[Effects of different accompanying symptoms of obstructive sleep apnea on the risk of cardiovascular and cerebrovascular and diabetes events].

Objective: To investigate the effects of different accompanying symptoms on the risk of cardiovascular and cerebrovascular and diabetes events in patients with obstructive sleep apnea (OSA). Methods: Patients diagnosed with OSA in the sleep center of Tangdu Hospital from January 4, 2011 to December 28, 2016 were retrospectively collected and divided into four groups according to accompanying symptoms: group A included OSA patients without insomnia and excessive daytime sleepiness (EDS), group B included OSA patients with insomnia, group C included OSA patients with EDS and group D included OSA patients with insomnia and EDS. Patients were followed up by telephone for 6 to 11 years. Outcome measures were composite cardiovascular and cerebrovascular and diabetes events (including new onset or recurrent heart disease, cerebral infarction, cerebral hemorrhage, newly diagnosed hypertension and diabetes). Kaplan-Meier method was used to draw survival curves, log-rank test was performed to compare the prognosis of OSA patients with insomnia and/or EDS symptoms, and multivariate Cox proportional hazards model was constructed to analyze the influencing factors of adverse outcome events in OSA patients. Results: Five hundred and four patients with OSA were included, and 307 patients [274 males and 33 females, aged (49±11) years] completed the follow-up, including 27 patients in group A, 143 patients in group B, 27 patients in group C, and 110 patients in group D. After a median follow-up of 7.7 years, 78 patients developed cardiovascular and cerebrovascular and diabetes events. Outcome events occurred in 1 patient (3.70%) in group A, 30 (20.98%) in group B, 10 (37.04%) in group C, and 37 (33.64%) in group D. Compared with patients in group A, there was a statistically significant difference in the incidence of outcome events in groups B (P=0.034), C (P=0.004), and D (P=0.003). After adjusting for age, sex, body mass index, apnea-hypopnea index, baseline cardiovascular and cerebrovascular risk factors and subsequent continuous positive airway pressure therapy, patients in group C (HR=9.67, 95%CI: 1.23-76.37, P=0.031) and group D (HR=11.35, 95%CI: 1.55-83.43, P=0.017) had an increased risk of cardiovascular and cerebrovascular and diabetes events when compared with group A. Conclusions: In OSA patients with successful long-term follow-up, insomnia and EDS symptoms are risk factors for the development of cardiovascular and cerebrovascular and diabetes events. Insomnia and EDS symptoms should be evaluated in patients with OSA during clinical practice to find the cause and carry out the targeted intervention.

A survey and cause analysis of community resilience in a Chinese city from the perspective of nursing.

BACKGROUND: Community resilience, which fully reflects the ability of communities to resist, absorb, recover or adapt to disasters, has attracted international attention. Nurses are an important force in disaster prevention, relief and postdisaster reconstruction. This study aims to test the current level of community resilience in Dujiangyan city, which was seriously damaged by the Wenchuan earthquake, and analyze the causes. METHODS: Community data from 952 residents, 574 families, 5 health care institutions and 12 communities in Dujiangyan city were collected by using stratified, cluster, map and systematic sampling methods. A new community resilience evaluation system from the perspective of nursing was used to test individual, family, health care and environmental resilience. RESULTS: In Dujiangyan city, average scores were obtained for community resilience (3.93 ± 0.12), individual resilience (4.07 ± 0.64), family resilience (4.07 ± 0.6), health care resilience (3.84 ± 0.33) and community environment resilience (3.69 ± 0.46). CONCLUSIONS: The urban communities in Dujiangyan city had acceptable resilience, with good family and individual resilience and medium health care and community environment resilience, but environmental resilience had the lowest score. Because conditions and resilience levels varied among the communities, targeted measures should be taken to improve resilience based on population characteristics, management, professional organizations, hardware and software facilities.

Effect and mechanism of miR-135a-5p/CXCL12/JAK-STAT axis on inflammatory response after myocardial infarction.

