Objective To investigate the genetic risk factors of deep vein thrombosis(DVT)after trauma.Methods In a nested case-control study,50 patients with DVT after traumatic lower extremity fractures and 50 patients without DVT were recruited.The two groups were matched with gender,age and fracture sites.Preoperative venography was performed to diagnose DVT in trauma patients.Genome wide association study(GWAS)was used to investigate the genetic risk factors for preoperative DVT after traumatic lower ex-tremity fractures.Genomic DNA in leukocytes from blood sample was extracted and used for GWAS.Results GWAS was conducted based on 2 662 single nucleotide variants(SNV)which were dispersed in 144 interested genes.Ten genes were found to have signifi-cant association with trauma-related DVT,including cofactors of hemostasis mechanism,i.e.,THBD,F5,SERPIND1 and ITGA2,the factors related to vitamin K-dependent(VKD)carboxylation,i.e.,GGCX and CALU,and the members of cytochrome P450 family,i.e.,CYP1A1,CYP3A4,CYP2C19 and CYP2B6.Conclusion DVT after trauma might be regulated by the cofactors of hemostasis mechanism,the factors related to VKD carboxylation and the members of cytochrome P450 family.The results of our study may provide reference and inspiration for genetic susceptibility of preoperative DVT after trauma.

Objective:To investigate the iodine nutrition status of key population in Fuzhou City, and to provide scientific basis for adjusting intervention strategies.Methods:From March to October 2021, a survey was conducted on iodine nutrition status of key population in 12 counties (cities, districts) of Fuzhou City. Each county (city, district) was divided into 5 sampling areas according to the east, west, south, north and middle directions. One township (street) was selected from each area, and 40 non-boarding children aged 8 - 10 (age balanced, half male and half female) from one primary school and 20 pregnant women (early, middle and late pregnancy balanced) were selected as survey subjects. Household salt samples and random urine samples were collected, and the salt iodine and urine iodine levels were tested by direct titration and arsenic and cerium catalytic spectrophotometry, respectively. Children's thyroid volume was measured by B-ultrasonography. At the same time, in cooperation with Fuzhou Maternal and Child Health Hospital, the thyroid stimulating hormone (TSH) testing results of heel blood of full-term natural delivery newborns in Fuzhou City in 2021 were collected.Results:A total of 2 400 children were monitored for salt iodine, urine iodine and goiter. The median salt iodine was 24.40 mg/kg, with an iodine salt coverage rate of 93.04% (2 233/2 400), a qualified rate of iodized salt of 97.40% (2 175/2 233), and a consumption rate of qualified iodized salt of 90.62% (2 175/2 400). The median urine iodine was 181.47 μg/L. The rate of goiter was 1.04% (25/2 400). A total of 1 200 pregnant women were monitored for salt iodine and urine iodine. The median salt iodine was 24.10 mg/kg, the coverage rate of iodized salt was 91.08% (1 093/1 200), the qualified rate of iodized salt was 97.90% (1 070/1 093), and the consumption rate of qualified iodized salt was 89.17% (1 070/1 200). The median urine iodine was 128.10 μg/L. The median TSH level in the heel blood of 14 242 newborns was 3.38 mU/L, and the proportion of TSH level > 5 mU/L was 30.96% (4 410/14 242).Conclusions:In 2021, children in Fuzhou City are at an appropriate level of iodine, but pregnant women are insufficient of iodine. We should continue to maintain comprehensive prevention and control measures mainly based on salt iodization, provide health education for pregnant women, and strengthen monitoring of TSH level in newborns.

