Objective To investigate the relationship and potential pathways between metal(loid)exposure and the risk of polycystic ovary syndrome(PCOS)in women of childbearing age. Methods This case-control study included 200 patients with PCOS(cases)and 896 non-PCOS controls with the age of 25-37 years.The concentrations of 29 metal(loid)s in the follicular fluid(FF)and clinical indicators in the serum were measured in all participants.Logistic regression analysis and mediation analysis were conducted to evaluate the associations between metal(loid)exposure and PCOS risk and investigate the possible roles of clinical indicators,respectively. Results Logistic regression analysis revealed an association between high copper levels in FF and increased PCOS risk(highest vs.lowest quartile:adjusted odds ratio=2.94,95%confidence interval:1.83-4.72).A high luteinizing hormone/follicle-stimulating hormone ratio and elevated levels of testosterone and anti-Müllerian hormone(AMH)were strongly associated with increased PCOS risk induced by high copper exposure.The mediation analysis indicated a mediating effect of AMH in the association between copper exposure and PCOS risk. Conclusion Copper may affect PCOS risk through the hypothalamic-pituitary-ovarian axis,mediated by AMH.Copper exposure and internal AMH levels are important indicators for early warning of PCOS development.

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

OBJECTIVE: To assess the value of single sperm sequencing in preimplantation genetic testing for monogenic disease (PGT-M). METHODS: A Chinese couple with two children whom had died of Spinal muscular atrophy (SMA) and attended the Jiangxi Provincial Maternal and Child Health Care Hospital in June 2020 was selected as the subject. Eleven single sperm samples were isolated by mechanical immobilization and subjected to whole genome amplification. Real-time PCR and Sanger sequencing were used to detect the SMN1 variants in the single sperm samples. Genomic DNA of the wife, her parents and the husband, as well as one single sperm sample harboring the SMN1 variant and two single sperm samples without the variant were used for the linkage analysis. Targeted capture and high-throughput sequencing were carried out to test 100 single nucleotide polymorphisms distributed within 2 Mb up- and downstream the variant site. The haplotypes linked with the SMN1 variants were determined by linkage analysis. Blastocyst embryos were harvested after fertilizing by intracytoplasmic sperm injection. Cells from the trophoblasts of each embryo were biopsied and subjected to whole genome amplification and targeted capture and high-throughput sequencing to determine their carrier status. Chromosomal aneuploidy of wild-type embryos was excluded. An euploid embryo of high quality was transferred. Amniotic fluid sample was taken at 18 weeks of gestation to confirm the status of the fetus. RESULTS: Genetic testing showed that the couple both had deletion of exons 7 ~ 8 of the SMN1 gene. The wife has inherited the deletion from her father, while the husband was de novo. The haplotypes of the husband were successfully constructed by single sperm sequencing. Preimplantation genetic testing has indicated that 5 embryos had harbored the heterozygous variant, 4 embryos were of the wild type, among which 3 were euploid. Prenatal diagnosis during the second trimester of pregnancy has confirmed that the fetus did not carry the deletion. CONCLUSION By single sperm sequencing and PGT-M, the birth of further affected child has been successfully avoided.
Humans ; Pregnancy ; Female ; Child ; Male ; Preimplantation Diagnosis ; East Asian People ; Semen ; Genetic Testing ; Muscular Atrophy, Spinal/genetics* ; Aneuploidy ; Blastocyst/pathology* ; High-Throughput Nucleotide Sequencing ; Spermatozoa

