Objective To investigate the applicative value of acoustic radiation force impulse imaging (ARFI) in the differential diagnosis of small hypoechoic thyroid nodules.Methods 31 patients were pathologically confirmed as having a total of 44 small hypoechoic thyroid nodules ≤ 1 cm in diameter,followed by analyses of the characteristics of their ARFI images,including virtual touch tissue imaging (VTI) and virtual touch tissue quantification (VTQ).Based on VTI images of the nodules,the hardness of small hypoechoic thyroid nodules was respectively scored,and the ratios of VTI images to gray scale image areas were calculated.With pathological diagnosis as the gold standard,VTI scores,area ratios and VTQ values of the ROC curve in diagnosis of thyroid malignant nodules were sketched so as to explore the optimal cut-off points in VTI scores,area ratios and VTQ values in the diagnosis of malignant nodules.Results By the ROC curve test,VTI score of 3 was determined as the cut-off point of areas ratio,with the sensitivity and specificity of diagnosing thyroid cancer being 96.0 ％ and 94.7％,respectively.There were 34 nodules with VTI score greater than 3 (including 9 benign nodules and 25 malignant nodules) and 10 nodules with VTI score of 3 or less (all benign nodules).Malignant thyroid nodules had higher ratio of VTI images to gray scale image area than that of the benign nodules (1.58 ± 0.18 vs 1.30 ± 0.10,P ＜0.05).When 1.47 was set as the cut-off point of areas ratio,the sensitivity and specificity of diagnosing thyroid cancer were 80.0％ and 94.7％,respectively.The VTQ value of 2.76 m/s in diagnosis of thyroid malignant nodules was designated as the cut-off point,with a sensitivity of 88.0 ％,specificity of 94.7 ％.Conclusions The ARFI technique is able to provide information of thyroid nodule hardness,which guarantees its high applicative value in the differential diagnosis of small hypoechoic thyroid nodules.

Objective To study the effect of blood glucose fluctuations on the prognosis of thrombolytic therapy in patients with acute cerebral infarction. Methods A total of 83 consecutive patients with acute cerebral infarction admitted to the Department of Neurology,General Hospital of Beijing Military Command ( the Affiliated 81st Brain Hospital ) from January to November 2013 were enrolled retrospectively. They were divided into cerebral infarction with type 2 diabetes mellitus group (DMCI group,n=47) and cerebral infarction without type 2 diabetes mellitus group (NDMCI group,n=36) according to whether they had diabetes mellitus or not and the results of oral glucose tolerance test at day 7 after admission. Continuous glucose monitoring system ( CGMS) was used to monitor glucose for 72 hours at day 7 after admission. The mean blood glucose, standard deviation of blood glucose level, mean blood glucose fluctuation,and hemorrhagic transformation during the follow-up period,as well as vascular recanalization were observed and compared. At day 90,the modified Rankin scale (mRS) score was used to evaluate the prognosis of the patients. Results ( 1 ) Comparing the dynamic glucose parameters of the patients with acute cerebral infarction in both groups,the mean blood glucose,standard deviation of blood glucose level,mean blood glucose fluctuations at 24 hours in patients of the DMCI group were higher than those of the NDMCI group ( 8 . 3 ± 2 . 6 mmol/L vs. 5 . 8 ± 1 . 3 mmol/L,2. 1 ± 0. 4 mmol/L vs. 1. 6 ± 0. 6 mmol/L,4. 3 ± 0. 8 mmol/L vs. 3. 6 ± 0. 5 mmol/L). There were significant differences (t=31. 419, 15.537,and 15. 372,respectively;all P<0. 01). (2) Four patients (8.5%) in the DMCI group had hemorrhagic transformation during the follow-up period,17 cases (36. 2%) had good recanalization,and 15 cases (31.9%) had good prognosis (the mRS score < 2 at day 90);1 patient (2.8%) in the NDMCI group had hemorrhagic transformation,21 patients (58. 3%) had good recanalization,and 21 cases (58. 3%) had good prognosis. There was significant difference between the recanalization after thrombolysis and the prognosis in patients of both groups (P<0. 05). Conclusion The great fluctuations of blood glucose in acute cerebral infarction patients with type 2 diabetes mellitus may be an important factor of affecting its prognosis of thrombolytic therapy.

