Objective:To investigate the changes of gene or protein expression and activity of matrix metalloprotein9 (MMP9) and tissue inhibitor ofmetalloproteinasel (TIMP1) in the carotid artery (CA) of 4 wk hindlimb unweighted rat.Methods:A 4 weeks(wk) hindlimb unweighted (HU) rat model was used to simulate the effect of weightlessness on the cardiovascular system.Transmission electron microscopy was used to detect the content of ECM.Reverse transcriptase polymerase chain reaction(RT-PCR) was conducted to measure the mRNA content MMP and TIMP1.Immunohistochemistry and Western blot technique were used to measure the protein abundance.Gelatin zymography was carried out to detect the activity of MMP9.Results:Compared to the control group (CON),the area of ECM was enhanced (P＜0.05) and the content of collage fiber was increased (P＜0.05) in the CA of HU rats;moreover,HU did not affect the mRNA expression of MMP9,but significantly reduced the protein content (P＜0.05) or enzymatic activity (P＜0.05).Accordingly,the mRNA or protein expression of TIMP1 in the CA was significantly increased by HU (P＜0.05).Conclusion:Simulated weightlessness caused imbalance between MMP and TIMP1 expression,which might contribute to the ECM aggregation and stiffness of CA.

To evaluate the feasibility of real-time myocardial contrast echocardiography (RTMCE) by quantitative analysis of myocardial perfusion in rabbits, transthoracic RTMCE was performed in 10 healthy rabbits by using continuous infusion of SonoVue into the auricular vein. The short axis view at the papillary muscle level was obtained. The duration of the time that the contrast took to appear in right heart, left heart and myocardium was recorded. The regional myocardial signal intensity (SI) versus refilling time plots were fitted to an exponential function: y(t) =A(1-e(-beta(t-t0))) + C, where y is SI at any given time, A is the SI plateau that reflects myocardial blood volume, and beta is the slope of the refilling curve that reflects myocardial microbubble velocity. The A, beta and Axbeta values at different infusion rate of SonoVue were analyzed and the A, beta and Axbeta values in each segment in the short axis view at the papillary muscle level were compared. All the animal experiments were successful and high-quality images were obtained. The best intravenous infusion rate for SonoVue was 30 mL/h. The contrast appeared in right heart, left heart and myocardium at 7.5+/-2.2 s, 9.1+/-2.4 s and 12.2+/-1.6 s respectively. After 16.6+/-2.3s, myocardial opacification reached a steady state. The mean A, beta and Axbeta value in the short axis view at the papillary muscle level were 9.8+/-3.0 dB, 1.4+/-0.5 s(-1) and 13.5+/-3.6 dBxs(-1) respectively. A, beta and Axbeta values showed no significant differences among 6 segments. It was suggested that RTMCE was feasible for quantitative analysis of myocardial perfusion in rabbits. It provides a non-invasive method to evaluate the myocardial perfusion in rabbit disease models.

Military flying labor hygiene is a discipline that focuses on influences of special flight environment and labor condition on human body and related prevent measures, with the core of flight fatigue. Health information and technique training can help flight surgeons to enhance professional competency and improve the prevention and recovery of military flying fatigue. The course construction of teaching system in this study included survey of demand, arrangement of content, identification of strategy, determination of evaluation, and feedback of results. Meanwhile, the textbook compilation, cultivation of teaching team and construction of laboratory were also needed. After a 4-year practice, a formal teaching system has been established and its teaching effectiveness has basically fulfilled the professional requirement for flight surgeons.

Objective:To study the chemical constituents in the roots of Tripterygium wilfordii. Methods: The compounds from Tripterygium wilfordii were isolated and purified by silica gel, Sephadex LH-20 and prep-HPLC chromatography, and their structures were elucidated based on the physiochemical properties and spectroscopic analysis. Results:Twelve compounds were isolated and iden-tified as wilforgine(1),wilforine(2),triptonoterpene methyl ether(3),glut-5-en-3β,28-diol(4),wilforol E(5),triptobenzene L (6),maytenoic acid(7),triptophenolide(8),celastrol(9),demethylzeylasteral(10),1-desacetyl wilforgine(11) and wilfortrine (12). Conclusion:The 1D and 2D NMR data of 1 and 2 are assigned for the first time,and the absolute configurations of 1 are con-firmed by X-ray single crystal diffraction.

