ß-Sitosterol Inhibits Rheumatoid Synovial Angiogenesis Through Suppressing VEGF Signaling Pathway.

Background: Rheumatoid arthritis (RA) is a chronic disabling inflammatory disease that causes synovial angiogenesis in an invasive manner and leads to joint destruction. Currently available pharmacotherapy for RA has unwanted side effects and limitations. Although anti-angiogenic therapy is regarded as a new potential treatment for RA, only a few anti-angiogenic drugs are available. An increasing number of studies have shown that ß-sitosterol (BSS) may exert inhibitory effects against angiogenesis. However, the mechanisms involved are still unclear. Methods: Based on the results of the gene set enrichment analysis (GSEA) of the transcriptome data of endothelial cells from RA patients, we evaluated the pharmacological effects of BSS on the tube formation, cell proliferation, and migration of human umbilical vein endothelial cells (HUVECs). Furthermore, the effects of BSS treatment on vascular endothelial growth factor receptor 2 (VEGFR2) were determined using molecular docking and Western blotting. Additionally, in the presence or absence of BSS, synovial angiogenesis and joint destruction of the ankle were investigated in collagen-induced arthritis (CIA) mice. The effect of BSS treatment on VEGFR2/p-VEGFR2 expression was verified through immunohistochemical staining. Results: The immunohistochemistry results revealed that BSS treatment inhibited angiogenesis both in vitro and in vivo. In addition, the results of 5-ethynyl-2'-deoxyuridine and cell cycle analysis showed that BSS treatment suppressed the proliferation of HUVECs, while the Transwell migration and stress fiber assays demonstrated that BSS treatment inhibited the migration of HUVECs. Notably, the inhibitory effect of BSS treatment on VEGFR2/p-VEGFR2 was similar to that of axitinib. In CIA mice, BSS also exerted therapeutic effects on the ankles by reducing the degree of swelling, ameliorating bone and cartilage damage, preventing synovial angiogenesis, and inhibiting VEGFR2 and p-VEGFR2 expression. Conclusion: Therefore, our findings demonstrate that BSS exerts an inhibitory effect on synovial angiogenesis by suppressing the proliferation and migration of endothelial cells, thereby alleviating joint swelling and bone destruction in CIA mice. Furthermore, the underlying therapeutic mechanisms may involve the inhibition of VEGF signaling pathway activation.

[Population structure and point pattern analysis of rare and endangered plant Helianthemum soongoricum in Ningxia, China]. / å®å¤çç¨€æ¿’å±æ¤ç‰©åŠæ—¥èŠ±ç§ç¾¤ç»“æž„å’Œç‚¹æ ¼å±€åˆ†æž.

Helianthemum songaricum is a second-class protected plant in China, threatened by decreased population size and fragmentation of distribution area. It is a new record species in Ningxia. We analyzed population structure, spatial distribution, and relationship of different age classes of H. songaricum living in sandy and gravel habitats. The results showed that majority of H. songaricum individuals were belonged to age-class Ⅲ. The age structure of the population was inverted triangle. The population was at a declining stage. The spatial pattern and spatial association between different age class of H. songaricum were greatly affected by habitat condition, with strong dependence on spatial scale. Compared with sandy habitat, H. songaricum population in gravel habitat tended to be clustered distribution, with a more obvious positive correlation among different age classes. The difference between two habitats was related to environmental condition and plant community structure. H. songaricum from age-class Ⅰ and Ⅱ had mutually dependent ecological relationships.

Splenectomy attenuates severe thermal trauma-induced intestinal barrier breakdown in rats.

The severe local thermal trauma activates a number of systemic inflammatory mediators, such as TNF-α, NF-κB, resulting in a disruption of gut barrier. The gastrointestinal tight junction (TJ) is highly regulated by membrane-associated proteins including zonula occludens protein-1 (ZO-1) and occludin, which can be modulated by inflammatory cytokines. As splenectomy has been shown to reduce secretion of cytokines, we hypothesized that (1) severe scald injury up-regulates TNF-α and NF-κB, meanwhile down-regulates expression of ZO-1 and occludin, leading to the increased intestinal permeability, and (2) splenectomy can prevent the burn-induced decrease in ZO-1 and occludin expression, resulting in improved intestinal barrier. Wistar rats undergoing a 30% total body surface area (TBSA) thermal trauma were randomized to receive an accessorial splenectomy meanwhile or not. Intestinal injury was assessed by histological morphological analysis, and serum endotoxin levels, TNF-α, NF-κB, ZO-1 and occludin levels were detected by Western blotting in the terminal ileum mucosal tissue. 30% TBSA burn caused a significant increase in serum endotoxin levels, but NF-κB, and TNF-α, and the average intestinal villus height and mucosal thickness were decreased significantly. Burn injury could also markedly decrease the levels of ZO-1 and occludin in terminal ileum mucosal tissue (all P<0.01). Splenectomy at 7th day after burn significantly reversed the burn-induced breakdown of ZO-1 and occludin (all P<0.01). The results of this study suggest that severe thermal injury damages the intestinal mucosal barrier. Splenectomy may provide a therapeutic benefit in restoring burn-induced intestinal barrier by decreasing the release of inflammatory cytokines and recovering TJ proteins.

