Objective:To explore the influencing factors of false-positive serological reaction of syphilis.Methods:A total of 166 patients with false-positive serological reaction of syphilis (false-positive group), 145 patients diagnosed with early syphilis without treatment (positive control group) and 124 persons undergoing entry physical examination (negative control group) were included from January 2017 to February 2020 in Beijing Tongren Hospital, Capital Medical University. The gender, age and underlying diseases of the three groups were compared. Logistic regression was used to analyze the influencing factors of false-positive serological reaction of syphilis. The efficacies of chemiluminescence immunoassay (CLIA) and toluidine red unheated serum test (TRUST) were compared. Paired t test or chi-square test was used for statistical analysis. Results:In the false-positive group (166 cases), the age of 117 cases were more than 50 years old and 49 cases <50 years old. There were significant differences in age ((53.1±13.8) vs (24.7±2.8), t=22.56, P<0.01), autoimmune disease (36.7%(61/166) vs 6.5%(8/124), χ2=35.93, P<0.01), hepatitis (9.6%(16/166) vs 3.2%(4/124), χ2=4.92, P=0.026) and tumor (6.6%(11/166) vs 0.8%(1/124), χ2=4.68, P=0.030) between the false-positive group and the negative control group. There were significant differences in gender (there were 91(54.8%) males and 75(45.2%) females in the false-positive group, and 103(71.0%) males and 42(29.0%) females in the positive control group, χ2=8.67, P=0.003), age ((53.1±13.8) vs (34.4±12.9), t=20.13, P<0.01) and autoimmune disease (36.7%(61/166) vs 6.9%(10/145), χ2=39.14, P<0.01) between the false-positive group and the positive control group. Multivariate logistic regression analysis showed that gender (odds ratio ( OR)=2.692, 95% confidence interval ( CI) 1.504-4.816, P=0.001), age ≥50 years old ( OR=30.512, 95% CI 15.959-58.335, P<0.01), autoimmune disease ( OR=2.677, 95% CI 1.258-5.695, P=0.011) and hepatitis ( OR=4.408, 95% CI 1.799-10.799, P=0.001) were the influencing factors of false-positive serological reaction of syphilis. In the false-positive group, the positive rate of TRUST was 84.9% (141/166), which was higher than that of CLIA (23.5%(39/166)). The difference was statistically significant ( χ2=126.25, P<0.01). CLIA was 1.0-10.0 cut off index (COI) in 36 patients, and >10.0 COI in three patients.The difference was statistically significant ( χ2=52.51, P<0.01). The titers were ≤1∶4 in 139 patients and≥1∶8 in two patients with TRUST positive.The difference was statistically significant ( χ2=262.35, P<0.01). The sensitivity and specificity of CLIA were 95.2% and 96.0%, respectively, and those of TRUST were 77.2% and 91.1%, respectively. Conclusions:The influencing factors of false-positive serological reaction of syphilis include patients age ≥50 years and with autoimmune disease or hepatitis. The false-positive rate of TRUST is significantly higher than CLIA.

[ ABSTRACT] AIM: To investigate the underlying genetic changes of a Chinese patient with infantile malignant osteopetrosis ( IMO) .IMO is a monogenic disease, mostly caused by mutations of TCIRG1 and CLCN7 genes.The former is believed a homozygous gene and only cause the disease in homozygous or compound heterozygous status.However, it has been reported that heterozygous mutations also cause the disease in 6 non-Chinese cases.METHODS:Genomic DNA was extracted from peripheral blood of the patient and his parents.All exons and splice sites of TCIRG1 and CLCN7 genes were amplified by PCR followed by Sanger sequencing.Mutation detection in the 2 genes was also investigated in the parents. Haplotypes were constructed by variations obtained in mutation detection and microsatillites flanking TCIRG1 gene in the family by Cyrillic.Chromosomal microarray analysis ( CMA) was performed to detect copy number variations ( CNV) of the patient and his mother.RESULTS:A novel mutation c.449_452delAGAG ( p.Gln149Glnfs16) was detected in the pa-tient.This mutation truncated 666 amino acids at the C terminal of the V-ATPase 116 kD isoform a3 protein.It wiped out the entire ATPase V0 complex and was predicted to result in total loss of protein function.This mutation was also detected in the patient’ s father.No pathogenic mutation was detected in CLCN7 gene.CMA did not reveal any CNV involving TCIRG1 or CLCN7 gene.CONCLUSION:We reported a novel heterozygous mutation of TCIRG1 gene causing IMO.This represents the first IMO case in China caused by heterozygous TCIRG1 gene mutation.

