Objective To explore the mechanism of Zishen Jianpi Huayu Tablets(Corni Fructus,Notoginseng Radix et Rhizoma,Astragali Radix,Puerariae Lobatae Radix,Spatholobi Caulis,Rehmanniae Radix)in the treatment of diabetic retinopathy(DR)by means of network pharmacology and molecular docking technique,and verified by in vitro experiments.Methods The active components of Zishen Jianpi Huayu Tablets and their corresponding target proteins were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the BATMAN-TCM database.Drug target proteins were converted to their corresponding gene names through the UniProt database.DR-related targets were searched using"diabetic retinopathy"as a keyword in GeneCards,DrugBank,OMIM,and TTD databases.Common targets between the disease and the drug were identified using the Venny tool.These common targets were analyzed using the String database,a protein-protein interaction(PPI)network was constructed.Topological heterogeneity analysis was performed using Cytoscape 3.9.1 to select core targets and create a PPI network diagram.These common targets were entered into the Metascape database for Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis to identify potential action pathways.Molecular docking of the main active components and core targets was performed using Auto Dock tools software,followed by further experimental validation.The CCK-8 assay was used to assess the effect of Zishen Jianpi Huayu Tablet medicated serum on the cell viability of Human Retinal Microvascular Endothelial Cells(HRmECs)under high glucose conditions,and RT-qPCR was used to measure the expression of IL-1β,AKT1,VEGFA,and TP53 mRNA in HRmECs.Results(1)The effective components and corresponding target proteins of Zishen Jianpi Huayu Tablets were screened by Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and BATMAN-TCM database.The disease-related targets of DR were searched by GeneCards,OMIM and TTD databases.The use of VENNY platform for drug active components target and DR disease-related target to take intersection(common target),that is,Zishen Jianpi Huayu Tablets in the treatment of DR potential target.The network of"drugs-active components-common targets"was constructed to screen out the key active components of Zishen Jianpi Huayu Tablets in the treatment of DR.Import the common target into STRING database,obtain the PPI network relationship,and screen out the core target.Metascape platform was used to analyze the GO function and KEGG pathway enrichment of the common targets.The key active components and core targets were verified by Autodock 4 software for molecular docking.(2)The drug-containing serum and blank serum of Zishen Jianpi Huayu Tablets was prepared.Human retinal microvascular endothelial cells(HRmECs)were randomly divided into 5 groups:the control group(low-sugar DMEM medium+10%blank serum),high-glucose group(high-sugar DMEM medium+10%blank serum)and Zishen Jianpi Huayu Tablets containing low-,medium-and high-dose serum(high-sugar DMEM medium+10%low-,medium-and high-dose drug containing serum)were detected after 48 hours of culture.The proliferative activity of HRmECs cells was detected by CCK-8 method,and the mRNA expressions of IL-1β,AKT1,VEGFA and TP53 in HRmECs cells were detected by RT-qPCR method.Conclusion Zishen Jianpi Huayu Tablets may act on core targets such as IL-1β,IL-6 and VEGFA,as well as key pathways such as NF-κB signaling pathway,AGE-RAGE signaling pathway and PI3K-AKT pathway through various active components such as quercetin,kaempferol and rehmannia flavonoids,so as to play a therapeutic role in DR.

Long-term care encompasses the effectiveness of life care and health services that are provided to individuals and groups with disabilities,aiming to enhance their physical and mental well-being and overall quality of life.In the context of an aging population,prioritizing long-term care quality for populations with disability becomes imperative.The presenting study examined the main practices of assuring long-term care quality in the United States across 3 critical dimensions of structure,process and outcome,using the Donabedian quality framework theory.The findings were subsequently applied to guide the evaluation of the long-term care quality assurance in China,which serves as a valuable reference for promoting the high-quality development of long-term care services in China.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

