Objective: To systematically evaluate the influencing factors for repeated implantation failure (RIF) after in vitro fertilization-embryo transfer (IVF-ET) in China, so as to provide the evidence for prevention of RIF. Methods: Literature on influencing factors for RIF in China were retrieved from CNKI, Wanfang Data, VIP, China Medical Literature Service System, PubMed, Web of Science, Cochrane Library and Embase from inception to September, 2024. A meta-analysis was performed using RevMan 5.3 and Stata 14.0 softwares. Literature were excluded one by one for sensitivity analysis. Publication bias was evaluated using Egger's test. Results: Initially 4 836 relevant articles were retrieved, and 12 of them were finally included, with a total sample size of 11 554 individuals. There were 10 case-control studies, 1 cohort study, and 1 cross-sectional study; and 10 high-quality studies and 2 medium-quality studies. The meta-analysis showed that factors including advanced age (OR=1.121, 95%CI: 1.035-1.215), prolonged infertility duration (OR=1.237, 95%CI: 1.091-1.403), abnormal hysteroscopy findings (OR=2.205, 95%CI: 1.119-4.348), positive anti-nuclear antibody (ANA) (OR=2.393, 95%CI: 1.473-3.886), and positive anti-beta2 glycoprotein Ⅰ antibody (β2-GPⅠ-Ab) (OR=2.824, 95%CI: 1.987-4.013) were associated with an increased risk of RIF; while factors including the large number of embryos transferred (OR=0.309, 95%CI: 0.098-0.973), thicker endometrium (OR=0.601, 95%CI: 0.556-0.650), and higher granulocyte colony-stimulating factor (G-CSF) levels (OR=0.657, 95%CI: 0.511-0.845) were associated with a reduced risk of RIF. Conclusion IVF-ET RIF is associated with age, infertility duration, number of embryos transferred, endometrial thickness, hysteroscopy findings, G-CSF levels, ANA and β2-GPⅠ-Ab.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

International registration of herbal drugs is a necessary prerequisite for the internationalization of Chinese materia medica. North America and European Union occupy an important position in the world herbal drugs market, and their drug administration and quality supervision requirements are relatively complete and progressiveness. By summarizing the definition of herbal drugs in North America and European Union, combing and interpreting the relevant laws, regulations and policy documents, this article constructed the registration path of herbal drugs, and discussed the current status of market registration of herbal drugs in North America and European Union based on the examples of successful marketing of herbal drugs under current application and approval in overseas markets. This article believed that in the future, an internationally matched TCM quality standard evidence system should be built, clinical trials of TCM products in line with international standards should be carried out, standards that are the same or higher than international mainstream GMP should be developed, the registration path of TCM compounds should be explored, and professionals to establish an international registration application team should be recruited to provide theoretical and practical support for China's overseas registration of Chinese TCM products, promote TCM products to enter the world mainstream market, and achieve high-quality development of TCM internationalization.

Objective To investigate the effect of eosinophil(EOS)/neutrophil(NER)in peripheral blood on asthma recurrence in children with bronchial asthma(BA)after treatment.Methods A prospective cohort study was conducted in the study.BA children admitted to the hospital from February 2020 to February 2022 were selected as the research objects.All children were treated regularly and their condition was under con-trol.After a follow-up of 6 months,the recurrence of the children was recorded.EOS/NER,interleukin(IL)-4 and IL-5 of children with and without relapse before treatment and at 1 week of treatment were compared.Lo-gistic regression analysis model was established to test the effect of EOS/NER on the recurrence of asthma in children with BA after treatment.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of EOS/NER,IL-4 and IL-5 before treatment for the recurrence risk of BA children after treatment.Results A total of 128 children with BA were included.25 cases recurred after 6 months of follow-up,with a recurrence rate of 19.53%.EOS/NER,IL-4 and IL-5 of BA children after 1 week of treatment were lower than those before treatment(P<0.05).EOS/NER,IL-4 and IL-5 of recurrent children before treat-ment and 1 week after treatment were higher than those of non-recurrent children(P<0.05).There were no statistically significant differences in EOS/NER,IL-4,IL-5 levels between children of different genders,age groups,and treatment regimens before and after 1 week of treatment(P>0.05).Increased EOS/NER,in-creased level of IL-4 and increased level of IL-5 had effect on the recurrence of BA children after treatment and may be risk factors for recurrence(OR>1,P<0.05).The ROC curve showed that area under the curve of EOS/NER before treatment for predicting the recurrence was 0.810(95%CI:0.724-0.896,P<0.001)in BA patients after 6 months of treatment,with moderate predictive value.Conclusion EOS/NER before treat-ment in BA children may be an independent risk factor for recurrence after treatment,and has moderate pre-dictive value for recurrence risk.

