1.Evaluation of brain glymphatic system function in patients with bipolar disorder based on diffusion tensor imaging along the perivascular space
Liqian CUI ; Huixing ZENG ; Yixin CHEN ; Yizhi ZHANG ; Jinbiao LI ; Wenhao DENG ; Liping CAO
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(5):400-405
Objective:To investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space(DTI-ALPS)in bipolar disorder Ⅰ(BD-Ⅰ).Methods:A total of 44 BD-Ⅰ patients(BD-Ⅰ group) admitted to the Affiliated Brain Hospital of Guangzhou Medical University from January 2012 to December 2017 were selected.In addition, totally 30 healthy controls (HC group) were recruited. The diffusion tensor image data were analyzed retrospectively, and along the perivascular space (ALPS) index was calculated. Hamilton anxiety scale (HAMA), 17-item Hamilton depression rating scale (HAMD-17), Young mania rating scale (YMRS) and global assessment function (GAF) were used to evaluate the severity of anxiety, depression, mania and social function respectively. SPSS 25.0 software was used for t-test, Z-test and chi-square test, and the differences in clinical data and DTI-ALPS index between the two groups were compared. The partial correlation test was used to analyze the correlations between DTI-ALPS index and the clinical indicators such as HAMA, HAMD-17, YMRS and GAF. Results:The DTI-ALPS indexes in left(1.69±0.17), right(1.44±0.15) and bilateral cerebral hemispheres(1.56±0.15) of BD-Ⅰ group were lower than those in HC group ((1.71±0.15), (1.46±0.13) and (1.58±0.12)), but the differences were not statistically significant ( t=-0.441, -0.545, -0.556, all P>0.05). After controlling for gender, age, years of education and course of disease, there were significant negative correlations between bilateral average DTI-ALPS index and somatic anxiety ( r=-0.334, P=0.038), as well as between right DTI-ALPS index and somatic anxiety( r=-0.349, P=0.030) in BD-Ⅰ group. Conclusion:The dysfunction of cerebral glymphatic system is not obvious in BD-Ⅰ patients, but their anxiety may be related to dysfunction cerebral glymphatic system.
2.Qualitative study on the experiences of undergraduate nursing interns using nursing information systems
Danni HE ; Yanfei CHEN ; Shihua CAO ; Xiaohong ZHU ; Wenhao QI ; Xiaomin CHEN ; Lihua QIAN
Chinese Journal of Modern Nursing 2024;30(16):2131-2136
Objective:To deeply understand the inner experiences of undergraduate nursing interns using Nursing Information Systems (NIS) and provide references for formulating relevant intervention strategies.Methods:A descriptive phenomenological approach was adopted for this qualitative study. Purposeful sampling was used to select undergraduate nursing interns from four comprehensive hospitals in Hangzhou during February to May 2023 for semi-structured interviews. The interview data were analyzed using Colaizzi's seven-step method to extract themes.Results:Four themes were identified in this study: insufficient preparedness of undergraduate nursing interns in using NIS, low engagement of undergraduate nursing interns in using NIS, perceived benefits of using NIS by undergraduate nursing interns, and adaptation strategies of undergraduate nursing interns using NIS.Conclusions:There are issues such as insufficient preparedness and low engagement among undergraduate nursing interns in using NIS. Some respondents experience emotions such as anxiety, fatigue, and decreased enthusiasm. It is recommended that colleges and internship hospitals pay attention to the clinical work demands and the learning needs of nursing interns, thus providing education and support for the use of NIS.
3.Mid- and long-term results of surgical treatment of brachiocephalic Takayasu arteritis
Jintao SHAN ; Zhaohui HUA ; Peng XU ; Hui CAO ; Zhouyang JIAO ; Likun SUN ; Shirui LIU ; Lei XIA ; Wenhao XUE ; Zhen LI
Chinese Journal of Surgery 2024;62(3):229-234
Objective:To examine the mid - and long-term outcomes of surgical treatment of brachiocephalic Takayasu arteritis.Methods:This is a retrospective case series study. The clinical data of 39 patients,which had been diagnosed as brachiocephalic Takayasu arteritis (244 cases),who underwent surgical treatment,were analyzed between July 2012 to November 2022 at Department of Endoluminal Vascular Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 34 females, aged (37.9±14.0)years (range:13 to 71 years). Despite medical treatment, the patients suffered severe ischemic symptoms continually and then underwent surgical interventions. Among them, 20 patients underwent endovascular procedures, 11 underwent open surgical procedures, and 8 underwent hybrid procedures. Patients were followed up through outpatient visits at 1, 3, 6 months after surgery and once every year later. Follow-up was conducted until November 2022. Operation status, postoperative complications and re-intervention of patients were recorded and the Kaplan-Meier survival curves were used to analyze postoperative vascular patency rates.Results:All 39 surgeries were successful, with no intraoperative death or serious complications. The follow-up period was (48.8±38.2) months(range:1 to 123 months). Thirty-three patients experienced symptom relief after surgery, and 6 patients required secondary surgical interventions. The patency rates for the endovascular treatment group at 1-, 3-, 5-, and 10-year were 95.0%, 75.2%, 60.2%, and 60.2%, respectively, while the patency rates for open surgery were all 90.9%. In the hybrid surgery group, the patency rates at 1-, 3-, 5-, and 8-year were all 87.5%.Conclusion:For patients with brachiocephalic Takayasu arteritis, choice of an appropriate blood flow revascularization intervention should be based on the patient′s condition,and the mid-and long-term outcomes are satisfactory.
