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 identify the risk factors of venous thromboembolism (VTE) in postoperative renal transplantation recipients by Meta-analysis, and to provide evidence-based reference for clinical staff to develop early VTE prevention strategies.Methods:PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP database, Wanfang database and Chinese Biomedical Literature Database were searched to collect the studies on the risk factors of postoperative VTE in kidney transplant recipients. The search period was from the establishment of the database to March 10, 2024. After literature screening, data extraction and quality evaluation were conducted independently by two researchers, Meta-analysis was performed using RevMan 5.3 software.Results:A total of 15 literatures with 20 influencing factors were included. Meta-analysis showed that age ( MD = 6.36, 95% CI 2.56-10.17, P<0.05), body mass index ( MD = 1.83, 95% CI 0.15-3.50, P<0.05), VTE history ( OR = 2.04, 95% CI 1.08-3.86, P<0.05), blood transfusion history ( OR = 3.77, 95% CI 2.43-5.83, P<0.05), glomerular filtration rate ( MD = -5.54, 95% CI -9.93 - -0.91, P<0.05), donor age ( MD = 3.18, 95% CI 1.10-5.25, P<0.05), combination of malignant tumor ( OR = 2.87, 95% CI 1.45-5.68, P<0.05), end-stage renal disease as polycystic kidney disease ( OR = 1.76, 95% CI 1.39-2.22, P<0.05), and interstitial nephritis ( OR = 1.60, 95% CI 1.06-2.40, P<0.05) were the influencing factors for postoperative VTE in renal transplant recipients. Conclusions:Clinical medical staff should actively identify high-risk groups for VTE after kidney transplantation by considering the 8 influencing factors determined by this study, and take targeted measures early to reduce the risk of postoperative VTE.

In June 2018,sows at a pig farm in Jiamusi,Heilongjiang Province,suffered a large num-ber of miscarriages,and subsequently weaned piglets at the farm began to show persistent high fe-ver symptoms at around 35 days of age,with some pigs having a fever of more than 41.5 ℃.In or-der to determine the cause of this outbreak,63 clinical samples from this farm were tested.The re-sults showed that 60 out of 63 samples were positive for the porcine reproductive and respiratory syndrome virus(PRRSV)antigen.Subsequently,PRRSV antigen-positive plasmid was transfected into African green monkey embryonic kidney cells(Marc-145),and after three generations of blind transmission,indirect immunofluorescence assay(IFA)was performed.The results showed that one PRRSV strain,named HLJ38,was successfully isolated.Then the whole genome of HLJ38 strain was sequenced and then analyzed in detail by bioinformatics software.Sequence analysis showed that there were three deletions of 131 amino acids(323-433 aa,483 aa and 504-522 aa)in the derived sequence of Nsp2 gene of HLJ38 strain,which was consistent with the molecular ge-netic marker of NADC30 PRRSV.The phylogenetic tree analysis showed that HLJ38 and NADC30 PRRSV in GenBank belong to lineage 1 subgroup,and the nucleotide homology of HLJ38 and NADC30 PRRSV in GenBank was only 85.2％and 84.6％.Recombinant analysis showed that HLJ38 was a recombinant NADC30-like PRRSV,and the recombinant gene fragments were de-rived from multiple strains,among which the fragment of 1-201 nt was provided by VR2332 strain and fragment of 6 641-8 061 nt derived from the HP-PRRSV strain.In summary,the re-sults showed that the outbreak in this pig farm may be caused by the recombination of PRRSV strains among different lineages,and the recombinant circulating strains not only have certain pathogenicity but also suggest that the existing commercial vaccines provide limited cross-protec-tion against them.Recombination between different lineages increases the genetic diversity of PRRSV and aggravates the difficulty of prevention and control of PRRS in pig farms.Therefore,it is necessary to continuously monitor the epidemic dynamics of PRRSV in pig farms and take effec-tive measures in time to curb the spread of PRRS.

As a unique type of job burnout,caregiving burnout not only reduces the quality of care,but also significant impacts the physical and mental health of both caregivers and care recipinets,extending its affects to families and society at large.This paper reviews the concept,measurement tools,and theoretical models of caregiv-ing burnout;and examines its antecedent and consequential variables.Future research should focus on distinguishing between formal and informal caregiving burnout,improving measurement methods,and developing effective inter-vention strategy tailoered to Chinese culture context.

In June 2018,sows at a pig farm in Jiamusi,Heilongjiang Province,suffered a large num-ber of miscarriages,and subsequently weaned piglets at the farm began to show persistent high fe-ver symptoms at around 35 days of age,with some pigs having a fever of more than 41.5 ℃.In or-der to determine the cause of this outbreak,63 clinical samples from this farm were tested.The re-sults showed that 60 out of 63 samples were positive for the porcine reproductive and respiratory syndrome virus(PRRSV)antigen.Subsequently,PRRSV antigen-positive plasmid was transfected into African green monkey embryonic kidney cells(Marc-145),and after three generations of blind transmission,indirect immunofluorescence assay(IFA)was performed.The results showed that one PRRSV strain,named HLJ38,was successfully isolated.Then the whole genome of HLJ38 strain was sequenced and then analyzed in detail by bioinformatics software.Sequence analysis showed that there were three deletions of 131 amino acids(323-433 aa,483 aa and 504-522 aa)in the derived sequence of Nsp2 gene of HLJ38 strain,which was consistent with the molecular ge-netic marker of NADC30 PRRSV.The phylogenetic tree analysis showed that HLJ38 and NADC30 PRRSV in GenBank belong to lineage 1 subgroup,and the nucleotide homology of HLJ38 and NADC30 PRRSV in GenBank was only 85.2％and 84.6％.Recombinant analysis showed that HLJ38 was a recombinant NADC30-like PRRSV,and the recombinant gene fragments were de-rived from multiple strains,among which the fragment of 1-201 nt was provided by VR2332 strain and fragment of 6 641-8 061 nt derived from the HP-PRRSV strain.In summary,the re-sults showed that the outbreak in this pig farm may be caused by the recombination of PRRSV strains among different lineages,and the recombinant circulating strains not only have certain pathogenicity but also suggest that the existing commercial vaccines provide limited cross-protec-tion against them.Recombination between different lineages increases the genetic diversity of PRRSV and aggravates the difficulty of prevention and control of PRRS in pig farms.Therefore,it is necessary to continuously monitor the epidemic dynamics of PRRSV in pig farms and take effec-tive measures in time to curb the spread of PRRS.

