Dentofacial deformity is a disorder of the volume and morphological structure of the jaws and the positional relationship between the maxilla and mandible caused by abnormal development of the jaws, which is manifested by abnormal facial morphology, malocclusion and dysfunction of the stomatognathic system. Orthognathic surgery is an important means of treating dentofacial deformity, and the development of specialized nursing plans for orthognathic surgery needs to be developed based on the diagnostic and treatment characteristics and needs of different disease courses. This article proposed recommended nursing practices as a means of constructing a specialized nursing model for orthognathic surgery and providing standardized management for orthognathic patients throughout the entire cycle by reviewing previous literature and summarizing the nursing practice experience of our hospital in treating more than 3 000 patients undergoing orthognathic surgery and classify clinical nursing evidence according to the Oxford Evidence Grading Standards. The model is divided into three main phases: prehospital early referral care, in-hospital intensive care, and posthospital extended care, and contains five modules: case management, psychological intervention, nutritional guidance, management of complications, and functional recovery. In the pre-hospital early referral care stage, the specific nursing measures include digital surgical design, psychological care, and nutritional guidance; in the in-hospital cluster care stage, the specific nursing measures include four modules, such as management of complications, orofacial functional recovery, nutritional instructions, and psychological interventions; and in the post-hospital extended care stage, the patients need to be provided with case management, psychological guidance, nutritional guidance, and other nursing care. Post-hospital extended care stage, need to provide patients with case management, psychological guidance, nutritional guidance and other care.

ObjectiveTo investigate the effects and mechanism of the combination of arsenic trioxide （ATO） and its dimethylarsinic acid （DMAV） metabolite on apoptosis of human acute promyelocytic leukemia NB4 cells by affecting the balance of metabolic reaction. MethodsThe rats were injected with the same amount of sterile normal saline， ATO（1.6 mg·kg^-1）， and DMAV（4， 8， 16， and 32 mg·kg^-1） combined with ATO（1.6 mg·kg^-1）， respectively， to obtain the corresponding drug-containing serum. The effect of drug-containing serum on the proliferation of NB4 cells was detected by the cell counting kit-8 （CCK-8 ）method. Apoptosis was detected by flow cytometry with Annexin-V-FITC/PI double staining. Intracellular reactive oxygen species （ROS） accumulation was detected by flow cytometry using fluorescent probe DCFH-DA. The changes of mitochondrial membrane potential （Δψm） were detected by the fluorescence probe JC-1. Western blot detected the expression of apoptosis-related proteins， namely B-cell lymphoma-2（Bcl-2）-associated X protein（Bax）/Bcl-2， Cytochrome C， cleaved Caspase-9， and cleaved Caspase-3， as well as c-Jun N-terminal kinase（JNK） phosphorylation levels. Results①The Combination of the two drugs had a higher proliferation inhibition rate and more apoptosis than ATO alone. ②The combination of two drugs can significantly increase the production of ROS compared with any single treatment group. ③The Δψm was significantly reduced in the two-drug combination group compared with any single treatment group. ④Compared with either group， the combination group significantly released Cytochrome C， significantly down-regulated the expression of Bcl-2， and up-regulated the expression of Bax， cleaved Caspase-3， and cleaved Caspase-9. ⑤The phosphorylation level of JNK was significantly up-regulated in the two-drug combination group compared with any single treatment group. ConclusionThe combination of DMAV and ATO may synergistically induce mitochondrial apoptosis through ROS-mediated oxidative stress， triggering Δψm dissipation and Cytochrome C release. By activating Caspase-9/Caspase-3 and the phosphorylation level of JNK， the Bcl-2 family protein （Bax/Bcl-2） was regulated to promote the apoptosis of NB4 cells.

