A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex(MOC)was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine(TCM).The strategy possessed four characteristics:1)The tailored database consisted of metabolites derived from big data-originated reference compound,metabolites predicted in silico,and MOC chemical profile-based pseudomolecular ions.2)When profiling MOC-derived metabolites in vivo,attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds,as reported by most papers,but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites.3)Metabolite traceability was performed,especially to distinguish isomeric prototypes-derived metabolites,prototypes of MOC compounds as well as phase Ⅰ metabolites derived from other MOC compounds.4)Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification.Using this strategy,134 metabolites were swiftly characterized after the oral administration of MOC to rats,and several metabolites were reported for the first time.Furthermore,17 potential active metabolites were discovered by targeting the motilin,dopamine D2,and the serotonin type 4(5-HT4)receptors,and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model.This study extends the application of mass spectrometry(MS)to rapidly profile TCM-derived metabolites in vivo,which will help pharmacologists rapidly discover potent metabolites from a complex matrix.

Objective To systematically evaluate the effect of hysteroscopic uterine septum resection on the pregnancy live birth rate in patients with septate uterus.Methods The randomized controlled studies and cohort studies on the impact of hysteroscopic uterine septum resection on the pregnancy live birth rate in the patients with septate uterus were retrieved from PubMed,Web of Science,CNCN.cn,and Wanfang databases.The retrieval time was from the establishment of the database to March 2024.The NOS scale was used to con-duct the literature quality evaluation.The Statal0.0 statistical software was used for conducting the meta a-nalysis,and the main evaluation index was the pregnancy live birth rate.Results A total of 9 articles on the treatment of septate uterine were included,involving 821 subjects,including 528 septate uterine patients with hysteroscopic uterine septum resection and 293 septate uterine patients with conservative treatment.The meta analysis showed that the live birth rate in the patients with septate uterine undergoing hysteroscopic uterine septum resection was higher than that in the patients with septate uterine undergoing the conservative treat-ment(I2=38.0％,OR=1.60,95％CI:1.05-2.44,P=0.028).Conclusion Hysteroscopic uterine septum resection could improve the pregnancy outcome and increase the live birth rate.It is a minimally invasive sur-gery with good effect and high safety,which has good clinical application prospects and is worth popularizing.

Objective:To explore the characteristics of T cells and natural killer (NK) cells in cerebrospinal fluid of patients with multiple sclerosis (MS).Methods:Cerebrospinal fluids from patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls attending the Second Hospital of Lanzhou University from January 2023 to October 2024 were collected and analyzed by single-cell RNA sequencing (scRNA-seq) and flow cytometry, and T and NK cell characteristics were summarized and compared in the two groups. The proposed time-series analysis was used to explore the differentiation trajectories of T cells and NK cells.Results:A total of 3 patients with RRMS and 3 healthy controls underwent scRNA-seq, and 6 patients with RRMS and 4 healthy controls underwent flow cytometry. The composition of cerebrospinal fluid T and NK cell subtypes was similar in the RRMS group and the healthy control group, but the proportion of the cell subtypes differed. The RRMS group exhibited significantly higher frequencies of CD4 +Naive T- IL7R [1 529/9 055(16.89%) vs 1 423/9 910(14.36%), χ2=22.980, P<0.001], CD4 +Naive T- CCR7 [1 573/9 055(17.37%) vs 948/9 910(9.57%), χ2=250.114, P<0.001], and CD4 +Naive T- LTB [1 369/9 055(15.12%) vs 1 079/9 910(10.89%), χ2=75.336, P<0.001] subsets compared to controls. Conversely, the control group demonstrated greater proportions of CD4 +Th1- GZMA [1 255/9 910(12.66%) vs 719/9 055(7.94%), χ2=113.213, P<0.001] and CD8 +Tem- GZMK cells [1 607/9 910(16.22%) vs 1 232/9 055(13.61%), χ2=25.326, P<0.001] than the RRMS group. The transcription factors and gene expression of each T cell subtype were also different between the 2 groups, and CD4 initial T cells and CD8 effector T cells were located at the beginning and the end of the differentiation trajectory, respectively. Conclusions:The cerebrospinal fluid of MS patients is characterized by increased expression of genes involved in T cell differentiation and over-activation of immune cells.