Objective:To analyze the epidemiological characteristics of norovirus (NoV) acute gastroenteritis (AGE) outbreaks caused by GII.17[P17] variant in China, 2022.Methods:Information and specimens of AGE outbreaks between January and December 2022 were collected. NoV RNA was detected in all specimens by real-time RT-PCR. The viral genome of the positive specimens were amplified, sequenced and analyzed.Results:Between January and December 2022, 360 AGE outbreaks were reported cumulatively, of which 266 outbreaks successfully obtained genotype results. GII.17 [P17] was one of the main genotypes and detected in 34 outbreaks (12.78%, 34/266), with the highest number of outbreaks detected in spring (6 outbreaks in March and 7 outbreaks in May), mainly in childcare facilities and primary schools (61.76%, 21/34). According to the result of NoV genotype analysis in different age groups, 14 strains of GII.17 [P17] in this study belonged to Cluster III b and SC III branch of Cluster III (Kawasaki308) in the capsid region and polymerase region, respectively, and both belonged to the same cluster as the variant strain (GZ41621 strain) that caused the NoV AGE outbreaks in China during the 2014/15 season. Compared to reference strains of Cluster I, Cluster II and Cluster III a, Cluster III b was provided with 22 amino acid mutations in VP1. The main amino acid changes in the subgroup of Cluster III b including the virus strains isolated in this study were at T294I and Q299R of antigen epitope A, an insertion mutation occurred at antigen epitope D, H353Q at the site I of the human histo-blood group antigen receptor binding site. The selection pressure analysis detected a large number of negative selection sites, indicating that negative selection plays an important role in the evolution of VP1 genes.Conclusions:GII.17 [P17] was one of the primary genotypes responsible for NoV diarrhea outbreaks in China in 2022. Phylogenetic analysis had revealed that it still belonged to the same cluster as the novel GII.17 [P17] variant (strain GZ41621) that caused NoV epidemics in China during the 2014/15 season, exhibiting minor amino acid variations at the potential epitope.

Objective:To investigate the influence of maternal autoimmune diseases and anticoagulants, including low-molecular-weight heparin (LMWH) and aspirin, on the fetal fraction of maternal plasma cell-free DNA of non-invasive prenatal testing (NIPT).Methods:A prospective cohort study was conducted on women with singleton pregnancies receiving NIPT in the Nanjing Drum Tower Hospital from March 2021 to July 2022. NIPT was carried out using a polymerase chain reaction (PCR)-free amplification platform. In this study, four types of maternal autoimmune diseases, which were antiphospholipid syndrome, undifferentiated connective tissue disease, Sj?gren's syndrome, and systemic lupus erythematosus (SLE), and two anticoagulants, LMWH and aspirin, were studied. Univariate and multivariate linear regression models were used to analyze the factors influencing fetal fraction of maternal plasma cell-free DNA.Results:A total of 4 102 singleton pregnant women were enrolled in the prospective cohort, and 3 948 were finally included after excluding the cases with unclear dosing time of LMWH or aspirin, other autoimmune diseases, conceiving through ovulation induction alone, and having true positive or failed NIPT result. There were 96 cases with antiphospholipid syndrome, 35 with undifferentiated connective tissue disease, 34 with Sj?gren's syndrome, and 18 with SLE. A total of 108 patients only received LMWH treatment, 121 only received aspirin treatment, and 113 received both LMWH and aspirin treatment. Univariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.423), conceived by assisted reproductive technology ( B=－0.803), male fetus ( B=－0.458), undifferentiated connective tissue disease ( B=1.774), and SLE ( B=3.467) had influence on the fetal fraction (all P<0.05). Multivariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.415), conceived by assisted reproductive technology ( B=－0.585), male fetus ( B=－0.322), SLE ( B=3.347) and undifferentiated connective tissue disease ( B=1.336) were factors influencing fetal fraction (all P<0.05). Conclusions:Maternal use of LMWH or aspirin does not affect fetal fraction when performing NIPT on a PCR-free amplification platform, but undifferentiated connective tissue disease and SLE are the influencing factors. Therefore, pregnant women should be informed before the NIPT that the fetal fraction of maternal plasma cell-free DNA may be affected by maternal autoimmune diseases.

Objective:To investigate the perioperative adverse events and complications of flow-diverter devices in the treatment of unruptured intracranial aneurysms.Methods:This is a retrospective case series study. The clinical and imaging data of 174 patients with unruptured intracranial aneurysms treated with flow-diverter devices in the Department of Neurointervention, Department of Neurology, the First Medical Center of Chinese People′s Liberation Army General Hospital from January 2020 to January 2024 were retrospectively analyzed. There were 63 males and 111 females, with an age of (53.9±11.4) years (range:23 to 76 years).The occurrence, development and outcome of perioperative complications and related adverse events during treatment were collected and analyzed. The degree of aneurysm embolization was evaluated using the O′Kelly-Marotta (OKM) grading system,with OKM grade C and D as successful occlusion.Results:A total of 187 flow-diverter devices (from 7 different brands) were implanted in 174 patients (with 294 aneurysms). Of these, 151 cases involved standalone stent embolization, 26 cases involved stent embolization combined with coil assistance, and 5 cases involved the use of two flow-diverter devices simultaneously. Twenty-nine cases (16.7%,29/174) suffered intraoperative adverse events, including 10 cases of poor stents deployment, 3 cases of stents migration into the aneurysm sac, 1 cases of abnormal guidewire movement, 4 cases of ischemic events. Complications occurred in 10 patients (5.7%, 10/174), and neurological deficits occurred in 5 patients (2.9%, 5/174). A total of 129 patients completed follow-up for more than 12 months after surgery. There were 117 aneurysms with OKM grade D and 22 with OKM grade C, showing a satisfactory healing rate of 77.7% (139/179).Conclusion:The effect of flow-diverter devices in the treatment of intracranial aneurysms is satisfactory, but complications and adverse events cannot be ignored, especially the relatively high incidence of perioperative adverse events, which requires neurointerventional physicians to be vigilant.

