Objective:To investigate the clinical and genetic characteristics of children with 45, X/46, XY mosaicism.Methods:The retrospective study included 20 children diagnosed with 45, X/46, XY and 45, X/46, X,+mar mosaicism in the First Affiliated Hospital of Zhengzhou University from 2018 to 2022. The clinical features, gonadal pathology, treatment and follow-up were summarized. Genetic tests were performed by SRY gene test, azoospermia factor region (AZF) deletion test, copy number variation-sequencing (CNV-seq). Age at first diagnosis was compared between boys and girls using independent sample t-test. Results:The 20 patients included 3 boys and 17 girls, and the age at first diagnosis were (7.6±5.5) years, it is (2.1±1.9) years in boys, (8.7±5.4) years in girls, significantly younger for boys ( t=-3.86, P=0.004). The chief complaint was external genitalia malformation for boys, and short stature (13 cases) and dysplastic external genital for girls (4 cases). Five girls presented with features of Turner syndrome. The gonadal phenotypes included mixed gonadal dysplasia (MGD, 6 cases), complete gonadal dysplasia (CGD, 10 cases), unilateral ovotestis (2 cases), possible ovaries (1 case) and undetermined gonad (1 case). One female with dysplastic genital was reassigned to male, and the gender of the remaining cases remained unchanged. Seven females were treated with recombinant human growth hormone. The height increased by (17±7) cm during the (2.9±1.2) years follow-up. No gonadal malignancy was observed. The karyotype was 45, X/46, XY in 16 cases, and 45, X/46, X,+mar in 4 cases. All of the 4 marker chromosomes were derived from Y chromosome confirmed by CNV-seq. SRY gene was detected in all 20 patients genome, and AZF deletion was found in 7 girls. Conclusions:45, X/46, XY mosaicism presented with dysplastic external genital or female with remarkable short stature. Gonadal phenotypes included MGD, CGD and ovotestis. AZF microdeletions were found in the majority of female cases.

The contents recorded in the rotation registration manual is not only the quantitative indicators for evaluating the quality of residency training, but also the important basis for training assessment and issuance of training certificates. In order to solve the problems of data authenticity, information delay, and repeated entry in the rotation registration manual for residency training, Shanghai East Hospital, Tongji University, launched a project to dock the electronic rotation registration manual with the hospital information system. Through the establishment of the project team, the development of working mechanisms, and the implementation of the project, data analysis was used for process reformation and system optimization, so as to continuously improve management efficiency and medical safety while solving problems and form a set of implementation system with reference significance in practice.

Allergic conjunctivitis is the most common type of allergic eye disease, and the incidence in children and adolescents is increasing year by year. Drug therapy can only relieve some symptoms and only in a short period, while allergen immunotherapy is currently a therapy that can significantly improve the symptoms of chronic allergy and the course of the disease. This method has been used abroad for many years but has yet to be reported in China. The author reviews the effective mechanism and clinical efficiency of allergen immunotherapy and provides a reference for the further clinical application in China.

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with disorders of sex development (DSD). METHODS: Five children with DSD who presented at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2020 were enrolled. In addition to chromosomal karyotyping, whole exome sequencing (WES), SRY gene testing, and CNV-seq were also carried out. RESULTS: Child 1 and 2 had a social gender of female, whilst their karyotypes were both 46,XY. No pathogenic variant was identified by WES. The results of CNV-seq were 46,XY,+Y (1.4) and 46,XY,-Y (0.75), respectively. The remaining three children have all carried an abnormal chromosome Y. Based on the results of CNV-seq, their karyotypes were respectively verified as 45,X[60]/46,X,del(Y)(q11.221)[40], 45,X,16qh+[76]/46,X,del(Y)(q11.222),16qh+[24], and 45,X[75]/46,XY[25]. CONCLUSION CNV-seq may be used to verify the CNVs on the Y chromosome among children with DSD and identify the abnormal chromosome in those with 45,X/46,XY. Above results have provided a basis for the clinical diagnosis and treatment of such children.
Humans ; Child ; Female ; DNA Copy Number Variations ; Chromosome Aberrations ; Karyotyping ; Exome Sequencing ; Disorders of Sex Development/genetics*

