Clinical characteristics and genetic analysis of a fetus with Melnick-Needles syndrome due to variant of FLNA gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a fetus with Melnick-Needles syndrome (MNS).@*METHODS@#A fetus with MNS diagnosed at Ningbo Women and Children's Hospital in November 2020 was selected as the study subject. Clinical data was collected. Pathogenic variant was screened by using trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing.@*RESULTS@#Prenatal ultrasonography of the fetus had shown multiple anomalies including intrauterine growth retardation, bilateral femur curvature, omphalocele, single umbilical artery, and oligohydramnios. Trio-WES revealed that the fetus has harbored hemizygous c.3562G>A (p.A1188T) missense variant of the FLNA gene. Sanger sequencing confirmed that the variant was maternally derived, whilst its father was of a wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+PM2_Supporting+PP3+PP4).@*CONCLUSION@#The hemizygous c.3562G>A (p.A1188T) variant of the FLNA gene probably underlay the structural abnormalities in this fetus. Genetic testing can facilitate accurate diagnosis of MNS and provide a basis for genetic counseling for this family.

Genetic analysis of a Chinese pedigree featuring non-simplex blepharocheilodontic syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a Chinese pedigree featuring non-simplex blepharocheilodontic syndrome.@*METHODS@#Whole exome sequencing was carried out to detect genetic variant and copy number variations (CNVs) in the pedigree. Suspected variants were verified by Sanger sequencing and qPCR.@*RESULTS@#The fetus and its elder brother, father and grandfather were found to harbor a heterozygous c.83delG (p.A29Rfs*55) variant of the CTNND1 gene, which was unreported previously. In addition, its elder brother was also found to be a double heterozygote for a c.235delC (p.L79Cfs*3) variant of GJB2 gene and a c.538C>T (p.R180X) variant of GJB3 gene, which were respectively inherited from his mother and father. CNVs analysis revealed a de novo heterozygotic deletion (1.46 Mb) at 17q12 in the mother, which was confirmed by qPCR. Based on American College of Medical Genetics and Genomics guidelines, the c.83delG variant, the c.235delC variant and the 17q12 microdeletion were predicted as pathogenic, while the c.538C>T variant was of uncertain significance.@*CONCLUSION@#The c.83delG (p.A29Rfs*55) variant of the CTNND1 gene probably underlay the pathogenesis of non-simplex blepharocheilodontic syndrome in this pedigree. The double heterozygous variants of c.235delC (p.L79Cfs*3) of GJB2 gene and c.538C>T (p.R180X) of GJB3 gene probably underlay the hearing loss in the elder brother. The bilateral renal cysts in the mother may be attributed to the 17q12 microdeletion. Above results have provided guidance for genetic counseling and prenatal diagnosis for this pedigree.

Enlarged multicystic dysplastic kidneys with oligohydramnios during infancy caused by NPHP3 gene mutation / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genomic abnorm ality of a fetus enlarged multicystic dysplastic kidneys with oligohydramnios caused by NPHP3 gene mutation.@*METHODS@#The fetuse was found to have multicystic dysplastic kidneys with oligohydramnios upon ultrasonography during the second trimester. Following induced abortion, fetal tissue was collected for the extraction of DNA, chromosomal microarray analysis (CMA) and whole exome sequencing (WES). Sanger sequencing was used to verify the suspected variants in the family.@*RESULTS@#Antenatal ultrasound examination at 19 weeks showed "polycystic" kidneys with Oligohydramnios. Delivery was by induced labour because of the critically low amniotic fluid volume. Testing of CMA was normal. WES showed a compound heterozygous mutation of c.1817G>A, p.W606X; c.432dupA, p.E145Rfs*18 mutations are novel mutations in this study.@*CONCLUSION@#The research may further expand the NPHP3 gene mutation spectrum. Enlarged multicystic dysplastic kidneys with oligohydramnios caused by NPHP3 gene mutation at least include one or two splice site mutation, frameshift mutation or nonsense mutation foetal poor prognosis.

