Objective To explore the key signaling pathways and molecules of bone sialoprotein (BSP) to promote proliferation and differentiation of preosteoclasts RAW264.7. Methods RAW264.7 cells were treated with BSP and the inhibitors of signaling pathway molecules. MTS and TRAP staining kits were used to evaluate the effects of proliferation and differentiation. The activity assay kits of Calcineurin, AKT, JNK, ERK and p38 were used to detect their activities. Results Inhibiting ERK and p38 can inhibit cell proliferation induced by BSP significantly, while inhibiting AKT, Calcineurin and PI3K can reduce the role of promoting the differentiation by BSP. With increasing treatment time of BSP, the activity of Calcineurin in RAW264.7 cells increased. Furthermore, the activity of AKT was maximum at 48 h after treated with BSP, while the activity of JNK, ERK and p38 were maximum at 24 h after treated with BSP. Conclusions BSP mainly regulates the ERK and p38 of MAPK pathway to promote RAW264.7 cell proliferation, and regulates AKT, PI3K and Calcineurin pathways to promote RAW264.7 cell differentiation.

ObjectiveTo evaluate reliability and psychiatric clinical value of quantum resonance spectrometer (QRS) application in depression symptoms detection.MethodsThe psychiatric symptoms of 97 cases respectively obtained from QRS test and psychiatrist check were performed comparative analysis.The detecting order and checking order was under an order of go to see doctor random.ResultsSensitivity and negative predictive value of QRS were 100％ same as psychiatrists'examination in eating disorders; also specificity and positive predictive were 100％ in depressed mood,will weaken and sleep disorders.Kappa values were all greater than 0.8 of QRS in slow thinking,depressed mood,will weaken and other symptoms.The AUC of ROC line were all greater than 0.9 of QRS in slow thinking,depressed mood,will weaken,et al.11 symptoms.ConclusionQRS could be used as secondary depression diagnostic tools,provide a new basis for clinical diagnosis.

ObjectiveTo know about the correlation analysis of the physical and mental status of organ transplanted patients' family members during the patients' rehabilitation period and the long term survival of the transplanted organs.MethodsA total of 600 organ transplanted patients' family members were investigated by Zung self-rating anxiety scale (SAS) and simple coping style questionnaire.The results underwent subsequent analysis.ResultsAnxious state of organ transplanted patients' family members was more severe than that of domestic norm (P<0.01).There were some differences in terms of anxious state of family members with different genders,education backgrounds,income and the resource of medical expenditure (P<0.05).Family members most took positive coping styles,whereas fewer adopted negative coping styles (P<0.01).Positive coping styles were negatively correlated with the anxiety of family members (P<0.01) and positively correlated with long term survival of transplanted organ(P<0.05).However,negative coping styles of family members were significantly positively correlated with their anxiety (P<0.05) and were negatively correlated with long term survival of transplanted organ.ConclusionsThe anxiety generally exists in organ transplanted patients' family members.There are differences in terms of anxious state among family members of different genders,different education backgrounds,income or with the resource of medical expenditure.The more they adopt positive coping styles,the lower anxiety level they show and the longer the transplanted organ survive.Conversely,the more they adopt negative coping styles,the higher anxious level they show and the shorter the transplanted organ survive.

Objective To evaluate the efficacy and safety of short-term sensor-augmented insulin-pump (SAP) therapy for poorly controlled patients with type 1 diabetes mellitus (T1DM).Methods Sixty T1DM patients with glycosylated hemoglobin (HbA1c)>9.0% were randomly assigned to 2 groups treated with SAP or multiple daily insulin injection ( MDI) for 6 days, then all patients converted to MDI therapy. Results Compared with MDI group and before therapy, the mean blood glucose concentration ( MBG) , SD of blood glucose, mean amplitude of glycemic excursion ( MAGE) and 24-h area under curve at 10.0 ( AUC10.0 ) levels in SAP group significantly decreased after 6-day therapy ( compared with MDI group:t=1.761,P=0.028, t=2.569,P=0.037, t=2.712,P=0.020, t=2.985,P=0.014, compared with before therapy:t=3.128,P=0.006, t=2.689,P=0.024, t=2.966,P=0.013, t=3.076,P=0.009);while there was no difference in 24-h area under curve at 3.9 (AUC3.9) between groups (P>0.05).After 1 month follow-up HbA1c levels decreased in SAP group (t=2.344,P=0.023) and were significantly lower than those in MDI group (t=1.844, P=0.035).There was no difference in daily insulin dosage, fasting C peptide (FCP) and postprandial 2h C peptide (2hCP) between two groups (P>0.05).Age (t=2.125, P=0.012) and SAP therapy (t=3.376, P=0.009) were independently correlated with the HbA1c after 1 month.Conclusion Short-term SAP therapy is effective and safe for poorly controlled T1DM patients with rapid glucose lowering and glycemic excursions reduction.

