Objective To investigate the correlation between neuropeptide S receptor(NPSR)single nucleotide polymorphism(SNP)(rs323917,rs323920,rs323922,rs2530547,rs324957)and primary insomnia(PI).Methods A total of 157 patients diagnosed with PI in the outpatient department of Center of Sleep Medicine,Gansu Provincial People's Hospital from December 2016 to May 2019 were selected as PI group,and 133 healthy physical examination subjects during the same period were selected as control group.Venous blood samples were collected and DNA,polymerase chain reaction(PCR)amplification and agarose gel electrophoresis were extracted.rs323917,rs323920,rs323922,rs2530547,rs324957 single nucleotide loci were genotypized by target site sequencing.Meanwhile,standard polysomnosis monitoring was performed to analyze the correlation between gene polymorphism and PI.Results There were no significant differences in the genotype distribution of NPSR SNP sites(rs323917,rs323920,rs323922,rs2530547)and allele frequency and rs324957 allele frequency between two groups(P＞0.05).There was significant difference in genotype distribution of rs324957(P=0.034).There was no significant difference in the frequency of different haplotypes between two groups(P＞0.05).Conclusion The expression of rs324957 SNP genotypes in NPSR may be related to PI,and AG genotype is dominant.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objective To explore the specific plasma exosomal protein expression in Coronary Heart Disease(CHD)with phlegm-turbidity syndrome(PTS),so as to provide biological reference for the diagnosis of CHD with PTS.Methods A total of 20 CHD patients with PTS and 20 healthy subjects at the same period were included.Plasma exosomes were extracted from all subjects using the qEV size exclusion method.First,10 CHD cases with PTS and 10 healthy subjects were randomly selected,and differentially expressed proteins between the two groups were screened using label free non-targeted protein quantification analysis.Then,MRM targeting protein labeling technique was applied to verify the differentially expressed proteins in the remaining subjects.Results Compared with healthy controls,214 differentially expressed plasma exosomal proteins(61 up-regulated and 153 down-regulated)were found in CHD patients with PTS,mainly related to cholesterol metabolism,complement and coagulation cascade,and immune effects.ANXA6,C4BPB,F8,CFB,APOE,C9,and CLU proteins were further validated by MRM targeting protein.Conclusion CHD patients with PTS had differences in plasma exosomal protein expression from healthy controls,and the differential proteins are mainly related to cholesterol metabolism,complement,and the coagulation cascade.

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic bio-markers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the"masking"effect caused by high-abundance proteins.The relative abundance of middle-and low-abundance proteins increased substantially from 2.54％to 54.41％,and the top 20 high-abundance proteins decreased from 83.63％to 25.77％.Notably,our method can quantify approxi-mately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins iden-tified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

Neonatal skin care is still an important aspect of newborn care. At present, although there are nursing standards for various types of neonatal skin problems, there are different reports on complete evidence-based neonatal skin care practices. The American Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN) developed and published the fourth edition of the Evidence- based Clinical Practice Guideline for Neonatal Skin Care in 2018. The guideline gives detailed guidance on the assessment of neonatal skin, identification of risk of neonatal skin damage, intervention of neonatal skin care, method of promoting neonatal skin development, and treatment of neonatal skin damage. However, nurses in China know little about this guideline. In order to facilitate nurses' understanding and application of this guideline to guide clinical practice, the content of this guideline is specially interpreted.

OBJECTIVE： To observe improvement effects of fingolimod on middle cerebral artery occlusion/reperfusion （MCAO/R） injury model rats. METHODS： Male SD rats were randomly divided into sham operation group， model group and fingolimod low-dose， medium-dose and high-dose groups （0.5， 1， 2 mg/kg）， with 8 rats in each group. Except for sham operation group， MCAO/R injury model was induced by suture-occluded method in other groups. Administration groups were given relevant medicine intragastrically after reperfusion [1 h after reperfusion （1st day）， 22.5 h after reperfusion （2nd day）， and then every 24 h until 142.5 h of reperfusion （7th day）]. Sham operation group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 7 d. The scores of neurological deficit and balance beam test， the times of memory error [work memory error （WME）， reference memory error （RME） and total error] were recorded in each group. The contents of serum inflammatory cytokines （IL-6， IL-8， IL-10， TNF-α） were determined by ELISA， and triphenyl tetrazolium chloride staining method was used to detect the rate of cerebral infarction. RESULTS： Compared with sham operation group， neurological deficit scores （at different time points of 1st-7th day after administration）， balance beam test scores （2nd， 4th， 7th day after administration）， times of memory error （2nd， 4th， 7th day after administration）， the contents of serum inflammatory cytokines and the rate of cerebral infarction were increased significantly in model group （P＜0.05 or P＜0.01）. Compared with model group， neurological deficit scores （low-dose group at different time points of 3rd-7th day， medium-dose and high-dose groups at different time points of 2nd-7th day after administration）， balance beam test scores （low-dose group at 7th day， medium-dose group at 4th and 7th day， high-dose group at 2nd， 4th， 7th day）， RME times and total error times （low-dose group at 4th and 7th day， medium-dose group and high-dose group at 2nd， 4th， 7th day after administration）， WME times （administrations groups at 7th day after administration）， serum contents of IL-6， IL-8 and IL-10 （administrations groups）， serum contents of TNF-α （medium-dose and high-does groups） and cerebral infarction rate （medium-dose and high-dose groups） were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Intragastric administration of fingolimod can significantly reduce neurological deficit score， balance beam test score and the times of memory error in MCAO/R injury model rats， and has a protective effect on cerebral tissue and memory function. These effects may be related to the down-regulation of inflammatory cytokines such as IL-6 and TNF-α by fingolimod.

