Objective:To explore the efficacy of non-invasive prenatal testing (NIPT) of fetal free DNA in maternal peripheral blood in fetuses with increased nuchal translucency (NT).Methods:A retrospective analysis was conducted on 1 184 singleton pregnant women that underwent chromosomal microarray analysis (CMA) at Nanjing Drum Tower Hospital, Nanjing University Medical School from June 2014 to December 2022 due to fetal increased NT (≥3.0 mm). These subjects were categorized based on whether the increased NT was accompanied by other high-risk factors into isolated increased NT without advanced maternal age (further subdivided into 3.0 mm≤NT<3.5 mm, 3.5 mm≤NT<4.0 mm, and NT≥4.0 mm subgroups), isolated increased NT with advanced maternal age, increased NT with nasal bone abnormalities, increased NT with other soft markers, and increased NT with structural abnormalities groups. Assuming the sensitivity and specificity of NIPT and expanded NIPT at this center were both 100%, genomic abnormalities outside the detection range of NIPT or expanded NIPT were termed as residual risk of NIPT or expanded NIPT. Chi-square test and Bonferroni correction were used to compare the residual risks of NIPT and expanded NIPT among the three subgroups of isolated increased NT without advanced maternal age group. Results:(1) In the group of isolated increased NT without advanced maternal age: For the 3.0 mm≤NT<3.5 mm subgroup (329 cases), 19 abnormalities were detected by CMA [12 cases of chromosome aneuploidy, seven cases of pathogenic copy number variation (pCNV)], with residual risks of NIPT and expanded NIPT both at 2.1% (7/329). For the 3.5 mm≤NT<4.0 mm subgroup (173 cases), 29 abnormalities were detected by CMA (17 cases of chromosome aneuploidy, nine cases of pCNV, three cases of chromosome unbalanced translocation), with residual risks of NIPT at 8.1% (14/173) and expanded NIPT at 7.5% (13/173). For the NT≥4.0 mm subgroup (270 cases), CMA detected abnormalities in 70 cases (50 cases of chromosome aneuploidy, 16 cases of pCNV, three cases of unbalanced translocations, and one case of sex chromosome abnormality combined with pCNV). The residual risk of NIPT was 12.2% (33/270), and the residual risk of expanded NIPT was 7.0% (19/270). The residual risks of NIPT and expanded NIPT in the 3.0 mm≤NT<3.5 mm subgroup were lower than those in the 3.5 mm≤NT<4.0 mm and NT≥4.0 mm subgroups (Bonferroni correction, all P<0.017). (2) In the group of 92 cases with isolated increased NT and advanced maternal age, CMA detected abnormalities in 36 cases (29 cases of chromosome aneuploidy, five cases of pCNV, one case of trisomy 21 combined with sex chromosome abnormality, and one case of trisomy 18 combined with sex chromosome abnormality). The residual risk of NIPT was 7.6% (7/92), and that of expanded NIPT was 5.4% (5/92). (3) In the group of 49 cases with increased NT combined with nasal bone abnormalities, CMA detected abnormalities in 24 cases (23 cases of chromosome aneuploidy and one case of pCNV). The residual risks of NIPT and expanded NIPT were both 2.0% (1/49). (4) In the group of 26 cases with increased NT combined with other soft markers, CMA detected abnormalities in nine cases (six cases of chromosome aneuploidy, one case of pCNV, and two cases of chromosome unbalanced translocations). The residual risks of NIPT and expanded NIPT were both 11.5% (3/26). (5) In the group of 245 cases with increased NT combined with structural abnormalities, CMA detected abnormalities in 121 cases (107 cases of chromosome aneuploidy, seven cases of pCNV, four cases of chromosome unbalanced translocations, one case of trisomy 21 combined with trisomy 20, and two cases of trisomy 18 combined with sex chromosome abnormalities). The residual risk of NIPT was 16.7% (41/245), and that of expanded NIPT was 4.1% (10/245). Conclusions:For isolated NT≥3.5 mm or NT≥3.0 mm combined with other high-risk factors, chorionic villus sampling in early pregnancy can be recommended, advancing the timing of prenatal diagnosis from the second trimester to the first trimester. For fetuses with isolated 3.0 mm≤NT<3.5 mm, the 2.1% residual risk of chromosomal abnormalities should be fully informed during counseling, even if the risk of NIPT is low.

