Objective:To reassess the pathogenicity of copy number variants (CNVs) involving chromosomal microdeletions and microduplications classified as variants of uncertain significance (VUS).Methods:This retrospective study analyzed 1 882 pregnant women who underwent invasive prenatal diagnosis for chromosomal microarray analysis (CMA) at the First Medical Center, Chinese PLA General Hospital between January 1, 2018, and December 31, 2022. The results were classified according to the American College of Medical Genetics and Genomics guidelines, with 82 fetuses rated as VUS selected for the study. We analyzed invasive prenatal diagnostic indications, followed up on fetal ultrasound findings, parental origin identification results, and pregnancy outcomes, and reclassified VUS CNVs based on the latest evidence. Descriptive statistical analysis was applied to the data.Results:(1) Among the 82 fetuses with VUS CNVs, prenatal diagnostic indications included fetal structural abnormalities detected by ultrasound (21 cases, 25.6%), abnormal non-invasive prenatal testing (NIPT) results (12 cases, 14.6%), high-risk serum screening (seven cases, 8.5%), advanced maternal age (≥35 years at expected delivery, 28 cases, 34.1%), and other indications (14 cases, 17.1%). Sixteen cases (19.5%) exhibited abnormal phenotypes, with seven pregnancies terminated due to severe structural abnormalities detected by prenatal ultrasound. Seventy-five live births were followed up for 25 (13-66) months. (2) Among the 82 cases, five fetuses had two VUS CNVs detected by CMA, while the remaining 77 had only one, totaling 87 VUS CNVs. Of these, 63 (72.4%) were chromosomal microduplications and 24 (27.6%) were chromosomal microdeletions. The size of the CNV segments ranged from 0.85 (0.05-5.61) Mb, with 82 segments less than 2 Mb. Parental origin identification was refused by 44 cases (53.7%), while 38 (46.3%) underwent the test, revealing eight (21.0%) de novo variants and 30 (78.9%) inherited from either parent (12 maternal and 18 paternal). (3) Among the 87 VUS CNVs, the ratings of 11 CNVs (12.6%) changed after re-evaluation. This included one 4p16.2 microdeletion and two 15q11.2 microdeletions being upgraded to pathogenic, one 16p13.11 microduplication being upgraded to likely pathogenic, one Xp22.31 microduplication and two 2q13 microdeletions being downgraded to likely benign, and four Xp22.31 microduplications being downgraded to benign. (4) Among the 16 fetuses with abnormal phenotypes, seven with prenatal abnormalities terminated pregnancies, including six with structural abnormalities and one with severe fetal growth restriction. After re-evaluation, one case was upgraded to pathogenic, while six remained VUS. Nine live births with postnatal abnormal phenotypes showed no change in classification after re-evaluation. Among the 66 cases (80.5%) without abnormal phenotypes, 10 had their classifications changed after re-evaluation. Conclusions:Fetuses with VUS CNVs often exhibit no significant abnormal phenotypes and have a relatively favorable prognosis, however, further floow-up is still needed. Parental origin identification can provide valuable insights for genetic counseling.