OBJECTIVE: To investigate the regulatory role of miR-135a-5p/CXCL12/JAK-STAT signaling axis in inflammatory response after myocardial infarction (MI). MATERIALS AND METHODS: With the construction of mouse model with MI by ligation of left descending coronary artery, modeling mice were subdivided into sh-NC group, sh-CXCL12 group, agomir-NC group, miR-135a-5p agomir group and miR-135a-5p-agomir+pcDNA-CXCL12 with intravenous injection of corresponding adenovirus, and no modeling was made for mice in the sham operation group. Simulation of MI in vivo was realized by hypoxia model in vitro, with the establishment of groups including mimic-NC group, miR-135a-5p mimic group, inhibitor-NC group, miR-135a-5p inhibitor group, sh-NC group, sh-CXCL12 group, oe-NC group, oe-CXCL12 group, mimic NC+oe-NC group, miR-135a-5p mimic+oe-NC group, and miR-135a-5p mimic+oe-CXCL12 group. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the level of miR-135a-5p, CXCL12, TNF-α, IL-1ß and IL-6, and Western blot were further performed to detect the mRNA and protein expression of JAK2/p-JAK2 and STAT3/p-STAT3, respectively. Hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to evaluate MI in mice. Dual-Luciferase reporter assay was used to verify the targeting relationship between miR-135a-5p and CXCL12. Annexin V-fluorescein isothiocyanate/propidium iodide (V-FITC/PI) double staining analysis by flow cytometry was used to detect apoptosis. RESULTS: After hypoxia of myocardial cell line H9c2 for 24 h, there were increased expression of CXCL12, decreased expression of miR-135a-5p, increased number of apoptotic cells, as well as upregulated levels of TNF-α, IL-1ß and IL-6 (all p<0.05). Meanwhile, similar results were found in the myocardial tissues. Dual-Luciferase reporter assay indicated that miR-135a-5p could target the expression of CXCL12. Transfection of miR-135a-5p mimic or sh-CXCL12 could reduce the number of apoptotic myocardial cells and inhibit the level of TNF-α, IL-1ß and IL-6 (all p<0.05). Furthermore, miR-135a-5p mimic or sh-CXCL12 could result in the suppressed expression of p-JAK2 and p-STAT3 (all p<0.05). Compared with miR-135a-5p mimic +DMSO group, the expression of JAK2 and STAT3 in miR-135a-5p mimic +RO8191 group had no significant change (p>0.05); the expression of p-JAK2 and p-STAT3 was increased (all p<0.05), suggesting that miR-135a-5p negatively regulated the expression of CXCL12 and inhibited the activation of JAK-STAT signaling pathway. In addition, for further verification, experiments carried out in sh-NC group, sh-CXCL12 group, agomir-NC group and miR-135a-5p agomir group found that sh-CXCL12 and miR-135a-5p agomir resulted in decreased area of MI decreased, the number of apoptotic cells, the expression of p-JAK2 and p-STAT3 (all p<0.05); while compared with miR-135a-5p-agomir group, miR-135a-5p-agomir+pcDNA-CXCL12 group showed increased area of MI decreased, the number of apoptotic cells, the expression of p-JAK2 and p-STAT3 (all p<0.05). CONCLUSIONS: Inhibition of miR-135a-5p/CXCL12/JAK-STAT signaling axis can reduce inflammatory reaction and apoptosis after MI, and hence contribute to the improvement of the degree of myocardial injury.

Expression levels of PTEN, HIF-1α, and VEGF as prognostic factors in ovarian cancer.

