OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with autism spectrum disorder (ASD) in conjunct with congenital heart disease (CHD). METHODS: A child who was hospitalized at the Third People's Hospital of Chengdu on April 13, 2021 was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). A GTX genetic analysis system was used to analyze the WES data and screen candidate variants for ASD. Candidate variant was verified by Sanger sequencing and bioinformatics analysis. Real-time fluorescent quantitative PCR (qPCR) was carried out to compare the expression of mRNA of the NSD1 gene between this child and 3 healthy controls and 5 other children with ASD. RESULTS: The patient, an 8-year-old male, has manifested with ASD, mental retardation and CHD. WES analysis revealed that he has harbored a heterozygous c.3385+2T>C variant in the NSD1 gene, which may affect the function of its protein product. Sanger sequencing showed that neither of his parent has carried the same variant. By bioinformatic analysis, the variant has not been recorded in the ESP, 1000 Genomes and ExAC databases. Analysis with Mutation Taster online software indicated it to be disease causing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. By qPCR analysis, the expression level of mRNA of the NSD1 gene in this child and 5 other children with ASD was significantly lower than that of the healthy controls (P < 0.001). CONCLUSION The c.3385+2T>C variant of the NSD1 gene can significantly reduce its expression, which may predispose to ASD. Above finding has enriched the mutational spectrum the NSD1 gene.
Male ; Child ; Humans ; Autism Spectrum Disorder/genetics* ; Heart Defects, Congenital/genetics* ; Computational Biology ; Genomics ; Mutation ; RNA, Messenger/genetics* ; Histone-Lysine N-Methyltransferase/genetics*

OBJECTIVE: This study aimed to evaluate the clinical effect of periodontal microscopic surgery on the augmentation of attached gingiva and determined the clinical principle on how to use minimally invasive surgery to improve the surgery success rate. METHODS: Twenty patients with insufficient attached gingiva around implants were selected. Periodontal microscopic surgery for free gingival graft was performed to increase the width of the attached gingiva around the implants. The survival state of the free gingiva was observed after surgery, and the width of the attached gingiva around the implants was recorded before and after surgery and 1 year after surgery. The shrinkage rate of the free gingival flap 1 year after surgery was analyzed to evaluate the stability of the flap. RESULTS: The flaps of the 20 cases all survived. One year after the operation, the width of the attached gingiva was (3.05±0.44) mm, which increased compared with that of preoperation (2.56±0.31) mm
and decreased compared with that of postoperative day (2.13±0.28) mm. The shrinkage rate of the attached gingiva was 41.22%±5.04%. CONCLUSIONS The application of microscopic surgery on the augmentation surgery of attached gingiva can increase the success rate and improve the quality and quantity of attached gingiva around implants.
Dental Implants ; Gingiva ; surgery ; Humans ; Microsurgery ; Oral Surgical Procedures ; Surgical Flaps

Moyamoya disease is an uncommon cerebral disease, but its morbidity is relatively high in East Asian populations. Ivy sign refers to the dot or linear high signal phenomenon in MRI T1 enhanced sequence in patients with moyamoya disease. It mainly distributes in the pial surface of cerebral cortex or within subarachnoid space. It has important significance for diagnosing moyamoya disease and assessing the staging and prognosis of moyamoya disease. This article briefly reviews this imaging finding and its significance.

Objective To investigated the effect of the risk factors for stroke on the development of leptomeningeal colateral circulation in patients with middle cerebral artery occlusion. Methods Patients with acute ischemic stroke confirmed as middle cerebral artery occlusion by imaging were extracted from the Nanjing Stroke Registry Program between June 2006 and December 2011. The baseline clinical data were colected. Leptomeningeal colateral circulation was assessed by angiography. Results A total of 137 patients were enroled, including 100 males and 37 females; mean age 55. 26 ± 11. 71 years. The colateral circulation of 65 patients (47. 4% ) was good. Univariate analysis showed that the ages (52. 3 ± 13. 2 years vs. 57. 9 ± 9. 5 years; t = 2. 866, P = 0. 005) and the proportion of hypertension (52. 3% vs. 70. 8% ; χ2 = 4. 978, P =0. 026) in the good colateral circulation group were significantly lower than those in the poor colateral circulation group. Multivariate logistic regression analysis showed that age was an independent risk factor for affecting the leptomeningeal colateral circulation in patients with acute middle cerebral artery occlusion (odds ratio, 0. 965, 95% confidence interval 0. 934-0. 997, P = 0. 034). Conclusions Age is an independent risk factor for affecting the leptomeningeal colateral circulation in patients with middle cerebral artery occlusion.

