Preoperative prediction of risk groups for medulloblastoma in children with MRI features / 中华放射学杂志

Objective:To analyze the MRI features of medulloblastoma (MB) in children, and screen out the key signs that can predict the risk of MB before surgery.Methods:Clinical and radiological data of 62 children with MB confirmed by pathology in Shenzhen Children′s Hospital from December 2012 to December 2021 were retrospectively analyzed. According to the diagnosis and treatment guidelines for children with MB (2021 edition), the patients were divided into standard risk group (43 cases) and high risk group (19 cases). MRI features of MB were observed and recorded, including tumor site, location of tumor center, tumor morphology, signal intensity of T 1WI, T 2WI and diffusion weighted imaging (DWI), enhancement pattern, cystic lesion size, location and number, peritumoral edema and hydrocephalus, and the maximum diameter of tumor was measured. The χ 2 test or Fisher exact probability method was used to compare the differences in age, gender and MRI signs between the two groups. The t test of two independent samples was used to compare the differences in the maximum diameter of tumors between the two groups. The indicators with statistically significant differences were included in binary logistic regression analysis to obtain independent influencing factors associated with the risk groups. The receiver operation characteristic curve was used to evaluate the diagnostic efficacy. Results:There were significant differences in age ( P=0.026), enhancement pattern ( P=0.018), cystic lesion size ( P=0.005), location ( P=0.011) and number ( P=0.003) between standard risk group and high risk group. There were no significant differences in gender, tumor site, location of tumor center, tumor morphology, signal intensity of T 1WI, T 2WI and DWI, peritumoral edema, hydrocephalus and maximum diameter of tumor between the two groups ( P>0.05). Binary logistic regression results showed the age (OR=0.207, 95%CI 0.040-0.983, P=0.042) and the number of cystic lesions (OR=0.215, 95%CI 0.073-0.630, P=0.005) were the protective factors for MB in high risk group, the enhancement pattern Ⅲ (OR=5.226, 95%CI 1.516-52.920, P=0.048) was the dangerous factor for MB in high risk group. The area under the curve of the combined diagnosis of high risk MB was 0.845 (95%CI 0.741-0.949). Conclusions:The age and MRI signs the pattern of tumor enhancement Ⅲ and the number of cystic lesion can be used to predict the risk grouping of MB preoperatively. When the child is younger and MB enhancement pattern is mainly peripheral enhancement without obvious cystic change, it may indicate high risk MB.

Clinical, skeletal muscle pathological and genetic characteristics of fatal infantile hypertonic myofibrillar myopathy / 中华实用儿科临床杂志

Objective:To investigate the clinical, skeletal muscle pathological, and genetic characteristics of fatal infantile hypertonic myofibrillar myopathy (FIHMM).Methods:The clinical manifestations, laboratory assessments data and gene sequencing results of 10 patients diagnosed with FIHMM in Shenzhen Children′s Hospital from February 2017 to April 2021 were retrospectively analyzed.Magnetic resonance imaging (MRI) of both musculoskeletal system and the brain, and electromyogram (EMG) were performed in 3 cases, while muscle biopsy was performed in 2 cases.Results:Among these 10 cases, 1 case was from Northeast China and 1 case from East China, while the rest 8 cases were from South China.Eight of the 10 patients were male, and the other 2 cases were female.They were all born normal and not related to each other.The age of onset varied from 2 to 12 months.The main clinical manifestations for all the patients were progressive rigidity of the rectus abdominis (8 cases), neck muscles (7 cases), rectus abdominis (2 cases) and intercostal muscles (1 case), resulting in respiratory failure.Mildly to moderately elevated serum creatine kinase level was detected (436-5 804 IU/L) (reference range: 24-229 IU/L). Complex repetitive discharges can be seen in the EMG, without any myotonic potential.Muscle fiber degeneration, necrosis, and vacuolar degeneration were noted in the histopathological examination of the vastus lateralis and rectus abdominis.An abnormal red granular deposit was observed in a portion of the field of the modified Gomory Trichrome staining.Immunohistochemistry showed substantial deposition of desmin.Under the electron microscopy, the sarcomere structure of the muscle fibers was seriously disordered, with the destruction of Z-bands and the presence of granular deposits.The whole-exome sequencing identified the same homozygous variation c. 3G>A, p.Met1? of CRYAB gene in all the patients, but heterozygous variation in their parents. Conclusions:Axial muscles involvement, such as rectus abdominis rigidity, is the main clinical characteristic of FIHMM.c.3G>A, p.Met1? mutation in the CRYAB gene is a hotspot mutation in Chinese children.

DHX37 gene heterozygous variant—a frequent cause of embryonic testicular regression syndrome / 中华内分泌代谢杂志

Objective:To report embryonic testicular regression syndrome(ETRS) caused by DHX37 heterozygous variant for the first time in China and summarize the clinical manifestations of ETRS as to improve the understanding of doctors for this disease.Methods:The clinical data and whole exome sequencing results of five cases of ETRS from Shenzhen Children′s Hospital were collected. The reported cases of DHX37 heterozygous variant were reviewed.Results:Five patients with ETRS visited the doctors at the age of 2 months to 5 years and 5 months. Three patients raised as males came to hospital due to virilition and 2 female patients visited a doctor due to clitoral hypertrophy. No uterus was detected by ultrasound in all patients. The gonadal pathologies from 4 cases displayed no testicular tissue or gonadal dysgenesis, complicated with gonadoblastoma in one case. The genetic testing revealed that the heterozygous variant(c.923G>A, p. R308Q) in DHX37 was found in 2 cases, without variant in other 3 cases. According to the review, ETRS and 46, XY gonadal dysgenesis due to DHX37 herozygous variant was firstly reported in 2019. A total of 40 cases, including 21 cases of ETRS, presented with the virilition or female phenotype, with the disappearance of testicular tissue as the main pathologies. There is no report in China.Conclusion:The article summarized the clinical manifestations and whole exome sequencing results of 5 patients with ETRS, among which two cases were caused by DHX37 variants and one was complicated with gonadoblastoma.

