Objective:To develop a nomogram based on the monocyte-to-lymphocyte ratio (MLR) for predicting the risk of aortic-related adverse events within 30 days in patients with acute uncomplicated type B aortic intramural hematoma.Methods:This single-center retrospective cohort study screened consecutive patients with acute uncomplicated type B aortic intramural hematoma treated at the Emergency and Cardiovascular Medicine Departments of the General Hospital of the Northern Theater Command from April 2018 to April 2024. Patients were divided into two groups based on the optimal MLR cut-off value for predicting aortic-related adverse events: low MLR and high MLR group. MLR was defined as the ratio of monocytes to lymphocytes. Aortic-related adverse events were defined as a composite of aortic-related death or aortic intramural hematoma progression (including aortic dissection and penetrating aortic ulcers) within 30 days. The receiver operating characteristic (ROC) curve identified the optimal MLR cut-off value. Multivariate logistic regression was used to identify independent predictors of aortic-related adverse events within 30 days, based on which nomogram models were constructed: the clinical characteristics model and the clinical characteristics-MLR model. The DeLong test was used to evaluate the diagnostic performance of different risk models. The additional predictive value of MLR was assessed using the net reclassification index (NRI) and integrated discrimination improvement (IDI).Results:A total of 332 patients were included, of whom 217 were male (65.4%), with an average age of (64.3±9.4) years. A total of 107 aortic-related adverse events occurred during the 30-day follow-up period. The optimal cut-off value for MLR was 0.529. There were 189 cases in the low MLR group (MLR<0.529) and 143 cases in the high MLR group (MLR≥0.529). The rate of aortic-related adverse events was higher in the high MLR group compared to the low MLR group (44.1% (63/143) vs. 23.3% (44/189), P<0.001), mainly due to a higher rate of progression to aortic dissection (9.8% (14/143) vs. 1.1% (2/189), P<0.001) and penetrating aortic ulcers (31.5% (45/143) vs. 20.6% (39/189), P=0.025). Multivariate analysis identified diabetes ( OR=0.25, 95% CI 0.08-0.78, P=0.017), anemia ( OR=3.45, 95% CI 1.28-9.27, P=0.014), maximum descending aorta diameter ( OR=1.08, 95% CI 1.02-1.15, P=0.007), ulcer-like projections ( OR=4.04, 95% CI 2.26-7.24, P<0.001), and MLR ( OR=6.61, 95% CI 2.50-17.46, P<0.001) as independent predictors of aortic-related adverse events during the 30-day follow-up period. The clinical characteristics model includes diabetes, anemia, ulcer-like projections and maximum diameter of the descending aorta, and the clinical characteristics-MLR model includes the above clinical characteristics and MLR. The results of the DeLong test showed that the clinical characteristic-MLR model demonstrated a higher area under the ROC curve compared to the clinical characteristic model alone (0.784 (95% CI 0.736-0.841) vs. 0.742 (95% CI 0.691-0.788), P=0.031). The continuous NRI was 0.461 (95% CI 0.237-0.685, P<0.001) and the IDI was 0.077 (95% CI 0.043-0.112, P<0.001), indicating that the inclusion of the MLR in the model significantly improved the predictive accuracy. Conclusion:The integration of MLR with other clinical characteristics improves the early identification of high-risk patients with acute uncomplicated type B aortic intramural hematoma, optimizing clinical decisions and improving patient outcomes.