Dose requirements of remifentanil for intubation in nonparalyzed Chinese children.

BACKGROUND: The objective of this study was to determine ED50 and ED95 of remifentanil for intubation combined with propofol in nonparalyzed Chinese children. METHODS: Forty-seven American Society of Anesthesiologists Class I children aged 4-11 years weighing 14-33.5 kg underwent general anesthesia with 2.5 mg·kg(-1) of intravenous propofol followed by remifentanil in Wenzhou, China. The initial dose of remifentanil was 2.5 µg·kg(-1) injected over 60 s. Intubation was attempted 30 s after the completion of remifentanil injection. Level of difficulty to intubate was graded on a scoring system. If the initial intubation condition was deemed satisfactory, subsequent remifentanil doses were decreased by 0.25 µg·kg(-1). If the intubating condition was deemed unsatisfactory, subsequent remifentanil doses were increased by 0.25 µg·kg(-1). Mean arterial pressure, heart rate, and pulse oximetry were documented before and after induction, immediately after intubation, and 1 min after intubation. RESULTS: The ED50 of remifentanil used to render a satisfactory intubating condition used in combination with 2.5 mg·kg(-1) of propofol in nonparalyzed Chinese children was 2.30 µg·kg(-1) (95% confidence interval: 2.28-2.31 µg·kg(-1)), and the ED95 is 2.75 µg·kg(-1) (95% confidence interval: 2.59-3.35 µg·kg(-1)). These doses were lower than previously reported. CONCLUSION: When used in combination with 2.5 mg·kg(-1) of intravenous propofol, ED50 and ED95 of remifentanil for adequate intubation in nonparalyzed children were lower than previously reported, at 2.30 and 2.75 µg·kg(-1), respectively.

[A survey of Japanese encephalitis antibody migrant workers in Shenzhen 2009].

OBJECTIVE: To understand the immunological status of Japanese encephalitis (JE) antibodies amongst migrant workers and to provide epidemiological basis for public health strategies on JE prevention and control in Shenzhen. METHODS: A multi-stage random sampling method was used, and 1003 migrant workers aged 18 to 60 from 44 factories were investigated and their serum specimens were collected. The enzyme-linked immunosorbent assay (ELISA) was used to detect JE antibodies qualitatively. RESULTS: The gross IgG seroprevalence rate for JE was 20.2% (203/1003). Sex-specified seroprevalence was 21.2% (103/485) for male and 19.3% (100/518) for female, respectively (χ(2) = 579, P > 0.05). Age-specific seropositive rates were 22.6% (12/53) for those below 20 years old, 18.7% (120/642) for those between 20-years old, 26.0% (58/223) for those between 30-years old and 15.3% (13/85) for those on or above 40 years old (χ(2) = 7.96, P > 0.05). Proportions for self-reported positive immunization, non-immunization and unclear immunization history were 22.1% (30/136), 22.1% (51/231) and 19.2% (122/636), respectively (χ(2) = 501, P > 0.05). Seroprevalence by region of origins showed that workers from Guangdong province was the highest (30.5%, 50/164), followed by workers from Guangxi (29.7%, 22/74) whilst workers from Shan(3)xi (5.4%, 2/37) had the lowest rate. Seroprevalence rate for managers (29.0%, 31/107) was higher than that of technicians (7.1%, 1/14) (χ(2) = 21.78, P < 0.05). Serological positive rate of workers with university or above educational background was the highest (32.7%, 16/49), followed by that for individuals with college degree (10.3%, 10/97) (χ(2) = 13.02, P < 0.05). CONCLUSION: No associations are detected between JE seroprevalence and age, or sex, or self-reported immunization histories amongst migrant labor workers in Shenzhen. However, correlations between JE serological positive rate and region of origins, occupation and educational attainment are found to be significant. The gross seroprevalence of JE antibodies suggests that the level of JE antibodies amongst Shenzhen migrant workers is low and the population immunity barrier has yet to be established. It is necessary to strengthen prevention and control strategies of JE among labor workers of Shenzhen.