Protein arginine methyltransferase 5 (PRMT5) exhibits elevated expression levels in a variety of cancers and has emerged as a critical target for cancer therapy in recent years. However, first-generation PRMT5 inhibitors have exhibited inadequate selectivity, leading to significant hematological toxicity, thus limiting their clinical utility. The second-generation PRMT5 inhibitors have shown marked improvement in safety and efficacy by selectively targeting MTAP-null tumor cells without impacting normal cells. This review systematically summarizes the biological and functional roles of PRMT5 in MTAP-deficient tumor cells, and comprehensively analyzes the research and development process, molecular binding mechanisms, and the latest advancements in clinical trials of the five second-generation PRMT5 inhibitors currently under investigation, aiming to provide valuable insights for further in-depth studies in this field.

Objective:To explore the efficacy of non-invasive prenatal testing (NIPT) of fetal free DNA in maternal peripheral blood in fetuses with increased nuchal translucency (NT).Methods:A retrospective analysis was conducted on 1 184 singleton pregnant women that underwent chromosomal microarray analysis (CMA) at Nanjing Drum Tower Hospital, Nanjing University Medical School from June 2014 to December 2022 due to fetal increased NT (≥3.0 mm). These subjects were categorized based on whether the increased NT was accompanied by other high-risk factors into isolated increased NT without advanced maternal age (further subdivided into 3.0 mm≤NT<3.5 mm, 3.5 mm≤NT<4.0 mm, and NT≥4.0 mm subgroups), isolated increased NT with advanced maternal age, increased NT with nasal bone abnormalities, increased NT with other soft markers, and increased NT with structural abnormalities groups. Assuming the sensitivity and specificity of NIPT and expanded NIPT at this center were both 100%, genomic abnormalities outside the detection range of NIPT or expanded NIPT were termed as residual risk of NIPT or expanded NIPT. Chi-square test and Bonferroni correction were used to compare the residual risks of NIPT and expanded NIPT among the three subgroups of isolated increased NT without advanced maternal age group. Results:(1) In the group of isolated increased NT without advanced maternal age: For the 3.0 mm≤NT<3.5 mm subgroup (329 cases), 19 abnormalities were detected by CMA [12 cases of chromosome aneuploidy, seven cases of pathogenic copy number variation (pCNV)], with residual risks of NIPT and expanded NIPT both at 2.1% (7/329). For the 3.5 mm≤NT<4.0 mm subgroup (173 cases), 29 abnormalities were detected by CMA (17 cases of chromosome aneuploidy, nine cases of pCNV, three cases of chromosome unbalanced translocation), with residual risks of NIPT at 8.1% (14/173) and expanded NIPT at 7.5% (13/173). For the NT≥4.0 mm subgroup (270 cases), CMA detected abnormalities in 70 cases (50 cases of chromosome aneuploidy, 16 cases of pCNV, three cases of unbalanced translocations, and one case of sex chromosome abnormality combined with pCNV). The residual risk of NIPT was 12.2% (33/270), and the residual risk of expanded NIPT was 7.0% (19/270). The residual risks of NIPT and expanded NIPT in the 3.0 mm≤NT<3.5 mm subgroup were lower than those in the 3.5 mm≤NT<4.0 mm and NT≥4.0 mm subgroups (Bonferroni correction, all P<0.017). (2) In the group of 92 cases with isolated increased NT and advanced maternal age, CMA detected abnormalities in 36 cases (29 cases of chromosome aneuploidy, five cases of pCNV, one case of trisomy 21 combined with sex chromosome abnormality, and one case of trisomy 18 combined with sex chromosome abnormality). The residual risk of NIPT was 7.6% (7/92), and that of expanded NIPT was 5.4% (5/92). (3) In the group of 49 cases with increased NT combined with nasal bone abnormalities, CMA detected abnormalities in 24 cases (23 cases of chromosome aneuploidy and one case of pCNV). The residual risks of NIPT and expanded NIPT were both 2.0% (1/49). (4) In the group of 26 cases with increased NT combined with other soft markers, CMA detected abnormalities in nine cases (six cases of chromosome aneuploidy, one case of pCNV, and two cases of chromosome unbalanced translocations). The residual risks of NIPT and expanded NIPT were both 11.5% (3/26). (5) In the group of 245 cases with increased NT combined with structural abnormalities, CMA detected abnormalities in 121 cases (107 cases of chromosome aneuploidy, seven cases of pCNV, four cases of chromosome unbalanced translocations, one case of trisomy 21 combined with trisomy 20, and two cases of trisomy 18 combined with sex chromosome abnormalities). The residual risk of NIPT was 16.7% (41/245), and that of expanded NIPT was 4.1% (10/245). Conclusions:For isolated NT≥3.5 mm or NT≥3.0 mm combined with other high-risk factors, chorionic villus sampling in early pregnancy can be recommended, advancing the timing of prenatal diagnosis from the second trimester to the first trimester. For fetuses with isolated 3.0 mm≤NT<3.5 mm, the 2.1% residual risk of chromosomal abnormalities should be fully informed during counseling, even if the risk of NIPT is low.

