External auditory canal cholesteatoma in children: clinical manifestations.

PURPOSE: The purpose of this study was to explore the characteristics of external auditory canal cholesteatoma (EACC) among children and to describe its radiological findings on high-resolution computed tomography (CT) of the temporal bone in order to improve the diagnostic accuracy of primary EACC. METHODS: The clinical records and CT imaging features of 44 patients who were diagnosed with EACC between January 2017 and May 2022 at Shenzhen Children's Hospital were retrospectively reviewed. Clinical features, including external auditory canal wall findings, hearing damage, symptoms and physical examination findings, were analysed against the level of lesion involvement. The correlation between different types of EACC and the incidence of different clinical symptoms was analysed, and the degree of hearing impairment and the rate of bone wall destruction were examined using CT. RESULTS: The mean age at EACC onset was 9.02 ± 3.15 years, and the mean age at onset for EACC involving the right ear was older than that of EACC involving the left ear (P < 0.05). There were 44 patients (46 ears), including 10 ears with type I EACC, 23 ears with type II EACC, and 13 ears with type III EACC. Conductive hearing loss was the main type of hearing impairment observed among EACC patients. There were differences in types I, II and III EACC in terms of hearing impairment; specifically, there was a significant difference in moderate hearing impairment between type II and type III EACC patients (P < 0.05). The four most common symptoms were otorrhea, otalgia, itching and bleeding. The incidence of itching symptoms was greater in type I EACC than the incidence of otorrhea, and the incidence of otorrhea symptoms in type II and type III EACC was significantly greater than that in type I EACC(P < 0.05). There were no significant differences in the fracture rates of the anterior, posterior, superior or inferior walls of the external auditory canal within or between type II and type III EACC patients (P > 0.05). The failure rate of scute damage was significantly higher in type III EACC patients than in type II EACC patients (P < 0.05). CONCLUSION: The presence of otorrhea and hearing loss as well as the identification of granulation tissue during otoscopy suggest the need for a temporal bone CT scan. This imaging modality can aid in the early detection and accurate classification of EACC, thereby guiding the selection of appropriate surgical interventions and greatly assisting in preventing further progression of hearing impairment.

PROTOCOL: Effectiveness of behavioral interventions for smoking cessation among homeless persons: A systematic review and meta-analysis.

This is the protocol for an updated Campbell systematic review. The objectives are as follows: To evaluate the effect of behavioral interventions on smoking cessation among homeless individuals.

The role of IL-36 and 37 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has garnered considerable attention due to its morbidity and mortality. Although the precise mechanisms underlying HCC tumorigenesis remain to be elucidated, evidence suggests that host immunity plays a pivotal role in its development. IL-36 and IL-37 are important immunoregulatory cytokines classified as pro-inflammatory and anti-inflammatory respectively. In the context of HCC, the downregulation of intrahepatic IL-36 is inversely correlated with cirrhosis, but positively correlated with 5-year survival rates, suggesting that IL-36 offers protection during HCC development. However, IL-36 may lose its hepatoprotective effects as the disease progresses to HCC in the context of dysregulated immunity in cirrhotic patients. Substantially increased circulating IL-36 in HCC patients is likely a systemic response to HCC stimulation, but is insufficient to suppress progression towards HCC. Intrahepatic IL-37 is suppressed in HCC patients, consistent with the inverse correlation between intrahepatic IL-37 and the level of AFP in HCC patients, suggesting IL-37 exerts hepatoprotection. There is no significant difference in IL-37 among differentiations of HCC or with respect to clinical BCLC stages or cirrhosis status in HCC patients. However, IL-37 protection is demonstrated in an IL-37 transfected HCC animal model, showing significantly reduced tumour size. IL-36/37 may inhibit HCC by enhancing M1 tumour-associated macrophages while not affecting M2 macrophages. The interplay between IL-36 (pro-inflammatory) and IL-37 (anti-inflammatory) is emerging as a crucial factor in host protection against the development of HCC. Further research is needed to investigate the complex mechanisms involved and the therapeutic potential of targeting these cytokines in HCC management.

[Analysis of clinical features and genetic variant in a child with Cowden syndrome 1].

OBJECTIVE: To explore the genetic etiology of a child with Cowden syndrome 1 (CS1). METHODS: A child who had visited the Ningbo Women and Children's Hospital on August 26, 2022 was selected as the study subject. Clinical information of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The child, a 13-year-old boy, had manifested with severe mental retardation, hyperactivity, autistic behavior, sparse and prominent teeth, macrocephaly, and skin freckles on the penis. His mother had presented with multiple papules, hamartomatous polyps, thyroid adenoma and macrocephaly. WES results revealed that the child has harbored a nonsense c.781C>T (p.Q261*) variant of the PTEN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.781C>T variant was classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION: The c.781C>T variant of the PTEN gene probably underlay the pathogenesis in the child and his mother. Above finding has facilitated genetic counseling for this family.

[Clinical phenotype and genetic analysis of a fetus with Cardiac valvular dysplasia type 1].

OBJECTIVE: To explore the genetic basis for a fetus with Cardiac valvular dysplasia type 1 (CVDP1). METHODS: A CVDP1 fetus identified at the Ningbo Women and Children's Hospital on July 7, 2022 was selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were subjected to trio-whole exome sequencing (trio-WES), and candidate variants were verified by Sanger sequencing. RESULTS: The fetus had exhibited generalized edema, complex cardiac malformation, abdominal effusion, and enhanced intestinal and renal parenchymal echoes. Trio-WES revealed that it has harbored compound heterozygous variants of the PLD1 gene, namely c.2977C>T (p.R993*) and c.1460G>A (p.W487*), which were respectively inherited from its father and mother. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2977C>T (p.R993*) variant was evaluated to be likely pathogenic (PVS1_Moderate+PM2_Supporting+PM3+PP4), whilst the c.1460G>A (p.W487*) variant was evaluated to be pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION: The c.2977C>T (p.R993*) and c.1460G>A (p.W487*) compound heterozygous variants of the PLD1 gene probably underlay the CVDP1 in the fetus. Above discovery has enriched the mutational spectrum of the PLD1 gene and provided a guidance for genetic counseling and prenatal diagnosis in this family.