Identification of core pathogenic genes and pathways in elderly osteoporosis based on bioinformatics analysis / 中华预防医学杂志

Objective: Using bioinformatics methods to analyze the core pathogenic genes and related pathways in elderly osteoporosis. Methods: From November 2020 and August 2021, eight elderly osteoporosis patients who received treatment and five healthy participants who underwent physical examinations in Beijing Jishuitan Hospital were selected as subjects. The expression level of RNA in the peripheral blood of eight elderly osteoporosis patients and five healthy participants was collected for high-throughput transcriptome sequencing and analysis. The gene ontology (GO) analysis Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed for the differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was constructed using the STRING website and Cytoscape software, and the most significant modules and hub genes were screened out. Results: Among the eight elderly osteoporosis patients, there were seven females and one male, with an average age of 72.4 years (SD=4.2). Among the five healthy participants, there were four females and one male, with an average age of 68.2 years (SD=5.7). A total of 1 635 DEGs (847 up-regulated and 788 down-regulated) were identified. GO analysis revealed that the molecular functions of DEGs were mainly enriched in structural constituents of the ribosome, protein dimerization activity, and cellular components were mainly enriched in the nucleosome, DNA packaging complex, cytosolic part, protein-DNA complex and the cytosolic ribosome. KEGG pathway analysis showed that DEGs were mainly enriched in systemic lupus erythematosus and ribosome. Gene UBA52, UBB, RPS27A, RPS15, RPS12, RPL13A, RPL23A, RPL10A, RPS25 and RPS6 were selected and seven of them could encode ribosome proteins. Conclusion: The pathogenesis of elderly osteoporosis may be associated with ribosome-related genes and pathways.

Cross-sectional survey of cognitive status and attitude of different population about biobanking donation / 中华医院管理杂志

Objective To understand the cognition and attitude of patients, medical staff and medical examination people on biobanks and their willingness to donation. Methods A cross-sectional study was conducted among 452 individuals, including patients, medical staff and people receiving health checkup at a hospital in Beijing from July to September, 2017. The questionnaire assessed the respondents′demographic data, general knowledge about biobanking and the factors influencing their willingness to donate specimens to biobanks. Pearson′s Chi-square test, student t test or ANOVA were used for univariate analysis. Additionally, the linear regression analysis and logistic regression analysis were used for multivariate analyses. Results A total of 452 questionnaires were delivered, and the effective questionnaires amounted to 440, including 196 medical staff, 123 patients and 121 health checkup individuals. The awareness score of biobanks was significantly different among the medical staff, patients and health checkup individuals ( P < 0. 05 ) . After adjustment for potential risk factors, we found that the population characteristics and the experience of participation in a medical research were the independent beneficial factors of the awareness score. The percentage of the willingness of donation in medical staff, health checkup individuals and patients were 83. 7％, 76. 9％ and 70. 7％, respectively. The results of univariate analyses suggested that the population characteristics, education level, health conditions, the history of blood donation, and the experience of participation in a medical research were significantly associated with the willingness to donate ( all P <0. 05 ) . Population characteristics and health conditions were independently relevant to the willingness of donation, after multivariate analyses of logistic regression. Conclusions Despite the strong willingness to donate biospecimens, patients and health checkup individuals lack knowledge of biobanking. It is apparent that we need to strengthen promotions and to encourage the ethics and humanities to improve the knowledge of biosample donation, for healthy development of hospital-based biobanks.

