._G－Ct._T∣－∣Ct._G－Ct._A∣∣ was greater than or equal to 3， the interpretation results were homozygotes from the base pairs with minimum Ct values. According to the interpretation method， the results of real-time fluorescence PCR were revised， and it showed 1 case of G/G， 1 case of A/A， 4 cases of T/G， 5 cases of T/A and 8 cases of T/T， which were consistent with the results of multiplex PCR fragment analysis. ConclusionReferring to the multiplex PCR fragment analysis method， the interpretation of ABCB1 tri-allele by real-time fluorescence PCR is developed， and the two interpretation methods are in good agreement.