Aim To investigate the clinical characteristics and related factors of post-implantation syndrome(PIS)following the prophylactic application of non-steroidal anti-inflammatory drugs(NSAID)after thoracic endovascular aortic repair(TEVAR).Methods A total of 510 adult patients who had received prophylactic NSAID after TEVAR at General Hospital of Northern Theater Command from September 2013 to April 2024 were consecutively included in the study.The patients were divided into two groups based on the occurrence of PIS postoperatively:the PIS group(34 pa-tients,6.67％)and the non-PIS group(476 patients,93.33％).General information,past medical history and surgical features were compared between the two groups.Univariate and multivariate Logistic regression analysis were used to i-dentify predictors of PIS.The ROC curve was used to assess the overall diagnostic performance of the risk factors.Results The baseline data and clinical characteristics of PIS group and non-PIS group were compared.The rate of gen-der as male,chest and back pain on adimission,limb ischaemia on admission,systolic blood pressure on admission,use of angiotensin converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)drugs during hospitalization,preop-erative white blood cell(WBC)count and surgical approach involving an incision in PIS group were higher than those in non-PIS group,and the age,preoperative estimated glomerular filtration rate(eGFR)level and use of statin drugs during hospitalization were lower than those in non-PIS group,all differences were statistically significant.Postoperative C-reac-tive protein level,incidence of clinical adverse events during postoperative hospitalization,and time of postoperative hospi-talization were increased in PIS group compared with those in non-PIS group.There was no significant difference in the incidence of aortic adverse events between the two groups(P＜0.05).Univariate and multivariate Logistic regression a-nalysis identified patients' age＜60 years(OR=4.671,95％CI:1.348～16.188,P=0.015),increased preoperative WBC count(OR=3.582,95％CI:1.469～8.735,P=0.005),and surgical approach involving an incision(OR=8.339,95％CI:1.849～37.610,P=0.006)as independent predictors for PIS.The results of the ROC curve analysis showed that the area under the curve of patients' age＜60 years,increased preoperative WBC count,femoral arteriotomy ac-cess,and the three combined diagnoses in predicting the occurrence of PIS after TEVAR were 0.653(95％CI:0.573～0.733),0.686(95％CI:0.600～0.771),0.699(95％CI:0.627～0.770),0.826(95％CI:0.765～0.887).Conclusion Despite the prophylactic use of NSAID,some patients develop PIS after TEVAR.Patients' age＜60 years,elevated preoperative WBC count,and femoral artery incision approach are independent risk factors for PIS after preventive medication.Additionally,the incidence of PIS increased with the number of independent risk factors present.

Aim To investigate the clinical characteristics and related factors of post-implantation syndrome(PIS)following the prophylactic application of non-steroidal anti-inflammatory drugs(NSAID)after thoracic endovascular aortic repair(TEVAR).Methods A total of 510 adult patients who had received prophylactic NSAID after TEVAR at General Hospital of Northern Theater Command from September 2013 to April 2024 were consecutively included in the study.The patients were divided into two groups based on the occurrence of PIS postoperatively:the PIS group(34 pa-tients,6.67％)and the non-PIS group(476 patients,93.33％).General information,past medical history and surgical features were compared between the two groups.Univariate and multivariate Logistic regression analysis were used to i-dentify predictors of PIS.The ROC curve was used to assess the overall diagnostic performance of the risk factors.Results The baseline data and clinical characteristics of PIS group and non-PIS group were compared.The rate of gen-der as male,chest and back pain on adimission,limb ischaemia on admission,systolic blood pressure on admission,use of angiotensin converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)drugs during hospitalization,preop-erative white blood cell(WBC)count and surgical approach involving an incision in PIS group were higher than those in non-PIS group,and the age,preoperative estimated glomerular filtration rate(eGFR)level and use of statin drugs during hospitalization were lower than those in non-PIS group,all differences were statistically significant.Postoperative C-reac-tive protein level,incidence of clinical adverse events during postoperative hospitalization,and time of postoperative hospi-talization were increased in PIS group compared with those in non-PIS group.There was no significant difference in the incidence of aortic adverse events between the two groups(P＜0.05).Univariate and multivariate Logistic regression a-nalysis identified patients' age＜60 years(OR=4.671,95％CI:1.348～16.188,P=0.015),increased preoperative WBC count(OR=3.582,95％CI:1.469～8.735,P=0.005),and surgical approach involving an incision(OR=8.339,95％CI:1.849～37.610,P=0.006)as independent predictors for PIS.The results of the ROC curve analysis showed that the area under the curve of patients' age＜60 years,increased preoperative WBC count,femoral arteriotomy ac-cess,and the three combined diagnoses in predicting the occurrence of PIS after TEVAR were 0.653(95％CI:0.573～0.733),0.686(95％CI:0.600～0.771),0.699(95％CI:0.627～0.770),0.826(95％CI:0.765～0.887).Conclusion Despite the prophylactic use of NSAID,some patients develop PIS after TEVAR.Patients' age＜60 years,elevated preoperative WBC count,and femoral artery incision approach are independent risk factors for PIS after preventive medication.Additionally,the incidence of PIS increased with the number of independent risk factors present.