4.Outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network
Siyuan JIANG ; Chuanzhong YANG ; Xiuying TIAN ; Dongmei CHEN ; Zuming YANG ; Jingyun SHI ; Falin XU ; Yan MO ; Xinyue GU ; K. Shoo LEE ; Wenhao ZHOU ; Yun CAO
Chinese Journal of Pediatrics 2024;62(1):22-28
Objective:To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021.Methods:This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results:Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions:With the increasing number of extremely preterm infants at 22-25 weeks′ gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.
5.Mid- and long-term results of surgical treatment of brachiocephalic Takayasu arteritis
Jintao SHAN ; Zhaohui HUA ; Peng XU ; Hui CAO ; Zhouyang JIAO ; Likun SUN ; Shirui LIU ; Lei XIA ; Wenhao XUE ; Zhen LI
Chinese Journal of Surgery 2024;62(3):229-234
Objective:To examine the mid - and long-term outcomes of surgical treatment of brachiocephalic Takayasu arteritis.Methods:This is a retrospective case series study. The clinical data of 39 patients,which had been diagnosed as brachiocephalic Takayasu arteritis (244 cases),who underwent surgical treatment,were analyzed between July 2012 to November 2022 at Department of Endoluminal Vascular Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 34 females, aged (37.9±14.0)years (range:13 to 71 years). Despite medical treatment, the patients suffered severe ischemic symptoms continually and then underwent surgical interventions. Among them, 20 patients underwent endovascular procedures, 11 underwent open surgical procedures, and 8 underwent hybrid procedures. Patients were followed up through outpatient visits at 1, 3, 6 months after surgery and once every year later. Follow-up was conducted until November 2022. Operation status, postoperative complications and re-intervention of patients were recorded and the Kaplan-Meier survival curves were used to analyze postoperative vascular patency rates.Results:All 39 surgeries were successful, with no intraoperative death or serious complications. The follow-up period was (48.8±38.2) months(range:1 to 123 months). Thirty-three patients experienced symptom relief after surgery, and 6 patients required secondary surgical interventions. The patency rates for the endovascular treatment group at 1-, 3-, 5-, and 10-year were 95.0%, 75.2%, 60.2%, and 60.2%, respectively, while the patency rates for open surgery were all 90.9%. In the hybrid surgery group, the patency rates at 1-, 3-, 5-, and 8-year were all 87.5%.Conclusion:For patients with brachiocephalic Takayasu arteritis, choice of an appropriate blood flow revascularization intervention should be based on the patient′s condition,and the mid-and long-term outcomes are satisfactory.
6.CACNA1C rs58619945 genotype influences the cortical thickness of attention network among patients with Bipolar Ⅰ disorder
Xiaofei ZHANG ; Xiaoyu LIANG ; Xiaofang CHENG ; Jianshan CHEN ; Wenhao DENG ; Yizhi ZHANG ; Liqian CUI ; Xiongchao CHENG ; Xuan LI ; Chanjuan YANG ; Biyu YE ; Liping CAO
Chinese Journal of Medical Genetics 2024;41(9):1045-1052
Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.