Study on the mechanism of asporin in degeneration of intervertebral disc / 中华骨科杂志

Objective To explore the molecular regulation mechanism of asporin in the matrix synthesis and secretion of the intervertebral disc,and to clarify its role in degenerative lesions of intervertebral disc.Methods There were 8 cases of intervertebral disc tissue in patients with severe intervertebral disc herniation (including typical clinical symptoms,signs and Pfirrmann's grade Ⅲ).There were 6 male and 2 female with an average age of (20.25 ± 3.37) years old (ranged from 11 to 28 years).After primary culture and redifferentiation in alginate beads,cells were reseeded and treated with different concentrations of TGF-β1 for 6,12,18 and 24 h.Total RNA extracted from the cells and was subjected to real-time PCR analysis to examine the expression of asporin.After silencing the expression of endogenous asporin by siRNA,the cells stimulated 24 h with TGF-β1.Total RNA extracted from the cells and was subjected to real-time PCR analysis to examine the expression of asporin,collagen Ⅱ and proteoglycans.After treatment of specific p38 inhibitor or ERK inhibitor for 12 h,cells were stimulated with TGF-β1 for 24h.Protein extracted from the cells by protein extraction kit to examine the level of asporin.Results In the primary intervertebral disc cell experiment,TGF-β1 stimulation induced asporin transcription significantly in a dose and time dependent manner.After 24 h stimulation,a significant difference between different concentration groups (5,10 and 15 ng/ml) was observed,2.754±0.24,3.651 ±0.319 and 4.583±0.38,respectively (F=24.782,P=0.001).Knockdown of endogenous asporin led to the upregulated expression of aggrecan and collagen]Ⅱ (aggrecan:t=7.387,P=0.002,collagen Ⅱ:t=4.443,P=0.0113).Specific p38 inhibitor was used to block p38 phosphorylation,and TGF-β1 on asporin induction was significantly inhibited.Conclusion Our results have verified a functional feedback loop between TGF-β1 and asporin in human intervertebral annulus cells indicating that TGF-β1 can increase asporin expression,whereas asporin inhibits TGF-β 1 signaling pathway by negative feedback,thereby inhibiting TGF-β1 mediated synthesis of extracellular matrix,and TGF-31 can increase asporin expression by p38 in human intervertebral disc cells.

Population-Stratified Analysis of Bone Mineral Density Distribution in Cervical and Lumbar Vertebrae of Chinese from Quantitative Computed Tomography

OBJECTIVE: To investigate the bone mineral density (BMD) of cervical vertebrae in a population-stratified manner and correlate with that of the lumbar vertebrae. MATERIALS AND METHODS: Five hundred and ninety-eight healthy volunteers (254 males, 344 females), ranging from 20 to 64 years of age, were recruited for volumetric BMD (vBMD) measurements by quantitative computed tomography. Basic information (age, height, weight, waistline, and hipline), and vBMD of the cervical and lumbar vertebrae (C2-7 and L2-4) were recorded. Comparisons among sex, age groups and different levels of vertebrae were analyzed using analysis of variance. Linear regression was performed for relevance of different vertebral levels. RESULTS: The vBMD of cervical and lumbar vertebrae was higher in females than males in each age group. The vBMD of the cervical and lumbar vertebrae in males and the vBMD of lumbar vertebrae in females decreased with aging. In each age group, the vBMD of the cervical vertebrae was higher than that of the lumbar vertebrae with gradual decreases from C2 to C7 except for C3; moreover, the vBMD of C6 and C7 was significantly different from that of C2-5. Correlations of vBMD among different cervical vertebrae (females: r = 0.62-0.94; males: r = 0.63-0.94) and lumbar vertebrae (males: r = 0.93-0.98; females: r = 0.82-0.97) were statistically significant at each age group. CONCLUSION: The present study provided normative data of cervical vertebrae in an age- and sex-stratified manner. Sex differences in vBMD prominently vary with age, which can be helpful to design a more comprehensive pre-operative surgical plan.