Objective: To analyze and summarize the clinical and molecular characteristics of the patients with multiple congenital anomalies- hypotonia-seizures syndrome 1 (MCAHS 1). Method: Clinical data and test results were collected from a patient who was diagnosed with confirmed genetic basis of MCAHS 1 in Shanghai Children′s Medical Center since December 2015. The patient and his parents were examined by the next generation sequencing (NGS) technology using peripheral blood genomic DNA, and the relevant mutations identified by NGS were verified with Sanger sequencing. Related literature was searched from PubMed and Embase databases (from their establishment to January 2017) by using "PIGN gene" as a keyword, the retrieved articles were further reviewed for the clinical manifestations, results and prognosis of PIGN related variants. Result: A nearly 4-month-old Chinese boy was presented with epilepsy, hypotonia, developmental delay, accompanied by nearly normal laboratory test results. The NGS analysis revealed a compound heterozygous variations in the PIGN gene, included a known splice site mutation (c.963G>A) which was inherited from his father, and a novel nonsense mutation (c.2773A>T, p.Lys925*) which was inherited from his mother. Nine associated articles were retrieved. Including our patient, a total of 22 cases were identified as the PIGN variants. The most common clinical manifestations were developmental delay, hypotonia, and epilepsy.Missense varients were most frequently found. Prognosis was poor. Eight cases died, while survived cased suffered from refractory epilepsy, profound mental retardation, muscle weakness, etc. Conclusion MCAHS1 is characterized by epilepsy, severe developmental delay, hypotonia, and may be accompanied by multiple malformations of other systems. Homozygous or compound heterozygous variants in PIGN gene are the cause of the disease.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Teebi hypertelorism syndrome 1 (TBHS1). METHODS: A child with TBHS1 who was admitted to the Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine on July 13, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 13-year-old male, had manifested delayed growth and development. WES results revealed that he has harbored a heterozygous c.1244A>G variant of the SPECC1L gene, which was verified to be de novo in origin. The variant has not been included in the HGMD and gnomAD databases. As predicted by online software including PolyPhen-2, SIFT, and Mutation Taster, the variant may affect the function of protein domain. And PyMOL software has predicted that the structural stability of SPECC1L protein (p.Gln415Arg) might be reduced. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM6+PM1+PP4+PM2_Supporting+PP3). CONCLUSION The heterozygous c.1244A>G variant of the SPECC1L gene probably underlay the TBHS1 in this child. Above finding has expanded the genotypic and phenotypic spectrum of the SPECC1L gene and provided a basis for the clinical diagnosis of this child.
Adolescent ; Humans ; Male ; China ; Computational Biology ; Genomics ; Genotype ; Mutation

Alstr?m syndrome is a rare multisystem genetic disease caused by mutations in the ALMS1 gene.Both of its clinical diagnosis and treatment are very difficult.In 2020, the Consensus Clinical Management Guidelines for Alstr?m Syndrome, developed with the participation of many countries, was published in the Orphanet Journal of Rare Diseases.A systematic literature review on Alstr?m syndrome of the last 45 years until October 2019 was carried out and then the clinical management guideline for Alstr?m syndrome was proposed.In this report, the contents of the 2020 European guideline for Alstr?m syndrome would be introduced briefly with appropriate interpretation in order to provide reference.

OBJECTIVES: To analyze the clinical and genetic characteristics of children with autosomal dominant neurodevelopmental disorders caused by kinesin family member 1A (KIF1A) gene variation. METHODS: Clinical and genetic testing data of 6 children with KIF1A gene de novo heterozygous variation diagnosed in Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from the year 2018 to 2020 were retrospectively analyzed. Pathogenic variants were identified based on whole exome sequencing, and verified by Sanger sequencing. Moreover, the effect of variants on three-dimensional structure and stability of protein was analyzed by bioinformatics. RESULTS: Among 6 patients there were 4 males and 2 females, and the age of consultation varied from 7 months to 18 years. All cases had varying degrees of motor developmental delay since childhood, and 4 of them had gait abnormalities or fell easily. In addition, 2 children were accompanied by delayed mental development, epilepsy and abnormal eye development. Genetic tests showed that all 6 cases had heterozygous de novo variations of KIF1A gene, including 4 missense mutations c.296C>T (p.T99M), c.761G>A (p.R254Q), c.326G>T (p.G109V), c.745C>G (p.L249V) and one splicing mutation c.798+1G>A, among which the last three variants have not been previously reported. Bioinformatics analysis showed that G109V and L249V may impair their interaction with the neighboring amino acid residues, thereby impacting protein function and reducing protein stability, and were assessed as "likely pathogenic". Meanwhile, c.798+1G>A may damage an alpha helix in the motor domain of the KIF1A protein, and was assessed as "likely pathogenic". CONCLUSIONS KIF1A-associated neurological diseases are clinically heterogeneous, with motor developmental delay and abnormal gait often being the most common clinical features. The clinical symptoms in T99M carriers are more severe, while those in R254Q carriers are relatively mild.
Male ; Female ; Humans ; Child ; Retrospective Studies ; China ; Mutation ; Epilepsy/genetics* ; Neurodevelopmental Disorders/genetics* ; Kinesins/genetics*

A 2-year-old boy was admitted to Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine in Nov 30^th, 2018, due to polydipsia, polyphagia, polyuria accompanied with increased glucose levels for more than 2 weeks. He presented with symmetrical short stature [height 81 cm (－2.2 SD), weight 9.8 kg (－2.1 SD), body mass index 14.94 kg/m² (P₁₀-P₁₅)], and with no special facial or physical features. Laboratory results showed that the glycated hemoglobin A1c was 14%, the fasting C-peptide was 0.3 ng/mL, and the islet autoantibodies were all negative. Oral glucose tolerance test showed significant increases in both fasting and postprandial glucose, but partial islet functions remained (post-load C-peptide increased 1.43 times compared to baseline). A heterozygous variant c.1366C>T (p.R456C) was detected in GATA6 gene, thereby the boy was diagnosed with a specific type of diabetes mellitus. The boy had congenital heart disease and suffered from transient hyperosmolar hyperglycemia after a patent ductus arteriosus surgery at 11 months of age. Insulin replacement therapy was prescribed, but without regular follow-up thereafter. The latest follow-up was about 3.5 years after the diagnosis of diabetes when the child was 5 years and 11 months old, with the fasting blood glucose of 6.0-10.0 mmol/L, and the 2 h postprandial glucose of 17.0-20.0 mmol/L.
Male ; Child ; Humans ; Child, Preschool ; Infant ; Diabetes Mellitus, Type 2/complications* ; Mutation, Missense ; C-Peptide/genetics* ; China ; Insulin/genetics* ; Glucose ; Blood Glucose ; GATA6 Transcription Factor/genetics*