Objective:To understand the influencing factors of the elderly' s demand for the pension mode of medical-nursing combination in Urumqi. Methods: A questionnaire survey was conducted among 300 elderly people randomly selected in Urumqi. Results:Univariate analysis showed that there was significant difference between retirement monthly income, life self-care ability, type of chronic disease, the degree of understanding on the pension mode of medical-nursing combination, family support and the demand rate of the elderly for the pension mode of medical-nursing combination ( P< 0 . 05 ) . Two Logistic regression analysis showed that life selfcare ability, types of chronic diseases, the degree of understanding on the pension mode of medical-nursing combination, and family support factors were statistically significant. Conclusion:It should change the traditional concept of single pension mode, improve the medical-nursing combination service system to meet the needs of all levels of the elderly, establish a long-term care insurance system, and improve the training mechanism of the elderly.

Objective:To analyze the different expressions of miRNAs in peripheral blood of rheumatoid arthritis (RA) patients and the osteoclasts in rats,and to verify the key miRNAs in RA.Methods: The miRNAs expressions in monocyte and the co-cultured osteoclasts,peripheral blood of rheumatoid arthritis (RA) patients and normal were detected by miRCURYTM LNA Array.Real time PCR was applied to verify the reliability of miRNA array.The bioinformatics software and database were applied to predict and analyze target genes.Results: miRNA array results showed that 189 miRNAs changed in RA patients compared with the normal;211 miRNAs were changed in osteoclasts group compared with monocytes group.The expressions of ten miRNAs were all abnormal in RA patients and osteoclasts in rats.The results of Real time PCR were consistent with the array.Results of bioinformatics analysis showed that the target gene of miRNA significantly enriched in signaling pathways such as VEGF,MAPK signaling pathways.Conclusion: Some miRNAs had similar abnormal expressions in different species,and these miRNAs may influence the differentiation of the osteoclasts through regulating the related signal passways.

This article summed up the definition, incidence trend, situation on use of evaluation models, prevention and nursing care of lower extremity deep vein thrombosis (LEDVT). Although there are some researches on risk evaluation, prevention and nursing care of LEDVT after major orthopedic surgery(MOS) in China, a special risk evaluation scale suitable for patients after MOS is needed to be designed based on evidence-based medicine, foreign scales and national conditions combined with previous experience. If so, the reason of decreasing compliance of thrombosis prevention in patients can be understood deeply, the advantages of traditional Chinese medicine and traditional chinese medicine nursing can be exploited. Besides, a complete and specific model of traditional Chinese medicine and Western medicine nursing after MOS will be formulated with standard so as to improve nurses' consciousness of prevention in China and reduce the incidence of LEDVT in patients with major orthopedic surgery.

Objective To discuss the effect of early comprehensive development mode on physical, intelligence and mental development of premature infants, and explore the feasibility of comprehensive development mode of preterm infants generally applied in child care clinic. Methods 90 cases of premature infants in intervention group from the beginning of the hospital before the intervention, continuous monitoring and comprehensive intervention including general system health, parenting guidance, family activities, growth monitoring, intelligence assessment, individualized instruction, and so on, for the timely correction of the anomalies. The 90 infants in the control group were only given conventional child health care after 1 month of corrected age. Results The nervous system abnormalities were detected 192 person-times in control group, while 129 person-times in intervention group at 3 months old, the detected rate of nervous system anomaly was higher in the control group than that in the intervention group (χ2=14.574, P=0.000). The body length of the intervention group was (74.31± 2.34) cm, the control group was (72.82 ± 2.13) cm. The body weight of the intervention group was (9.42 ± 0.93) kg, the control group was (8.11 ± 0.90) kg at 12 months old. The growth of weight and length of intervention group were higher than those of control group. The difference was statistically significant ( t=4.467, 9.602, P < 0.05). The development quotient was also assessed, the big activity sport, fine motor, adaptability, social behavior, development quotient of intervention group were (96.40±7.83) points, (95.45± 7.87) points, (98.33±10.87) points, (105.65±7.51) points, (101.45±7.36) points, and the control group were (92.53±6.57) points, (89.27±8.02) points, (94.26±9.88) points, (100.31±8.13) points, (95.65±6.93) points. The difference was statistically significant (t=2.628-5.443, P < 0.05). Conclusions Application of integrated early childhood development in premature infants can find early neurodevelopmental deviations of children and contribute to early intervention on premature infants. Using a combination of family and outpatient intervention may reduce the incidence of neurological abnormalities, improve the level of development of the intelligence assessment and promote premature infant intelligence, motor development and social adaptation ability.