Regulation of colony-stimulating factor 1 receptor inhibitor pexidartinib on the senescence of mouse bone marrow-derived macrophages stimulated by lipopolysaccharide / 中华口腔医学杂志

Objective: To investigate the effects of colony-stimulating factor 1 receptor (CSF-1R) inhibitor pexidartinib (PLX3397) on the senescence of bone marrow-derived macrophages (BMDM) stimulated by lipopolysaccharide (LPS). Methods: BMDM were isolated and cultured from femurs and tibiae of 10 male C57BL/6 mice aged 6-8 weeks (obtained from Laboratory Animal Center of Guizhou Medical University). They were divided into blank control group, LPS group (treated with 1 μg/ml LPS for 24 h) as well as low, medium and high concentration PLX3397 pretreatment groups (treated with 100, 500 and 1 000 nmol/L PLX3397 for 4 h respectively followed by 1 μg/ml LPS for 24 h). The corresponding markers of macrophages were detected by flow cytometry. Cell viability was detected by cell counting kit-8 and cellular senescence was detected by senescence-associated-β-galactosidase (SA-β-gal) staining. Meanwhile, protein expressions of cycle-dependent kinase inhibitor p16, p21 and CSF-1R were detected by Western blotting, and the expressions of p16 and p21 were detected by intracellular immunofluorescence. Real-time fluorescence quantitative PCR (RT-qPCR) was used to investigate the mRNA levels of senescence-associated secretory phenotype (SASP) genes including interleukin (IL), IL-1β, chemokine-1/10 (CXCL-1/10), matrix metalloproteinase-8 (MMP-8), and transforming growth factor-β (TGF-β). Results: The rate of SA-β-gal positive staining in medium and high concentration PLX3397 pretreatment groups [(39.33±4.93)% and (36.33±3.06)% respectively] were significantly downregulated compared with LPS group [(52.00±3.00)%] (P=0.020, P=0.005). The expression of CSF-1R protein in low, medium and high concentration PLX3397 pretreatment groups were (0.74±0.18, 0.61±0.07, 0.54±0.06), all of which were significantly lower than that in LPS group (1.16±0.08) (P=0.013, P=0.002, P<0.001). The expression levels of CSF-1R mRNA in low, medium and high concentration PLX3397 pretreatment groups (1.04±0.06, 0.90±0.05, 1.18±0.08) showed similar trend (2.90±0.25) (P<0.001). The average fluorescence intensity of p16 in all PLX3397 pretreatment groups were 49.76±3.65, 48.21±1.72, 47.99±1.26 respectively, which were significantly lower than that in LPS group (66.88±5.85) (P=0.001, P<0.001, P<0.001). The average fluorescence intensity of p21 in medium and high concentration PLX3397 pretreatment groups were (34.43±3.62, 30.13±0.86), significantly lower than that in LPS group (46.82±5.33) (P=0.043, P=0.007). The expression of p16 protein in low, medium and high concentration PLX3397 pretreatment groups (0.56±0.04, 0.55±0.04, 0.35±0.19) were significantly lower than that in LPS group (0.98±0.10) (P=0.003, P=0.002, P<0.001), as well the expression of p21 protein (0.69±0.20, 0.42±0.08, 0.26±0.14) (P=0.032, P=0.002, P<0.001). According to the results of RT-qPCR, the expressions of IL-6, IL-1β, CXCL-1, CXCL-10 and MMP-8 in PLX3397 pretreatment groups were significantly lower than those in LPS group (P<0.001), while the expression of TGF-β increased (P<0.001). Conclusions: LPS could induce the cell senescence, increase the secretion of SASP and aggravate local inflammation by activating the CSF-1R on the cell surface of bone marrow-derived macrophages. CSF-1R inhibitor PLX3397 might attenuate CSF-1R activation associated with LPS and inhibit the senescence of bone marrow-derived macrophages induced by LPS.

Study on Government Responsibility in the Construction of General Practitioner System / 中国卫生经济

The aim of the general practitioner system is to ensure that residents access to basic medical and health services,improve the equity and accessibility of primary health services.The optimization of government behavior is the important prerequisite and guarantee for the improvement of system.At present,the China government has taken on all aspects of responsibility in the implementation process of the general practitioner system.Based on the main problems in the government's responsibility,it put forward some strategic suggestions for the successful implementation of the general practitioner system.

Masticatory efficiency and oral health-related quality of life with implant-retained mandibular overdentures

To evaluate masticatory efficiency [ME] and oral health-related quality of life [OHRQoL] in patients rehabilitated with implant-retained mandibular overdentures. In this randomized controlled clinical trial, 50 edentulous patients visiting the Implant Center and Department of Prosthodontics, West China College of Stomatology, Sichuan University, Chengdu, China between June 2010 and June 2012 were selected and received 2 implant-retained mandibular overdenture treatments. All patients were rehabilitated with maxillary complete dentures. The ME and OHRQoL were determined both one month before the mandibular complete denture was anchored to the osseointegrated implants, and 6 months after anchoring. Paired t-tests were used to compare means of ME, and oral health impact profile-49 [OHIP-49] domains scores between pre- and post-implant. Linear regression models were utilized to seek correlations between ME and OHIP domains scores. The ME increased from pre- to post-implant retained mandibular overdentures significantly [p<0.001]. The total OHIP score and 4 subscales scores were changed significantly from pre- to post-implant; namely, functional limitation, psychological discomfort, physical disability, and physical pain. The total OHIP score, functional limitation, physical disability, and physical pain subscale scores were related to ME. Implant-retained mandibular over dentures can significantly improve patients' ME and OHRQoL. The improvement in OHRQoL is mainly because of the improved ME. An improved chewing experience, and pain relief also contributes to improvement of OHRQoL