Right ventricle structure and function of New Zealand rabbits with chronic intermittent hypoxia by echocardiography / 中华医学超声杂志（电子版）

ObjectiveTo observe right ventricle (RV) structure and function of New Zealand rabbits with chronic intermittent hypoxia (CIH) for short-term (0-8 weeks) by echocardiography. MethodsTwenty-four healthy male New Zealand rabbits were set up CIH animal model for 8 weeks. RV structure?s systolic and diastolic function were measured by conventional and tissue Doppler echocardiography at 0, 1, 2, 4, 6 and 8 week and one rabbit was sacriifced randomly for RV myocytes and pulmonary tissue pathology examination. RV structure and function parameters at 0, 1, 2, 4, 6 and 8 week were analyzed by mixed effects model analysis.ResultsRV structure variables: RV, RA at 8 week increased compared with those at 0 week, but had no signiifcant difference (P>0.05); RV systolic function variables:RVFAC at 8 week increased compared with those at 0 week (F=3.45, P<0.05), TAPSE at 4, 6, 8 week increased compared with that at 0 week (F=3.11, 3.41 and 3.86, all P<0.05), RVMPI at 4 week decreased compared with that at 0 week (F=3.46, P<0.05), recovered to baseline at 6, 8 week. Isovolumetric relaxation time (IRTc) corrected by heart rate at 1, 2, 4 week decreased compared with that at 0 week (F=3.15, 3.31 and 3.17, all P<0.05), recovered to baseline at 8 week, ET of PA at 1, 2 week decreased compared with that at 0 week (F=3.01 and 3.15, both P<0.05), recovered to baseline at 4, 6, 8 week, AT of PA at 1, 2, 4 week decreased compared with that at 0 week (F=3.13, 3.15 and 3.32, all P<0.05), recovered to baseline at 6, 8 week. RV diastolic function variables: isovolumetric contraction time (ICTc) corrected by heart rate at 2, 4 week decreased compared with that at 0 week (F=3.13 and 3.33,both P<0.05), E/E? at 1, 2 week decreased compared with that at 0 week (F=3.13 and 3.44,bothP<0.05), recovered to baseline at 4, 6, 8 week, E/A at 4, 6, 8 week increased compared with that at 0 week (F=4.01, 3.82 and 3.37, all P<0.05), E?/A? at 8 week increased compared with that at 0 week (F=3.81, P<0.05). The myocardial pathology showed that RV myocardial cell structure was normal at 4 week. Nuclei enlarged, stain darkened and some cytoplasms loosed when exposed to CIH for 8 weeks. The structure of lung tissues was normal when exposed to CIH for 4 weeks. Inflammatory cell inifltrated, capillary engorged as well as the wall of pulmonary arterioles thickened slightly at 8 week.ConclusionsRV diastolic and systolic function showed compensatory and structure was normal in early CIH (0-8 week). RV diastolic function compensated earlier than systolic function. IRT and ICT were sensitive indicators of RV systolic and diastolic function compensation.

An evaluation of the mechanism of ABCA7 on cellular lipid release in ABCA7-HEC293 cell / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>ABCA7 is a member of the ABCA subfamily that shows a high degree of homology to ABCA1 and, like ABCA1, mediates cellular cholesterol and phospholipid release by apolipoproteins when transfected in vitro. However, expression of ABCA7 has been shown to be downregulated by increased cellular cholesterol while ABCA1 was upregulated.</p><p><b>METHODS</b>The underlying mechanism for this effect was examined in ABCA1 or ABCA7-transfected HEC293. Lipid content in the medium and cells was determined by enzymatic assays. Gene expression was quantitated by real time PCR, and protein content was determined by Western blotting.</p><p><b>RESULTS</b>While ABCA7 mRNA was decreased by 25-hydroxycholesterol treatment, ABCA1 was apparently increased. Treatment with the synthetic LXR agonist T0901317 (T09) upregulated ABCA1 expression and apoAI-mediated cellular lipid release in ABCA1-transfected HEC293 cells, but ABCA7 expression and cellular lipid release in ABCA7-transfected HEC293 cells showed no obvious changes.</p><p><b>CONCLUSION</b>The ABCA7 gene is regulated by sterol in a direction opposite to that of ABCA1.</p>