Objective To investigate the possible formation mechanism and imaging features of the hyperintense vessel sign (HVS) on fluid attenuated inversion recovery (FLAIR) in patients with ischemic stroke or transient ischemic attack (TIA).Methods The baseline data of the patients with middle cerebral artery (MCA) ischemic stroke or TIA with digital subtraction angiography (DSA) showing the lesions of MCA M1 segment in clinical practice were retrospectively retrieved from Nanjing Stroke Registry Program from January 2010 to July 2011.FLAIR was used to observe HVS,and DSA was used to evaluate the degree of vascular stenosis and cerebral collateral circulation.Results A total of 101 patients were enrolled,76 (75.2％) were males,and their mean age was 53.94 ± 13.47 years; 90 patients (89.1％) with ischemic stroke and 11 patients (10.9％) with TIA; 55 patients (54.5％) were HVS negative and 46 (45.5％) were HVS positive.Among the patients whose MCA stenosis ＜50％,50％-70％,70％-90％ and ≥90％,the positive rates were 0％ (0/8),25.0％ (3/12),17.6％ (3/17),and 62.5％ (40/64),respectively.There were significant differences (Z=-4.479,P＜ 0.001).The leptomeningeal collateral circulation of the HVS positive group was significantly more than that of the HVS negative group (Z =-6.196,P ＜ 0.001).Multivariate logistic regression analysis showed that the degree of MCA stenosis was an independent risk factor for influencing the formation of HVS (odds ratio 3.943,95％ confidence interval 2.03-7.659; P ＜0.001).Conclusions The formed intracranial leptomeningeal colhteral circulation after severe intracranial vascular stenosis or occlusion is a major pathophysiological basis of HVS formation on FLAIR sequences in patients with ischemic stroke or TIA.

Moyamoya disease is a rare cerebrovascular disease.Its incidence is higher in the East Asia.The pathogenesis of MMD remains unclear at present,but the epidemiological research both at home and abroad suggests that the genetic factors play an important role in the onset of MMD.This article briefly reviews the recent progress in research on MMD related genes.

Objective To evaluate the prognostic value of hyperintense vessel (HV) in patients with acute middle cerebral artery (MCA) occlusion.Methods Seventy-four consecutive patients with first ever stroke(48 male and 26 female,the mean age was (60.7 ± 15.3) years) in the territory of MCA,retrieved from Nanjing Stroke Registry Program between May 2009 and February 2011,were enrolled assubjects.All subjects completed brain MRI,and MRA or DSA indicated proximal MCA occlusion.According to the location and extent of HV,all subjects were classified into 3 groups:without HV,proximal HV and distal HV.Clinical data were obtained and compared among patients with different grades of HV.Logistic regression analysis was employed to confirm the relevant factors of prognosis 90 days after index stroke.Results HV was observed in 49 (66.2％ ) of the 74 enrolled patients.Among patients with HV,7 (9.4％ ) were classified as proximal HV and 42 ( 56.8％ ) as distal HV.Initial NIHSS score ( 11 ( 1 -22) ),10-day NIHSS score ( 13.5(4-25) ),infarction size ( ＞2/3:5 cases(6.8％ ) ),and 90-day mRSscore (3-6 scores:12 cases( 16.2％ )) were significantly lower in patients with distal HV than those without (15(6-25),Z=-3.544;7(0-22),Z=-4.461;20 cases(27.0％),x2 =20.916;27 cases (36.5％),x2 =22.689;all P＜0.01).The NIHSS score decreased from baseline to that on 10 days and the mRS score decreased from 10 days to that on 90 days in patients with distal HV was more than that in patients without distal HV. Multivariate analysis revealed that patients with older age ( OR =1.111,95％ CI 1.036-1.191,P=0.003),high infarction size (OR=3.679,95％ CI 1.35-10.025,P=0.011) worsened outcome,whereas distal HV (P =0.012,OR =0.131,95％ CI 0.027-0.638)improved outcome.Conclusion Distal HV on FLAIR may predict a favorable outcome in patients with acute middle cerebral artery occlusion.

Objective To study the patterns of collateral circulation in adults moyamoya disease (MMD). Methods One hundred and nineteen consecutive adult patients with MMD (ischemic or hemorrhagic type) were identified by digital cerebral angiography in Nanjing Stroke Registry Program of Jinling Hospital between August 2004 and January 2010.The extracranial and (or) intracranial collateral circulations ipsilateral to stroke hemisphere were regarded as the research objects,and furthermore,these collateral circulations were divided into three different grades:Grade 1 collateral (anterior cerebral artery (ACA) → meningeal arteries (MLA) → middle cerebral artery (MCA) ),Grade 2 collateral ( dilating and extensing anterior choroidal artery beyond choroid fissure,patent posterior communicating artery → posterior cerebral artery→MLA→ ACA and(or) MCA,posterior cerebral artery→MLA→ACA and (or) MCA and posterior choroidal artery → posterior pericallosal arteries → ACA ) and Grade 3 collateral (collateral originating from the external carotid artery supplying to cerebral blood flow). The relationship between collateral distribution patterns in adult MMD and Suzuki' s classification was analyzed.Results In 117 assessed vessel units of the collateral circulation ipsilateral to stroke hemisphere,there were a total of 200 collateral circulations.The percentage of numbers in Grade 1,Grade 2 and Grade 3 collateral was 11.5％(23/200),52.0％ (104/200) and 36.5％ (73/200),respectively.The distribution percentage of Grade 1 was gradually decreased from Suzuki's Ⅰ to Ⅵ,mainly distributed in the early stage of MMD ( Suzuki's Ⅰ -Ⅱ ) and accounted for 91.3％ (21/23; Z =- 7.270,P ＜ 0.01 ).The distribution percentage of Grade 3 was gradually increased from Suzuki' s Ⅰ to Ⅵ,especially in the late stage of MMD ( Suzuki' s Ⅴ-Ⅵ) and accounted respectively for 37.0％ (27/73) and 63.0％ (46/73; Z =-7.270,P ＜0.01 ).Compared with the total distribution of Grade 1 and 3 collateral circulation,the distribution percentage of Grade 2 was 6.7％ (7/104),7.7％ (8/104),15.4％ ( 16/104),40.4％ (42/104),14.4％ (15/104)and 15.4％ (16/104) from Suzuki' s Ⅰ to Ⅶ.Although there was not significant difference,Grade 2 mainly distributed in the medium stage of MMD ( Suzuki' s Ⅲ-Ⅳ ).Conclusions The patterns of collateral distribution is various,changing with the progression of MMD. Grade 2 collateral circulation accounts for a higher proportion,especially in the medium stage of the disease,which suggests that these collaterals play an important compensatory role of blood flow.