Objective:To construct and validate a risk prediction model for major complications 30 days after surgery in the elderly patients with hip fracture.Methods:A retrospective study was conducted to analyze the clinical data of 276 elderly patients with hip fracture who had been admitted to Department of Trauma and Orthopaedics, The Hospital Affiliated to Chengde Medical University from June 2019 to December 2021. There were 96 males and 180 females with an age of (74.5±9.3) years, and 139 femoral neck fractures and 137 intertrochanteric fractures. The outcome of this study was whether major complications occurred within 30 days after surgery. Multiple logistic regression analysis identified the risk factors for major complications in the elderly patients with hip fracture within 30 days after surgery. The forward step-by-step method and likelihood ratio test were used to screen the best prediction model. A nomogram was constructed to display the model. The stability and effectiveness of the model were evaluated by the receiver operating characteristic curve (ROC), Hosmer-Lemeshow goodness-of-fit test, clinical decision curve and clinical impact curve analysis.Results:Logistic regression analysis showed that decreased preoperative hemoglobin ( P< 0.05), time from admission to surgery >72 hours ( OR=3.001, 95% CI: 1.564 to 5.758, P<0.001), control of nutritional status (CONUT) score >4 points ( OR=3.394, 95% CI: 1.724 to 6.680, P<0.001), and age-adjusted modified frailty index (aamFI) >2 points ( OR=2.875, 95% CI: 1.548 to 5.339, P= 0.001), increased operation time ( OR=1.016, 95% CI: 1.006 to 1.025, P=0.001), and surgical bleeding >60 mL ( OR=2.373, 95% CI: 1.016 to 5.540, P=0.046) were independent risk factors for major complications within 30 days after surgery in the elderly patients with hip fracture. The area under the ROC curve in the logistic risk prediction model was 0.846 (95% CI: 0.799 to 0.889), and the results of Hosmer-Lemeshow goodness-of-fit test showed ( χ2=8.080, P=0.426). The clinical decision curve and clinical impact curve showed that the prediction model was accurate and effective. Conclusion:Based on the patients' preoperative hemoglobin, time from admission to surgery, control of nutritional status score, age-adjusted modified frailty index, operation time and surgical blood loss, this study has constructed successfully a risk prediction model for complications 30 days after surgery in the elderly patients with hip fracture which enables medical staff to predict the occurrence of major postoperative complications.

Aim To explore the correlation between carotid atherosclerosis(CAS)and neutrophil/lymphocyte ratio(NLR)in patients with early morning hypertension,and to construct a line chart model to predict the risk of CAS in patients with hypertension in the morning.Methods 255 patients with early morning hypertension hospitalized in the Affiliated Hospital of Chengde Medical College from October 2019 to November 2022 were collected,and their basic data,blood routine and blood biochemical indexes were collected.All selected patients need to improve 24-hour ambulatory blood pressure monitoring and carotid artery color ultrasound detection.According to the presence or absence of CAS,all selected patients were divided into morning hypertension with CAS group(n=197)and morning hypertension without CAS group(n=58).Multivariate Logistic regression analysis was used to explore the risk factors of early morning hypertension with CAS,and to construct and verify an individual line chart model to predict the risk of early morning hypertension pa-tients with CAS.Results The age,NLR,neutrophils(NE),monocytes(MO),white blood cell(WBC),total cho-lesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDLC)increased in the early morning hyperten-sion with CAS group compared with those in the morning hypertension group without CAS,while the HDLC decreased(P＜0.05).The results of multivariate Logistic regression analysis showed that the age,NLR and TC were higher in the early morning hypertension with CAS group than those in the early morning hypertension without CAS group,while HDLC was lower;Age,NLR and TC were independent risk factors of early morning hypertension with CAS,while HDLC was inde-pendent protective factors of morning hypertension with CAS.Based on the results of multivariate Logistic regression anal-ysis,an individualized line chart model for predicting early morning hypertension with CAS was constructed.The area un-der the ROC curve of the line chart model was 0.853(95％CI:0.802-0.904,P＜0.01).The result of Hosmer Leme-show fit test was x2=1.665(P＞0.05).Conclusions There was a positive correlation between NLR and morning hy-pertension with CAS,and NLR was an independent risk factor for morning hypertension with CAS.The individualized line chart model based on age,NLR,TC and HDLC can effectively predict the risk of hypertension with CAS in the early morn-ing,which provides a theoretical basis for early detection and prevention of atherosclerosis.