ObjectiveTo investigate growth hormone secretagogue receptor （GHSR） rs2922126 gene polymorphisms and their association with genetic susceptibility to nonalcoholic fatty liver disease （NAFLD） in the Chinese Han population in Qingdao， China， and to provide a basis for diagnosis and treatment. MethodsA total of 220 patients who were admitted to Qingdao Municipal Hospital from June 2022 to June 2023 and were diagnosed with NAFLD based on radiological examination were enrolled as NAFLD group， and 167 healthy individuals during the same period of time were enrolled as control group. Fasting blood samples were collected from all subjects， and related biochemical parameters were measured. Whole blood DNA was extracted， and polymerase chain reaction and MALDI-TOF mass spectrometer were used for genotyping. The chi-square test was used for comparison of categorical data between groups， and the independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups. The binary logistic regression analysis was used to investigate the risk of NAFLD. ResultsCompared with the control group， the NAFLD group had significantly higher age， body mass index （BMI）， fasting plasma glucose， triglyceride， gamma-glutamyl transpeptidase， alkaline phosphatase， alanine aminotransferase， and aspartate aminotransferase， as well as a significantly lower level of high-density lipoprotein （all P0.05）. The distribution of GHSR rs2922126 genotypes was consistent with the Hardy-Weinberg equilibrium， suggesting population representativeness in the subjects enrolled （NAFLD group： P=0.106； control group： P=0.849）. There was no significant difference in the distribution of AA， TA， and TT genotypes at GHSR rs2922126 locus between the control group and the NAFLD group （P=0.099）， and there was also no significant difference in allele frequency between the two groups （P=0.063）. In the recessive model of A allele， there was a significant difference in the distribution of AA homozygote and TA+TT genotype between the NAFLD group and the control group （P=0.032）. The binary logistic regression analysis showed that in the recessive model of A allele， AA homozygote carriers had an increased risk of NAFLD compared with TA+TT genotype carriers （odds ratio ［OR］=1.712， 95% confidence interval ［CI］： 1.045 — 2.807， P=0.033）. There was still a significant difference after adjustment for sex， age， and BMI （OR=2.156， 95%CI： 1.221 — 3.808， P=0.008）. In the NAFLD group， AA genotype carriers had a significantly higher serum level of total cholesterol （TC） than TT+TA carriers （Z=-1.99，P=0.046）. ConclusionGHSR rs2922126 AA genotype may be associated with the increased risk of NAFLD in the Chinese Han population in Qingdao， and GHSR rs2922126 AA genotype is associated with the increase in TC in NAFLD patients.

A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex (MOC) was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine (TCM). The strategy possessed four characteristics: 1) The tailored database consisted of metabolites derived from big data-originated reference compound, metabolites predicted in silico, and MOC chemical profile-based pseudomolecular ions. 2) When profiling MOC-derived metabolites in vivo, attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds, as reported by most papers, but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites. 3) Metabolite traceability was performed, especially to distinguish isomeric prototypes-derived metabolites, prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds. 4) Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification. Using this strategy, 134 metabolites were swiftly characterized after the oral administration of MOC to rats, and several metabolites were reported for the first time. Furthermore, 17 potential active metabolites were discovered by targeting the motilin, dopamine D2, and the serotonin type 4 (5-HT₄) receptors, and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model. This study extends the application of mass spectrometry (MS) to rapidly profile TCM-derived metabolites in vivo, which will help pharmacologists rapidly discover potent metabolites from a complex matrix.

OBJECTIVE To explore the epidemiological characteristics of common allergens among children with al-lergic rhinitis(AR)in a children's specialized hospital of Beijing.METHODS A total of 2120 children who met the diagnostic criteria of AR and were treated in otolaryngology department of Beijing Jingdu Children's Hospital from 2021 to 2023 were recruited as the research subjects.The specific immunoglobulin E(sIgE)of allergens was de-tected by western blot quantitative assay.The positive rates of the allergens were statistically analyzed according to the age,sex and years.The epidemiological characteristics and changing trends were observed.RESULTS The pos-itive rate of allergens was 47.78％among the 2120 children,in whom multiple allergies polysensitization were pre-dominant;the positive rate of allergens and polysensitization rate were the highest among the population aged be-tween 1 and 7 years old.The inhalational allergens were dominant,and the positive rate of the Candida group was highest.The positive rates of inhalant allergens and ingested allergens reached the peak at the age of 1-7 and then declined with age;milk and egg white were the two types of predominant ingested allergens in childhood.Among the 2120 children,there were significant differences in the positive rates of allergens between the male and the fe-male,and the positive rates of the male were higher than those of the female(P＜0.001).The positive rates of al-lergens generally showed upward trends during the 3 years,the positive rates of the inhalant allergens such as mugwort,cat hair and dog dandruff ascended by a large margin,and the positive rates of the ingested allergens such as milk,egg white and egg yolk showed remarkable rising trends.CONCLUSIONS The causes of AR are complicated.There are a variety of factors affecting the allergen test.The epidemiological characteristics of the al-lergens among the AR children are observed from multiple perspectives,which may provide references for preven-tion and treatment of the children with AR.