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for revealing the genetic etiology of fetuses with isolated ventricular septal defect (VSD). METHODS: From December 2017 to December 2020, 69 fetuses with isolated VSD were identified at the First Affiliated Hospital of Zhengzhou University. Meanwhile, 839 similar prenatal cases were selected from public databases including Wanfang data, Wanfang Medicine, and China National Knowledge Infrastructure (CNKI) by using keywords such as "Ventricular septal defect", "Copy number variation", and "Prenatal". A total of 908 fetuses with isolated VSD were analyzed. CNV-seq was carried out for 69 fetuses. RESULTS: Among the 908 fetuses, 33 (3.63%) were found to harbor pathogenic CNVs, which included 11 chromosomal aneuploidies (1.21%) and 22 pathogenic CNVs (2.42%). The pathogenic CNVs have involved 12 genetic syndromes, with those known to involve the heart development including 5 cases of 22q11.21 deletion syndrome, 2 cases of 4q terminal deletion syndrome, and 1 case of 9q subtelomere deletion syndrome. The outcome of pregnancies for 15 fetuses with pathogenic CNVs was known, of which 12 were terminated, and 3 had spontaneous closure of the ventricular septum after birth, but 1 of them had other abnormalities. CONCLUSION Fetuses with isolated VSD have a relatively high risk for chromosomal abnormalities, for which CNV-seq should be recommended.
Female ; Pregnancy ; Humans ; DNA Copy Number Variations ; Heart Septal Defects, Ventricular/genetics* ; 22q11 Deletion Syndrome ; Fetus

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for a woman featuring moderate intellectual disability (ID). METHODS: The patient had presented at the First Affiliated Hospital of Zhengzhou University on April 28, 2021. With informed consent, peripheral blood and amniotic fluid samples were collected for the extraction of genomic DNA. Pathogenic copy number variations (CNVs) were detected with CNV-seq, and single gene variants were detected by whole exome sequencing (WES) and Sanger sequencing. Candidate variant was verified by Sanger sequencing, and CNV-seq and multiplex ligation-dependent probe amplification (MLPA) were used to detect fetal CNVs. RESULTS: The 23-year-old woman had moderate ID, sideway walking, and unstable holding. Ultrasonography at 18⁺³ weeks' gestation had revealed no fetal abnormality. No pathogenic CNV was detected in the woman by CNV-Seq, while WES revealed that she has harbored a heterozygous c.1675C>T (p.Arg559*) variant of the DLG4 gene, which was verified by Sanger sequencing. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PVS1+PM2_supporting). Sanger sequencing has confirmed that the fetus has inherited this variant, and CNV-Seq also revealed that that fetus has harbored a 0.1 Mb heterozygous deletion at Xp21.1, which has encompassed the DMD gene, and the result was verified by MLPA. CONCLUSION The heterozygous c.1675C>T variant of the DLG4 gene probably underlay the mental retardation in this woman, and her fetus was found to harbor the same variant in addition with deletion of the DMD gene, which may predispose to ID type 62.
Female ; Humans ; Pregnancy ; Young Adult ; Disks Large Homolog 4 Protein ; DNA Copy Number Variations ; Fetus ; Genetic Testing ; Intellectual Disability/genetics* ; Pregnant Women

Objective To overview the methodological quality,report quality and evidence quality of the Meta-Analyses/Systematic Reviews(MAs/SRs)of acupuncture for post-stroke cognitive impairment(PSCI).Methods A search was conducted for MAs/SRs on PSCI using English or Chinese from inception to 20 February 2022 published in four Chinese databases:CNKI,Wanfang,VIP,CBM;and three English databases:PubMed,Embase and Cochrane Library.The MAs/SRs were evaluated for methodological quality using AMSTAR 2 and for reporting quality using PRISMA,and the quality of evidence was assessed using the GRADE system.Results A total of 18 MAs/SRs were included in this study,of which 89%showed the effectiveness and safety of acupuncture for PSCI.According to AMSTAR 2,1 study was of low methodological quality and 17 studies were of critically low quality;according to PRISMA,1 study was of high quality,16 studies were of moderate quality and 1 study was of poor quality;GRADE showed that of the 71 outcomes included,however,there was no evidence of high quality outcomes,with 10 of moderate quality,17 of low quality,and 44 of very low quality.Conclusion Acupuncture may be effective and safe in the treatment of PSCI,but in current acupuncture for PSCI is generally of low quality and should be interpreted with caution.