Analysis of TUBB2B gene variant in a fetus with complex cortical dysplasia with other brain malformations-7 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with dysgenesis of corpus callosum and other brain malformations.@*METHODS@#Whole exome sequencing was carried out for the fetus and its parents. Suspected pathogenic variants were verified by Sanger sequencing.@*RESULTS@#A novel de novo missense variant c.758T>A (p.L253Q) of the TUBB2B gene was identified, which was unreported previously. Based on the guidelines from the American College of Medical Genetics, the c.758T>A variant was predicted to be likely pathogenic. Bioinformatics analysis predicted that the leucine at position 253 was highly conserved among various species, and the c.758T>A variant may impact the formation of hydrogen bonds between Leu253 and Asp249 and Met257 residues, which in turn may affect the combination of GTP/GDP and function of the TUBB2B protein.@*CONCLUSION@#The c.758T>A variant of the TUBB2B gene probably underlay the fetal malformations in this Chinese family. Above discovery has enriched the spectrum of TUBB2B gene variants and provided a basis for genetic counseling and prenatal diagnosis.

Variation analysis of EPG5 gene in a Vici syndrome family / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of Vici syndrome in a Chinese family.@*METHODS@#Whole exome sequencing (WES) technology was used to detect gene variants in a fetus of abnormal ultrasonic structure without abnormalities in routine chromosome karyotype analysis and SNP-array. Sanger sequencing and bioinformatics prediction were performed for the suspected variants of the fetus and parents.@*RESULTS@#The fetus and the elder sister have carried c. 2427delC (p.T809fs) and c.1886A>T (p.E629V) compound heterozygous variants of the EPG5 gene, which were respectively inherited from their mother and father. Neither variant was reported previously. According to ACMG guidelines, the c.2427delC variant was predicted as pathogenic, while the c.1886A>T variant was of uncertain significance. PolyPhen-2 and PROVEAN software indicated that c.1886A>T variant was probably damaging.@*CONCLUSION@#The c.2427delC and c.1886A>T variants of the EPG5 gene probably underlie the pathogenesis of the Vici syndrome in this family. Above finding has enriched the variational spectrum of EPG5 gene and provided a basis for genetic counseling and prenatal diagnosis for the family.

Genetic analysis of a rare fetus with mandibulofacial dysostosis Guion-Almeida type / 中华医学遗传学杂志

OBJECTIVE@#To delineate the clinical and genetic features of a fetus with micrognathia, low-set ears, microtia, polyhydramnios and anechoic stomach by ultrasonography.@*METHODS@#Whole exome sequencing (WES) was carried out to detect genetic variant in the fetus, for which routine chromosomal karyotyping and chromosomal microarray analysis (CMA) yielded no positive finding. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#WES revealed that the fetus has carried a de novo nonsense c.2302C>T (p.Q768X) variant in exon 23 of the EFTUD2 gene, which was detected in neither parent. The variant was unreported previously and may lead to premature termination of the translation of EFTUD2 protein at the 768th amino acid. Bioinformatic analysis predicted the amino acid to be highly conserved and may alter the structure and function of the EFTUD2 protein.@*CONCLUSION@#The c.2302C>T variant of the EFTUD2 gene probably underlay the mandibulofacial dysostosis Guion-Almeida type in the fetus. Discovery of the novel variant has enriched variant spectrum of the EFTUD2 gene and provided a basis for genetic counseling and prenatal diagnosis for the family.

Research progress of anti-glutamic acid decarboxylase antibody-associated encephalitis / 中华神经科杂志

Anti-glutamic acid decarboxylase antibody-associated encephalitis is a kind of autoimmune encephalitis mediated by anti-glutamic acid decarboxylase antibody, which belongs to anti-neuronal intracellular synaptic protein antibody-associated encephalitis. Clinical manifestations include stiff-person syndrome, cerebellar ataxia, limbic encephalitis, seizures, etc., often associated with a variety of autoimmune diseases, rarely associated with tumors. Detection of anti-glutamic acid decarboxylase antibody is crucial for clinical diagnosis. Immunotherapy helps to relieve symptoms and improve prognosis. The incidence of this disease is low, and there are few reports at home and abroad. This paper intends to review the research on this encephalitis, hoping to improve the clinicians′ understanding and the level of diagnosis and treatment of the disease.