Objective:To study the relationship between the absorptive capacity of inpatients with infectious diseases and the structure of diseases in 65 secondary and tertiary general hospitals in Beijing,and to objectively analyze the current situation of space utilization of inpatients with infectious diseases,so as to provide data support for the formulation of relevant policies.Methods:The variability of spatial absorption capacity indicators for secondary and tertiary general hospitals in 6 urban districts and 10 suburbs were compared separately,and the correlation between the spatial absorption capacity of secondary and tertiary general hospitals and the structure of disease types was visualized and analyzed using quadrant bubble charts.Results:In terms of spatial absorption capacity,there was a statistically significant difference in the proportion of patients from suburban districts treated in the secondary and tertiary general hospitals in 6 urban districts of the Beijing(P=0.003),while there was no statistically significant difference in the proportion of patients from other districts treated in the secondary and tertiary general hospitals in 10 suburbs(P=0.336).The spatial absorption capacity and disease structure of the secondary and tertiary hospitals in 6 urban districts and the tertiary hospitals in 10 suburbs showed significant correlation,while the secondary hospitals in 10 suburbs showed no significant correlation.Conclusion:The tertiary general hospitals in 6 urban districts have superior infectious disease type structure indicators,with significantly stronger spatial absorption capacity and stronger correlation between these two,which plays the function of inpatient service of difficult and severe infectious diseases.Only the district hospitals in the outer suburbs can provide inpatient services for infectious diseases,and the number of cases admitted is large,which meets the needs of inpatient diagnosis and treatment of common infectious diseases in the district.It is necessary to strengthen the investment of infectious disease medical resources and capacity building in 10 suburban districts according to the actual situation.

Objective:The service capacity of infectious diseases department in Beijing secondary and tertiary general hospitals was quantitatively analyzed to provide objective data support for the construction of infectious diseases department.Methods:The scope of infectious diseases was defined by the DRG tool,and the service capacity of medical institutions was described by the Case Mix Index(CMI)and number of DRG groups.The differences in the service capacity of infectious diseases in 67 secondary and tertiary general hospitals in Beijing from 2016 to 2020 were analyzed by data visualization and generalized linear equation,and the disease structure of different hospitals at different levels was compared by selecting representative hospitals.Results:From 2016 to 2020,the mean CMI of tertiary hospitals ranged from 0.94 to 0.97,while that of secondary hospitals ranged from 0.70 to 0.72.From 2016 to 2019,the average number of DRG groups in tertiary hospitals ranged from 26.75 to 27.79,and the average number of DRG groups in secondary hospitals ranged from 15.32 to 15.77,and the average number of DRG groups in secondary and tertiary hospitals showed a significant decline in 2020.CMI and number of DRG groups had statistical significant difference at hospital level(P＜0.001),and number of DRG groups had statistical difference in time dimension(P＜0.001).Conclusion:The infectious disease service capacity of tertiary general hospitals is obviously stronger than that of secondary general hospitals,and the infectious disease medical service capacity of large tertiary hospitals is obviously ahead,while the overall service level of secondary hospitals is low.We should give full play to the advantages of top three hospitals to build a high ground for infectious disease department construction,and combine the spatial distribution of medical resources and demand characteristics to improve the infectious disease service capacity of secondary hospitals.

Objective To explore the expression and clinical significance of lysine oxidase (Lox) in primary lesion of esophageal carcinoma (ESCA) and bone metastasis lesion based on bioinformatics. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to screen for differentially expressed genes between ESCA and normal esophageal tissues. Follow-up information of patients with surgery for esophageal cancer in the Fourth Hospital of Hebei Medical University from January 2016 to December 2020 were screened, and the clinical materials of patients diagnosed as bone metastasis during the follow-up period were collected. Western blot was used to verify the expression of Lox in ESCA and normal esophageal tissues; immunohistochemical staining was used to detect the expression of Lox in human ESCA tissue and normal tissue; the impact of Lox expression on survival was explored by Kaplan-Meier curve and Cox regression. Results Through the analysis of ESCA data in GEPIA and TCGA databases, it was found that the expression of Lox in ESCA lesions was significantly higher than that in normal tissues (P<0.05); the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses found that Lox may be involved in the information conduction of various signaling pathways; the Western blot result showed that the expression of Lox in cancer tissue was higher than that in adjacent normal tissue (P<0.05); the analysis of follow-up data found that patients with high expression of Lox were more likely to have multiple bone metastases; survival analysis revealed that patients with high Lox expression had significantly shorter bone metastasis free survival and overall survival compared to patients with low Lox expression (P<0.05); Cox regression found that Lox was an independent risk factor for prognosis of patients with esophageal cancer bone metastasis. Conclusion Lox is highly expressed in ESCA and significantly related to clinical prognosis, which can be used as an effective target for the diagnosis and treatment of ESCA.

