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 distribution characteristics of treatment time for total marrow irradiation (TMI) or total marrow and lymphoid irradiation (TMLI) based on helical tomotherapy, establish a time parameter framework for the application of TMI/TMLI techniques, and provide a basis for optimizing clinical treatment efficiency, predicting patient tolerance, and streamlining workflow. Methods A retrospective analysis was conducted on 57 patients who received TMI/TMLI using helical tomotherapy between November 2024 and July 2025. Patients were stratified by height ( ≤ 130 cm group vs. > 130 cm group). Megavoltage computed tomography scanning time, beam-on time, and total treatment time were recorded. The relationship between height and treatment time was analyzed using Spearman correlation analysis. An independent samples t-test was used to compare treatment time between TMI and TMLI modes. Results In the ≤ 130 cm group, the mean megavoltage computed tomography scanning time, beam-on time, and total treatment time per fraction were (9.67 ± 1.47), (39.96 ± 9.08), and (49.63 ± 10.16) minutes, respectively. In the > 130 cm group, the corresponding times were (14.52 ± 1.17), (60.45 ± 11.19), and (74.97 ± 11.82) minutes, respectively. Treatment time was positively correlated with height (r = 0.756, P < 0.001). Among patients taller than 130 cm, there was no statistically significant difference in treatment time between the TMI and TMLI (P > 0.05). Conclusion Although helical tomotherapy requires a relatively long treatment time, its technical characteristics are well-suited for the extensive and complex target volumes involved in TMI/TMLI. Future technological upgrades and standardized stratification hold promise for enhancing both efficiency and precision, thereby expanding clinical applicability.

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 characteristics of familial hypercholesterolemia (FH) in children and provide a basis for clinical diagnosis and individualized treatment.Methods:Case series study. Clinical data of 24 children with FH, who were admitted to the Department of Endocrinology in Capital Center for Children′s Health, Capital Medical University, from January 2018 to January 2025, were analyzed. Follow-ups were performed every 3-6 months and ended in January 2025. According to the results of genetic testing, the children were divided into homozygous familial hypercholesterolemia (HoFH) group and heterozygous familial hypercholesterolemia (HeFH) group. The blood lipid levels of different subtypes, the efficacy of different treatments, and clinical outcomes were compared by Mann-Whitney U test. Results:The 24 children were from 17 families, including 14 males and 10 females, with a diagnostic age of 5.0 (3.0, 9.5) years. Genetic testing results showed that 22 cases (92%) had LDLR gene variants and 2 cases (8%) had APOB gene variants, all of which were inherited from parents. There were 5 cases (21%) of HoFH and 19 cases (79%) of HeFH, and 4 previously unreported new loci were identified. There were 6 children (25%) presented with xanthomas, including 5 cases of HoFH and 1 case of HeFH. The level of low-density lipoprotein cholesterol (LDL-C) in the HoFH group was significantly higher than that in the HeFH group ( P<0.05). Regarding treatment, 11 children received dietary control without taking medicine, 6 were treated with statins, 3 with ezetimibe, and 3 with statins combined with ezetimibe, and 1 underwent liver transplantation. None of the children receiving only dietary control achieved the target LDL-C level (<3.49 mmol/L or a reduction of >50%), and there was no statistically significant difference in LDL-C before and after dietary control ( P=0.158). After treatment with statins and (or) ezetimibe, LDL-C decreased in 12 children ( P<0.05); among them, 6 cases (all HeFH) reached the target LDL-C level. There was no statistically difference in LDL-C levels before and after treatment with atorvastatin and ezetimibe in 5 HoFH children( P>0.05). One HoFH child had LDL-C reduced to the normal range after liver transplantation. No serious adverse reactions were observed in all children during drug treatment. In the detection of vascular-related complications among 12 HeFH children, only 1 child had a slight thickening of the bilateral carotid intima-media, while no abnormalities were found in the others. Conclusions:Xanthoma is a characteristic manifestation of FH, but its incidence is relatively low in HeFH children. Family history and genetic testing are key evidences for the diagnosis of FH. Dietary control has limited efficacy in children with FH, and drug treatment should be initiated as early as possible. LDL-C levels in HoFH children are more difficult to control, if drug treatment shows poor efficacy, liver transplantation may be a better option.

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

Objectives:To investigate the influence of the mild photothermal effect of Au nanorods on the osteogenic differentiation of MC3T3-E1 osteoblast cells.Methods:Surface modification of Au nanorods was performed with bovine serum albumin(BSA)coating.The photothermal effect,photothermal stability and characteristics of AuNRs@CTAB and AuNRs@BSA were analyzed u-sing scanning electron microscopy(SEM),transmission electron microscopy(TEM),and a near-infrared laser.The biocompatibili-ty of AuNRs@BSA was evaluated using live/dead staining and the CCK-8 assay.The influence of the mild photothermal effect of AuNRs@BSA on the osteogenic differentiation of MC3T3-E1 was assessed by ALP staining,alizarin red staining,and semi-quanti-tative analysis.Results:Biocompatible and near-infrared light-responsive AuNRs@BSA were prepared.In vitro experiments dem-onstrated that the mild photothermal effect of AuNRs@BSA increased the ALP activity and mineralization ability of MC3T3-E1(P＜0.000 1).Conclusion:The mild photothermal effect of AuNRs@BSA can promote the osteogenic differentiation of MC3T3-E1 cells.