To evaluate the feasibility of real-time myocardial contrast echocardiography (RTMCE) by quantitative analysis of myocardial perfusion in rabbits,transthoracic RTMCE was performed in 10 healthy rabbits by using continuous infusion of Sono Vue into the auricular vein. The short axis view at the papillary muscle level was obtained. The duration of the time that the contrast took to appear in right heart,left heart and myocardium was recorded. The regional myocardial signal intensity (SI) versus refilling time plots were fitted to an exponential function:y(t) =A(1-e-β(t-t0)) + C,where y is SI at any given time,A is the SI plateau that reflects myocardial blood volume,and β is the slope of the refilling curve that reflects myocardial microbubble velocity. The A,β and A×β values at different infusion rate of SonoVue were analyzed and the A,β and A×β values in each segment in the short axis view at the papillary muscle level were compared. All the animal experiments were successful and high-quality images were obtained. The best intravenous infusion rate for Sono Vue was 30 mL/h. The contrast appeared in fight heart,left heart and myocardium at 7.5±2.2 s,9.1±2.4 s and 12.2±1.6 s respectively. After 16.6±2.3s,myocardial opacification reached a steady state. The mean A,β and A×β value in the short axis view at the papillary muscle level were 9.8±3.0 dB,1.4±0.5 s 1 and 13.5±3.6 dB×s-1 respectively.A,β and A×β values showed no significant differences among 6 segments. It was suggested that RTMCE was feasible for quantitative analysis of myocardial perfusion in rabbits. It provides a non-invasive method to evaluate the myocardial perfusion in rabbit disease models.

The liver is the most important digestive organ in the body. Several studies have explored liver biology and diseases related to the liver. However, most of these studies have only explored liver development, mechanism of liver regeneration and pathophysiology of liver diseases mainly based on two-dimensional (2D) cell lines and animal models.Traditional 2D cell lines do not represent the complex three-dimensional tissue architecture whereas animal models are limited by inter-species differences. These shortcomings limit understanding of liver biology and diseases. Liver organoid technology is effective in elucidating structural and physiological characteristics and basic tissue-level functions of liver tissue. In this review, formation strategies and a wide range of applications in biomedicine of liver organoid are summarized. Liver organoids are derived from single type cell culture, such as induced pluripotent stem cells (iPSCs), adult stem cells, primary hepatocytes, and primary cholangiocytes and multi-type cells co-culture, such as iPSC-derived hepatic endoderm cells co-cultured with mesenchymal stem cells and umbilical cord-derived endothelial cells. In vitro studies report that liver organoids are a promising model for regenerative medicine, organogenesis, liver regeneration, disease modelling, drug screening and personalized treatment. Liver organoids are a promising in vitro model for basic research and for development of clinical therapeutic interventions for hepatopathy.

The liver is the most important digestive organ in the body. Several studies have explored liver biology and diseases related to the liver. However, most of these studies have only explored liver development, mechanism of liver regeneration and pathophysiology of liver diseases mainly based on two-dimensional (2D) cell lines and animal models.Traditional 2D cell lines do not represent the complex three-dimensional tissue architecture whereas animal models are limited by inter-species differences. These shortcomings limit understanding of liver biology and diseases. Liver organoid technology is effective in elucidating structural and physiological characteristics and basic tissue-level functions of liver tissue. In this review, formation strategies and a wide range of applications in biomedicine of liver organoid are summarized. Liver organoids are derived from single type cell culture, such as induced pluripotent stem cells (iPSCs), adult stem cells, primary hepatocytes, and primary cholangiocytes and multi-type cells co-culture, such as iPSC-derived hepatic endoderm cells co-cultured with mesenchymal stem cells and umbilical cord-derived endothelial cells. In vitro studies report that liver organoids are a promising model for regenerative medicine, organogenesis, liver regeneration, disease modelling, drug screening and personalized treatment. Liver organoids are a promising in vitro model for basic research and for development of clinical therapeutic interventions for hepatopathy.