Prenatal diagnosis and genetic analysis of two fetuses with paternally derived 17q12 microdeletions / 中华医学遗传学杂志

OBJECTIVE@#To reported on two fetuses diagnosed with 17q12 microdeletion syndrome.@*METHODS@#The two fetuses were respectively found to have renal abnormalities and polyhydramnios upon second and third trimester ultrasonography. Umbilical cord blood of the first fetus and amniotic fluid of the second fetus were subjected to single nucleotide polymorphism array (SNP-array) analysis. After 17q12 microdeletion was found in the first fetus, SNP-array was carried out on peripheral blood samples of the parents to determine its origin. With the medical history of the parents taken into consideration, the father underwent high-throughput sequencing for 565 urinary system-related genes to exclude pathogenic or likely pathogenic variants associated with congenital malformations of the urinary and reproductive systems.@*RESULTS@#In both fetuses, SNP-array has revealed a 1.42 Mb deletion at 17q12, or arr[hg19]17q12 (34 822 465-36 243 365) × 1. In both cases the microdeletion was inherited from the father, in whom no urinary disease-related pathogenic or likely pathogenic variants was identified.@*CONCLUSION@#Paternally derived 17q12 microdeletions probably underlay the genetic etiology of the two fetuses with renal ultrasound abnormalities and polyhydramnios. SNP-array can enable the diagnosis and facilitate genetic counseling and prenatal diagnosis for the families.

Clinical value of routine non-invasive prenatal testing for the screening of non-target chromosomal abnormalities / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for the identification of sex chromosome aneuploidies (SCAs), copy number variants (CNVs) and rare autosomal trisomies (RATs).@*METHODS@#A total of 11 429 women with singleton pregnancy in Ningbo area were screened by NIPT. 106 women were subjected to invasive prenatal diagnosis due to high risk of chromosomal abnormalities other than 21, 18 and 13 aneuploidies. All cases were followed up for pregnancy outcome and postnatal status.@*RESULTS@#Sixty-six women were signaled by NIPT for fetal SCAs, among whom 54 were willing to undergo prenatal diagnosis. Eighteen cases of fetal SCAs were verified as true positives and 4 were suspected positives, which yielded a positive predictive value (PPV) of 33.3%. Half of the women decided to continue their pregnancy. Forty women were signaled by NIPT for fetal CNVs, among which 32 underwent prenatal diagnosis. 19 cases of fetal CNVs were verified as true positives and 3 cases were suspected positives, which yielded a PPV of 46.8%. All women with pathological or possibly pathological CNVs decided to terminate their pregnancies. Thirty-one women were signaled for with fetal RATs. Two fetuses were confirmed to harbor mosaicism trisomies by prenatal diagnosis, and 1 case was suspected to be positive, which yielded a PPV of 9.7%. All of the three women have decided to terminate their pregnancy.@*CONCLUSION@#In addition to aneuploidies of target chromosomes, NIPT also has important value for the detection of SCAs and CNVs. The results can help to further reduce birth defects. Nevertheless, in view of its low PPV, pregnant women with positive result still need appropriate genetic counseling and prenatal diagnosis to avoid unnecessary induced labor.

Study on the Situation and the Users' Demands of Chronic Disease Management Application in Guangzhou / 现代医院

Objective To understand the application status and users' demands of the chronic disease management application in Guangzhou. Methods From June to October 2017, 794 patients with chronic disease (hypertension as an example) and 25 community health workers were investigated and analyzed by questionnaire and personal interview in Guangzhou. Results The utilization rate of hypertension management type APP was 71. 7％ in Guangzhou, and that of community health service staff was 25. 0％. The demand of this kind of APP users lies in perfecting the basic function of chronic disease management, stressing market norms and technological innovation, emphasizing the health education of patients with chronic disease and continuous education of medical staff. Conclusion Currently, the chronic disease management applications can not meet the most practical and urgent needs of its users, so it is necessary to continuously evaluate the market and adjust the development strategy.

Evaluation of efficacy of Arndt endobronchial blocker for airway management during one-lung ventilation in pediatric patients / 中华麻醉学杂志