Understanding the regulatory networks for germ cell fate specification is necessary to developing strategies for improving the efficiency of germ cell production in vitro. In this study, we developed a coupled screening strategy that took advantage of an arrayed bi-molecular fluorescence complementation (BiFC) platform for protein-protein interaction screens and epiblast-like cell (EpiLC)-induction assays using reporter mouse embryonic stem cells (mESCs). Investigation of candidate interaction partners of core human pluripotent factors OCT4, NANOG, KLF4 and SOX2 in EpiLC differentiation assays identified novel primordial germ cell (PGC)-inducing factors including BEN-domain (BEND/Bend) family members. Through RNA-seq, ChIP-seq, and ATAC-seq analyses, we showed that Bend5 worked together with Bend4 and helped mark chromatin boundaries to promote EpiLC induction in vitro. Our findings suggest that BEND/Bend proteins represent a new family of transcriptional modulators and chromatin boundary factors that participate in gene expression regulation during early germline development.
Animals ; Cell Differentiation/genetics* ; Chromatin/metabolism* ; Embryonic Stem Cells ; Germ Cells/metabolism* ; Germ Layers/metabolism* ; Mice

Bivalves are species-rich mollusks with prominent protective roles in coastal ecosystems.Across these ancient lineages,colony-founding larvae anchor themselves either by byssus produc-tion or by cemented attachment.The latter mode of sessile life is strongly molded by left-right shell asymmetry during larval development of Ostreoida oysters such as Crassostrea hongkongensis.Here,we sequenced the genome of C.hongkongensis in high resolution and compared it to reference bivalve genomes to unveil genomic determinants driving cemented attachment and shell asymmetry.Importantly,loss of the homeobox gene Antennapedia(Antp)and broad expansion of lineage-specific extracellular gene families are implicated in a shift from byssal to cemented attachment in bivalves.Comparative transcriptomic analysis shows a conspicuous divergence between left-right asymmetrical C.hongkongensis and symmetrical Pinctada fucata in their expression profiles.Especially,a couple of orthologous transcription factor genes and lineage-specific shell-related gene families including that encoding tyrosinases are elevated,and may cooperatively govern asymmet-rical shell formation in Ostreoida oysters.

Objective To investigate and analyze the current situation of nurse standardized training in Dongguan City. Methods 55 hospitals in Dongguan City of current situation of nurse standardized training were investigated by the convenient stratified sampling method. Results A total of 55 hospitals (40 public hospitals and 15 private hospitals) responded to the survey. 54 questionnaires were statistically valid and 1 were invalid, with a recovery rate of 98. 18％. Compared with private hospitals, the standardized training of nurses in public hospitals was relatively good, and the degree of participation was higher, but there were still some defects, such as the uneven level of training teachers, imperfect training facilities and equipment, the training and assessment stage cannot be completed in accordance with the standardized training program of Dongguan nurses and the training methodsare not standardized. Conclusion The popularization of standardized training for nurses in hospitals at all levels in Dongguan should be further expanded, and the training programs should be more standardized and standardized, trainers should be trained in a unified manner to gain access so as to achieve homogenization.

Adenine ; Animals ; Gene Editing ; Mice ; Zygote ; metabolism

Objective To study the efficiency changes of private hospitals in Shenzhen and explore influencing factors for the utilization efficiency of health resources. Methods DEA-Tobit two-stage model was used to analyze the operating efficiency and influencing factors of Shenzhen′s private hospitals. Results The range of technical efficiency varied between 0.690 to 0.742 in six years, and the index of total factor production was consistent with the technical change index. The input and output indicators showed non-linear growth. The internal and external factors of sample hospitals jointly influence the efficiency of operation. Conclusions The two-stage method effectively reveals the dynamic efficiency change and the influencing factors of these hospitals in Shenzhen. The technical efficiency of sample hospitals fluctuates in waves in six years,with investment redundancy and insufficient output found. Sample hospitals need to strengthen their innovative application of diagnostic and therapeutic technology,and to strengthen their internal management and improve operating efficiency.