Objective Summarize the endocrine characteristics of 5 children with Wiedemann-Steiner syndrome(WDSTS)to enhance the early recognition capability of clinicians for this condition.Methods A retrospective analysis of the medical history,clinical manifestations,genetic testing,and treatment of 5 children with Wiedemann-Steiner syndrome treated in the endocrinology department of capital center for children's health,capital medical university from October 2020 to December 2024,summarizing the clinical characteristics of the disease.Results Among the 5 cases of WDSTS,there were 2 males and 3 females,with ages ranging from 1.9 to 10 years at the time of diagnosis.Cases 1 and 3 were born prematurely,and cases 1,2 and 5 were diagnosed as small for gestational age(SGA)infants.All 5 children exhibited distinctive facial features,hirsutism,sacral dimple,developmental delay,and adenoid hypertrophy,premature tooth replacement,feeding difficulties,and a high incidence of urinary system abnormalities.Four children complained of slow growth.Cases 1 and 4 were diagnosed with short stature.Cases 3 and 5 had normal height but were slightly shorter with advanced bone age.Case 5 also experienced early puberty.Case 2 was diagnosed with premature adrenarche and idiopathic central precocious puberty due to the presence of pubic hair and breast enlargement.Cases 1 and 3 were treated with recombinant human growth hormone(rhGH),which resulted in significant height growth(approximately 10 cm/year).However,treatment was discontinued in Case 1 due to a significant advancement in bone age.Conclusions WDSTS should be considered in patients presenting with short stature,distinctive facial features,hirsutism,developmental delay,and multiple system deformities.While rhGH treatment can help improve height in these patients,the potential for accelerated bone age maturation during treatment requires careful monitoring.

Objectives:To investigate the influence of the mild photothermal effect of Au nanorods on the osteogenic differentiation of MC3T3-E1 osteoblast cells.Methods:Surface modification of Au nanorods was performed with bovine serum albumin(BSA)coating.The photothermal effect,photothermal stability and characteristics of AuNRs@CTAB and AuNRs@BSA were analyzed u-sing scanning electron microscopy(SEM),transmission electron microscopy(TEM),and a near-infrared laser.The biocompatibili-ty of AuNRs@BSA was evaluated using live/dead staining and the CCK-8 assay.The influence of the mild photothermal effect of AuNRs@BSA on the osteogenic differentiation of MC3T3-E1 was assessed by ALP staining,alizarin red staining,and semi-quanti-tative analysis.Results:Biocompatible and near-infrared light-responsive AuNRs@BSA were prepared.In vitro experiments dem-onstrated that the mild photothermal effect of AuNRs@BSA increased the ALP activity and mineralization ability of MC3T3-E1(P＜0.000 1).Conclusion:The mild photothermal effect of AuNRs@BSA can promote the osteogenic differentiation of MC3T3-E1 cells.

Objective Summarize the endocrine characteristics of 5 children with Wiedemann-Steiner syndrome(WDSTS)to enhance the early recognition capability of clinicians for this condition.Methods A retrospective analysis of the medical history,clinical manifestations,genetic testing,and treatment of 5 children with Wiedemann-Steiner syndrome treated in the endocrinology department of capital center for children's health,capital medical university from October 2020 to December 2024,summarizing the clinical characteristics of the disease.Results Among the 5 cases of WDSTS,there were 2 males and 3 females,with ages ranging from 1.9 to 10 years at the time of diagnosis.Cases 1 and 3 were born prematurely,and cases 1,2 and 5 were diagnosed as small for gestational age(SGA)infants.All 5 children exhibited distinctive facial features,hirsutism,sacral dimple,developmental delay,and adenoid hypertrophy,premature tooth replacement,feeding difficulties,and a high incidence of urinary system abnormalities.Four children complained of slow growth.Cases 1 and 4 were diagnosed with short stature.Cases 3 and 5 had normal height but were slightly shorter with advanced bone age.Case 5 also experienced early puberty.Case 2 was diagnosed with premature adrenarche and idiopathic central precocious puberty due to the presence of pubic hair and breast enlargement.Cases 1 and 3 were treated with recombinant human growth hormone(rhGH),which resulted in significant height growth(approximately 10 cm/year).However,treatment was discontinued in Case 1 due to a significant advancement in bone age.Conclusions WDSTS should be considered in patients presenting with short stature,distinctive facial features,hirsutism,developmental delay,and multiple system deformities.While rhGH treatment can help improve height in these patients,the potential for accelerated bone age maturation during treatment requires careful monitoring.