DMRT1 gene variant/haploinsufficiency and 46, XY disorders of sex development / 中华内分泌代谢杂志

Objective:To summarize the clinical manifestations of four patients with 46, XY disorders of sex development(46, XY DSD)due to doublesex and mab-3 related transcription factor 1(DMRT1)gene variant/haploinsufficiency, and to improve the understanding of clinicians for this disease.Methods:The medical history, physical examination, endocrine function assessment, gonadal pathology, and genetic data of 4 patients with 46, XY DSD were retrospectively collected.Results:A heterozygous new missense mutation in DMRT1 was found in one child. The chief complain was primary amenorrhoea at the age of 15 years, with the external masculinisation score(EMS)0. The DMRT1 haploinsufficiency was found in 3 cases, 1.2 Mb, 5.1 Mb, and 6.0 Mb fragments were deleted at the 9p, and one of 3 cases had 33.3 Mb repeats in the 5p. All patients visited doctor under 1 year. Two patients were raised as females, and one was raised as male. All chief complains were external genital abnormalities, EMS of them were 1, 0, and 5 respectively. Endocrine evaluation of 2 out of 4 children showed varying degrees of primary hypogonadism, and presented with complete gonadal dysgenesis. One patient showed a well function of Leydig cells and poorly function of Sertoil cells, and presented with mixed gonadal dysgenesis. One of 3 cases was diagnosed with gonadoblastoma at the age of 18 months. Patient No.4 didn′t agree with the gonadal biopsy. The chromosome karyotypes of 4 children were 46, XY.Conclusions:The visiting ages of 46, XY DSD patients caused by DMRT1 variation were older than those of patients caused by DMRT1 haploinsufficiency. The clinical manifestations are complex, and gonadal function can vary from normal to complete gonadal dysgenesis. Such patients are at high risk of gonadoblastoma and young onset. Gonadal biopsy should be performed as early as possible.

Expression and significance of growth factor receptor binding protein 2 -associated binding protein -1 and glioma-associated oncogene homologue -1 in pediatric medulloblastoma / 中华实用儿科临床杂志

Objective To explore the expressions of growth factor receptor binding protein 2 -associated bin-ding protein -1 (Gab -1 )and glioma -associated oncogene homologue -1 (Gli -1 )in pediatric medulloblastoma,and to analyze their correlation between clinical and pathological characteristics and prognosis in pediatric medulloblastoma. Methods Elivision immunohistochemistry was used to detect the expressions of Gab -1 and Gli -1 protein in tissue microarray of 40 paraffin embedded pediatric medulloblastoma specimens.Chi -square test or Fisher exact test was used to analyze the correlation between Gab -1 and Gli -1 protein expressions with gender,age,tumor location and pathological subtypes.Follow -up data were handled by using Kaplan -Meier survival analysis and Cox regression anal-ysis.Results Positive expression ratios of Gab -1 and Gli -1 protein in 40 pediatric medulloblastoma were 35.0%and 55.0%,respectively.The positive expression rate of Gab -1 in medulloblastoma tissues had no statistical signifi-cance between different genders[male:30.4%(7 /23 cases)vs.female:41 .2%(7 /17 cases)],age[0.05).There were statistical differences of positive expression rate of Gli -1 protein in different age groups[0.05).Kaplan -Meier survival analysis showed that the age,the expressions of Gab -1 and Gli -1 protein were correlated with prognosis of pediatric medulloblastoma(all P <0.05).Cox regression indicated that the age,pathological subtypes and the expression of Gli -1 protein were independent prognostic indicators in pediatric medulloblastoma(all P <0.05).Conclusion Expression of Gab -1 and Gli -1 protein is significantly correlated with the prognosis of medulloblastoma,and the positive expression is a marker of unfavorable prognosis.

Study the effect and mechanism of edaravone on acute ischemic cerebrovascular disease / 重庆医学

Objective To explore the clinical effect of edaravone on acute ischemic cerebrovascular disease ,and to observe its effect on serum C‐reactive protein (CRP) and matrix metalloproteinase‐9(MMP‐9) level .Methods Eighty four patients with acute ischemic cerebral vascular disease who were treated in our hospital during 2012 May to 2013 December were selected and divided in‐to observation group and control group ,with 42 cases in each group .The control group was treated with anti‐platelet ,regulating blood pressure and blood lipid ,reducing intracranial pressure ,improve microcirculation and other comprehensive treatment ;the pa‐tients in observation group were treated with increased dose of edaravone on the basis of the control group .America national institu‐tes of health stroke scale(NIHSS) and activities of daily living scale (ADL) were used to evaluate the neurological function and ac‐tivities of daily living ability of patients before and after the treatment ,the CRP and MMP‐9 level were detected before and after treatment ,and the adverse reaction during the treatment was recorded .Results After one week and two weeks after treatment , there were significant differences between treatment group and control group in the NIHSS score and ADL score (P0 .05) .Conclusion Edaravone could improve the clinical treatment effect of acute ischemic cerebrovascular disease ,and reducing se‐rum CRP and MMP‐9 level mechanism pathway might be involved in the regulation of its pharmacodynamics .