Objective To analyze the differences in the expression of specific antibodies targeting different human immunodeficiency virus (HIV) antigens among patients at different clinical stages in Qiandongnan Prefecture of Guizhou Province, and to explore their association with the clinical staging of acquired immunodeficiency syndrome. Methods A total of 307 HIV-positive blood samples from Qiandongnan of Guizhou Province were selected for specific HIV antibody immunoblotting assays. CD3+CD4+T cell counts andHIV viral load nucleic acid testing were performed on the blood samples. Multivariate regression analysis was conducted on relevant indicators during HIV infection and AIDS stages. Results Among the 307 HIV-infected individuals, 218 were male and 89 were female, with a mean age of (48.53±16.03) years. The composition ratios of specific antibodies gp160, gp120, gp41, p66, p51, p31, p55, p24 and p17 were 98.7%, 90.9%, 92.2%, 74.3%, 66.4%, 86.6%, 3.9%, 97.4% and 73.9%, respectively. Multivariate binary Logistic regression model analysis showed that expression of p24-specific antibodies were more likely to be judged as influencing factors in the infection stage (OR=0.158, 95%CI, 0.032 to 0.768, P < 0.05). There was a certain correlation between p24-specific antibodies and the clinical staging of HIV infection (OR=0.217, 95%CI, 0.005 to 0.944, P < 0.05). Using the ratio of CD3⁺ CD4⁺ T cell count to viral load when p24 was specifically expressed as the test variable, and the clinical stage as the state variable (AIDS stage=1, infection stage=2), a receiver operating characteristic (ROC) curve was plotted. The area under the curve was 0.653 (95%CI, 0.529 to 0.774, P < 0.05). Conclusion Differential expression of p24-specific antibodies may indicate that patients are in the infection stage and could potentially serve as an early warning indicator of immune function for HIV-infected individuals.

Objective: To analyze the prevalence and related factors of pediatric flexible flatfoot (PFF) among 7-8 year old children in Changzhou, so as to provide a feasible basis for the prevention and treatment of PFF. Methods: From December 2023 to February 2024, a total of 1 685 children aged 7-8 from 10 primary schools in Changzhou were selected by stratified cluster random sampling method, and screened for PFF by using a foot optical assessment recording device. Information including sex, body mass index (BMI), diet, exercise and shoe wearing habits were collected. The valgus angle of the hindfoot was measured on the body surface by using an orthopedic measuring ruler in the standing position. Pain levels were evaluated by using visual analogue score (VAS) for children with flatfoot syndrome. Multivariate Logistic analysis was used to analyze related factors of PFF. Results: The overall detection rate of PFF was 27.4%, and there was a significant difference in the detection rate of PFF between boys and girls, with 30.3% and 24.1% respectively ( χ 2=7.96, P < 0.01 ). Most cases of PFF were mild flatfoot (60.8%) and bilateral ( 60.4% ). Approximately 13.2% of children with PFF had flatfoot syndrome, with a mean VAS of (2.86±0.73). About 56.1% of children with PFF had a normal valgus angle of the hindfoot. Sex, high BMI and preference for shoe last with front upturned shoe shape were positively correlated with the detection of PFF ( OR= 1.74, 1.54, 1.13, P <0.05). After stratified by sex, regular exercise in boys and age in girls were negatively correlated with the detection of PFF ( OR=0.40, 0.64, P <0.05). Conclusions The detection rate of PFF in 7-8 year old children is high. Additionally, PFF combined with flatfoot syndrome or valgus hindfoot is relatively rare and is likely to be underestimated, which emphasizes the importance of early detection and intervention for PFF.

Objective:To construct T cell receptor β (TCRβ) repertoires in children with SARS-CoV-2 infection, and analyze the differences in TCRβ repertoires between children with SARS-CoV-2 infection and healthy children.Methods:Whole blood samples from 5 children infected with SARS-CoV-2 Delta variant and from 5 healthy children were collected. After RNA quality inspection and repertoires construction, high-throughput sequencing was conducted to analyze the differences in clonal expansion and diversity indices of the TCR repertoires between children infected with SARS-CoV-2 and healthy children. The frequency of use of TCRβ VJ genes was statistically analyzed using unpaired T-tests.Results:We successfully constructed the TCRβ repertoires of children infected with SARS-CoV-2 using high-throughput sequencing technology. The diversity index of the TCR repertoire in children infected with SARS-CoV-2 (9.78±1.23) was significantly lower compared to that in healthy children (13.40±2.12) ( P<0.05), and the TCR clonal expansion index in children infected with SARS-CoV-2 (0.18±0.07) was significantly higher compared to that in healthy children (0.06±0.06) ( P<0.05). A preliminary comparison of the frequency of use of TCRβ repertoire VJ genes found that, in children infected with the SARS-CoV-2, the most common V and J genes were TRBV28 and TRBJ2-1, respectively. Conclusions:The construction of the TCRβ repertoires in children infected with SARS-CoV-2 using high-throughput sequencing technology has revealed characteristic features of the TCRβ repertoires in these children. This is of significant reference value for unveiling the characteristics of the T-cell repertoires in children infected with SARS-CoV-2 and for the rapid construction of TCRβ immunological repertoires in other viral infections.