OBJECTIVE: To summarize the clinical and genetic characteristics of a child with 46,XX Ovotesticular disorder of sex development (46,XX OTDSD) due to copy number variation of SOX3 gene. METHODS: A 46,XX male patient presented at the Capital Center for Children's Health, Capital Medical University in November 2024 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents and subjected to trio whole-genome sequencing. Skewed X-chromosome inactivation was tested in the child and his mother. A literature review was carried out on 46,XX males associated with mutations of the SOX3 gene. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: SHERLL2025056). RESULTS: The 10-year-old boy presented with hypospadias and cryptorchidism at birth. Chromosome analysis at one year and a half revealed a 46,XX karyotype. Gonadal biopsy showed testicular tissue, while ultrasound at the age of 10 detected ovotesticular tissue. Whole-genome sequencing identified a 660 kb duplication in the Xq27.1 region, which was derived from his mother. X-chromosome inactivation testing showed random inactivation in the child and mild non-random inactivation in the mother. Literature review has found 11 publications involving 15 patients (including our case), among whom 14 had a male social gender. They had primarily presented with hypospadias at birth but had no significant endocrine abnormalities. Most patients had experienced testicular failure after puberty. SOX3 related 46,XX males are mainly caused by de novo duplications, although a few maternal carriers had been discovered. CONCLUSION Duplication of the SOX3 gene probably underlay the pathogenesis is this 46,XX male. Individuals with 46,XX SRY negative male phenotypes should be routinely screened for SOX3 gene variants. Structural variations of the SOX3 gene can lead to complete or partial sex reversal in 46,XX individuals with minimal impact on intellectual and motor development, as well as other endocrine hormones.
Child ; Humans ; Male ; 46, XX Disorders of Sex Development/genetics* ; DNA Copy Number Variations ; Gene Duplication ; Phenotype ; SOXB1 Transcription Factors/genetics*

Objective To investigate the risk factors for postoperative recurrence and metastasis in patients with T1 stageⅢ/Ⅳ clear cell renal cell carcinoma(ccRCC), and to analyze the influence of surgical methods on prognosis, so as to provide prognostic evaluation and treatment guidance for clinical practice. Methods A retrospective analysis was conducted on 398 patients diagnosed with T1 stage Ⅲ/Ⅳ ccRCC who underwent either partial nephrectomy(PN)or radical nephrectomy(RN)at Jiangsu Province Hospital during Jan. 2008 and Sep. 2022. The patients were divided into recurrence group(n=49)and non-recurrence group(n=349)according to whether the tumor recurred during the follow-up period. The general, clinical data and prognosis were compared between the two groups. Univariate and multivariate Cox regression analyses were used to explore the factors influencing disease-free survival(DFS)and overall survival(OS)after surgery. Subgroup analysis using Kaplan-Meier curves was performed for T1a and T1b patients. Results During the median follow-up of 67(42, 98)months, the recurrence group was characterized by older age, larger tumor diameter, higher proportion of T1b stage, and more complex tumor anatomy. Univariate and multivariate Cox regression analyses showed that age ≥55 years and R.E.N.A.L. score ≥7 were independent risk factors for poorer DFS and OS(P＜0.05). Subgroup analysis revealed that PN or RN did not significantly affect DFS or OS in T1a patients and OS in T1b patients, while RN significantly improved DFS in T1b patients(P＜0.05). Conclusion Age ≥55 years and R.E.N.A.L. score ≥7 are independent risk factors for poor DFS and OS in highgrade T1 ccRCC patients. For T1b patients, RN may improve DFS.

Objective:To analyze the clinical and genetic characteristics of children diagnosed with Noonan-syndrome associated with loose anagen hair (NS-LAH).Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with NS-LAH by the Endocrinology Department of the Capital Institute of Pediatrics from January 2018 to June 2024. This analysis encompassed the patients′ demographic information, clinical manifestations, distinguishing features, treatment regimens, and prognostic outcomes to elucidate their clinical characteristics. Additionally, whole-exome sequencing and Sanger sequencing were utilized to investigate the genetic etiology within the families, and the identified variations were interpreted according to the guidelines of the American College of Medical Genetics and Genomics.Results:Among the 5 NS-LAH patients, there were 3 boys and 2 girls, with ages at diagnosis ranging from 2.3 to 7.7 years old. All patients presented with short stature as a primary complaint. Birth histories were generally unremarkable, though case 2 and 5 of macrosomia were noted. In addition to the characteristic facial features of Noonan syndrome, short stature, and varying degrees of intellectual and motor developmental delay, all 5 patients exhibited sparse hair that was easily shed, as well as enlarged head circumferences. Four patients showed structural cardiac abnormalities, which included a case of hypertrophic cardiomyopathy, 2 cases of atrial septal defect, and 1 case of patent foramen ovale. Genetic analysis revealed heterozygous missense variantion in SHOC2 gene in 4 patients, comprising 3 cases with c.4A>G (p.S2G) and one case with c.519G>C (p.M173I). Additionally, one patient was found to have a heterozygous missense variantion c.146C>G (p.P49R) in PPP1CB gene. Three children were diagnosed with growth hormone deficiency and treated with growth hormone for 1.7, 2.7 and 0.5 years. This resulted in significant improvements in height, with annual increases of 11.8, 8.4 and 13.0 cm, respectively. Among the 4 patients with SHOC2 variantions, 2 developed systemic lupus erythematosus and 1 exhibited symptoms of arthritis.Conclusions:Growth failure is the primary complaint in patients with NS-LAH. Key characteristic findings include enlarged head circumference and sparse, loose hair. Growth hormone deficiency is commonly associated with NS-LAH, and growth hormone therapy is generally effective. Furthermore, patients carrying the classic variantion in SHOC2 (c.4A>G) may have an increased risk of developing autoimmune diseases.