OBJECTIVE To investigate the protective effect of artesunate(Art)against apoptosis and mitophagy induced by NaF in osteocytes MLO-Y4,and to explore the molecular mechanism.METHODS MLO-Y4 cells were treated with NaF(2 mmol·L-1)for 48 h to establish an in vitro model of osteocytes injuries,and the cells were divided into the cell control group,NaF(2 mmol·L-1)group and NaF+Art 0.25,0.50 and 1.00 μmol·L-1 groups.The cells were pretreated for 2 h and NaF was added for 48 h.The cell survival of MLO-Y4 cells was detected by MTT assay.The cell viability of MLO-Y4 cells was measured by Calcein-AM staining.The lactate dehydrogenase(LDH)content in the supernatant was examined by the LDH detection kit.The level of intracellular reactive oxygen species(ROS)was examined by DCFH-DA staining.The malondialdehyde(MDA)content and superoxide dismutase(SOD)activity were detected by chemical colorimetry.Apoptosis was measured by Hoechst33342 staining and Annexin-V/PI staining.The level of mitochondrial membrane potential(MMP)was measured by JC-1 staining.The formation of autophagic vacuoles and morphological mitochondrial changes were observed via Lyso-tracker staining and Mito-Tracker staining.The ATP content was detected with the luciferase method.The expression of microtubule-associated protein light chain 3(LC-3)in mitochon-dria was examined by immunofluorescence staining.Protein expressions of LC-3,P62,E3 ubiquitin-ligase(Parkin)and PTEN-induced putative kinase 1(PINK1)were detected by Western blotting.RESULTS Compared with the cell control group,the cell survival rate and cell viability were significantly reduced in the NaF group(P<0.01),LDH content in the supernatant,the level of intracellular ROS,the MDA content,apoptosis rate and autophagic vesicle formation were remarkably increased(P<0.01),protein levels of Parkin and PINK1,and the conversion of LC-3Ⅱ from LC-3Ⅰ were markedly upregulated along with the elevation of LC-3 in damaged mitochondria(P<0.01),while P62 levels,SOD activity,MMP and ATP contents were reduced in NaF cells(P<0.05,P<0.01).Compared with NaF group,the cell viability and survival rate of MLO-Y4 cells in NaF+Art 0.25,0.50 and 1.00 μmol·L-1 groups were significantly increased(P<0.01);the content of LDH in supernatants was decreased obviously(P<0.01);the levels of intracellular ROS and MDA content were markedly reduced(P<0.05,P<0.01);the apoptosis rate and autophagic vesicle formation were remarkably decreased(P<0.05,P<0.01);protein levels of Parkin and PINK1,and the conversion of LC-3Ⅱ from LC-3Ⅰ were markedly down-regulated along with the accumulation of LC-3 in damaged mitochondria(P<0.01);MMP and ATP content were also reduced(P<0.05,P<0.01);while SOD activityand P62 levelwere significantly increased(P<0.05,P<0.01).CONCLU-SION Art has a protective effect against oxidative damage induced by NaF in MLO-Y4 cells,which might be related to the inhibition of apoptosis and mitophagy.

Objective To examine the correlation between the gene of phosphate and tension homology deleted on chromosometen (PTEN gene) polymorphism and schizophrenia (SCZ) associated with the type 2 diabetes mellitus (T2DM ) in Shanghai Han population. Methods The study recruited 591 long-stay schizophrenic inpatients including 304 with and 287 without type 2 diabetes mellitus, 206 patients with the type 2 diabetes mellitus and 205 normal subjects from Shanghai Han population. SNPs of PTEN gene (rs1234225, rs12569998, rs1234223) were genotyped by using Taqman genotyping. The frequency distributions of allele, genotype and haplotype between groups were analyzed. Results There were significant differences in the frequency of rs1234223 genotype (P=0.01) and allele distribution (P=0.02) between the SCZ with type 2 diabetes mellitus group and the SCZ without type 2 diabetes mellitus group. The difference of genotype frequencies remained statistically significant (P=0.03) but the allele distribution was not (P=0.06) after Bonferroni correction. Haplotype analysis showed that TTC haplotype was less common in the SCZ with type 2 diabetes mellitus group than in the SCZ without type 2 diabetes mellitus group (P=0.02). Conclusions PTEN gene may be a susceptibility gene for schizophrenia with type 2 diabetes mellitus in Chinese Han population. The TTC haplotype may be a protective factor for schizophrenia with type 2 diabetes mellitus.

Objective:To explore the current situation of evidence-based practice competence of masters of nursing specialist at Class Ⅲ hospitals and its influencing factors so as to provide decision-making basis for optimizing the construction and educational management of clinical teaching base for masters of nursing specialist.Methods:From July to October 2021, 141 masters of nursing specialist of Class Ⅲ hospitals in Tianjin were selected as subjects by purposive sampling. All students were investigated with the Chinese version of Evidence Based Practice Evaluation Competence Questionnaire (EBP-COQ) and the Barriers to Research Utilization Scale. Multiple linear regression was used to analyze the influencing factors.Results:Among 141 masters of nursing specialist, the total scores of the EBP-COQ and the Barriers to Research Utilization Scale were 95.35 ± 11.90 and 72.52 ± 26.28 respectively. Multiple linear regression analysis showed that the influencing factors of evidence based practice competence of masters of nursing specialist included the results of availability and the awareness of evidence-based nursing ( r = -2.85, -2.41, both P<0.05). Conclusions:Masters of nursing specialist have the intermediate level of evidence-based practice competence and positive attitudes to evidence based practice, but their evidence-based knowledge and skills need to be improved. Clinical teaching base managers should pay attention to the training of evidence-based nursing practice ability of professional nursing master students, provide more supportive resources and environment, and promote the development of specialty nursing practice.