Objective:To clarify the anti-inflammatory effects and anti-endoplasmic reticulum stress effects of resolvin D2 (RvD2) in viral myocarditis mice and to explore its possible mechanism.Methods:Fifty male BALB/c mice were collected and assigned corresponding numbers. Then 40 male BALB/c mice were selected randomly with 10 mice in each group. They were set as normal control group, RvD2 control group, viral myocarditis group and RvD2 treatment group. Afterwards, mice in the RvD2 control group received continuous intraperitoneal injection of RvD2 for 7 days, while mice in the viral myocarditis group received intraperitoneal injection of Coxsackievirus B3 virus (CVB3) in the purpose of constructing an animal model of viral myocarditis. Then, mice in the RvD2 treatment group were given continuous intraperitoneal injection of RvD2 for 7 days. After these 7 days, the mice of each group were sacrificed and their cardiac tissue and serum samples were taken. The expression levels of serum inflammatory factors including IL-1β and TNF-α were detected by ELISA in each group of mice, and HE staining were used to detect the inflammatory cell infiltration in myocardial tissue of each group. Meanwhile, the expression levels of inflammation-related proteins IL-1β, TNF-α as well as endoplasmic reticulum stress-related proteins like GRP78 and Chop in the myocardial tissue in each group of mice were detected by Western blot experiment. The remaining 10 BALB/c mice were treated with intraperitoneal injection of RvD2 as well as GPR18 protein inhibitors after constructing the animal model of viral myocarditis mentioned above. In the end, the expression levels of GPR18 protein, inflammation-related proteins including IL-1β and TNF-α as well as endoplasmic reticulum stress-related proteins like GRP78 and Chop in the myocardial tissue of each group were detected by Western blot experiments.Results:Compared with the normal control group, the expression levels of inflammatory factors IL-1β and TNF-α in the serum of mice with viral myocarditis were significantly increased, and the degree of infiltration of inflammatory cells in myocardial tissue was also significantly increased. Besides, the expression levels of the inflammation-related proteins IL-1β, TNF-α as well as endoplasmic reticulum stress-related proteins including GRP78 and Chop increased largely. While compared with the viral myocarditis group, the expression levels of serum inflammatory factors IL-1β and TNF-α in the mice of the RvD2 treatment group were significantly reduced and the degree of infiltration of inflammatory cells in the cardiac tissue was significantly reduced. Also, the expression levels of inflammation-related proteins IL-1β and TNF-α as well as endoplasmic reticulum stress-related proteins GRP78 and Chop were significantly reduced. After intraperitoneal injection of RvD2 and GPR18 inhibitor, in the mice treated with viral myocarditis, the expression levels of IL-1β, TNF-α and endoplasmic reticulum stress-related proteins like GRP78 and Chop in myocardial tissue of these mice significantly increased when it came to compare with the RvD2 treatment group, while the expression levels of GPR18 protein were significantly reduced.Conclusions:RvD2 can inhibit the inflammatory response and endoplasmic reticulum stress injury in mice with viral myocarditis by binding to the membrane protein receptor GPR18, thus exerting a protective effect on heart.