A novel probe (DNSBN) towards biothiols on the basis of 4-hydroxynaphthalimide as fluorophores and 2, 4-dinitrobenzenesulfonyloxy group as specific recognition site was designed and synthesized.The result of absorption and fluorescence spectral analyses indicated that the probe had high sensitivity and selectivity towards cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), and the detection was not affected by other 17 kinds of natural amino acids.Meanwhile, it was confirmed that DNSBN was a ratiometric probe through the fluorescence titration experiment, and the fluorescent intensity at 555 nm had a high linear relationship with biothiols concentration in the range of 0-20 μmol/L.The detection limits (3σ) of Cys, Hcy and GSH were 25.9, 92.0 and 77.9 nmol/L, respectively.The absorption, emission and mass spectra indicated that biothiols could be engaged in nucleophilic substitution reaction with 2,4-dinitrobenzenesulfonate, which induced the sulfonic esters decomposed.With the departure of receptor unit, the d-PeT progress (donor-excited photoinduced electron transfer) was blocked with an obvious colorimetric and fluorescence change.Finally, HeLa cell imaging experiments verified that DNSBN had good biocompatibility and could be used to detect exogenous biothiols.

OBJECTIVE: To investigate 18β-sodium glycyrrhetinic acid impact on nasal mucosa epithelial cilia in rat models of allergic rhinitis (AR). METHOD: AR models were established by ovalbumin-induction. Wister rats were randomly divided into groups as normal group, model group, budesonide (0.2 mg/kg) group and sodium glycyrrhetinic acid (20 mg/kg and 40 mg/kg) group after the success of AR models. At 2 weeks and 4 weeks after treatment, the behavioral changes of rats were observed and recorded, and nasal septum mucosae were collected after 2 week and 4 week intervention, and the morphological changes of nasal mucosae were observed by electron microscope. RESULT: Model group developed typical AR symptoms, the total score in all animals was > 5. With budesonide and sodium glycyrrhetinic acid treatment, the AR symptoms were relieved, and the total scores were reduced significantly (P < 0.01). Compared with the model group: after 2 weeks' intervention, thick mucous secretions on the top of columnar epithelium cilia in rat nasal mucosa was significantly reduced, and cilia adhesion, lodging, shedding were relieved in budesonide group and sodium glycyrrhetinic acid group, the relieve in budesonide group was slightly better than that in sodium glycyrrhetinic acid group; after 4 week intervention, Cilia adhesion, lodging, shedding were completely vanished, and the cilia were ranged in regular direction in budesonide group and sodium glycyrrhetinic acid group. Cilia in sodium glycyrrhetinic acid (20 mg/kg) group was more orderly, smooth than that in budesonide group and sodium glycyrrhetinic acid group (40 mg/kg), and the condition of cilia in sodium glycyrrhetinic acid group (20 mg/kg) was similar to the normal group. CONCLUSION 18β-sodium glycyrrhetinic acid is effective to restrain the pathological changes of nasal mucosa cilia in rat models of AR.
Animals ; Budesonide ; pharmacology ; Cilia ; drug effects ; Disease Models, Animal ; Glycyrrhetinic Acid ; analogs & derivatives ; pharmacology ; Nasal Mucosa ; drug effects ; Ovalbumin ; Random Allocation ; Rats ; Rhinitis, Allergic ; drug therapy

Objective To investigate the application of fetuses with talipes equinovarus (TE) using chromosomal microarray analysis (CMA) technology. Methods From May 2012 to June 2015, 54 fetuses were found with TE and with or without other structural anomalies by prenatal ultrasound. Karyotyping was taking for them all, and the fetuses with normal karyotypes took another CMA test. The data were analyzed with CHAS software. Finally all the cases were followed up to know about their pregnancy outcomes. Results One of the 54 cases was detected with abnormal karyotype which was trisomy 18 (2%, 1/54). CMA was undertaken to the remaining fetuses, they were divided into 2 groups, including isolated TE group (n=38) and complex TE group (n=15). The detection rate of clinical significant copy number variations (CNV) by CMA was 11% (6/53), while isolated and complex TE group were 5% (2/38) and 4/15, respectively (P=0.047). Of the 53 cases, 51 cases were successfully followed up. Eleven cases were found without TE after birth, and the false positive rate (FPR) of TE was 22%(11/51). Conclusions Whole-genome high-resolution CMA increased the detection rate by 11% in fetuses with TE. With the FPR and the detection rate of the clinical significant CNV of 2 groups, whole-genome CMA could be recommended to the fetuses with complex TE group but normal karyotypes. A series of ultrasonic tests should be suggested to the isolate TE group, while with the abnormal ultrasound, fetuses would be suggested to have CMA test for decreasing the rates of invasive prenatal diagnosis and FPR.