OBJECTIVE To explore the epidemiological characteristics of common allergens among children with al-lergic rhinitis(AR)in a children's specialized hospital of Beijing.METHODS A total of 2120 children who met the diagnostic criteria of AR and were treated in otolaryngology department of Beijing Jingdu Children's Hospital from 2021 to 2023 were recruited as the research subjects.The specific immunoglobulin E(sIgE)of allergens was de-tected by western blot quantitative assay.The positive rates of the allergens were statistically analyzed according to the age,sex and years.The epidemiological characteristics and changing trends were observed.RESULTS The pos-itive rate of allergens was 47.78％among the 2120 children,in whom multiple allergies polysensitization were pre-dominant;the positive rate of allergens and polysensitization rate were the highest among the population aged be-tween 1 and 7 years old.The inhalational allergens were dominant,and the positive rate of the Candida group was highest.The positive rates of inhalant allergens and ingested allergens reached the peak at the age of 1-7 and then declined with age;milk and egg white were the two types of predominant ingested allergens in childhood.Among the 2120 children,there were significant differences in the positive rates of allergens between the male and the fe-male,and the positive rates of the male were higher than those of the female(P＜0.001).The positive rates of al-lergens generally showed upward trends during the 3 years,the positive rates of the inhalant allergens such as mugwort,cat hair and dog dandruff ascended by a large margin,and the positive rates of the ingested allergens such as milk,egg white and egg yolk showed remarkable rising trends.CONCLUSIONS The causes of AR are complicated.There are a variety of factors affecting the allergen test.The epidemiological characteristics of the al-lergens among the AR children are observed from multiple perspectives,which may provide references for preven-tion and treatment of the children with AR.

Objective:To explore the characteristics of T cells and natural killer (NK) cells in cerebrospinal fluid of patients with multiple sclerosis (MS).Methods:Cerebrospinal fluids from patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls attending the Second Hospital of Lanzhou University from January 2023 to October 2024 were collected and analyzed by single-cell RNA sequencing (scRNA-seq) and flow cytometry, and T and NK cell characteristics were summarized and compared in the two groups. The proposed time-series analysis was used to explore the differentiation trajectories of T cells and NK cells.Results:A total of 3 patients with RRMS and 3 healthy controls underwent scRNA-seq, and 6 patients with RRMS and 4 healthy controls underwent flow cytometry. The composition of cerebrospinal fluid T and NK cell subtypes was similar in the RRMS group and the healthy control group, but the proportion of the cell subtypes differed. The RRMS group exhibited significantly higher frequencies of CD4 +Naive T- IL7R [1 529/9 055(16.89%) vs 1 423/9 910(14.36%), χ2=22.980, P<0.001], CD4 +Naive T- CCR7 [1 573/9 055(17.37%) vs 948/9 910(9.57%), χ2=250.114, P<0.001], and CD4 +Naive T- LTB [1 369/9 055(15.12%) vs 1 079/9 910(10.89%), χ2=75.336, P<0.001] subsets compared to controls. Conversely, the control group demonstrated greater proportions of CD4 +Th1- GZMA [1 255/9 910(12.66%) vs 719/9 055(7.94%), χ2=113.213, P<0.001] and CD8 +Tem- GZMK cells [1 607/9 910(16.22%) vs 1 232/9 055(13.61%), χ2=25.326, P<0.001] than the RRMS group. The transcription factors and gene expression of each T cell subtype were also different between the 2 groups, and CD4 initial T cells and CD8 effector T cells were located at the beginning and the end of the differentiation trajectory, respectively. Conclusions:The cerebrospinal fluid of MS patients is characterized by increased expression of genes involved in T cell differentiation and over-activation of immune cells.

Central venous catheterization plays an important role in the rescue of critically patients. Commonly used central veins in clinical practice include subclavian vein, internal jugular vein, and femoral vein. Serious complications after catheterization can endanger patients′ lives in severe cases. It is necessary to improve the understanding and treatment of serious complications of central vein catheterization in clinical work. A case of iliac vein dissection caused by right femoral vein catheterization was summarized in this article, and the catheter was successfully removed under digital subtraction angiography direct vision after the distal end of the catheter penetrated the vascular wall and reached the peritonea, which provided reference for the treatment of iatrogenic injury caused by central vein catheterization.

Objective To assess the feasibility of establishing a nude mouse model of endometriosis fibrosis of human origin and to determine whether endometrial mesenchymal stem cells are involved in inducing endometriosis fibrosis.Methods Four endometrial tissue specimens were collected and transplanted 1∶3 into 12 BABL/c nude mice by subcutaneous injection.The morphology and volume of the lesions were recorded.The nude mice were sacrificed on the 15th day after transplantation to observe the morphology of the lesions and their adhesion to the periphery of the abdominal wall.HE staining was used to judge the result of modelling,Masson staining was used to assess the extent of fibrosis,and immunofluorescence was used to track the role of endometrial mesenchymal stem cells in the fibrotic process of endometriosis.Results The volume of ectopic lesions in nude mice increased over time and showed restricted,vesicular-like changes.The tight adhesion of the lesions to the abdominal wall,endometrioid glands,and collagen fiber deposition were seen microscopically.The success rate of the modelling was 83.4%,and the collagen fiber volume fraction of the lesions was significantly higher after modelling(P＜0.01).Confocal imaging suggested that endometrial mesenchymal stem cells(SUSD2+)differentiated into myofibroblasts(α-SMA+)in vivo.Conclusions The nude mouse model established by human allogeneic transplantation via subcutaneous injection was consistent with the lesion characteristics of endometriosis fibrosis.The modelling method is simple and feasible and provides a better reference model for further investigating the pathogenesis of endometriosis fibrosis.In addition,in vivo observations using the model indicated that endometrial mesenchymal stem cells are involved in inducing the formation of endometriosis fibrosis.