To investigate the clinical symptoms and endoscopic features of rectal benign lymphoid polyps, a retrospective analysis was conducted on 15 consecutive cases (16 lesions) who underwent endoscopic resection at the First Affiliated Hospital of Shandong First Medical University between April 2015 and June 2023, with postoperative pathological confirmation of rectal benign lymphoid polyps. The results showed that among the 15 patients, 6 were male and 9 were female, with a mean age of 52.6 years. Colonoscopy was performed in 8 patients due to clinical symptoms, among whom 7 presented with abdominal pain. All 16 lesions were submucosal, including 14 solitary and 1 multiple. The lesions were located in the lower rectum ( n=10) and mid-rectum ( n=6), with a mean long diameter of 0.5 cm. Fourteen lesions exhibited regular shape as flat circles or hemispheres. The surface mucosa appeared normal or gray-white in 11 lesions, and varying degrees of capillary dilation were observed in 8 lesions, among which 2 exhibited prominent capillaries resembling a "wheel-shaped" pattern. Endoscopic ultrasonography (EUS) was performed in 10 lesions prior to endoscopic resection: 4 originated from the third layer, 3 from the second layer, and 3 from both the second and third layers. Five lesions appeared as homogeneous hypoechoic masses, 3 were hyperechoic, and 2 showed mixed echogenicity. Therefore, the clinical symptoms of rectal benign lymphoid polyps are non-specific. Endoscopically, the presence of "wheel-shaped" pattern of dilated capillaries may serve as a diagnostic clue. When EUS demonstrates hyperechoic or mixed echogenicity, it could aid in the differential diagnosis from rectal neuroendocrine neoplasms.

To investigate the clinical symptoms and endoscopic features of rectal benign lymphoid polyps, a retrospective analysis was conducted on 15 consecutive cases (16 lesions) who underwent endoscopic resection at the First Affiliated Hospital of Shandong First Medical University between April 2015 and June 2023, with postoperative pathological confirmation of rectal benign lymphoid polyps. The results showed that among the 15 patients, 6 were male and 9 were female, with a mean age of 52.6 years. Colonoscopy was performed in 8 patients due to clinical symptoms, among whom 7 presented with abdominal pain. All 16 lesions were submucosal, including 14 solitary and 1 multiple. The lesions were located in the lower rectum ( n=10) and mid-rectum ( n=6), with a mean long diameter of 0.5 cm. Fourteen lesions exhibited regular shape as flat circles or hemispheres. The surface mucosa appeared normal or gray-white in 11 lesions, and varying degrees of capillary dilation were observed in 8 lesions, among which 2 exhibited prominent capillaries resembling a "wheel-shaped" pattern. Endoscopic ultrasonography (EUS) was performed in 10 lesions prior to endoscopic resection: 4 originated from the third layer, 3 from the second layer, and 3 from both the second and third layers. Five lesions appeared as homogeneous hypoechoic masses, 3 were hyperechoic, and 2 showed mixed echogenicity. Therefore, the clinical symptoms of rectal benign lymphoid polyps are non-specific. Endoscopically, the presence of "wheel-shaped" pattern of dilated capillaries may serve as a diagnostic clue. When EUS demonstrates hyperechoic or mixed echogenicity, it could aid in the differential diagnosis from rectal neuroendocrine neoplasms.