Objective To study the effect of intranasal nerve growth factor (NGF) on the expression of amyloid-β,peptide (Aβ) in the central nervous system in rats with traumatic brain injury (TBI).Methods Eighty rats were randomly divided into sham(n =26),control(n =27) and treatment group (n =27 ).They were subjected to the modified Feeney' s weight-drop model.The treatment group was treated with NGF administered by nasal route,and the control group was given phosphate-buffered saline (PBS).Beam walking and Morris water maze test were performed in the three groups.The concentration of Aβ40 and Aβ42 in the injured ipsilateral hippocampus was elevated by ELISA measurement.Immunohistochemistry was used to detect the amyloid precursor protein (APP) positive cells near the region of injury in the hippocampus in rats after TBI.Results NGF group traversed the beam significantly quicker (s) than control group ( 19.00 + 6.99 vs 27.33 ± 7.39 respectively,F2,15 =12.87,P =0.028 ).Morris water maze performance revealed that mean time of latency in the NGF group was significant shorter than vehicle group,and significant memory retention in NGF group as evidenced by a greater percentage of the 60 s allotted time spent in the target quadrant (45.82％ ± 11.15％ vs 33.99％ ± 3.46％,F2,15 =6.814,P=0.037),as well as the number crossing of the former site of the removed platform in NGF group was significant more than control group (8.60 ±2.73 vs 3.60 ±2.06,F2,15 =5.346,P =0.04).The Aβ42 level in control group was increased significantly higher than NGF group as indicated by ELISA measurements.While the Aβ40 level did not have similar shown.Immunohistochemical staining showed that APP level had significant differences among three groups ( F2,15 =8.672,P =0.003).The APP level in NGF group did not alter with control group.Conclusion Intranasal administration of NGF can regulate Aβ42 overproduction,improve the motor and cognitive function after brain injury in rats.

Objective To investigate the relationship between serum levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) and Suzuki' s grading system in adult moyamoya disease (MMD).Methods Fifty-two adult patients with MMD,who were diagnosed in Jinling hospital between April 2009 and January 2010,were retrieved from the Nanjing Stroke Registry Program (NSRP).Sixteen sex- and age-matched healthy individuals with MMD patients consisted of the control group.Using enzyme-linked immunosorbent assay,serum concentrations of VEGF and MMP-9 were compared between adult MMD patients and healthy individuals.By Suzuki' s six-grading system,patients were divided into different subgroups,and the correlation of serum levels of VEGF and MMP-9 corresponding to different subgroup and Suzuki's grading was respectively analyzed.In addition,the correlation of serum levels of VEGF and MMP-9 was also evaluated.Results Serum VEGF concentrations in ischemic and hemorrhagic MMD patients was respectively ( 289.4 + 69.2 ) pg/ml and ( 324.3 ± 95.6 ) pg/ml and were significantly higher compared to those in healthy controls ( ( 63.5 ± 7.6 ) pg/ml; F =69.43,P ＜ 0.01 ).Similar findings were observed for MMP-9 ( ( 499.4 ± 76.2 ) ng/ml and ( 531.2 + 100.2 ) ng/ml versus (257.1 ±30.7) ng/ml; F =66.023,P ＜0.01 ).With the increase of Suzuki' s grading,serum levels of VEGF and MMP-9 respectively showed a high trend ( r =0.879,P ＜ 0.01:r =0.838,P ＜ 0.01 ).In addition,a positive correlation between serum levels of VEGF and MMP-9 was found in the MMD group( r =0.590,P ＜0.01 ).Conclusion The results show that serum levels of VEGF and MMP-9 in adult MMD are higher than those in healthy controls,which may play a role in neovascularization in MMD,and moreover,serum levels of VEGF and MMP-9 show a high trend with the progression of MMD,which suggest that serum levels of VEGF and MMP-9 can reflect the severity of MMD.