Objective:To develop a nomogram based on the monocyte-to-lymphocyte ratio (MLR) for predicting the risk of aortic-related adverse events within 30 days in patients with acute uncomplicated type B aortic intramural hematoma.Methods:This single-center retrospective cohort study screened consecutive patients with acute uncomplicated type B aortic intramural hematoma treated at the Emergency and Cardiovascular Medicine Departments of the General Hospital of the Northern Theater Command from April 2018 to April 2024. Patients were divided into two groups based on the optimal MLR cut-off value for predicting aortic-related adverse events: low MLR and high MLR group. MLR was defined as the ratio of monocytes to lymphocytes. Aortic-related adverse events were defined as a composite of aortic-related death or aortic intramural hematoma progression (including aortic dissection and penetrating aortic ulcers) within 30 days. The receiver operating characteristic (ROC) curve identified the optimal MLR cut-off value. Multivariate logistic regression was used to identify independent predictors of aortic-related adverse events within 30 days, based on which nomogram models were constructed: the clinical characteristics model and the clinical characteristics-MLR model. The DeLong test was used to evaluate the diagnostic performance of different risk models. The additional predictive value of MLR was assessed using the net reclassification index (NRI) and integrated discrimination improvement (IDI).Results:A total of 332 patients were included, of whom 217 were male (65.4%), with an average age of (64.3±9.4) years. A total of 107 aortic-related adverse events occurred during the 30-day follow-up period. The optimal cut-off value for MLR was 0.529. There were 189 cases in the low MLR group (MLR<0.529) and 143 cases in the high MLR group (MLR≥0.529). The rate of aortic-related adverse events was higher in the high MLR group compared to the low MLR group (44.1% (63/143) vs. 23.3% (44/189), P<0.001), mainly due to a higher rate of progression to aortic dissection (9.8% (14/143) vs. 1.1% (2/189), P<0.001) and penetrating aortic ulcers (31.5% (45/143) vs. 20.6% (39/189), P=0.025). Multivariate analysis identified diabetes ( OR=0.25, 95% CI 0.08-0.78, P=0.017), anemia ( OR=3.45, 95% CI 1.28-9.27, P=0.014), maximum descending aorta diameter ( OR=1.08, 95% CI 1.02-1.15, P=0.007), ulcer-like projections ( OR=4.04, 95% CI 2.26-7.24, P<0.001), and MLR ( OR=6.61, 95% CI 2.50-17.46, P<0.001) as independent predictors of aortic-related adverse events during the 30-day follow-up period. The clinical characteristics model includes diabetes, anemia, ulcer-like projections and maximum diameter of the descending aorta, and the clinical characteristics-MLR model includes the above clinical characteristics and MLR. The results of the DeLong test showed that the clinical characteristic-MLR model demonstrated a higher area under the ROC curve compared to the clinical characteristic model alone (0.784 (95% CI 0.736-0.841) vs. 0.742 (95% CI 0.691-0.788), P=0.031). The continuous NRI was 0.461 (95% CI 0.237-0.685, P<0.001) and the IDI was 0.077 (95% CI 0.043-0.112, P<0.001), indicating that the inclusion of the MLR in the model significantly improved the predictive accuracy. Conclusion:The integration of MLR with other clinical characteristics improves the early identification of high-risk patients with acute uncomplicated type B aortic intramural hematoma, optimizing clinical decisions and improving patient outcomes.

Objective:To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) and/or copy number variation sequencing (CNV-seq) for the prenatal diagnosis for women with advanced maternal ages, and to explore the challenges of prenatal genetic counseling brought by the types of fetal CNVs and uncertainty of related phenotypes.Methods:A retrospective analysis was carried out on 1 841 women with advanced maternal age who underwent interventional prenatal diagnosis at the Prenatal Diagnosis Center of Xiamen University Affiliated Women and Children′s Hospital from January 2017 to December 2020. Routine chromosomal karyotyping analysis and CMA/CNV-seq detection were carried out.Results:CMA/CNV-seq had detected pathogenic variants in 2 cases which had failed karyotyping analysis. Two hundred and twenty one fetal chromosomal abnormalities were detected by karyotyping analysis, among which 187 were detected by CMA/CNV-seq. CMA/CNV-seq analysis of 23 cases with balanced chromosome structural aberrations and 10 cases with low proportion mosaicisms (including a marker chromosome) had yielded a negative result. In addition, 26 cases (26/1 841, 1.4%) with pathogenic CNVs were discovered among those with a normal karyotype, of which 13 (50.0%) were recurrent CNVs associated with neurocognitive impairment, with 22q11.21 microdeletions and microduplications being the most common types (26.92%).Conclusion:The combination of karyotyping analysis and CMA/CNV-seq not only increased the rate of prenatal diagnosis, but also complemented with each other, which has facilitated genetic counseling and formulation of prenatal diagnosis strategy for the affected families.