OBJECTIVE: To explore the genetic etiology for a child with ocular dysplasia. METHODS: Clinical examination was carried out. Medical history of the child was collected. Genomic DNA was extracted from peripheral blood samples. Chromosomal microarray analysis (CMA) was used to detect potential genomic copy number variations. RESULTS: Ultrasonography revealed cataracts in both eyes of the child. MRI showed increased extracranial space, supratentorial ventricular dilatation, reduced white matter volume, increased T2WI signal and a large occipital cisterna. CMA showed that the patient carried a 249 kb microdeletion at Xq25q26.1 region, namely [hg19]arrXq25q26.1 (128 652 372 - 128 901 629)×0. CONCLUSION The child was diagnosed with Lowe syndrome, for which the 249 kb microdeletion at Xq25q26.1 is probably accountable.
Child ; Chromosome Aberrations ; DNA Copy Number Variations ; Humans ; Microarray Analysis ; Oculocerebrorenal Syndrome

Cleidocranial dysplasia (CCD) is a rare congenital disorder, typically characterized by persistently open skull sutures, aplastic or hypoplastic clavicles, and supernumerary teeth. Mutations in the gene encoding the runt-related transcription factor 2 (RUNX2) protein are responsible for approximately two thirds of CCD patients. We report a 20-year-old CCD patient presenting not only with typical skeletal changes, but also complex dental anomalies. A previously undiagnosed odontoma, 14 supernumerary teeth, a cystic lesion, and previously unreported fused primary teeth were discovered on cone-beam computed tomography (CBCT) scans. Mutation analysis identified the causal c.578G>A (p.R193Q) mutation in the RUNX2 gene. At 20 years of age, the patient had already missed the optimal period for dental intervention. This report describes the complex dental anomalies in a belatedly diagnosed CCD patient, and emphasizes the significance of CBCT assessment for the detection of dental anomalies and the importance of early treatment to achieve good outcomes.
Clavicle ; Cleidocranial Dysplasia* ; Cone-Beam Computed Tomography ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; Humans ; Odontoma ; Skull ; Sutures ; Tooth, Deciduous ; Tooth, Supernumerary ; Transcription Factors ; Young Adult

OBJECTIVETo explore the genetic etiology of fetuses with multicystic dysplastic kidney (MCDK) by chromosome microarray analysis (CMA).

METHODSSeventy-two fetuses with MCDK were analyzed with conventional cytogenetic technique, among which 30 fetuses with a normal karyotype were subjected to CMA analysis with Affymetrix CytoScan HD arrays by following the manufacturer's protocol. The data was analyzed with ChAS software.

RESULTSConventional cytogenetic technique has revealed three fetuses (4.2%) with identifiable chromosomal aberrations. CMA analysis has detected pathogenic CNVs in 5 fetuses (16.7%), which included two well-known microdeletion or microduplication syndromes, i.e., 17q12 microdeletion syndrome and Williams-Beuren syndrome (WBS) and three submicroscopic imbalances at 4q35.2, 22q13.33, and 1p33. PEX26, FKBP6, TUBGCP6, ALG12, and CYP4A11 are likely the causative genes.

CONCLUSIONCMA can identify the submicroscopic imbalances unidentifiable by conventional cytogenetic technique, and therefore has a significant role in prenatal diagnosis and genetic counseling. The detection rate of pathogenic CNVs in fetuses with MCDK was 16.7% by CMA. 17q12 microdeletion syndrome and WBS are associated with MCDK. Mutations of PEX26, FKBP6, TUBGCP6, ALG12, and CYP4A11 genes may be the causes for MCDK.

Adult ; Chromosomes ; genetics ; Female ; Fetus ; Humans ; Male ; Microarray Analysis ; methods ; Multicystic Dysplastic Kidney ; genetics ; Pregnancy ; Prenatal Diagnosis ; methods ; Young Adult

OBJECTIVETo explore the genetic etiology of fetuses with ventricular septal defects (VSD) using chromosomal microarray analysis (CMA).