Objective A scoping review of clinical research studies on acupuncture and moxibustion intervention in mild cognitive impairment(MCI),to get a comprehensive understanding of the current state of research in the field,in order to provide reference for the key research direction and clinical decision-making of acupuncture and moxibustion intervention in MCI in the future.Methods Systematic searches were carried out in Chinese and English databases(such as CNKI,Wanfang,VIP,China Biomedical Database,Pubmed,Web of Science,Embase,The Cochrane library),and trial registration platforms(such as WHO ICTRP and Clinical Trials.gov).the clinical studies and Systematic Reviews(SRs)and/or Meta-analyses(MAs)of acupuncture and moxibustion in the treatment of MCI were collected.The search language is limited to Chinese and English,and the search time is from the establishment to July 27,2022.The final included studies were summarized from the aspects of annual publication trend,the patterns of Traditional Chinese medicine(TCM)syndrome differentiation,acupuncture treatment plan,and outcome indicators of clinical studies.AMASTAR 2 was used to evaluate the methodological quality of SRs/MAs,and evidence mapping was constructed using bubble charts,etc.Results 108 original clinical studies and 9 SRs/MAs were included.The included clinical studies were randomized controlled trials.From 2006 to 2022,the number of publications generally showed an upward trend.Kidney essence deficiency syndrome was the most common dialectical classification in TCM.Special acupuncture treatment regimens are most common as interventions.And outcome measures were mainly Mini-Mental State Examination,Montreal Cognitive Assessment,and Activities of Daily Living,and so on.The assessment of AMSTAR 2 showed at least more than 2 critical flaws,the methodological quality of included SRs/MAs was critically low.Conclusion At present,acupuncture and moxibustion intervention for MCI has a good development prospect and is worthy of in-depth study,but there are still problems such as a single type of clinical study,lack of unified standards for TCM syndrome differentiation,and further standardization of outcome indicator reporting.In addition,the quality of existing evidence for SRs/MAs is generally low,and more in-depth studies are needed to clarify the clinical efficacy and safety of acupuncture and moxibustion intervention for MCI.

OBJECTIVE: To explore the genetic basis for a rare case with Disorder of sex development. METHODS: Clinical data of the patient was collected. Chromosomal karyotyping, SRY gene testing, whole exome sequencing (WES), low-coverage massively parallel copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and whole genome sequencing (WGS) were carried out. RESULTS: The patient, a 14-year-old female, had manifested short stature and dysplasia of second sex characteristics. She was found to have a 46,XY karyotype and positive for the SRY gene. No pathogenic variant was found by WES, except a duplication at Yp11.32q12. The result of CNV-seq was 47,XYY. FISH has confirmed mosaicism for a dicentric Y chromosome. A 23.66 Mb duplication on Yp11.32q11.223 and a 5.16 Mb deletion on Yq11.223q11.23 were found by WGS. The breakpoint was mapped at chrY: 23656267. The patient's karyotype was ultimately determined as 46,X,psu idic(Y)(q11.223)/46,X,del(Y)(q11.223). CONCLUSION The combination of multiple methods has facilitated clarification of the genetic etiology in this patient, which has provided a reference for the clinical diagnosis and treatment.
Female ; Humans ; Adolescent ; DNA Copy Number Variations ; In Situ Hybridization, Fluorescence ; Y Chromosome ; Sexual Development ; Mosaicism

The paper reports two cases of lipoprotein glomerulopathy (LPG) in children. The Sanger sequencing results in 2 cases indicated apolipoprotein E gene mutation[c.127 (exon3) C>T, p.R43C (p.Arg43Cys); c.494 (exon4) G>C, p.R165P (p.Arg165Pro),respectively]. Renal pathological presentation of two children showed that a large number of lipoprotein emboli were formed in the glomerular capillary loop, and the diagnosis of LPG was confirmed. The onset of LPG has no specific clinical manifestation, which is easy to be undiagnosed or misdiagnosed. Renal biopsy is a diagnostic means, glucocorticoid treatment is ineffective, and long-term lipid-lowering treatment may be required for LPG.