Objective:To explore the clinical phenotype and genetic variant in a Chinese pedigree affected with Hunter syndrome and create immortalized cell lines for the affected pedigree members.Methods:A pedigree of six members who had visited Xi′an Children′s Hospital in July 2022 was selected as the study subject. Clinical data was collected. Whole exome sequencing was carried out for the pedigree members. Candidate variant was verified by Sanger sequencing. In addition, peripheral B lymphocytes were transfected with Epstein-Barr virus to create immortalized cell lines, which were then subjected to enzyme activity analysis.Results:The patient, a five-year-and-seven-month-old boy, had exhibited stiff limbs and enlarged joints. He had developed hernia, scaphocephaly, and barrel chest from 3 months of age. His uncle also had stiff limbs, poor hearing, blindness, and right oblique inguinal hernia. Above features had resembled those of Hunter syndrome. Genetic testing revealed that both the child and his uncle had harbored an IDS (NM_000202.8): c. 823G>A (p.D275N) variant, which was unreported previously. Bioinformatic analysis indicated that the D275 to be a highly conserved site, and the D275N variant may affect the stability of the protein′s spatial conformation, thereby decrease the catalytic activity of the enzyme. The successfully constructed immortalized lymphoblastoid cell lines for the child and his parents showed increased volume, irregular shape, burr structure and cluster growth. And the value of IDS activity of the patient′s immortalized lymphoblastoid cells was below the limit of detection. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS3+ PM2_Supporting+ PM5+ PP1+ PP3). Conclusion:Above finding has enriched the phenotypic and mutational spectra of Hunter syndrome, and provided a basis for the genetic counseling for this pedigree. The creation of immortalized cell lines has offered a model for further investigation of the impact of variant on the function of IDS and development of targeted drugs.

Objective:To analyze the clinical characteristics of a child with Congenital disorder of glycosylation due to compound heterozygous variants of COG6 gene ( COG6-CDG). Methods:A child who was admitted to Xi′an Children′s Hospital on January 10, 2023 was selected as the study subject. Clinical data were collected. Pathogenic variants were analyzed by whole exome sequencing, and candidate variants were verified by Sanger sequencing, in vitro experiments and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Xi′an Children′s Hospital (No. 20230101). Results:The child, a 1-month-8-day-old male, was admitted for diarrhea and weight loss for one month. He had presented with cholestasis, diarrhea, facial dysmorphism, poor response, bilateral Simian crease, and brain atrophy. After discharge, he had continued to have high fever, feeding difficulty, and deceased finally. Whole exome sequencing results showed that he had harbored compound heterozygous variants of the COG6 gene, namely c. 807delT (p.F269Lfs*37) and c. 1746+ 1G>C (p.Gly565_Met582del). Sanger sequencing verified that the variants were inherited from his father and mother, respectively. In vitro experiments verified that the c. 1746+ 1G>C variant could affect the mRNA splicing and produce a truncated protein, whilst the c. 807delT variant could significantly reduce gene expression at both mRNA and protein levels. Based on the guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP), the variants were classified as pathogenic (PVS1+ PM3+ PM2_Supporting) and likely pathogenic (PVS1+ PM2_Supporting), respectively. Conclusion:The c. 807delT (p.F269Lfs*37) and c. 1746+ 1G>C (p.Gly565_Met582del) compound heterozygous variants of the COG6 gene probably underlay the pathogenesis of this child. Above finding has enriched the mutational spectrum of COG6-CDG and provided a basis for the genetic counseling for this family.

Objective:To analyze the treatment outcomes and prognoses of children with head and neck non-parameningeal rhabdomyosarcoma (HNnPM RMS).Methods:A retrospective analysis was performed on the clinical data of children with HNnPM RMS admitted to Beijing Children′s Hospital from September 2012 to September 2022. The clinical features, comprehensive treatment modes and prognoses of the patients were analyzed. The overall survival rate (OS) and event free survival rate (EFS) were calculated using the Kaplan-Meier method, and univariate analysis was performed using the Log-rank test.Results:A total of 70 children were included in this study, 38 males and 32 females, with a median age of 47 months (2-210 months). Pathological subtypes including the embryonal in 27 cases, the alveolar in 36 cases and the spindle cell and sclerosing in 7 cases. Thirty children (83.3%) with alveolar type were positive for FOXO1 gene fusion. All 70 children underwent chemotherapy, including 38 with neoadjuvant chemotherapy and 32 with adjuvant chemotherapy. Sixty of 70 children underwent surgery, of whom, 10 underwent two or more surgeries. There were 63 children underwent radiotherapy, including 54 with intensity-modulated radiation therapy, 4 with particle implantation and 5 with proton therapy. The median follow-up was 45 (5-113) months, the 5-year OS was 73.2%, and the 5-year EFS was 57.7%. Univariate analysis showed lymph node metastasis ( χ2=5.022, P=0.025), distant metastasis ( χ2=8.258, P=0.004), and high Intergroup Rhabdomyosarcoma Study (IRS) group ( χ2=9.859, P=0.029) as risk factors for poor prognosis. Before June 2016, the 5-year OS based on BCH-RMS-2006 scheme was 63.6%, and after 2016, the 5-year OS based on CCCG-RMS-2016 scheme was 79.6%. Conclusion:Multidisciplinary combined standardized treatment can offer good treatment outcome and prognosis for children with HNnPM RMS. Local control is a key to the efficacy of comprehensive treatment.