This paper focused on factors which affected on different color of northern and southern region vinegar-processed frankincense.Meanwhile,contents of six main boswellic acids were also determined to elaborate the influence of heat in chemical components.Vinegar-processed frankincense from northern and southern region was collected.And different temperature and time were used in the processing of frankincense to receive the vinegar-processed frankincense samples.The color difference meter was utilized combining with the PCA statistic analysis method.The Zorbax ExtendC18 chromatographic column (4.6 mm × 50 mm,1.8 μm) was used with acetonitrile-0.1％ phosphoric acid as the mobile phase and gradient elution.The velocity of flow was 1 mL· min-1.The detection wavelength was 210 nm and 250 nm.The column temperature was 30℃.The results showed that the color of northern region processed frankincense was yellow or pale brown.And the southern region processed frankincense was pale brown or dark brown.It showed the difference on processed degree.The L* value of the northern processed frankincense was 75.327 to 80.746 and the L* value of southern processed was 44.321 to 49.527.The a* value of the northern processed frankincense was 5.378 to 6.502 and the a* value of southern processed was 9.423 to 9.978.There was no significant difference on b*.There were certain differences on L* and a* among vinegar-processed frankincense with the same surface color.The color parameter results of self-made vinegar-processed frankincense indicated that along with changes of processing temperature and time,the color,L* and a* change.Even frankincense processed for 30 min with mild fire,it will not achieve the color parameter value of the southern region vinegar-processed frankincense.However,after 11 min processing with medium fire,the color can be achieved.The content determination results showed that four contents,including α-boswellic acid,β-boswellic acid,3-acetyl-α-boswellic acid and 3-acetyl-β-boswellic acid were increased.Contents of 11-carbonyl-3-boswellic acid and 3-acetyl-11-carbonyl-β-boswellic were decreased after being processed.The range of increasing or decreasing by medium fire was higher than mild fire.At the same temperature,as the increasing of processing time,the content has an increasing or decreasing tendency.It was concluded that temperature was the main factor influencing the color of vinegar-processed frankincense from northern and southern regions.Different processing degrees also make influence on the contents of chemical compounds.The color parameter value can be used to evaluate the color of processed frankincense.

β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 (A>G) mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor (BE) system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 (A>G) mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 (A>G) homozygous mutation. Data showed that base editor could precisely correct HBB -28 (A>G) mutation in the patient's primary cells. To model homozygous mutation disease embryos, we constructed nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured (IVM) oocytes. Notably, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.
APOBEC-1 Deaminase ; genetics ; metabolism ; Base Sequence ; Blastomeres ; cytology ; metabolism ; CRISPR-Cas Systems ; Embryo, Mammalian ; metabolism ; pathology ; Female ; Fibroblasts ; metabolism ; pathology ; Gene Editing ; methods ; Gene Expression ; HEK293 Cells ; Heterozygote ; Homozygote ; Humans ; Point Mutation ; Primary Cell Culture ; Promoter Regions, Genetic ; Sequence Analysis, DNA ; beta-Globins ; genetics ; metabolism ; beta-Thalassemia ; genetics ; metabolism ; pathology ; therapy

Targeted point mutagenesis through homologous recombination has been widely used in genetic studies and holds considerable promise for repairing disease-causing mutations in patients. However, problems such as mosaicism and low mutagenesis efficiency continue to pose challenges to clinical application of such approaches. Recently, a base editor (BE) system built on cytidine (C) deaminase and CRISPR/Cas9 technology was developed as an alternative method for targeted point mutagenesis in plant, yeast, and human cells. Base editors convert C in the deamination window to thymidine (T) efficiently, however, it remains unclear whether targeted base editing in mouse embryos is feasible. In this report, we generated a modified high-fidelity version of base editor 2 (HF2-BE2), and investigated its base editing efficacy in mouse embryos. We found that HF2-BE2 could convert C to T efficiently, with up to 100% biallelic mutation efficiency in mouse embryos. Unlike BE3, HF2-BE2 could convert C to T on both the target and non-target strand, expanding the editing scope of base editors. Surprisingly, we found HF2-BE2 could also deaminate C that was proximal to the gRNA-binding region. Taken together, our work demonstrates the feasibility of generating point mutations in mouse by base editing, and underscores the need to carefully optimize base editing systems in order to eliminate proximal-site deamination.
APOBEC-1 Deaminase ; genetics ; metabolism ; Animals ; Bacterial Proteins ; genetics ; metabolism ; Base Sequence ; CRISPR-Associated Protein 9 ; CRISPR-Cas Systems ; Cytidine ; genetics ; metabolism ; Embryo Transfer ; Embryo, Mammalian ; Endonucleases ; genetics ; metabolism ; Gene Editing ; methods ; HEK293 Cells ; High-Throughput Nucleotide Sequencing ; Humans ; Mice ; Mice, Inbred C57BL ; Microinjections ; Plasmids ; chemistry ; metabolism ; Point Mutation ; RNA, Guide ; genetics ; metabolism ; Thymidine ; genetics ; metabolism ; Zygote ; growth & development ; metabolism ; transplantation