The new-generation non-invasive prenatal screening technology (NIPT2.0) is a new method successfully realized in recent years based on high-throughput sequencing to synchronously and accurately detect fetal chromosomal aneuploidies, microdeletion/microduplication syndromes and dominantly inherited monogenic disorders. NIPT2.0 can circumvent the shortcomings of previous non-invasive prenatal screening techniques (NIPT and NIPT Plus) including incapability to detect fetal monogenic disorders, insufficient accuracy of detection and low positive predictive values for certain chromosomal abnormalities (in particular trisomy 13, sex chromosomal abnormalities, and small-segment microdeletions and microduplication syndromes). How to apply NIPT2.0 reasonably and normatively to maximize its clinical value has become an issue which requires clarification. The Reproductive Health Branch of the Chinese Maternal and Child Health Care Association has organized experts to fully discuss and jointly drafted this consensus, which has put forwards suggestions over the clinical application strategy for NIPT2.0, including the scope of application, target disease, pre-test consultation, clinical application pathway, post-test genetic counseling and intervention, quality control and limitations, for the reference by peers, with a view to standardize its application and provide better clinical service.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective:To establish the reference values and neurological intervention cutoffs for cerebral ventricular size in neonates born at 33 +0-41 +6 weeks of gestation and to investigate the influential factors and reliability of the related indices. Methods:This study prospectively recruited 1 370 1-to 7-day neonates born or hospitalized at the Hunan Provincial Maternal and Child Health Care Hospital from February to August 2021. All the neonates, who were born between 33 +0 and 41 +6 weeks of gestation, were subjected to ultrasound scanning to obtain the indices, including ventricular index (VI), anterior horn width (AHW), thalamo-occipital distance (TOD), and ventricular height (VH). The reference value and neurological intervention cutoff for each index were set. Quantile regression was used to estimate the correlation between each index and continuous covariates [gestational age at birth (GA) and birth weight (BW)]. Mann-Whitney U test was used to analyze the differences in the medians of indices in different categorical covariates groups (males/females, left/right lateral ventricles, vaginal delivery/cesarean section, and singleton/multiple births). Intraclass correlation coefficient (ICC) calculated by a two-way mixed effect model and absolute agreement was used to access intra-rater reliability; ICC via a two-way random effect model and absolute agreement was utilized to rate inter-rater reliability (pool reliability: ICC below 0.50; moderate reliability: ICC between 0.50 and 0.75; good reliability: ICC between 0.75 and 0.90; excellent reliability: ICC exceeding 0.90). Results:The upper limits of reference values for AHW, TOD, VI, and VH in 555 (40.5%) preterm neonates were 2.7-3.5 mm, 20.9-22.5 mm, 12.6-13.7 mm, and 3.8-4.9 mm, and in 815 (59.5%) term newborns were 3.4-4.3 mm, 18.6-21.3 mm, 14.2-14.7 mm, and 3.4-3.8 mm, respectively. The cutoff of neurosurgical intervention for each index was the upper limit of reference value plus 4 mm. AHW median was positively correlated with GA [partial regression coefficient (PRC): 0.12, P<0.05], while TOD and VH medians were negatively correlated with GA (PRC:－0.31 and－0.06, both P<0.05). VI, AHW, and TOD medians were positively associated with BW (PRC: 0.46, 0.23, and 0.97, all P<0.05). The medians of VH, AHW, and TOD in the left cerebral ventricular exceeded those in the right cerebral ventricular, respectively (VH: 2.0 vs 1.8 mm, U=836 071.50; AHW: 1.8 vs 1.7 mm, U=874 141.50; TOD: 13.6 vs 12.5 mm, U=738 409.00, all P<0.05). The medians of AHW and VI in male neonates were greater than those in female newborns, respectively (AHW: 1.8 vs 1.7 mm, U=834 124.00; VI: 11.1 vs 10.8 mm, U=884 156.50, both P<0.05). The neonates delivered vaginally had greater AHW median, but smaller TOD median than those delivered by cesarean section (AHW: 2.0 vs 1.6 mm, U=685 546.00, P<0.001; TOD: 13.1 vs 12.9 mm, U=850 797.00, P=0.010). The AHW median in singleton newborns exceeded that in multiple births (1.9 vs 1.4 mm, U=356 999.00, P<0.001). The lower limits of 95% confidence intervals for intra-rater and inter-rater ICCs exceeded 0.75 and 0.50, respectively. Conclusion:Reference values and surgical intervention thresholds for VI, AHW, TOD, VH of newborns with a gestational age of 33 +0-41 +6 weeks were preliminarily established, and the reliability of these indicators were verified.