Objective:To analyze the gene variants of a patient affected with Duchenne/Becker muscular dystrophy in a pedigree and further explore the genotype-phenotype correlation for providing basis for family genetic counseling.Methods:The clinical features and family history of family members were collected.Multiplex ligation-dependent probe amplification(MLPA)was utilized to detect copy number variation of target genes.The pathogenic variations were ana-lyzed by whole exome sequencing(WES).The suspected gene variations were verified by Sanger sequencing.For the splice site mutations,mini-gene was constructed and expressed in vitro to detect the number of transcript and cDNA se-quence.Results:The proband of this family is a male,with no obvious involvement of the lower limbs.Laboratory tests showed an elevated level of creatine kinase(CK)in peripheral blood(700-1600 U/L),and electromyography showed myogenic damage.MLPA did not detect pathogenic exon copy number variation in dystrophin(DMD)gene.Genetic testing showed the proband carried a maternal hemizygotic splicing variation of DMD gene(NM_004006.2):c.2622+2T＞C.An in vitro mini-gene splicing assay confirmed that this splicing mutation could affect RNA splicing.According to clinical features and genetic testing results,the proband was speculated first proof of Duchenne/Becker muscular dys-trophy(DMD/BMD)caused by DMD gene mutation.Conclusion:This study identified the pathogenic variation of a proband with DMD/BMD of DMD gene,which enriched the variation spectrum of DMD/BMD in China.It was con-firmed that the splicing variation of the DMD gene c.2622+2T＞C can produce multiple transcripts leading to different functional impairments,and based on the specificity of temporal and spatial expression,it corresponded to the mild clin-ical manifestations of the patient,providing some reference value for the correlation between genotype and phenotype.

The clinical data of a case with late-onset isolated sulfite oxidase deficiency(ISOD)admitted in the Department of Neurology, Children′s Hospital, Zhejiang University School of Medicine in July 2021 were retrospectively analyzed.Fifteen previously published cases of late-onset ISOD were also reviewed.The patient was a girl, who was hospitalized because of " motor regression with mental retardation for 5 days" at 1 year old.The manifestations of the patient were extrapyramidal symptoms, regression of motor development and seizures.The level of urinary sulfites in the patient was increased.Magnetic resonance imaging (MRI) features were bilateral pallidus and substantia nigra.Gene sequencing suggested a pure missense mutation of the sulfite oxidase( SUOX) gene c. 650(exon5)G>A(p.Arg217Gln). In 16 cases of late-onset ISOD, the median age at onset and diagnosis was 10.5 months and 34.0 months, respectively.The common clinical manifestations were hypotonia (13 cases), seizures (10 cases), movement disorders (9 cases), and ectopia lentis (6 cases). The most common brain MRI feature was pallidus changes (11 cases), followed by lesions of substantia nigra (5 cases), and cerebral atrophy (4 cases). Fourteen cases of late-onset ISOD showed a positive urinary sulfite test.The missense mutation of the SUOX gene was found in 9 cases.It suggested that brain MRI involvement of bilateral pallidus, high excretion of urine sulfites and the missense mutation of the SUOX gene were important diagnostic clues for late-onset ISOD.