Objective To evaluate the efficacy of Arndt endobronchial blocker (AEB) for airway management during one-lung ventilation (OLV) in pediatric patients.Methods Thirty pediatric patients,aged 4 months-12 yr,weighing 5.6-26.0 kg,of American Society of Anesthesiologists physical status Ⅱ-Ⅳ,scheduled for elective thoracotomy under OLV requiring the use of single lumen tracheal tube assisted by AEB,were enrolled in this study.OLV was performed with the AEB placed outside the single lumen tracheal tube in pediatric patients below 2 years old and with AEB inserted through the single lumen tracheal tube in pediatric patients ≥ 2 years old.The rate of successful establishment of artificial airway at first attempt,time of establishing artificial airway,time of pulmonary collapse,AEB malpositions and airway pressure before and after OLV were recorded,and the efficacy of lung collapse was evaluated.Results The rate of successful tracheal intubation of extraluminal and endoluminal AEB placement at first attempt was 100％ in 30 pediatric patients,and no high airway pressure was found after OLV.The efficacy of lung collapse was poor in one patient and good in one patient,and intraoperative AEB malpositions were found in two patients among the pediatric patients used extraluminal AEB placement.The efficacy of lung collapse was good in one patient,intraoperative AEB malposition was found in one patient,and SpO2 was decreased after OLV in one patient among the pediatric patients used endoluminal AEB placement.Conclusion Reasonably selecting the method of placing AEB followed by enhancing intraoperative airway management can be safely and effectively applied for OLV in pediatric patients.

A survey of statistical methods used in nursing papers for bachelor's degree / 现代临床护理

Objective To investigate the statistical methods used in nursing papers for bachelor's degree. Method We collected 160 nursing theses for bachelor's degree in 2016 in our college and analyze the statistical methods. Results A total of 80 papers used statistical methods consisting of statistical table, statistical inference, single factor analysis, variance analysis and statistical description. Among them, the statistical methods in 66 papers (82.5%) were misused. About 139 misuses of statistical tables was found in papers, and about 23 misuses of statistical inference in papers, taking up 45.4%. Conclusions The nursing undergraduates are familiar with the application of statistical methods, but the methods tend to be simple and unitary. Therefore, it is a need to enhance their practice in using statistical methods.

Clinical significance of carbon nanoparticles in breast cancer lymphadenectomy / 中国基层医药

Objective To evaluate the clinical application value of active carbon nanoparticles to guide breast cancer tiny lymphadenectomy.Methods 50 patients with breast cancer were enrolled in the study and were divided into two groups by random number table.Active carbon particle was injected locally to guide the regional lymph nodes dissection in 25 cases as study group,and the traditional method was performed in 25 cases as observation group.Numbers of dissected lymph nodes were compared between two groups.Results The average number of eliminated small lymph nodes in the study group was dramatically more than that in the observation group[(23.60 ±4.61)vs. (14.60 ±5.16),t =3.47,P <0.05].There was significant difference between the study group and the observation group in the small ambulant lymph nodes[(5.80 ±1.49)vs.(2.89 ±1.66),t =2.91,P <0.05)].Conclusion Active carbon injected locally can eliminate not only more small lymph nodes,but also more small ambulant lymph nodes.

Antitumor activity of steroid saponins extracted from Paris polyphylla var.yunnanensis against lung adenocarcinoma cells in vitro and in vivo / 中草药

Objective To study the antitumor activity of steroid saponins,such as Rhizoma Paridis saponins,Rhizoma Paridis saponin Ⅰ,and diosgenin,extracted from Paris polyphylla var.yunnanensis against lung adenocarcinoma cells.Methods Taking mouse lung adenocarcinoma LA795 cell line and its T739-bearing mice as models,the antitumor activity of steroid saponins of P.polyphylla var.yunnanensis against lung adenocarcinoma cells was carried out in vitro and in vivo.The inhibitory activity of Rhizoma Paridis saponins,Rhizoma Paridis saponin Ⅰ,and diosgenin on the LA795 cell line was studied by means of MTT assay and their antitumor effects in vivo were carried on inbred strains of mice(T739) affected by LA795 metastatic lung cancer.Results The MTT assay of in vitro cytotoxicity of Rhizoma Paridis saponins,Rhizoma Paridis saponin Ⅰ,and diosgenin showed strong cytotoxicity against the growth of LA795 cells.IC50 Values were 24.33 ?g/mL,1.85,and 149.75 ?mol/L,respectively.The tumor weight in all treated groups was significantly lower than that in the control group and the inhibition of tumor growth were 41.82%,29.44%,and 33.94% in their high-dose groups.The metastasis of tumor cells was inhibited by different degrees in treated groups.Conclusion Steroid saponins of P.polyphylla var.yunnanensis have tumoricidal activity on lung adenocarcinoma cell line,both in vitro and in vivo.