Objective:To analyze the clinical and genetic characteristics of children diagnosed with Noonan-syndrome associated with loose anagen hair (NS-LAH).Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with NS-LAH by the Endocrinology Department of the Capital Institute of Pediatrics from January 2018 to June 2024. This analysis encompassed the patients′ demographic information, clinical manifestations, distinguishing features, treatment regimens, and prognostic outcomes to elucidate their clinical characteristics. Additionally, whole-exome sequencing and Sanger sequencing were utilized to investigate the genetic etiology within the families, and the identified variations were interpreted according to the guidelines of the American College of Medical Genetics and Genomics.Results:Among the 5 NS-LAH patients, there were 3 boys and 2 girls, with ages at diagnosis ranging from 2.3 to 7.7 years old. All patients presented with short stature as a primary complaint. Birth histories were generally unremarkable, though case 2 and 5 of macrosomia were noted. In addition to the characteristic facial features of Noonan syndrome, short stature, and varying degrees of intellectual and motor developmental delay, all 5 patients exhibited sparse hair that was easily shed, as well as enlarged head circumferences. Four patients showed structural cardiac abnormalities, which included a case of hypertrophic cardiomyopathy, 2 cases of atrial septal defect, and 1 case of patent foramen ovale. Genetic analysis revealed heterozygous missense variantion in SHOC2 gene in 4 patients, comprising 3 cases with c.4A>G (p.S2G) and one case with c.519G>C (p.M173I). Additionally, one patient was found to have a heterozygous missense variantion c.146C>G (p.P49R) in PPP1CB gene. Three children were diagnosed with growth hormone deficiency and treated with growth hormone for 1.7, 2.7 and 0.5 years. This resulted in significant improvements in height, with annual increases of 11.8, 8.4 and 13.0 cm, respectively. Among the 4 patients with SHOC2 variantions, 2 developed systemic lupus erythematosus and 1 exhibited symptoms of arthritis.Conclusions:Growth failure is the primary complaint in patients with NS-LAH. Key characteristic findings include enlarged head circumference and sparse, loose hair. Growth hormone deficiency is commonly associated with NS-LAH, and growth hormone therapy is generally effective. Furthermore, patients carrying the classic variantion in SHOC2 (c.4A>G) may have an increased risk of developing autoimmune diseases.

Objective:To analyze the efficacy and safety of curcumin in the treatment of knee osteoarthritis.Methods:The randomized controlled trials of curcumin in the treatment of knee osteoarthritis published from January 2011 to August 2021 were retrieved. The bias risk of the included literatures was evaluated by Revman 5.3 software, and the efficacy related indexes and the incidence of adverse events were analyzed by Stata 16.0 software. The weighted mean difference ( WMD) was calculated for the difference of efficacy indexes, the odds ratio ( OR) was calculated for the difference of safety indexes, the difference was compared by t test. Results:① A total of 9 relevant literatures were included, all of which were in English. ② A total of 724 patients were included in the study, of which 383 were treated with curcumin capsules and 341 were treated with placebo. ③ The visual analogue scale/score (VAS) of patients treated with oral curcumin at 3-4, 6 and 8 weeks were significantly lower than those of patients treated with oral placebo, the differences were statistically significant [weighted mean difference ( WMD)=-1.09, 95% CI (-1.44, -0.73), P<0.001; WMD=-1.52, 95% CI (-2.35, -0.69), P<0.001; WMD=-1.20, 95% CI(-1.71, -0.69), P<0.001]. ④ The western Ontario and McMaster universities osteoarthritis index (WOMAC) scores of patients treated with oral curcumin for 3-4 and 6-8 weeks were significantly lower than those of patients treated with oral placebo, and the differences were statistically significant [ WMD=-7.96, 95% CI(-14.89, -1.04), P=0.020; WMD=-15.34, 95% CI(-20.51, -10.18), P<0.001]. Specifically, the WOMAC pain and stiffness scores of patients treated with oral curcumin for 6-8 weeks were significantly lower than those of patients treated with oral placebo, and the differences were statistically significant [ WMD=-2.16, 95% CI(-3.69, -0.63), P=0.010; WMD=-1.00, 95% CI (-1.54, -0.46), P<0.001]. The WOMAC joint function scores of patients treated with oral curcumin for 3-4 and 6-8 weeks were significantly lower than those of patients treated with oral placebo, the difference was statistically significant [ WMD=-3.21, 95% CI(-4.51, -1.92), P<0.001; WMD=-7.07, 95% CI(-11.19, -2.94), P<0.001]. ⑤ There was no significant difference in the incidence of adverse events between oral curcumin and placebo [ OR=1.19, 95% P(0.74, 1.90), P=0.478]. Conclusion:Compared with placebo, oral curcumin can significantly alleviate the pain, stiffness and joint function of patients with knee osteoarthritis, and its safety is similar to placebo.