OBJECTIVE: To investigate the perinatal clinical phenotype and genetic characteristics of two fetuses with ring chromosome 21 mosaicisms. METHODS: Two fetuses who were diagnosed at the Xiamen Maternal and Child Health Care Hospital in November 2021 were selected as the study subjects. Clinical data of the two fetuses were collected. Conventional G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out for the fetuses and their parents. RESULTS: Prenatal ultrasonography of fetus 1 has revealed absence of nasal bone, ventricular septal defect, persistent left superior vena cava, and mild tricuspid regurgitation. Chromosomal karyotyping was 46,X?,dic r(21;21)(p12q22;q22p12)[41]/45,X?,-21[9]. CMA has revealed a 30.00 Mb quadruplication at 21q11.2q22.3 and a 3.00 Mb deletion at 21q22.3. For fetus 2, ultrasonography has revealed pointed echo of the nasal bone. The fetus was found to have a karyotype of 46,X?,r(21)(p12q22)[83]/45,X?,-21[14]/46,X?,dic r(21;21)(p12q22;q22p12)[3]. CMA has revealed a 5.10 Mb quadruplication at 21q22.12q22.3 and a 2.30 Mb deletion at 21q22.3. CONCLUSION The perinatal phenotype of the two fetuses with ring chromosome 21 mosaicisms is related to the duplication of chromosomal segments near the breakpoints of the chromosomal deletions. The combined chromosomal karyotyping and CMA has enabled prenatal diagnosis and genetic counseling for these families.
Pregnancy ; Female ; Humans ; Mosaicism ; Ring Chromosomes ; Vena Cava, Superior ; Chromosome Aberrations ; Prenatal Diagnosis ; Microarray Analysis ; Fetus/diagnostic imaging*

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts are still under-represented in genome-wide genetic studies. Here, we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combined with single-cell sequencing data from the developing human brain, we found that the expression of genes with de novo mutations was specifically enriched in the pre-, post-central gyrus (PRC, PC) and banks of the superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and healthy controls, we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls, suggesting the potential structural deficits associated with ASD. Finally, we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas, the insula, as well as the frontal lobes in ASD patients. This work indicated that combinatorial analysis with genome-wide screening, single-cell sequencing, and brain imaging data reveal the brain regions contributing to the etiology of ASD.
Humans ; Autism Spectrum Disorder/metabolism* ; Autistic Disorder ; Exome Sequencing ; DNA Copy Number Variations ; East Asian People ; Brain/metabolism* ; Mutation/genetics* ; Genetic Predisposition to Disease/genetics*

Genetic composition plays critical roles in the pathogenesis of autism spectrum disorder (ASD). Especially, inherited and de novo intronic variants are often seen in patients with ASD. However, the biological significance of intronic variants is difficult to address. Here, among a Chinese ASD cohort, we identified a recurrent inherited intronic variant in the CHD7 gene, which is specifically enriched in East Asian populations. CHD7 has been implicated in numerous developmental disorders including CHARGE syndrome and ASD. To investigate whether the ASD-associated CHD7 intronic variant affects neural development, we established human embryonic stem cells carrying this variant using CRISPR/Cas9 methods and found that the level of CHD7 mRNA significantly decreased compared to control. Upon differentiation towards the forebrain neuronal lineage, we found that neural cells carrying the CHD7 intronic variant exhibited developmental delay and maturity defects. Importantly, we found that TBR1, a gene also implicated in ASD, was significantly increased in neurons carrying the CHD7 intronic variant, suggesting the intrinsic relevance among ASD genes. Furthermore, the morphological defects found in neurons carrying CHD7 intronic mutations were rescued by knocking down TBR1, indicating that TBR1 may be responsible for the defects in CHD7-related disorders. Finally, the CHD7 intronic variant generated three abnormal forms of transcripts through alternative splicing, which all exhibited loss-of-function in functional assays. Our study provides crucial evidence supporting the notion that the intronic variant of CHD7 is potentially an autism susceptibility site, shedding new light on identifying the functions of intronic variants in genetic studies of autism.

Objective:To explore the application of weighted adjustments of dropout rates in sensitivity analysis of medically repeated measurements data and the implementation with SAS 9.4 software.Methods:By compiling SAS codes, mixed-effects models for repeated measures were used to conduct the covariance analysis of multivariable repeated measurements data. Meanwhile, the overall dropout rate and the dropout rates of each group were used to make weighted adjustments by applying pattern-mixture models, which was considered to be a sensitivity analysis to validate the stability of results.Results:The dropout rates of placebo group, low-dose and high-dose groups were 8.77%, 11.79% and 16.15%, respectively, the differences were significant ( P=0.025). The results of mixed-effects models for repeated measures showed the differences of curative effect indicators changes from baselines of between high-dose, low-dose groups and placebo group were significant ( P=0.008 and P=0.002). The results of pattern-mixture models considering weighted adjustments of the respective groups' dropout rates were consistent with those of mixed-effects models for repeated measures. Conclusions:The pattern-mixture models considering weighted adjustments of dropout rates can be used in the sensitivity analysis of repeated measurements data. The SAS codes can provide a practical basis for the popularization and application of weighted adjustments of dropout rates in the sensitivity analysis of repeated measurements data.

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.