Seaweed is a traditional Chinese medicine homologous to food, in which polysaccharides are responsible for anti-cancer by enhancing immunity, inducing cancer cell apoptosis, inhibiting cancer cell invasion and metastasis or directly scavenging oxidative free radicals that induce cancer cell changes. Among them, regulating immunity and promoting cancer cell apoptosis are intensively studied due to the important role in preventing cancer. Here we reviewed seaweed in the apoptosis-inducing signaling pathways including PI3K/AKT, ROS and JNK and discussed challenges in studying seaweed.

Objective:To evaluate the efficacy and influencing factors of surgery combined with neoadjuvant chemoradiotherapy in the treatment of children with non-orbital head and neck rhabdomyosarcoma (HNRMS).Methods:Information from 45 children diagnosed as non-orbital HNRMS and subjected to surgery combined with neoadjuvant chemoradiotherapy in Beijing Children′s Hospital affiliated to Capital Medical University from August 2017 to July 2021 was analyzed. The patients included 25 males and 20 females, aged from 1 to 17 years old. The primary tumor site, pathological subtype, clinical stage, risk group, therapeutic regimen, resection range and outcome of all cases were also collected. The survival curves were made using the Kaplan-Meier method and the potential prognostic factors were investigated by Cox regression analysis.Results:Fifteen (33.3%) of 45 children achieved negative surgical margin under complete tumor resection. The postoperative pathological results showed that there were 20 cases of embryonic subtype, 19 cases of alveolar subtype and 6 cases of spindle sclerosis subtype. The postoperative follow-up time ranged from 4 to 71 months, with a median of 26 months. During the follow-up period, 13 children died, among whom brain metastasis was the most common cause of death, accounting for 7/13. The 3-year overall survival rate was 67.6%. Multivariate analysis showed that non-embryonic subtype ( HR=6.26, 95% CI: 1.52-25.87, P=0.011) and failure to reach R0 resection ( HR=9.37, 95% CI: 1.18-74.34, P=0.034) were independent risk factors affecting overall survival rate. Conclusion:Surgery combined with neoadjuvant chemoradiotherapy can offer a good efficacy for children with non-orbital HNRMS. Non-embryonic subtype and resection without negative operative microscopic margins are independent risk factors for poor prognosis, and brain metastasis is the main cause of death in these children.

OBJECTIVE: To analyze the clinical features, biochemical characteristics and molecular pathogenesis of a girl with isovaleric acidemia. METHODS: Clinical features, blood spot amino acid profiles and urinary organic acid profiles of the patient were analyzed. Targeted capture, next generation sequencing and Sanger sequencing were carried out to detect potential variant of the IVD gene. RESULTS: The patient presented with poor weight gain, poor feeding, lethargy, and a "sweaty feet" odor 10 days after birth. Biochemical test suggested hyperammonemia. Blood spot amino acid profiles displayed a dramatic increase in isovalerylcarnitine (C5: 3. 044, reference range 0.04 - 0.4 μmol/L). Organic acid analysis of her urine sample revealed a high level of isovaleric glycine (669. 53, reference range 0 - 0.5). The child was ultimately diagnosed with isovaleric acidemia, and was found to harbor a paternally derived heterozygous variant c.149G>A (p.R50H) and a maternally derived heterozygous variant c.1123G>A (p.G375S) of the IVD gene. Her elder brother was a heterozygous carrier of c.1123G>A (p.G375S) variant. The c.149G>A (p.R50H) was a known pathogenic variant, while the c.1123G>A (p.G375S) variant was previously unreported. CONCLUSION The pathogenesis of the patient was delineated from the perspective of genetics, which has provided a basis for clinical diagnosis, treatment as well as genetic counseling.
Amino Acid Metabolism, Inborn Errors/genetics* ; Child ; Female ; Heterozygote ; Humans ; Isovaleryl-CoA Dehydrogenase/genetics* ; Male ; Mutation