Objective:To explore the correlation between middle cerebral artery (MCA) pulsatility index (PI) and total magnetic resonance imaging (MRI) burden in elderly patients with cerebral small vessel diseases (CSVD).Methods:A total of 203 CSVD inpatients aged 60 years and above who were hospitalized in the Department of Neurology of Hebei General Hospital from March 2017 to December 2020 were enrolled. The clinical data, transcranial Doppler ultrasound parameters and brain MRI data were collected. According to the total burden score, the patients were divided into low burden group (0-1 point) and high burden group (2-4 points). Univariate and multivariate Logistic regression analysis was used to analyze the correlation between MCA PI and total MRI burden in the elderly patients with CSVD. Subsequently, the receiver operating characteristic curve was used to evaluate the value of MCA PI for predicting the high MRI burden of CSVD in the elderly.Results:Hypertension ( OR=2.569, 95% CI 1.068-6.182, P=0.035), systolic blood pressure ( OR=1.033, 95% CI 1.006-1.061, P=0.016), creatinine ( OR=1.044, 95% CI 1.009-1.079, P=0.013) and MCA PI ( OR=1.125, 95% CI 1.087-1.166, P<0.001) were independently correlated with the increasing total MRI burden in the elderly patients with CSVD. Spearman rank correlation analysis revealed that there was strong and positive correlation between MCA PI and high MRI burden in the elderly patients with CSVD ( r=0.65, P<0.001). The analysis showed that when the cut-off for MCA PI was 1.11, it could identify high MRI burden of CSVD in the elderly. The area under the curve was 0.908 (95% CI 0.864-0.953, P<0.001). The sensitivity and specificity were 0.852 and 0.880, respectively. The positive predictive value was 92.38%, and the negative predictive value was 77.70%. Conclusion:The MCA PI is positively correlated with total MRI burden in the elderly patients with CSVD, and has a higher value in predicting the total MRI burden in the elderly CSVD patients, which probably bring brighter prospects for its clinical application.

Nucleic acid detection technique has good sensitivity and specificity and is widely used in in vitro diagnosis, animal and plant commodity quarantine, forensic identification, and other fields. However, it is susceptible to carryover contamination during the operation and leads to false-positive results, which seriously affects the detection accuracy. Therefore, finding an effective solution to prevent and eliminate nucleic acid carryover contamination has become particularly urgent. This study compared several different methods for removing nucleic acid contamination and confirmed that sodium hypochlorite solution and PCRguard reagent could effectively eliminate nucleic acid carryover in the liquid and on surfaces of different materials. Besides, the combination of sodium hypochlorite solution and PCRguard can solve the nucleic acid aerosol contamination. This study proposes solutions for the routine prevention of carryover contamination and removal of aerosol that has occurred in molecular diagnostic laboratories.
Laboratories ; Nucleic Acids ; Pathology, Molecular

OBJECTIVE: To explore the clinical characteristics and genetic basis for a pedigree affected with propionic acidemia. METHODS: Trio whole exome sequencing (WES) was used to screen potential variants in the proband and his parents. Sanger sequencing was carried out for the elder sister of the proband, and prenatal diagnosis was carried out at 18th gestational week upon the next pregnancy of his mother. RESULTS: Two novel heterozygous variants, PCCA c.1845+1G>A and c.446delA, were detected by WES, for which his father and mother were respectively heterozygous carriers. His elder sister also inherited the PCCA c.1845+1G>A variant from her father, while the fetus was heterozygous for the PCCA c.1845+1G>A variant. Above results were confirmed by Sanger sequencing. CONCLUSION Identification of the PCCA c.1845+1G>A and c.446delA variants by WES has facilitated genetic counseling and prenatal diagnosis for this family.

OBJECTIVE: To assess the value of preimplantation genetic test (PGT) based on next generation sequencing (NGS) for achieving pregnancy for 71 couples with one partner carrying a reciprocal or Robertsonian translocation. METHODS: Following blastocyst biopsy, whole genome of single cell was amplified, and PGT was performed by NGS. The subjects included 60 couples with one partner carrying a reciprocal translocation and 11 with one partner carrying a Robertsonian translocation. The results of PGT, implantation and prenatal diagnosis for all of the couples were analyzed. RESULTS: In total 301 embryos were obtained for the 71 couples through 92 ovulation cycles, 287 (95.3%) of which were successfully diagnosed by NGS. Eighty-five euploidy embryos were identified for the reciprocal translocation carrier group. In 18 cycles, no euploid embryo was obtained. Cancellation rate for the cycles was 19.5%. For reciprocal translocation carrier group and Robertsonian translocation carrier group, the rates for implantation, early abortion, and clinical pregnancy were 89.3% (42/47), 25.5% (12/47), 63.8% (30/47), and 88.8% (8/9), 22.2% (2/9), and 66.6% (6/9), respectively. The result of prenatal diagnosis was consistent with the that of PGT. CONCLUSION PGT based on NGS can effectively identify euploid embryos and reduce recurrent abortions and termination of pregnancies, achieving a satisfactory rate for clinical pregnancy.
Female ; Fertilization in Vitro ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Pregnancy ; Preimplantation Diagnosis ; methods ; Translocation, Genetic