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.

As a unique type of job burnout,caregiving burnout not only reduces the quality of care,but also significant impacts the physical and mental health of both caregivers and care recipinets,extending its affects to families and society at large.This paper reviews the concept,measurement tools,and theoretical models of caregiv-ing burnout;and examines its antecedent and consequential variables.Future research should focus on distinguishing between formal and informal caregiving burnout,improving measurement methods,and developing effective inter-vention strategy tailoered to Chinese culture context.

Objective:To identify the risk factors of venous thromboembolism (VTE) in postoperative renal transplantation recipients by Meta-analysis, and to provide evidence-based reference for clinical staff to develop early VTE prevention strategies.Methods:PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP database, Wanfang database and Chinese Biomedical Literature Database were searched to collect the studies on the risk factors of postoperative VTE in kidney transplant recipients. The search period was from the establishment of the database to March 10, 2024. After literature screening, data extraction and quality evaluation were conducted independently by two researchers, Meta-analysis was performed using RevMan 5.3 software.Results:A total of 15 literatures with 20 influencing factors were included. Meta-analysis showed that age ( MD = 6.36, 95% CI 2.56-10.17, P<0.05), body mass index ( MD = 1.83, 95% CI 0.15-3.50, P<0.05), VTE history ( OR = 2.04, 95% CI 1.08-3.86, P<0.05), blood transfusion history ( OR = 3.77, 95% CI 2.43-5.83, P<0.05), glomerular filtration rate ( MD = -5.54, 95% CI -9.93 - -0.91, P<0.05), donor age ( MD = 3.18, 95% CI 1.10-5.25, P<0.05), combination of malignant tumor ( OR = 2.87, 95% CI 1.45-5.68, P<0.05), end-stage renal disease as polycystic kidney disease ( OR = 1.76, 95% CI 1.39-2.22, P<0.05), and interstitial nephritis ( OR = 1.60, 95% CI 1.06-2.40, P<0.05) were the influencing factors for postoperative VTE in renal transplant recipients. Conclusions:Clinical medical staff should actively identify high-risk groups for VTE after kidney transplantation by considering the 8 influencing factors determined by this study, and take targeted measures early to reduce the risk of postoperative VTE.

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.

Objective:To analyze the genetic and clinical characteristics, treatment and prognosis of patients diagnosed with maturity onset of diabetes of the young (MODY) 12 subtype.Methods:This retrospective study collected and analyzed data from 5 children with MODY12 subtype caused by ABCC8 gene variants who underwent inpatient and outpatient genetic testing at Beijing Children′s Hospital from January 2016 to December 2023. Their clinical and genetic features, treatment, and follow-up results were analyzed.Results:Among the 5 patients with MODY12 subtype, 4 were male and 1 was female, with an age of 13.4 (5.5, 14.6) years. Four of the patients were born large for gestational age, while one was born small for gestational age. Two patients were overweight or obese. Three patients exhibited typical symptoms of diabetes, while 2 were incidentally found to have elevated blood glucose level. One patient was found to have diabetic ketoacidosis at onset, who was diagnosed with congenital hyperinsulinism during the neonatal period and received diazoxide treatment, and experienced intellectual developmental delay. All 5 patients had autosomal dominant inherited diabetes within 3 generations. The fasting blood glucose at onset was 7.5 (6.5, 10.0) mmol/L, the haemoglobin A1c (HbA1c) was 11.8% (7.5%, 13.5%), and the fasting C-peptide was 1.2 (1.1, 2.2) μg/L. The duration of follow-up was 15 (9, 32) months. One patient underwent lifestyle intervention, 2 received metformin orally, 1 received insulin therapy, and the other received subcutaneous injection of insulin combined with sulfonylurea orally. At the last follow-up, the median fasting blood glucose was 6.1 (5.1, 7.0) mmol/L, the HbA1c was 5.9% (5.7%, 7.1%), and the fasting C-peptide was 1.7 (0.9, 2.9) μg/L. One patient developed diabetic retinopathy. There were 4 missense variations in ABCC8 gene and one in-frame deletion, all of which were maternally inherited heterozygotes.Conclusions:MODY12 subtype is a heterogeneous disorder with the age of onset from infancy to adolescence. It can present as mild hyperglycemia or diabetic ketoacidosis, and has a high incidence of obesity. Definitive diagnosis can be achieved through genetic test, and individualized treatment is recommended based on glucose levels.