Objective:To carry out carrier screening among people of childbearing age, detect the pathogenic genes of monogenic genetic diseases and analyze the carrier status of pathogenic variants, so as to provide fertility guidance and intervention measures for high-risk families.Methods:From August 2022 to August 2023, 1 533 families of childbearing age who met the criteria were recruited in the Chinese PLA General Hospital, including a total of 3 044 subjects. According to the standard enrollment procedure, 223 genes (197 autosomal recessive genes and 26 X-linked genes) of the subjects were tested. According to the screening results, genetic counseling and fertility guidance were provided to the subjects. Invasive prenatal diagnosis was performed for high-risk couples (both couples being carriers of the same autosomal recessive disease gene or the woman was a carrier of X-linked disease gene), and their pregnancy pattern, outcome and offspring phenotype were followed up.Results:(1) A total of 3 044 cases from 1 511 couples and women of childbearing age from 22 families were included for carrier screening. Totally 1 503 families chose simultaneous screening and 30 families chose sequential screening out of the 1 533 families. Among the 3 044 subjects, 1 603 individuals carried at least one pathogenic or likely pathogenic variant, and the overall carrier rate was 52.66% (1 603/3 044). A total of 2 292 pathogenic or likely pathogenic variants were detected, and 0.75 variants (2 292/3 044) were detected per capita. (2) The three genes with the highest carrier rates were GJB2 (8.67%, 264/3 044), CYP21A2 (3.19%, 97/3 044) and PAH (3.09%, 94/3 044). There were 32 genes with a carrier rate ≥1/200, 17 genes with a carrier rate ≥1/100, and 7 genes with a carrier rate ≥1/50. (3) Thirty-eight high-risk families were identified. After excluding G6PD gene mutation, there were 33 high-risk families, of which 25 couples were carriers of the same autosomal recessive gene, 9 women were carriers of X-linked gene, and 1 family was double high-risk couple with both autosomal recessive and X-linked gene. After further excluding the GJB2 c.109G>A mutation, 21 high-risk families were identified. Preimplantation genetic testing for monogenic disease was performed in 12 families after genetic counseling. Prenatal diagnosis was completed in 4 out of 5 high-risk families who conceived naturally. Two fetuses carried the parental variants and terminated the pregnancy, one fetus did not carry the parental variants but was induced due to trisomy 21 syndrome, and one fetus was a carrier of congenital disorders of glycosylation type 1a.Conclusions:Carrier screening effectively identifies high-risk genetic disease families and provides reproductive guidance to prevent the birth of affected children. However, establishing multidisciplinary team is essential for managing complex cases. Implementation should prioritize prenatal institutions with genetic counseling or diagnostic expertise for monogenic disorders or established referral networks.

Objective:To carry out carrier screening among people of childbearing age, detect the pathogenic genes of monogenic genetic diseases and analyze the carrier status of pathogenic variants, so as to provide fertility guidance and intervention measures for high-risk families.Methods:From August 2022 to August 2023, 1 533 families of childbearing age who met the criteria were recruited in the Chinese PLA General Hospital, including a total of 3 044 subjects. According to the standard enrollment procedure, 223 genes (197 autosomal recessive genes and 26 X-linked genes) of the subjects were tested. According to the screening results, genetic counseling and fertility guidance were provided to the subjects. Invasive prenatal diagnosis was performed for high-risk couples (both couples being carriers of the same autosomal recessive disease gene or the woman was a carrier of X-linked disease gene), and their pregnancy pattern, outcome and offspring phenotype were followed up.Results:(1) A total of 3 044 cases from 1 511 couples and women of childbearing age from 22 families were included for carrier screening. Totally 1 503 families chose simultaneous screening and 30 families chose sequential screening out of the 1 533 families. Among the 3 044 subjects, 1 603 individuals carried at least one pathogenic or likely pathogenic variant, and the overall carrier rate was 52.66% (1 603/3 044). A total of 2 292 pathogenic or likely pathogenic variants were detected, and 0.75 variants (2 292/3 044) were detected per capita. (2) The three genes with the highest carrier rates were GJB2 (8.67%, 264/3 044), CYP21A2 (3.19%, 97/3 044) and PAH (3.09%, 94/3 044). There were 32 genes with a carrier rate ≥1/200, 17 genes with a carrier rate ≥1/100, and 7 genes with a carrier rate ≥1/50. (3) Thirty-eight high-risk families were identified. After excluding G6PD gene mutation, there were 33 high-risk families, of which 25 couples were carriers of the same autosomal recessive gene, 9 women were carriers of X-linked gene, and 1 family was double high-risk couple with both autosomal recessive and X-linked gene. After further excluding the GJB2 c.109G>A mutation, 21 high-risk families were identified. Preimplantation genetic testing for monogenic disease was performed in 12 families after genetic counseling. Prenatal diagnosis was completed in 4 out of 5 high-risk families who conceived naturally. Two fetuses carried the parental variants and terminated the pregnancy, one fetus did not carry the parental variants but was induced due to trisomy 21 syndrome, and one fetus was a carrier of congenital disorders of glycosylation type 1a.Conclusions:Carrier screening effectively identifies high-risk genetic disease families and provides reproductive guidance to prevent the birth of affected children. However, establishing multidisciplinary team is essential for managing complex cases. Implementation should prioritize prenatal institutions with genetic counseling or diagnostic expertise for monogenic disorders or established referral networks.