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with N-acetylglutamate synthase deficiency. METHODS: Trio whole exome sequencing (WES) was carried out for the pedigree. Pathogenicity of the identified variant was predicted based on the latest recommendation of the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was provided for subsequent pregnancy through Sanger sequencing. RESULTS: Trio WES showed that the proband has carried compound heterozygous c.68delG and c.796G>C variants of NAGS gene, for which the mother and father were respectively heterozygous carriers. Neither variant was reported previously. Based on the ACMG guidelines, the c.68delG variant was classified as "likely pathogenic" (PVS1+PM2), while the c.796G>C variant was classified as with "uncertain significance" (PM2+BP4). Sanger sequencing validated the above findings, and only detected the heterozygous c.796G>C variant in the amniotic fluid sample. The fetus was followed up till 6 month after birth with no obvious abnormality. CONCLUSION The compound heterozygous c.68delG and c.796G>C variants of the NAGS gene probably underlay the disorder in this pedigree, and the resulth asenabled genetic counseling and prenatal diagnosis for this pedigree.
Amino-Acid N-Acetyltransferase/genetics* ; China ; Female ; Genetic Testing ; Humans ; Male ; Mutation/genetics* ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Urea Cycle Disorders, Inborn/genetics* ; Whole Exome Sequencing

TORCH, which is considered as a series of pathogens, including the Toxoplasma gondii, Rubella virus, Cytomegalovirus or Herpes simplex virus, often infects the pregnant women to induce the the fetus or newborn infection by transplacental infection or exposure to contaminated genital tract secretions at delivery. Increasing evidence have been confirmed that the infection of TORCH may cause the miscarriage, premature birth, malformed fetus, stillbirth, intrauterine growth retardation, neonatal multiple organ dysfunction and other adverse pregnancy outcomes. For most TORCH-infections cases may lacking the effective treatments during pregnancy, and it is important to achieve the effacing monitoring of TORCH infections before and during pregnancy. The laboratory testing of TORCH has the great significance. However, the consensus opinions still need to improve the the standardization of TORCH testing process and the correct interpretation. Based on the characteristics of the TORCH detection method, this article gives a consensus opinion on the standardized detection and clinical application of TORCH from the laboratory perspective according to the characteristics and types of infection of different pathogens.

Objective: To investigate the features of chest CT imaging and dynamic changes of severe coronavirus disease 2019 (COVID-19). Methods: The clinical and computed tomography (CT) data of 17 patients diagnosed with severe COVID-19 admitted to Chongqing Public Health Medical Center from January 24 to February 6, 2020 were collected. The first chest CT manifestations and the dynamic changes of imaging during treatment were retrospectively analyzed. Results: The first chest CT manifestations of the 17 patients showed that 16 cases presented with peripheral and subpleural distributions, and 2 cases presented with 3 lobes involved, one case with 4 lobes involved and 14 cases with 5 lobes involved, and 17 cases presented with ground-glass opacities, ten cases with consolidation, seven cases with subpleural line, nine cases with air bronchogram, 3 cases with thickened lobular septum, two cases with bronchiectasis, two cases with pleural effusion, two cases with lymphadenopathy with the short diameter of 1.0-1.2cm. Among 16 patients who underwent repeated CT examination, the lesions of 8 patients showed continuous improvement, and those of the other 8 patients showed fluctuating changes. Conclusions The CT findings of severe COVID-19 patients are mainly ground-glass opacities and consolidation, with the peripheral distribution. The range of lesions is wide, with 5-lobe involvement mostly. Lymphadenopathy or pleural effusion is rare. Chest CT is useful for the evaluation for the therapeutic effects.