This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

An adsorption and concentration sampling device for volatile organic compounds(VOCs)was designed in this work,which improved the long-term monitoring stability of the online monitoring system for VOC adsorption and concentration,and solved the issue of rapid attenuation of responses toward higher carbon compounds.The designed VOC desorption device achieved an average heating rate of 40 ℃/s,with a relative standard deviation(RSD)of 0.4％.Quantitative analysis of mixture of 116 kinds of different VOC standard gases was performed,and the test results showed that the qualification rate of standard curves increased significantly from 90％to 99％,the proportion of detection limits below 0.1 nmol/mol improved from 85％to 90％,and the proportion of residual levels in the system below 0.1 nmol/mol also increased from 85％to 90％.The stable monitoring period was extended from 20 d to over 30 d,making it more conducive to long-term unattended monitoring by the developed instrument.

Surfactant is a kind of substance that can significantly reduce the surface/interface tension.Surfactant is an important substance that affects the preparation technology,stability and safety of nanoformulation.By combing the structure classification of surfactants and their function mechanism in nanoformulation,combined with the research status at home and abroad,the application and research of surfactants in the listed nanoformulation were described,in order to provide reference for the research and development of new nanoformulation.

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

A rapid analytical method for determination of paraquat and diquat in tea samples was established by improving the QuEChERS pre-treatment method combined with ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry(UPLC-MS/MS).Four kinds of tea powder were extracted by using acetonitrile-0.1％formic acid solution(3∶7,V/V)and ultrasonic treatment,and the supernatant was purified with 400 mg C18 and 400 mg PSA and separated on hydrophilic HILIC(100 mm×2.1 mm,1.8 μm)column by using 0.1％formic acid aqueous solution(Containing 5 mmol/L ammonium formate)and acetonitrile as mobile phases.In the electrospray ion source positive ion mode(ESI+),multiple reaction monitoring scanning technology(MRM)was used for determination,and the matrix-matched standard solution external standard method was used for quantitative analysis.The results showed that paraquat obtained good linear relationship in the content range of 0.18-200 μg/kg and diquat obtained good linear relationship in the content range of 0.36-200 μg/kg,and the correlation coefficients(R2)were 0.9939-0.9976 and 0.9959-0.9987,respectively.The limits of detection(LODs)were 0.06 and 0.12 μg/kg,and the limits of quantitation(LOQs)were 0.18 and 0.36 μg/kg,respectively.The average spiked recoveries for tea samples varied from 84.4％to 128.8％,with the relative standard deviations(RSDs)from 0.6％to 13.5％.The method was simple and efficient,with accurate quantification ability and low detection limit,which could realize efficient determination of paraquat and diquat in tea samples.

Objective To investigate the dosimetric effects of different calculation grid size(CGS)in helical tomotherapy(HT)planning system on stereotactic body radiation therapy(SBRT)for non-small cell lung cancer(NSCLC).Methods Nine NSCLC patients receiving radiation therapy for the first time at some hospital from March 2019 to December 2022 were selected as the subjects.SBRT planning was carried out through the HT system with three different CGS plans(Fine,Normal,and Coarse)and the same pitch,modulation factor(MF)and optimization conditions,and the target area indexes of the three CGS plans were compared including conformity index(CI),homogeneity index(HI),dosimetric parameters of the organ at risk(OAR),point dose verification pass rate,treatment time,number of monitor units and Sinograms.SPSS 22.0 was used for statistical analysis.Results For target area HI,there weres significant differences between CGS Fine plan and Coarse plan and between CGS Normal plan and Coarse plan(P＜0.05),while no statistical differences were found between CGS Fine plan and Normal plan(P＞0.05).For target area CI,there were significant differences between CGS Fine plan and Coarse plan(P＜0.05),while no statistical differences were found between CGS Fine plan and Normal plan and between CGS Normal plan and Coarse plan(P＞0.05).For OAR dosimetric parameters,CGS Fine plan and Coarse plan had significant differences in heart Dmax and Dmean,esophageal Dmax and Dmean,V5,V20,V30 and Dmean of the whole lung and affected lung,V5 and Dmax of the affected lung and heart V10 and V30(P＜0.05),CGS Normal plan and Coarse plan had obvious differences in esophageal Dmax(P＜0.05),and the remained dosimetric parameters were not statistically significant(P＞0.05).Fine,Normal and Coarse plans had the point dose verifica-tion pass rates being 0.96％,1.50％and 1.77％,respectively.In terms of treatment time and number of monitor units,there were significant differences between Fine plan and Coarse plan(P＜0.05)while no statistical differences were found between Fine and Normal plans and between Normal and Coarse plans(P＞0.05).Sinograms analyses showed Fine plan had evenly distributed segment color gradient,Coarse plan had areas of very dark and very light color gradients and Normal plan was somewhere in between.Conclusion Low CGS has to be used as much as possible to obtain accurate dose distribution during SBRT planning for NSCLC patients,which contributes to the execution of the radiation therapy plan and the prevention of ad-verse effects.[Chinese Medical Equipment Journal,2024,45(2):52-57]

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To explore the role of bone marrow mesenchymal stem cells(BMSC),an essential element of the bone marrow microenvironment,in multidrug resistance(MDR)of K562 cells,as well as the reversal effect of tetrandrine(TET)on BMSC-mediated MDR and its potential mechanism.Methods:A mixed co-culture system and a transwell co-culture system for BMSC and K562 cells were established,and the cells were divided into different groups and treated with daunorubicin(DNR)alone or combined with TET and DNR.The CCK-8 assay was used to detect the proliferation of K562 cells in each group,and the cell inhibition rate was calculated.Cytometric bead array(CBA)was used to detect the expression levels of IFN,IL-2,IL-6 and IL-10 in the supernatant of different groups.RT-qPCR and Western blot were used to detected the expression of STAT3 at mRNA and protein levels,respectively.Results:Compared with K562+DNR group,the inhibition rate of DNR on K562 cell proliferation in K562+BMSC+DNR group was significantly decreased(P＜0.05),while the levels of IL-6 in the culture supernatant and phosphorylated STAT3 in K562 cells were significantly increased(P＜0.05).Compared with K562+BMSC+DNR group,the inhibition rate of DNR on K562 cell proliferation in K562+BMSC+DNR+TET group was significantly increased(P＜0.05),while the level of IL-6 and phosphorylated STAT3 was significantly decreased(P＜0.05).Conclusion:BMSC can promote the drug resistance of leukemia cells,and TET may reverse the BMSC-mediated drug resistance via inhibiting IL-6/STAT3 signaling pathway.