Objective:To reassess the pathogenicity of copy number variants (CNVs) involving chromosomal microdeletions and microduplications classified as variants of uncertain significance (VUS).Methods:This retrospective study analyzed 1 882 pregnant women who underwent invasive prenatal diagnosis for chromosomal microarray analysis (CMA) at the First Medical Center, Chinese PLA General Hospital between January 1, 2018, and December 31, 2022. The results were classified according to the American College of Medical Genetics and Genomics guidelines, with 82 fetuses rated as VUS selected for the study. We analyzed invasive prenatal diagnostic indications, followed up on fetal ultrasound findings, parental origin identification results, and pregnancy outcomes, and reclassified VUS CNVs based on the latest evidence. Descriptive statistical analysis was applied to the data.Results:(1) Among the 82 fetuses with VUS CNVs, prenatal diagnostic indications included fetal structural abnormalities detected by ultrasound (21 cases, 25.6%), abnormal non-invasive prenatal testing (NIPT) results (12 cases, 14.6%), high-risk serum screening (seven cases, 8.5%), advanced maternal age (≥35 years at expected delivery, 28 cases, 34.1%), and other indications (14 cases, 17.1%). Sixteen cases (19.5%) exhibited abnormal phenotypes, with seven pregnancies terminated due to severe structural abnormalities detected by prenatal ultrasound. Seventy-five live births were followed up for 25 (13-66) months. (2) Among the 82 cases, five fetuses had two VUS CNVs detected by CMA, while the remaining 77 had only one, totaling 87 VUS CNVs. Of these, 63 (72.4%) were chromosomal microduplications and 24 (27.6%) were chromosomal microdeletions. The size of the CNV segments ranged from 0.85 (0.05-5.61) Mb, with 82 segments less than 2 Mb. Parental origin identification was refused by 44 cases (53.7%), while 38 (46.3%) underwent the test, revealing eight (21.0%) de novo variants and 30 (78.9%) inherited from either parent (12 maternal and 18 paternal). (3) Among the 87 VUS CNVs, the ratings of 11 CNVs (12.6%) changed after re-evaluation. This included one 4p16.2 microdeletion and two 15q11.2 microdeletions being upgraded to pathogenic, one 16p13.11 microduplication being upgraded to likely pathogenic, one Xp22.31 microduplication and two 2q13 microdeletions being downgraded to likely benign, and four Xp22.31 microduplications being downgraded to benign. (4) Among the 16 fetuses with abnormal phenotypes, seven with prenatal abnormalities terminated pregnancies, including six with structural abnormalities and one with severe fetal growth restriction. After re-evaluation, one case was upgraded to pathogenic, while six remained VUS. Nine live births with postnatal abnormal phenotypes showed no change in classification after re-evaluation. Among the 66 cases (80.5%) without abnormal phenotypes, 10 had their classifications changed after re-evaluation. Conclusions:Fetuses with VUS CNVs often exhibit no significant abnormal phenotypes and have a relatively favorable prognosis, however, further floow-up is still needed. Parental origin identification can provide valuable insights for genetic counseling.

OBJECTIVETo explore the relationship between nurse occupational stress and salivary alpha- amylase (SAA).

METHODSEvaluation of occupational stress was conducted in 131 nurses. The activity of SAA was determined using enzyme-linked immunosorbent assay (ELISA).

RESULTSThe activity of SAA in nurses varied with age and working years. The baseline, work period, recovery, average activities of >35 age group were less than those of ≤ 30 age group; work period, recovery, average activities of ≤ 10 years group were higher than other two groups; there was no statistical difference between SAA vitalities of different degree groups (P>0.05). In nurses with high scores for job demands, the activity of SAA in working period was significantly higher than that in nurses with low scores (P < 0.05). The baseline SAA activity in nurses with high scores for role conflict and ambiguity was significantly higherthan thatin nurses with low scores (P < 0.05). The baseline SAAactivity was positively correlated with workload, role conflict, and role ambiguity (P < 0.05). The activity of SAA in working period was negatively correlated with task control, decision control, and technology utilization (P < 0.05), and was positively correlated with quantitative load, load change, work monotony, and workload (P < 0.05). The activity of SAA in recovery period was negatively correlated with task control, decision control, resource control, and technology utilization (P < 0.01). The average activity of SAA was negatively correlated with task control, decision control, resource control, technology utilization, opportunity for participating in decision-making, and promotion (P < 0.05), and was positively correlated with quantitative load, load change, workload, and role ambiguity (P < 0.05).