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Antigens, CD34/metabolism* ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear/metabolism* ; Peptides/metabolism*

Purpose: The aim of this paper is to develop a scale for measuring the perinatal bereavement care competence of midwives and assess its psychometric properties. Methods: The Perinatal Bereavement Care Competence Scale was developed in four phases. (1) Item generation: 75 items were formulated based on a literature review and interviews with midwives. (2) Delphi expert consultation: 15 experts evaluated whether the items were clear/appropriate/relevant to the questionnaire dimensions, and the items were optimized. (3) Pilot test: The comprehensibility, acceptability, and time required to complete the questionnaire by midwives were assessed. (4) Evaluation of reliability and validity: The scale was validated by initial item analysis, exploratory and confirmatory factor analyses, and internal consistency reliability and testeretest reliability. Results: The final scale consisted of six dimensions and 25 items: maintaining belief (three items), knowing (four items), being with (six items), preserving dignity (four items), enabling (five items), and self-adjustment (three items). Exploratory factor analysis yielded a six-factor structure that was consistent with the theoretical framework and explained 70.8% of the total variance. Confirmatory factor analysis indicated a good fit for the six-factor model. Cronbach's a for the scale was 0.931, and the test eretest reliability coefficient was 0.968. Conclusion The Perinatal Bereavement Care Competence Scale is a valid and reliable instrument for measuring the competence of midwives in caring for bereaved parents who have experienced perinatal loss.

Abstract Comprehensive sexuality education is an important part of quality education, primary and secondary schools are the most suitable places for sex education. This paper sorts out the current status of sexuality education for primary and secondary school students in developed countries after presenting the overall significance of school based sexuality education, and further points out the problems and urgency of sexuality education for primary and secondary school students in China. It also put forward the way to new directions for advocacy, including the comphrehensive sexuality education curriculum system, training of sexuality education teachers, the positive and active role of families, as well as social and community support for sexuality education in schools.

Objective:To explore the effect of exercise rehabilitation on pulmonary function, aerobic capacity and quality of life in children with bronchial asthma.Methods:According to the PICOS principle, China National Knowledge Infrastructure (CNKI) , VIP, Wanfang Database, SinoMed, Web of Science, Cochrane Library, PubMed, Embase and CINAHL were used to search for all Chinese and English randomized controlled trials on the effect of exercise rehabilitation on children with bronchial asthma from January 1, 2000 to December 23, 2021. The Cochrane manual was used to systematically review the literature. Meta-analysis was performed using RevMan 5.3.Results:Finally, 15 articles were included, with a total of 936 subjects. Meta-analysis results showed that exercise rehabilitation could improve percentage of forced vital capacity in the predicted value (FVC%) [mean difference ( MD) =2.75, 95% confidence interval ( CI) (1.22-4.28) , P=0.000 4] , percentage of forced expiratory volume in one second in predicted value (FEV 1%) [standardized mean difference ( SMD) =0.22, 95% CI (0.07-0.36) , P=0.003] , percentage of peak expiratory flow in the predicted value (PEF%) [ MD=7.15, 95% CI (3.30-11.00) , P=0.000 3] , maximum oxygen uptake (VO 2max) [ MD=5.86, 95% CI (2.53-9.19) , P=0.000 6] and quality of life [ MD=0.67, 95% CI (0.43-0.91) , P<0.000 01] , but there was no statistically significant difference in improving the ratio of FEV 1% to FVC% (FEV 1/FVC%) [ MD=-0.97, 95% CI (-3.55-1.61) , P=0.46] . Conclusions:Exercise rehabilitation can improve partial pulmonary function, aerobic capacity and quality of life in children with asthma. However, it still needs to continue to be promoted in the clinical practice, in order to verify its effectiveness with more high-quality research.