7.Mechanism of LINC01410 promoting proliferation and migration in esophageal squamous cell carcinoma
Fei CAO ; Wenhao YU ; Xiaonan TANG ; Zidong MA ; Tingmin CHANG ; Yabin GONG ; Mingjuan LIAO ; Xiaohong KANG
China Oncology 2024;34(8):753-762
Background and purpose:Long non-coding RNA(lncRNA)LINC01410,with a length of 647 bp,participates in a variety of tumor biological processes.However,the role and mechanism of LINC01410 involved in esophageal squamous cell carcinoma(ESCC)remain unclear.This study aimed to explore the potential mechanism of LINC01410 promoting ESCC proliferation and invasion,to provide a potential prognostic indicator and therapeutic target for individuals with ESCC.Methods:Gene Expression Profiling Interactive Analysis 2(GEPIA2)databases were used to analyze the expression of LINC01410 and overall survival in esophageal squamous cell carcinoma data set in the Cancer Genome Atlas(TCGA).Gene Set Enrichment Analysis(GSEA)was performed to identify the underlying signaling pathways involved in the biological effects of LINC01410 in ESCC.A total of 62 pairs of ESCC tissues and paracancerous tissues from ESCC patients who underwent radical surgery in the Department of Thoracic Surgery at the First Affiliated Hospital of Xinxiang Medical College and the First People's Hospital of Pingdingshan City from January 2020 to December 2021 were collected.This project has been approved by the Hospital Ethics Committee(First Affiliated Hospital of Xinxiang Medical College,No.2018036;First People's Hospital of Pingdingshan City,No.2019-018).The expression of LINC01410 in ESCC tissues was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).We transfected EC109 cells with LV-NC or LV-over/LINC01410 and EC9706 cells with shRNA-NC or shRNA-LINC01410.Stable transfected cells(EC109/NC,EC109/OE,EC9706/NC and EC9706/KD)were selected in primary cell culture medium containing puromycin.The expression of LINC01410 was detected by RTFQ-PCR.The impact of LINC01410 on ESCC cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and colony formation assays.The effect of LINC01410 on ESCC cell invasion was detected by transwell migration assay.T cell factor/lymphoid enhancer factor 1(TCF/LEF1)luciferase reporter assay was performed to validate the effect of LINC01410 on the activity of canonical Wnt/β-catenin signaling pathway.The expressions of Wnt/β-catenin and epithelial-mesenchymal transition(EMT)signal pathway related proteins in ESCC cells were detected by Western blot.Results:By analyzing the LINC01410 expression from ESCC samples in TCGA by GEPIA2,we found LINC01410 was consistently increased in ESCC tumors compared with normal tissues(P<0.05),and high LINC01410 expression was associated with poorer overall survival(OS).RTFQ-PCR assay showed that expressions of LINC01410 were higher in esophageal cancer tissues and esophageal cancer cells(EC109 and EC9706)than in precancerous tissues and HEEC cells(P<0.05).The expression level of LINC01410 was significantly correlated with invasion range,lymph node metastasis and TNM stage in ESCC patients(P<0.01).LINC01410 expression was also upregulated in EC109/OE,however the expression of LINC01410 in EC9706/KD was decreased(P<0.01).MTT assay showed overexpression of LINC01410 increased the viability of EC109 cells,while knockdown of LINC01410 decreased the viability of EC9706 cells(P<0.01).Colony formation assay indicated that overexpression of LINC01410 enhanced the clonogenic ability of ESCC cells,while knockdown of LINC01410 reduced colony formation(P<0.01).Transwell migration assay showed that LINC01410 overexpression drastically increased the number of migratory cells,while silencing of LINC01410 suppressed the migration in EC9706 cells(P<0.01).GSEA revealed that Wnt/β-catenin and EMT pathways were significantly enriched in ESCC samples with a high level of LINC01410.TCF/LEF1 luciferase reporter assay showed higher levels of Wnt-dependent activities were observed in EC109/OE cells,whereas silenced LINC01410 in EC9706 cells led to contrary results(P<0.01).Western blot analysis showed that overexpression of LINC01410 in EC109 cell significantly increased the expression levels of N-cadherin,β-catenin,cyclin D1,c-Myc and decreased E-cadherin expression,while knockdown LINC01410 resulted in opposite results.Conclusion:LINC01410 promotes proliferation and metastasis of ESCC,which might be caused by activation of Wnt/β-catenin and EMT signaling pathways.
8.Anatomical research of positional relationship between protective channel and sural nerve during Achilles tendon repair using channel assisted minimally invasive repair technique.
Zhonghe WANG ; Wenhao CAO ; Hongzhe QI ; Lingtong KONG ; Haoyu LIU ; Chen CHEN ; Lianhua LI ; Lijun SUN ; Hua CHEN
Chinese Journal of Reparative and Reconstructive Surgery 2024;38(11):1325-1329
OBJECTIVE:
To evaluate the positional relationship between protective channel and sural nerve while treating acute Achilles tendon rupture with channel assisted minimally invasive repair (CAMIR) technique based on anatomical observations of cadaver specimens.
METHODS:
Twelve adult cadaveric lower limb specimens (6 left, 6 right) were utilized. A CAMIR device was implanted at a distance of 4 cm from the proximal end of the specimen to the Achilles tendon insertion. The skin was incised along the tendon's medial side, the sural nerve was dissected, and the positional relationship with the protective channel was observed. The distance from the sural nerve-Achilles tendon intersection to the calcaneal insertion, the vertical distance between protective channel and the calcaneal insertion, and the horizontal distance between the sural nerve and protective channel were measured by using vernier caliper.