CONCLUSIONThe occupational stress in 131 nurses is correlated with the activity of SAA, which can be used as an objective biomarker for identification and evaluation of occupational stress.

Biomarkers ; Humans ; Nurses ; psychology ; Occupational Diseases ; epidemiology ; Salivary alpha-Amylases ; analysis ; Stress, Psychological ; diagnosis ; epidemiology ; Work ; Workload

Objective To study the changes of urodynamics of middle-aged(35-55 years old)female patients with urinary incontinence and improve the diagnosis and treatment.Methods Analyze and compare the urodynamics between 56 cases of middle-aged female patients with urinary incontinence and 17 cases of normal control.Results Among the 56 patients,33 cases with stress incontinence(SUI group 58.93％),9 cases with urgency urinary incontinence(UUI group 16.07％),14 cases with mixed urinary incontinence(SUI/UUI group 25.00％).There was significant difference on maximum flow rate(Qmax[27.72 ± 5.21]ml/s vs[20.45 ±7.15]ml/s,P ＜0.05)between the SUI group and control group.The beginning of a sense of capacity(FS),normal urination feeling(ND),strong feeling of urination(SD)and urgent urination feeling(UD)were (135.65 ± 42.73)ml,(166.24 ± 51.42)ml,(315.75 ±42.34)ml,(320.24 ± 45.03)ml and(132.70 ±40.65)ml,(160.70 ± 50.44)ml,(320.75 ± 42.34)ml,(335.75 ± 51.98)ml in the UUI group and control group respectively.And there were significant differences on the four indexes between UUI group and control group(P ＜ 0.05).There was significant difference on ALPP([62.29 ± 25.40]cm H2O vs[88.30 ± 28.54]cm H2O,P ＜0.05)between the SUI group and SUI/UUI group.Pressure at maximum flow rate(Pdet-Qmax,[24.29 ± 6.24]cm H2O vs[34.45 ± 8.20]cm H2 O,maximum urethral pressure(M UP([68.20 ± 18.27]cm H2O vs[87.14 ± 17.26]cm H2O)and maximum urethral closure pressure(MUCP([74.24 ±35.75]cm H2O vs[90.66 ±30.10]cm H2O)in SUI group were significantly lower than those in control group(P ＜0.05)Conclusion There were large groups of middle-aged female urinary incontinence in patients and the classification is more complex.It shows important guiding significance for diagnosis and selecting proper treatments by detecting urodynamic.

Objective To explore the mechanism of the influence on mice brain of environmental tobacco smoke. Methods After the mice were placed into the bench for 8 weeks, the region of the mice brain was localized and the expression of neurotransmitters and neurotransmitters receptors were detected by immunohistochernistry.Results ( 1 ) The expression of GABA in the mice cerebral cortex ( CC ) ( 0. 25 ± 0. 06 ) and the hippocampus (Hip) (0. 19 ± 0. 07 ) were much higher in the ETS-exposed group than that in the control group(P＜ 0. 05 ). (2)The expression of nAChR on CC(0. 31 ±0. 10) was much more in the ETS-exposed group than that in control group(P＜0.05). (3) The expression of NMDAR( Glu receptors) on the CC and striate cortex were much higher in the ETS-exposed group(0.32 ±0. 10,0.38 ±0. 14), NIC-inhaling group(0.31 ±0. 08,0.31 ± 0. 11 ) than that in control group(P＜0. 05 ). Conclusions Long-term ETS-exposed and NiC-exposed environment could change the expression of neurotransmitter and its receptors.

Most researchers consider that high exposure to heavy metals can result in hemorrhagic gastritis,hepatonecrosis,cancer,even death.There are many routes for heavy metals to get into human body,for instance absorption by gastrointestinal tract,cutaneous absorption etc.In this paper,the author reviewed the recent researches on brain function damage induced by heavy metals via olfactory pathway.Some heavy metals have especial affinity with brain tissue and cause functional disorder and death of nerve cells,and the mechanisms were discussed in detail.