OBJECTIVE: To analyze the prognosis of fetuses identified with de novo variants of unknown significance (VOUS) by chromosome microarray analysis (CMA). METHODS: A total of 6 826 fetuses who underwent prenatal CMA detection at the Prenatal Diagnosis Center of Drum Tower Hospital from July 2017 to December 2021 were selected as the study subjects. The results of prenatal diagnosis, and outcome of fetuses identified with VOUS of de novo origin were followed up. RESULTS: Among the 6 826 fetuses, 506 have carried VOUS, of which 237 were detected for the parent-of-origin and 24 were found to be de novo. Among the latters, 20 were followed up for 4 to 24 months. Four couples had opted elective abortion, 4 had developed clinical phenotypes after birth, and 12 were normal. CONCLUSION Fetuses with VOUS should be continuously follow-up, in particular those carrying de novo VOUS, in order to clarify their clinical significance.
Pregnancy ; Female ; Humans ; DNA Copy Number Variations ; Follow-Up Studies ; Prenatal Diagnosis/methods* ; Chromosomes ; Microarray Analysis/methods* ; Fetus ; Chromosome Aberrations

Mortality review is an important way to identify deficiencies and gaps in the healthcare system and can effectively improve the quality and safety of healthcare delivery.It analyzes and summarizes the relevant domes-tic and international literature and review the current development,methods and characteristics of different applica-tion areas of death case review at home and abroad,with a view to guiding healthcare departments or institutions to establish a scientific and standardized mortality review system.

Objective:To determine the relationship between health self-empowerment level and health self-management skill in older adults.Methods:A household survey was conducted from June 2020 to April 2021, among older adults in two communities each in Zhuzhou and Changsha selected by stratified cluster sampling. Data were collected through a general questionnaire, simplified. Elders Health Empowerment Scale, and Rating Scale of Health Self-Management Skill for Adults. A total of 444 questionnaires were distributed, of which 425 were valid. Pearson correlation and hierarchical regression analyses were used to analyze the relationship between health self-empowerment level and health self-management skill.Results:Final sample included 425 elderly people. Health self-empowerment was at medium to high level (30.9±5.6), whereas health self-management was at medium level (146.2±21.7); and the two factors were significantly correlated (Pearson coefficient was 0.724). After controlling for confounding factors (demographic characteristics), health self-empowerment independently accounted for 34.3% of the variation in health self-management ability.Conclusion:Health self-empowerment positively affects health self-management ability among older adults, which suggests the importance of stimulating health self-empowerment awareness in the process of health self-management.

MicroRNAs(miRNAs)are trans-acting small regulatory RNAs that work coordinately with transcription factors(TFs)to shape the repertoire of cellular mRNAs available for translation.Despite our growing knowledge of individual plant miRNAs,their global roles in gene regulatory networks remain mostly unassessed.Based on interactions obtained from public databases and curated from the literature,we reconstructed an integrated miRNA network in Arabidopsis that includes 66 core TFs,318 miRNAs,and 1712 downstream genes.We found that miRNAs occupy distinct niches and enrich miRNA-containing feed-forward loops(FFLs),particularly those with miRNAs as intermediate nodes.Further analyses revealed that miRNA-containing FFLs coordi-nate TFs located in different hierarchical layers and that intertwined miRNA-containing FFLs are associated with party and date miRNA hubs.Using the date hub MIR858A as an example,we performed detailed molecular and genetic analyses of three interconnected miRNA-containing FFLs.These analyses revealed individual functions of the selected miRNA-containing FFLs and elucidated how the date hub miRNA fulfills multiple regulatory roles.Collectively,our findings highlight the prevalence and importance of miRNA-containing FFLs,and provide new insights into the design principles and control logics of miRNA regulatory networks governing gene expression programs in plants.

