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 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 genotype and genetic characteristics of rubella virus (RV) circulated in Qinghai province.Methods:The throat swabs were collected from suspected rubella cases in two cities of Qinghai province in 2010 and 2019, respectively. After nucleic acid detection and virus isolation, the target genotyping sequences (739 nucleotide fragments of E1 gene) of positive virus isolates were amplified and determined. The sequences of the viruses were compared with 32 reference strains of 13 genotypes recommended by World Health Organization(WHO) to determine the genotype, and the genetic relationship between Qinghai isolates and RV strains from other provinces of China was also analyzed.Results:In this study, four RV virus strains were isolated, and the genetic relationship analysis showed that these virus strains were classified into 1E-Cluster A sub-genotype and 2B-Cluster C sub-genotype, which was basically consistent with the epidemic trend of RV in other provinces of China. The four virus strains in Qinghai province were highly conserved at the amino acid level, but region-specific mutation sites were also found.Conclusions:This study provides some laboratory data for the formulation of rubella prevention and control strategy in Qinghai province..

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.

Objective To estimate the effect of early fluid removal on the early postoperative recov-ery in children after surgical repair of congenital heart disease with enlarged right ventricle via a randomized trial. Methods One hundred and twenty patients with right-sided complex congenital heart defect who un-derwent cardiac surgery by cardiopulmonary bypass during January 2017 to June 2017 were enrolled and were divided into two groups,Group-E and Group-C,when the hemodynamics was stable within 3 hours after the surgery. Patients in Group-E were treated with early fluid removal,but Group-C remained conventional thera-py. The data of the hemodynamics and outcomes were collected from the postoperative day to the 2nd day post-operation. Results Fluid removal therapy was started in Group-E at (4. 39 ± 0. 85) h postoperatively vs (10. 17 ± 2. 77) h in Group-C (P < 0. 05). Patients in Group-E showed lower extravascular lung water index (ELWI),lower fluid overload and lower NT-proBNP compared with patients in Group-C on the first day of post-operation(P < 0. 01). Also, the advantages remained in Group-E on the second day but the ELWI showed no remarkable difference. The rate of reintubation(P < 0. 05),the duration of mechanical ventilation and the length of ICU stay (P < 0. 01)were significantly reduced in Group-E. Conclusion In patients with right ventricle enlarged complex congenital heart defect who underwent cardiac surgery by cardiopulmonary bypass,utilizing early negative fluid balance when the hemodynamics are stable and the right ventricle is ob-viously enlarged could achieve negative fluid balance,get extubated and discharge from ICU earlier,also pres-ent lower extravascular lung water index, lower incidence of weaning-induced pulmonary edema and reintubation.