To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents.

A derivatizaton method combined with gas chromatography-mass spectrometry(GC-MS)was established for detection of isobutyl chloroformate(IBCF)residue in active pharmaceutical ingredient of agatroban.The extraction and derivatization reagents,derivatization time,qualitative and quantitative ions were selected and optimized,respectively.The possible mechanism of derivatization and characteristic fragment ions fragmentation were speculated.The agatroban samples were dissolved and extracted by methanol,and the residual IBCF was derived with methanol to generate methyl isobutyl carbonate(MIBCB).After 24 h static derivatization at room temperature,IBCF was completely transformed into MIBCB,which could be used to indirectly detect IBCF accurately.The results showed that the linearity of this method was good in the range of 25-500 ng/mL(R2=0.9999).The limit of detection(LOD,S/N=3)was 0.75 μg/g,and the limit of quantification(LOQ,S/N=10)was 2.50 μg/g.Good recoveries(95.2%-97.8%)and relative standard deviations(RSDs)less than 3.1%(n=6)were obtained from agatroban samples at three spiked levels of IBCF(2.50,25.00,50.00 μg/g),which showed good accuracy of this method.Good precision of detection results was obtained by different laboratory technicians at different times,the mean value of spiked sample solution(25.00 μg/g)was 24.28 μg/g,and the RSD was 2.1%(n=12).The durability was good,minor changes of detection conditions had little effect on the results.Under the original condition and conditions with initial column temperature±5℃,heating rate±2℃/min,column flow rate±0.1 mL/min,the IBCF content of spiked sample solution(25.00 μg/g)was detected,the mean value of detection results was 24.16 μg/g,and the RSD was 2.2%(n=7).Eight batches of agatroban samples from two manufacturers were detected using the established method,and the results showed that no IBCF residue was detected in any of these samples.The agatroban samples could be dissolved by methanol,and then the IBCF residue could be simultaneously extracted and derived with methanol as well.This detection method had the advantages of simple operation,high sensitivity,low matrix effect and accurate quantification,which provided a new effective method for detection of IBCF residue in agatroban.

Objective To explore the prevention and treatment of vasovagal reflex during and after operation in diseases of urinary system.Methods From February 2020 to April 2023,1436 patients who completed inpatient surgery in Department of Urology,Songshan Hospital,Qingdao University Medical College were selected to analyze the emergency management measures of vasovagal reflex during and after operation and summarize the diagnosis and treatment experience.Results Among 1436 patients,vasovagal reflex occurred in 4 cases during operation and 14 cases after operation,with an incidence of 1.25%.Most patients showed simultaneous decrease in blood pressure and heart rate.After intravenous injection of atropine and dopamine,blood pressure and heart rate returned to normal,and various concomitant symptoms disappeared,and no death cases were reported.Conclusion Urological specialists should pay attention to vasovagal reflex,sum up experience,do early identification,timely treatment to ensure the safety of patients.

Objective To analyze the competition status and spatial autocorrelation of Beijing medical market from 2015 to 2019.Methods The Herfindahl-Hirschman Index(HHI)was used to calculate the degree of market competi-tion in 16 districts of Beijing,and the Moran index was used to calculate the spatial autocorrelation of market compe-tition.Results Except for the number of discharged patients,the average HHI of the number of health technicians,the number of beds and the total number of medical visits in 16 medical markets in Beijing from 2015 to 2019 showed a downward trend between 0.2 and 0.4,and the spatial global Moran index of the HHI index was all less than 0,showing a spatial negative correlation with the degree of competition in the medical market.Conclusion The medical market competition in Beijing is strengthened,the competition gap between urban and rural areas is large,and the competition in adjacent markets is mutually exclusive.It is suggested to strengthen the differentiated develop-ment of hospitals,strengthen the balanced layout between regions,and promote the low-competitive market with cross-regional medical association,forming a positive spillover effect.