Objective: To evaluate the application value and significance of low-depth whole-genome sequencing for copy number variations (CNV-Seq) in the genetic diagnosis and prenatal diagnosis of X-linked ichthyosis (XLI) due to STS gene deletion. Methods: Clinical data were collected from 3 616 subjects who received CNV-Seq, and single-gene test results were collected from 7 patients or pedigrees with ichthyosis in The First Affiliated Hospital of Zhengzhou University in 2018. The 3 616 samples included 2 891 prenatal samples from pregnant women (most were amniotic fluid samples, some fetal villus samples, very few umbilical blood samples) and 725 peripheral blood samples from other subjects. Genomic DNA was extracted from amniocytes or peripheral blood, and then subjected to CNV-Seq. Quantitative PCR (qPCR) and single nucleotide polymorphism (SNP) -comparative genomic hybridization (CGH) array were performed to verify the detected CNVs. Pathogenicity of the CNVs was analyzed according to the database of genomic variants (DGV) , database of genomic variation and phenotype in humans using ensembl resources (DECIPHER) , clinical genome resource (ClinGen) and online Mendelian inheritance in man (OMIM) . Results: Of the 3 616 subjects receiving CNV-Seq, Xp22.31 deletion was identified in prenatal samples from 6 pregnant women, including 5 male and 1 female fetuses. The deleted fragment of Xp22.31 covered the XLI region containing the major gene STS. The parental CNV-Seq showed that the Xp22.31 deletion was spontaneous mutation in 2 of the 6 fetuses, and inherited from the parents in the other 4 fetuses. qPCR confirmed that the female fetus was a carrier of a complete heterozygous deletion of the STS gene, and there was a complete deletion of the STS gene in the other 5 male fetuses. SNP-CGH array also confirmed that the female fetus was heterozygous Xp22.31 deletion carrier, which was consistent with the CNV-Seq results. Ichthyosis gene panel sequencing in the 7 patients with ichthyosis showed 1 with harlequin ichthyosis, 2 with ichthyosis vulgaris, 3 with XLI, and no causative mutation in 1. CNV-Seq confirmed that Xp22.31 deletion existed in the above 2 patients with XLI due to STS gene deletion. Moreover, Xp22.31 duplication was found in 16 out of 3 616 subjects receiving CNV-Seq, but they were all individuals or fetuses with normal phenotype. Conclusions CNV-Seq is a stable and reliable method for screening whole-genome CNVs, and can be applied to genetic diagnosis and prenatal diagnosis of XLI due to STS gene deletion. The deletion of Xp22.31 fragment containing the STS gene can cause XLI, and the duplication of the same region is highly likely to be the polymorphic variation.

Objective To study the phosphorylation of AKT2 protein and autophagy activation in cardiac tissues of mice infected with coxsackievirus B3 (CVB3) for further analyzing the regulatory mecha-nism of PI3K/AKT2/mTOR signaling pathway on autophagy activation in viral myocarditis. Methods Thir-ty BALB/c mice were randomly divided into three groups (n=10): control group, myocarditis group and AKT activator-treated group. Those in the latter two groups were intraperitoneally injected with CVB3 to es-tablish the mouse model of acute viral myocarditis. Daily intraperitoneal injection of 0.04 mg/g of Akt acti-vator (SC79) was given to each mouse in the AKT activator-treated group 24 hours after CVB3 infection for 7 consecutive days,while the mice in the other two groups were given the same dose of normal saline. HE staining was used to observe the infiltration of inflammatory cells and tissue necrosis. Expression of CVB3 and inflammatory cytokines such as IL-1β and IL-6 in cardiac tissues at mRNA level was detected by q-PCR. Brain natriuretic peptide(BNP) and cardiac troponin I(cTnI) were measured by ELISA to evaluate myocardial injury. Changes in the expression of autophagy-related protein LC3 and Beclin1 at protein level as well as PI3K/AKT2/mTOR pathway were analyzed by Western blot assay. Results Compared with the con-trol group,massive inflammatory cell infiltration was observed in cardiac specimens of mice with myocarditis, but no obvious tissue necrosis was detected. Moreover,expression of CVB3 and inflammatory factors in car-diac tissues at mRNA level,levels of BNP and cTnI in blood,LC3Ⅱto LC3Ⅰratio as well as Beclin1 pro-tein level in cardiac tissues were significantly increased after CVB3 infection(P<0.05),whereas the activi-ty of PI3K/AKT2/mTOR signaling pathway was decreased. AKT activator not only down-regulated the LC3Ⅱ to LC3Ⅰratio and the expression of Beclin1 protein, but also enhanced the activation of PI3K/AKT2/mTOR signaling pathway in cardiac tissues of mice with myocarditis (P<0.05). Conclusion Enhanced autophagy and suppressed PI3K/AKT2/mTOR signaling pathway are observed in cardiac tissues of mice with myocarditis,indicating that the activation of autophagy may be regulated by PI3K/AKT2/mTOR signaling pathway.