The biological safety evaluation of a new developed silicone rubber for inflatable silastic prosthesis / 华西口腔医学杂志

<p><b>OBJECTIVE</b>The biological safety of a new developed silicone rubber for inflatable silastic prosthesis (SRISP) was evaluated.</p><p><b>METHODS</b>Following the GB/T 16886.10-2005 standard, YY/T 0127.13-2009 standard, and GB/T 16886.11- 2011 standard, samples were prepared and tested by animal experiments, such as guinea pig maximization test, oral mucous membrane irritation test, and short-term systemic toxicity test (oral route).</p><p><b>RESULTS</b>No obvious erythema and edema in the guinea pig abdominal skin were observed after 24, 48, and 72 h of stimulating touch, thus indicating that SRISP does not cause potential skin sensitivity. No local response to SRISP was found, and the visual observation and pathological findings of oral mucosa were normal and similar to that of the control group. Therefore, SRISP had no irritation response to oral mucosa. No clinical signs of toxicity were observed in rats, and no significant differences in weight and weight relative growth rate between extract group and blank control group (P > 0.05) were found. Thus, SRISP had no short-term systemic toxicity.</p><p><b>CONCLUSION</b>These results indicated that SRISP met the requirement of biomedical materials and had good bio- security.</p>

Cytotoxicity of a new type silicone rubber for maxillofacial prosthesis: an in vitro evaluation / 生物医学工程学杂志

This study evaluated the cytotoxicity of a new type silicone rubber for maxillofacial prosthesis, which was developed by the present authors. According to the GB/T16886. 5- 2003, the samples were prepared and tested with cell counting kit-8 (CCK-8) assay, the relative growth rate (RGR) was calculated, and morphology of L929 cells were observed by scanning electron microscope and phase contrast microscope. The results showed that RGR of L929 cells were 91.65% (24 h), 87.03% (48 h), 87.30% (72 h), respectively, and the level of cytotoxicity was grade 1. The L929 cells showed typical fusiform shape and their morphology did not changed significantly after 24 h, 48 h and 72 h. These data indicated that the newly-developed silicone rubber material, as a maxillofacial prosthesis material, should be a safe biomaterial.

Impact of systolic blood pressure on visit-to-visit blood pressure variability in middle-aged and elderly people / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the impact of systolic blood pressure (SBP) on visit-to-visit blood pressure variability (BPV) in middle-aged and elderly people.</p><p><b>METHODS</b>Visit-to-visit BPV was determined in 5440 workers in the Kailuan study cohort from 2006 to 2007. The subjects were ≥ 40 years-old and had no history of stroke, transient ischemic attack or myocardial infarction. Participants were divided into five groups according to different levels of SBP. Linear regression was used to analyze the related factors which might affect BPV.</p><p><b>RESULTS</b>Mean systolic BPV of all subjects was 10.35 mm Hg [coefficient of variation (CV 7.96%)]. The mean systolic BPV of males was 10.54 mm Hg (CV 7.90%) while the mean SBPV of females was 10.06 mm Hg (CV 7.90%). The BPV of males was significant higher than that of females (P < 0.001). CV of SBP was similar between males and females. Furthermore, higher SBP was associated with higher BPV. There were significant differences in BPV between different groups with different levels of SBP (P < 0.001). Linear regression analysis demonstrated that SBP, age, gender, high-sensitivity C-reactive protein (hsCRP) were affecting factors of BPV. Twenty mm Hg SBP increase was linked with 2.02 mm Hg BPV increase and 0.388%CV increase. Age increase of 1 year was associated with 0.044 mm Hg BPV increase and 0.029% CV increase.</p><p><b>CONCLUSION</b>SBP, age, gender and hsCRP are important factors affecting BPV in middle-aged and elderly people. Higher SBP is closely related to greater BPV in this cohort.</p>

Application of 'waist circumference cutoff point' in screening diabetes mellitus among rural residents in mid-western area of Shandong province,China / 中华流行病学杂志

Objective To determine the value and the optimal cutoff point of waist circumference (WC) in screening diabetes mellitus (DM) and to provide evidence for DM prevention and identifying population at risk in mid-western rural areas of Shandong province.Methods A sample consisting 16 341 rural residents was selected and studied.All participants were physically examined on height,weight,WC and fasting plasma glucose (FPG).Oral glucose tolerance test (OGTT) was performed for subjects with FPG valued from 6.1 to 7.0 mmol/L.DM was defined according to the criteria set by WHO in 1999.Area under the curve (AUC),sensitivity,specificity and Youden index were computed based on the receiver operating characteristic (ROC) curve analysis.Optimal cutoff point was determined by the maximum of Youden index.Results The prevalence rates of DM for males and females increased along with the rise of WC (trend test X2=72.01,122.65,P＜0.01 ).It appeared significantly higher in those with WC 85 cm in females and≥80 cm in males,with those WC ＜85 cm for females and ＜80 cm for males,in particular.AUCs were 0.639 and 0.655 for males and females respectively and both had significant differences (t=7.22,11.07,P ＜0.01 ).However,the AUCs did not show significant difference (t=0.70,P ＞ 0.05) between males and females.The Youden index reached maximum when WC approached 85 cm for females (24.90%) and 80 cm for males (24.39%).The sensitivity and specificity were 58.04%and 66.86%for males,and 67.08%and 57.31%for females.Conclusion WC seemed to be an effective indicator for screening the DM.The optimal cutoff point of WC would be 85 cm for females and 80 cm for males in screening DM and defining the population at risk in this area.