Objective To investigate the effect of Mex3c gene knockout on embryonic neural tube development and its possible mechanisms.Methods The NCBI database was used to analyze the expression of Mex3c gene in various tissues of mice.Fluorescence in situ hybridization(FISH)was employed to detect the expression of Mex3c in neural tubes of Mex3c+/+mice at different developmental stages(E12.5 d,E14.5 d).Sexual mature mice were mated at a ratio of Mex3c+/-male to female(1:1)in the same cage.Embryos were collected and genotyped using PCR.They were divided into 3 groups based on their genotype:wild-type group(Mex3c+/+,WT group),homozygous knockout group(Mex3c-/-,KO group),and heterozygous knockout group(Mex3c+/-).HE staining was employed to observe the development of neural tubes in the 3 groups of embryos.Immunofluorescence staining and Western blotting were performed to detect the proliferation and apoptosis of embryonic neural stem cells in the WT and KO groups.Transmission electron microscopy was used to observe the ultrastructure of the neural tubes and mitochondria in the WT and KO groups.RNA was extracted from the neural tubes of WT and KO groups for RNA-seq sequencing.The R.3.6.3 software was used to perform KEGG signaling pathway enrichment analysis on differentially expressed genes.RT-qPCR was used to validate the sequencing results.Results The NCBI database analysis and FISH detection results showed that the Mex3c gene was mainly expressed in the central nervous system of embryos.HE staining results showed that there was no significant difference in the development of embryonic neural tubes between KO group,WT group,and heterozygous knockout group at E12.5 d and E13.5 d.However,at E14.5 d,the embryonic neural tube development in KO group was delayed and the phenotype was significantly abnormal compared with those in WT group.Therefore,the embryonic neural tube tissues of KO group and WT group at E14.5 d were selected for subsequent experiments.The immunofluorescence staining results showed that the PCNA positive cell rate in KO group was significantly lower than that in WT group(P<0.001).The Western blotting results showed that the Bax/Bcl-2 ratio in KO group was higher than that in WT group(P<0.01).Transmission electron microscopy observation showed that compared with WT group,the synaptic gap in KO group disappeared,the mitochondrial of the embryonic neural tube in KO group were swollen,the mitochondrial cristae were disrupted,and the structure was significantly abnormal.The results of RNA-seq analysis showed that a total of 377 differentially expressed genes were obtained,including 101 up-regulated genes and 276 down-regulated genes.KEGG signaling pathway enrichment analysis revealed that the main signaling pathways of differentially expressed genes were enriched in the neuroactive ligand receptor interaction signaling pathways.The RT-qPCR validation results showed that the mRNA expression levels of Avpr1a,Drd1,Htr7,Sstr1,Oxtr and Gabra5 in this signaling pathway were down-regulated(P<0.05 or P<0.01),which was consistent with the RNA-seq results.Conclusion Mex3c plays an important role in the development of neural tubes in mouse embryos,which may participate in regulating the proliferation and apoptosis of neural stem cells through neural active ligand receptor interaction signaling pathways,thereby affecting the development of neural tubes.

Objective To investigate the effect of exosomal miR-146a-5p expression on gray matter volume in patients with major depressive disorder(MDD).Methods A total of 113 MDD patients(MDD group)and 107 healthy controls(HC)(HC group)were selected.Peripheral blood was collected and exosomes were isolated to quantify miR-146a-5p expression.Brain high-resolution T1 WI images of MDD and HC were obtained via MR,and gray matter volume was computed via SPM12 software.The interaction effect of"Depression×miR-146a-5p expression"on gray matter volume was analyzed using SPM's Flexible factorial design,and the between-group difference was assessed by extracting the mean value,thus to analyze whether MDD-related gray matter volume abnormalities were dependent on miR-146a-5p expression.Results Exosomal miR-146a-5p expression was significantly elevated in MDD group compared to HC group.Voxel-based factorial analysis revealed a relationship between high miR-146a-5p expression in MDD group and reduced gray matter volume in the anterior and posterior cingulate cortices(independent voxel threshold P＜0.001,AlphaSim corrected),and a significantly reduced gray matter volume as compared with HC group was detected in the two regions.Conclusion The exosomal miR-146a-5p is overexpressed in patients with MDD and may be associated with specific cortical atrophy in patients with MDD.

Albendazole sulfoxide and ivermectin compound pouring agent were prepared with dime-thyl sulfoxide and 1,2-propanediol as solvents.The central composite design response surface method was used to optimize the formula of pouring agent.Franz diffusion cell method was used to investigate the transdermal performance of pouring agent in vitro.The permeation amounts of the two drugs were determined by HPLC.The best formula of pouring agent was ivermectin 0.5％,al-bendazole sulfoxide 5％,dimethyl sulfoxide 52％,propylene glycol 39％,and the rest was 100％anhydrous ethanol.The cumulative permeation amounts of ivermectin and albendazole sulfoxide were up to 20.78 μg/cm2 and 249.02 μg/cm2,respectively.The in vitro release model of the two drugs accords with the first-order kinetic equation.There is a good linear relationship between al-bendazole sulfoxide and ivermectin in the range of 1-100 mg/L and the peak area.The precision and stability RSD of the two methods are less than 2％.The preparation process of albendazole sul-foxide compound pouring agent is simple,stable and easy to pour.The established HPLC method is simple and accurate,and can be used for the determination of albendazole sulfoxide and ivermectin in pouring agent.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

Type B insulin resistance syndrome(TBIR)is a rare autoimmune disease caused by the presence of autoantibodies against insulin receptors in the human body,leading to severe refractory hyperglycemia or refractory hypoglycemia.This article reports a case of TBIR patient,summarizes and analyzes its epidemiological characteristics and diagnosis and treatment methods,providing a basis for clinical treatment.

The digital economy promotes economic growth and changes in employment patterns,but it also exposes platform workers to the risk of losing their basic medical insurance rights and interests.Based on the theory of inclusive governance,this paper constructs a three-dimensional analysis framework of opportunity-process-result for the participation mechanism,analyzes the international experiences of basic medical insurance participation mechanism for platform workers,and puts forward suggestions for optimizing the basic medical insurance participation mechanism in light of China's actual situation.The finding shows that the value orientation of realizing the universal health of medical insurance,the inclusive and coordinated participation mechanism,and the fair treatment of sharing and unification are the main strategies to deal with the issue of medical insurance participation of platform workers in the international arena.Therefore,it is recommended to firstly,expand and improve the basic medical insurance system covering the whole population with the concept of the supremacy of the right to health;secondly,promote the synergistic development among the stakeholders to enhance the systemic resilience of the basic medical insurance;and lastly,strengthen the function of mutual assistance and mutual aid of the basic medical insurance to promote the common prosperity effect of the basic medical insurance.