Objective:To investigate the sedative effect after congenital heart disease surgery in children under the bi-spectral index monitoring(BIS).Methods:A prospective cohort study was performed, we selected 264 children with congenital heart disease who were admitted to the cardiac intensive care unit at Shanghai Children′s Medical Center from September 2018 to August 2019, 126 cases in the intervention group, and 138 cases in the control group.The control group used Ramsay sedation score to evaluate the sedative effect, meanwhile the intervention group was evaluated by Ramsay sedation score and BIS.The incidence of adverse events related to extubation performed within 8 hours after congenital heart disease surgery, and the length of stay in ICU between two groups were compared.The average mechanical ventilation time of the patients whose mechanical ventilation time was more than 8 hours in two groups was compared.The use of sedative drugs midazolam and morphine in children with mechanical ventilation time for more than 24 hours and liver damage, and the incidence of respiratory depression during ventilator withdrawal were analyzed.Results:In children with early extubation, there were 62 cases in the intervention group and 70 cases in the control group.Compared with the control group, the intervention group had a low incidence of extubation-related adverse events (including unplanned extubation, dysphoria after sputum aspiration, and inhalation inhibition after extubation). The average mechanical ventilation time in the intervention group[(8.18±1.95)h] was less than that in the control group[(9.53±1.37)h, P<0.05] of the patients whose mechanical ventilation time was more than 8 hours but less than 24 hours.In children with mechanical ventilation time more than 24 hours, 28 cases were in the intervention group and 35 cases in the control group.The average doses of midazolam and morphine in the intervention group[(1.82±0.40)μg/(kg·min), (8.64±3.03)μg/(kg·h)] were less than those in the control group[(2.73±0.79) μg/(kg·min), (14.32±5.01)μg/(kg·h), all P<0.05]. Among the 28 children in the intervention group with mechanical ventilation time more than 24 hours, 13 cases had liver damage, and 15 cases of the 35 children in the control group had liver damage.The average doses of midazolam and morphine in the intervention group[(1.42±0.51)μg/(kg·min), (6.88±2.17)μg/(kg·h)] were lower than those in the control group[(2.25±0.62)μg/(kg·min), (11.88±3.56)μg/(kg·h), all P<0.05]. The incidence of inhalation inhibition in the intervention group was lower than that in the control group ( χ2=48.303, P<0.05). Conclusion:The sedation after congenital heart disease surgery in children under the BIS is effective.

Objective:To analyze the epidemiological characteristics of rubella and the genetic characteristics of rubella virus (RV) circulated in Qinghai province in 2020, so as to provide scientific basis for optimization and improvement of local rubella prevention and control strategy.Methods:The rubella epidemiological characteristics were analyzed by summarizing the data on the rubella incidence in Qinghai province in 2020 from the National Notifiable Disease Reporting System. Through Qinghai provincial measles and rubella laboratory network, throat swab samples from susceptible rubella outbreak and sporadic cases in 2020 were collected and identified. RV strains were obtained after three passages of virus isolation from positive samples. After extracting the viral RNA, the 739 nucleotide fragments within the E1 gene were amplified and determined to identify the genotype and sub-genotype of the Qinghai strains in 2020 and further analyzed the molecular differences between Qinghai strains and the RV strains circulated in China.Results:In 2020, the rubella incidence in Qinghai province had shown an obvious upward trend, and the age of onset had shifted to adolescents in the 10-19 years of age group (accounting for 94.9%). Totally 29 RV strains were isolated from four high incidence areas of rubella in Qinghai province. All RV strains were identified as sub-genotype 2B-L2c, which is also the dominant subtype of RV circulated in China. In addition, virological surveillance data showed that there were different transmission chains of sub-genotype 2B-L2c in Qinghai province in 2020, and an outbreak might be caused by different transmission chain viruses.Conclusions:The accumulation of rubella susceptible population aged 10-19 years and the transmission of new imported 2B-L2c virus had led to the rubella reemergence and outbreaks in several cities in Qinghai province in 2020.

Objective:To understand the status quo of post-traumatic growth and family environment of parents of children with hemodialysis and analyze the relationship between them.Methods:From April 2017 to May 2019, parents of 200 children with hemodialysis in Children's Hospital Affiliated to Zhengzhou University were selected as research objects by convenience sampling. The general information questionnaire, Post-traumatic Growth Inventory (PTGI) , Family Environment Scale-Chinese Version (FES-CV) was used for the survey. Pearson correlation analysis and stratified regression analysis were used to explore the relationship between parents' post-traumatic growth and family environment. A total of 200 questionnaires were issued and 183 valid questionnaires were returned, with an effective response rate of 91.5%.Results:The total score of PTGI of 183 parents of children with hemodialysis was (61.95±15.54) , and that of FES-CV was (49.27±7.38) . The total score of PTGI of parents of children with hemodialysis were positively correlated with family environment intimacy, emotional expression, independence, success, culture, entertainment, morality and religion and organizational subscale scores ( P<0.05) , and negatively correlated with scores of environmental contradictions and control subscales ( P<0.05) . The results of stratified regression analysis show that after controlling general data, intimacy and emotional expression in the family environment were the main influencing factors for the post-traumatic growth of the parents of hemodialysis children. Conclusions:The post-traumatic growth of parents of children with hemodialysis is closely related to the family environment. Clinical nurses should take targeted measures to help parents get support from within the family, help them actively cope with diseases and improve post-traumatic growth.