METHODSA total of 248 fetuses were divided into isolated VSD group, VSD with other cardiac and/or great vessels malformation group, VSD with extra-cardiac anomalies group (including malformation and sonographic soft markers), and VSD with both cardiac and extra-cardiac anomalies group. Standard karyotyping was carried out for all fetuses, and CMA was performed for 6 fetuses with an abnormal karyotype and a proportion of fetuses with a normal karyotype. All cases were followed up, and neonates were followed up until 1 year of age.

RESULTSChromosomal abnormalities were identified in 60 (24.2%) of the 248 fetuses. For 6 of the fetuses subjected to further CMA analysis, the origin of abnormal chromosomes were clarified, among which 2 have overlapped with the critical region of Wolf-Hirschhorn syndrome. Candidate genes for VSD included WHSC1, LBX1, LDB3 and BBS10. For 143 fetuses with a normal karyotype, CMA has identified pathogenic copy number variations (CNVs) in 11 cases (7.7%). These included 9 well-known microdeletion or microduplication syndromes, including 22q11.2 microdeletion, 17p11.2 microdeletion (Smith-Magenis syndrome), 17p13.3 microdeletion (Miller-Dieker syndrome), 1p36 microdeletion, 1q21.1 microduplication and 4q deletion. Candidate genes for VSD included TBX1, LZTR1, FAT1, AKAP10, SKI, PRDM26, GJA5, ERCC4 and YWHAE. For 48.7% of the fetuses with benign CNVs, spontaneously closure has occurred within the first year of life.

CONCLUSIONCMA may increase the detection rate of submicroscopic imbalances by 7.7%. No significant correlation between different groups of VSD and the pathogenic CNVs was observed. Whole-genome CMA should be recommended to the fetuses with VSD but a normal karyotype. Nearly half of VSDs with benign CNVs may close spontaneously within the first year of life.

Chromosome Aberrations ; Chromosome Deletion ; DNA Copy Number Variations ; Heart Septal Defects, Ventricular ; genetics ; Humans ; Infant ; Infant, Newborn ; Karyotyping ; Microarray Analysis ; methods ; Prenatal Diagnosis ; methods

OBJECTIVETo assess the value of genome-wide high-resolution chromosomal microarray analysis (CMA) for the delineation of pathogenesis for fetal ventriculomegaly diagnosed by ultrasound or magnetic resonance imaging (MRI).

METHODSThree hundred and forty-one cases of fetal ventriculomegaly were collected. The samples were grouped based on the extent of lateral ventricular dilatation, presence of additional features, site of occurrence, and the maternal age. All samples were subjected to karyotyping analysis. For those with a normal karyotype, DNA was extracted and hybridized with an Affymetrix CytoScan HD array. All cases were followed up.

RESULTSAmong the 341 fetuses, 21 (6.2%) were detected with an abnormal karyotype. For the 320 cases with a normal karyotype, 179 (55.9%) have accepted CMA analysis. Potentially pathogenic CNVs were identified in 12 (6.7%) of the 179 cases, whose sizes ranged from 198 kb to 8.71 Mb. These included a 1q21.3q23.1 deletion, a 2q37.3 deletion, a 3p14.1p13 deletion, a 6q25.3 deletion, a 8q11.23 duplication, a 10q21.1 deletion, a 15q11.2 deletion and a 16p13.11p12.3 duplication, a 22q13.33 duplication, a 22q11.21 duplication and a Xp21.1 duplication (Duchenne muscular dystrophy). Pathogenic CNVs were detected respectively in 7.5% and 3.1% of those with mild and severe ventriculomegaly (P=0.615), in 6.1% and 7.4% of those with isolated and non-isolated ventriculomegaly (P=0.732), in 5.6% and 7.9% of those with unilateral and bilateral ventriculomegaly (P=0.511), and in 6.7% of both elderly and non-elderly groups (P=1.000).

CONCLUSIONThe detection rate for abnormal karyotypes among fetuses with ventriculomegaly was 6.2%. CMA can increase the detection rate by approximately 6.7%. There was no significant correlation between ventriculomegaly and presence of pathogenic CNVs. In clinical practice, fetuses with ventriculomegaly and a normal karyotype should be considered for CMA analysis.

Adult ; Chromosome Aberrations ; Female ; Fetus ; abnormalities ; Humans ; Hydrocephalus ; genetics ; Karyotyping ; methods ; Microarray Analysis ; methods ; Pregnancy ; Prenatal Diagnosis ; Young Adult