RESULTS:
Anatomical examination demonstrated a variable positional relationship between the sural nerve and protective channel, with the sural nerve positioned above (8 specimens) or below (4 specimens) the protective channel. The distance from the sural nerve-Achilles tendon intersection to the calcaneal insertion was (105.67±14.94) mm, the vertical distance between protective channel and the calcaneal insertion was (93.20±9.57) mm, and the horizontal distance between the sural nerve and protective channel was (0.31±0.14) mm.
CONCLUSION
The use of CAMIR technique for the treatment of acute Achilles tendon rupture can effectively avoid iatrogenic injury to the sural nerve.
Humans
;
Achilles Tendon/injuries*
;
Sural Nerve/anatomy & histology*
;
Cadaver
;
Minimally Invasive Surgical Procedures/methods*
;
Tendon Injuries/surgery*
;
Rupture/surgery*
;
Adult
;
Male
;
Calcaneus/injuries*
;
Female
;
Plastic Surgery Procedures/methods*
9.A comparative study of dynamic versus static rehabilitation protocols after acute Achilles tendon rupture repair with channel assisted minimally invasive repair technique.
Zhonghe WANG ; Lingtong KONG ; Wenhao CAO ; Junjun TANG ; Hongzhe QI ; Meijing DOU ; Haoyu LIU ; Chen CHEN ; Hua CHEN
Chinese Journal of Reparative and Reconstructive Surgery 2024;38(12):1492-1498
OBJECTIVE:
To explore the difference in effectiveness between a dynamic rehabilitation protocol and a traditional static rehabilitation protocol after the treatment of acute Achilles tendon rupture with channel assisted minimally invasive repair (CAMIR) technique through a prospective comparative trial, aiming to provide a reference for clinically selecting a feasible treatment regimen.
METHODS:
Patients with acute Achilles tendon rupture admitted between June 2021 and June 2022 were included in the study, with 60 patients meeting the selection criteria. They were randomly divided into a dynamic rehabilitation group ( n=30) and a static rehabilitation group ( n=30) using a computer-generated random number method. There was no significant difference in baseline data such as gender, age, body mass index, smoking history, injured side, cause of injury, and disease duration between the two groups ( P>0.05). After Achilles tendon anastomosis by using CAMIR technique, the dynamic rehabilitation group implemented early partial weight-bearing training with the assistance of an Achilles heel boot and controlled ankle joint exercises for 6 weeks, while the static rehabilitation group maintained a non-weight-bearing status during this period. Complications in both groups were recorded. At 3 and 6 months after operation, the Achilles tendon total rupture score (ATRS) was used to evaluate the degree of functional limitation of the Achilles tendon in the affected limb, and the 12-Item Short Form Health Survey (SF-12 scale) was used to assess the patients' quality of life, including physical component summary (PCS) and mental component summary (MCS) scores.
RESULTS:
No sural nerve injury occurred during operation in both groups. All patients were followed up 12-18 months (mean, 14 months). The dynamic rehabilitation group had significantly higher ATRS scores at 3 and 6 months after operation compared to the static rehabilitation group ( P<0.05). At 3 months after operation, the dynamic rehabilitation group had significantly lower PCS, MCS, and SF-12 total scores compared to the static rehabilitation group ( P<0.05). At 6 months, all quality of life scores in the two groups were similar ( P>0.05). Two cases (6.6%) in the dynamic rehabilitation group and 5 cases (16.7%) in the static rehabilitation group developed complications, with no significant difference in incidence of complications ( P>0.05).
CONCLUSION
For acute Achilles tendon rupture, the dynamic rehabilitation protocol after Achilles tendon anastomosis by using CAMIR technique can improve early functional recovery and maintains comparable safety and effectiveness compared to static rehabilitation.
Humans
;
Achilles Tendon/surgery*
;
Minimally Invasive Surgical Procedures/methods*
;
Rupture/surgery*
;
Female
;
Male
;
Tendon Injuries/rehabilitation*
;
Prospective Studies
;
Treatment Outcome
;
Anastomosis, Surgical/methods*
;
Recovery of Function
;
Middle Aged
;
Adult
;
Plastic Surgery Procedures/methods*
10.Genetic background of idiopathic neurodevelopmental delay patients with significant brain deviation volume.
Xiang CHEN ; Yuxi CHEN ; Kai YAN ; Huiyao CHEN ; Qian QIN ; Lin YANG ; Bo LIU ; Guoqiang CHENG ; Yun CAO ; Bingbing WU ; Xinran DONG ; Zhongwei QIAO ; Wenhao ZHOU
Chinese Medical Journal 2023;136(7):807-814
BACKGROUND:
Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV).
METHODS:
We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development.
RESULTS:
We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron.
CONCLUSION
Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child
;
Humans
;
Neurodevelopmental Disorders/epidemiology*
;
Genetic Testing
;
Phenotype
;
Brain/pathology*
;
Genetic Background
;
SOX Transcription Factors/genetics*

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