Objective To explore the research dynamics and hotspots of project management in the field of hospital man-agement,and analyze the contents that still need to be improved,so as to provide references for the subsequent research,and provide hospital managers with practical experience in hospital management.Methods Based on the PubMed database,we used the citexs data analysis platform to analyze the literature and big data from January 2012 to December 2022 on the application of project management in the field of hospital management.Results The effective literature was retrieved from 4236 articles,and the analysis found thatthe annualnumberofpublicationsinthisfield hasbeenincreasing,2021 sawthe highestannualnumberof 573 articles,and the fastest growth rate was 20.36% in 2017.The country with the most publications is the United States(1 546 articles,36.5% ),the research institution with the most publications is Monash University,Australia,the journal with the most publications is BMJ Open(124 articles),and the key words with the highest frequency of occurrence in the retrieved literature are quality improvement,primary care improvement,covid-19,telemedicine.Conclusion The research in this field has been rapidly developed and is in a fast rising phase.In almost every organization and industry,the share of project management or"projectization"is increasing,and project management has become an important part of hospital management research and prac-tice.In the context of building a modern hospital management system,the application of project management to hospital manage-ment is an effective means of improving the level of fine hospital management.

Objective To analyze how enterovirus D68 (EV-D68) protease 2A affects the anti-vi-ral interferon typeⅠ(IFN-Ⅰ) pathway in 293T cells following infection. Methods Western blot was used to detect the expression of recombinant protease 2A, IFN-α and signal transducers and activators of tran-scription 1 (STAT1) at protein level. Expression of EV-D68 viral protein (VP1) and protease 2A was ana-lyzed by immunofluorescence at different time points. Cytopathic effects were recorded to calculate 50％ cell culture infective dose ( CCID50 ) . Expression of the genes involved in the anti-viral IFN-Ⅰ pathway was measured by real-time PCR (RT-PCR). Results The recombinant plasmid pCLIPf-2A was successfully constructed and the expression of recombinant protease 2A could be detected by Western blot 24 h after transfection. The recombinant protease 2A promoted the proliferation of EV-D68 at the late stage of infection and induced the production of IFN-α. Expression of the genes involved in the anti-viral IFN-Ⅰ pathway at mRNA level was up- or down-regulated to different degrees with various trends in different groups following infection. Expression of STAT1 was enhanced in all groups. Conclusions EV-D68 protease 2A promoted the activation of anti-viral IFN-Ⅰpathway in response to viral infection and enhanced the proliferation of virus at the late stage of infection.

Objective To compare the clinical effects between sutureless bridge intrascleral fixation and ciliary sul-cus suture suspension of intraocular lens(IOL)1 year postoperatively.Methods In this retrospective study,14 patients(14 eyes)who underwent sutureless bridge intrascleral IOL fixation in the No.988 Hospital of Joint Logistic Support Force of PLA from March 2019 to January 2022 were taken as the intrascleral fixation group and 15 patients(15 eyes)who under-went IOL ciliary sulcus suture suspension in the same period were taken as the suture suspension group.During the 1-year follow-up,the preoperative and postoperative uncorrected visual acuity(UCVA),best corrected visual acuity(BCVA)(logMAR),spherical equivalent(SE),endothelial cell count(ECC),intraocular pressure(IOP)and IOL position were compared between the two groups.Results At 1,6 and 12 months postoperatively,the UCVA in both groups significant-ly increased compared with those before surgery(all P＜0.05),and UCVA in the intrascleral fixation group were better than those in the suture suspension group at all postoperative time points(F=4.560,6.411 and5.373;all P＜0.05).At 1,6 and 12 months postoperatively,there was no significant difference in BCVA in both groups compared with those before surgery(all P＞0.05),but BCVA in the intrascleral fixation group were better than those in the suture suspension group at all postoperative time points(F=6.170,6.957 and 10.624;all P＜0.05).After surgery,eyes in the intrascleral fixation group showed hyperopia drift,while eyes in the suture suspension group showed myopia drift.At 1,6 and 12 months post-operatively,the SE of the intrascleral fixation group were(0.59±0.30)D,(0.57±0.27)D and(0.64±0.29)D,respec-tively,and those of the suture suspension group were(-0.75±0.44)D,(-0.72±0.42)D and(-1.12±0.64)D,re-spectively.At 6 months postoperatively,the ECC of both groups were significantly lower than those before surgery(t=8.579 and 21.929;both P＜0.001).The IOP in both groups were within the normal range preoperatively and stable during the follow-up.The IOL were centrally located without obvious decentration or tilt during the follow-up.In addition,there were no vitreous and retinal complications.Conclusion Both sutureless bridge intrascleral IOL fixation and IOL ciliary sulcus suture suspension can obtain a favorable prognosis of visual acuity with refractive shift,while sutureless bridge in-trascleral fixation shows better clinical outcomes.