Background::Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.Methods::We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models.Results::In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5) and rural areas (123.0/10 5) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5), the western region had a slightly lower mortality (123.5/10 5), and the eastern region had the lowest mortality (97.3/10 5). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. Conclusion::The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.

Objective:To investigate the perioperative adverse events and complications of flow-diverter devices in the treatment of unruptured intracranial aneurysms.Methods:This is a retrospective case series study. The clinical and imaging data of 174 patients with unruptured intracranial aneurysms treated with flow-diverter devices in the Department of Neurointervention, Department of Neurology, the First Medical Center of Chinese People′s Liberation Army General Hospital from January 2020 to January 2024 were retrospectively analyzed. There were 63 males and 111 females, with an age of (53.9±11.4) years (range:23 to 76 years).The occurrence, development and outcome of perioperative complications and related adverse events during treatment were collected and analyzed. The degree of aneurysm embolization was evaluated using the O′Kelly-Marotta (OKM) grading system,with OKM grade C and D as successful occlusion.Results:A total of 187 flow-diverter devices (from 7 different brands) were implanted in 174 patients (with 294 aneurysms). Of these, 151 cases involved standalone stent embolization, 26 cases involved stent embolization combined with coil assistance, and 5 cases involved the use of two flow-diverter devices simultaneously. Twenty-nine cases (16.7%,29/174) suffered intraoperative adverse events, including 10 cases of poor stents deployment, 3 cases of stents migration into the aneurysm sac, 1 cases of abnormal guidewire movement, 4 cases of ischemic events. Complications occurred in 10 patients (5.7%, 10/174), and neurological deficits occurred in 5 patients (2.9%, 5/174). A total of 129 patients completed follow-up for more than 12 months after surgery. There were 117 aneurysms with OKM grade D and 22 with OKM grade C, showing a satisfactory healing rate of 77.7% (139/179).Conclusion:The effect of flow-diverter devices in the treatment of intracranial aneurysms is satisfactory, but complications and adverse events cannot be ignored, especially the relatively high incidence of perioperative adverse events, which requires neurointerventional physicians to be vigilant.

OBJECTIVE: To explore the genetic characteristics of a Chinese pedigree affected with van der Woude syndrome (VWS). METHODS: A proband who had visited the Drum Tower Hospital Affiliated to Nanjing University Medical School in May 2020 for "two previous pregnancies with cleft lip and palate" was selected as the study subject. Trio-whole exome sequencing (trio-WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of her pedigree members (8 individuals from four generations) and bioinformatic analysis. Chromosomal microarray analysis (CMA) was used to rule out copy number variations in the fetuses. RESULTS: Trio-WES revealed that the proband and her father had both harbored a heterozygous c.742G>T (p.G248C) missense variant of the IRF6 gene, for which her mother was of the wild type. The variant was located in a region with important functions and has not been reported previously. Prediction with several software suggested that it is likely to have a significant impact on the protein structure/function and is highly correlated with the specific phenotypes in this pedigree. Sanger sequencing confirmed co-segregation of the genotypes and phenotypes in the pedigree. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was rated as likely pathogenic (PM1+PM2_Supporting+PP1+PP3+PP4). Based on the above results, pre-implantation genetic diagnosis was carried out for the proband, which has led to birth of a healthy offspring with normal results for both site testing and CMA. CONCLUSION The IRF6: c.742G>T (p.G248C) heterozygous variant probably underlay the VWS in this pedigree. Above finding has also enabled reproductive guidance for the proband.
Humans ; Female ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Pedigree ; DNA Copy Number Variations ; East Asian People ; Interferon Regulatory Factors/genetics* ; Mutation