OBJECTIVE: Epithelial ovarian cancer is associated with high mortality, mostly because of delayed diagnosis, necessitating the search for novel diagnostic and prognostic markers. Here we evaluated the association between expression levels of phosphatase and tensin homolog (PTEN), hypoxia-inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF), and ovarian cancer. PATIENTS AND METHODS: Expressions of these proteins were assessed by immunohistochemistry in 21 specimens of normal ovary tissues and 76 specimens of ovarian cancer tissues. Associations with pathological characteristics and prognosis were determined using chi-square test, Kaplan-Meier method, log-rank test, and Cox regression model. RESULTS: Expression of PTEN in ovarian cancer tissue was negatively associated with clinical stage and differentiation degree. A reverse trend was observed in association between expression of HIF-1α and VEGF, and the clinical stage of the disease. PTEN expression negatively correlated with HIF-1α and VEGF expression levels, whereas both latter positively correlated with each other. The overall survival of patients with positive PTEN expression was significantly longer than that of those with negative expression; the opposite trend was observed with HIF-1α and VEGF. The differentiation degree and expressions of HIF-1α and PTEN were dependent predictors, whereas VEGF expression, clinical stage and lymph node metastasization were independent prognostic factors in these patients. CONCLUSIONS: PTEN, HIF-lα, and VEGF were found to be prognostic markers in ovarian cancer, with VEGF also being as an independent prognostic factor. Combined detection of their expression levels may be useful for determination of the degree of malignancy, metastasis, and prognosis of ovarian cancer.

Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer.

Cancer cells are known to execute reprogramed metabolism of glucose, amino acids and lipids. Here, we report a significant role of cholesterol metabolism in cancer metastasis. By using label-free Raman spectromicroscopy, we found an aberrant accumulation of cholesteryl ester in human pancreatic cancer specimens and cell lines, mediated by acyl-CoA cholesterol acyltransferase-1 (ACAT-1) enzyme. Expression of ACAT-1 showed a correlation with poor patient survival. Abrogation of cholesterol esterification, either by an ACAT-1 inhibitor or by shRNA knockdown, significantly suppressed tumor growth and metastasis in an orthotopic mouse model of pancreatic cancer. Mechanically, ACAT-1 inhibition increased intracellular free cholesterol level, which was associated with elevated endoplasmic reticulum stress and caused apoptosis. Collectively, our results demonstrate a new strategy for treating metastatic pancreatic cancer by inhibiting cholesterol esterification.

CD44+/CD24+ cervical cancer cells resist radiotherapy and exhibit properties of cancer stem cells.

OBJECTIVE: The aim of the study is to investigate the radiosensitivity of CD44+/CD24+ cervical cancer cells and to explore its mechanism of radiotherapy resistance. Moreover, we further to test whether the CD44+/CD24+ cervical cancer cells had the characteristics of stem cells. MATERIALS AND METHODS: The human squamous cell carcinoma SiHa cells were cultured in vitro, and CD44+/CD24+ SiHa cells were sorted by FACS analysis. CD44+/CD24+ SiHa cells and the parental SiHa cells were given several fractionated irradiation at a cumulative dose of 8 Gy, 16 Gy, 30 Gy, respectively. Survival curves were obtained and fitted using clonogenic assays, and the radiosensitivity of tumor cells was compared according to the radiobiological parameters, including Do, Dq, N and SF 2. Morphological changes of cell apoptosis were determined using Hoechst 33258 fluorescence staining. The ultrastructural changes in cells with apoptosis were observed by transmission electron microscopy. Cell apoptosis rate was determined by FCAS analysis. DNA "ladder" in apoptotic cells was detected by gel electrophoresis. The mRNA levels of cell apoptosis-related genes were detected by RT-PCR assay. Balling capacities of CD44+/CD24+ SiHa cells and parental SiHa cells were detected by suspension culture without FBS. The in vivo tumorigenicity was detected by inoculating CD44+/CD24+ SiHa and parental SiHa cells into nude mice. RESULTS: The FACS analysis results demonstrated that there was a concomitant increase in the percentage of CD44+/CD24+ cells as the increasing irradiation doses. Colony formation assay results showed that the colony formation rate of CD44+/CD24+ SiHa cells was significantly higher than that of parental SiHa cells (p < 0.05). Moreover, the data from Hoechst 33258 staining, DNA fragment gel electrophoresis, transmission electron microscopy and FACS analysis showed that CD44+/CD24+ SiHa cells had no cell apoptosis after irradiation treatment. RT-PCR results showed that the mRNA levels of bcl-2, surviving and OCT4 were significantly higher in CD44+/CD24+ SiHa cells than that of parental SiHa cells (p < 0.01). CD44+/CD24+ SiHa cells could form more compact cell spheres with a larger volume than that of parental SiHa cells (p < 0.05). CD44+/CD24+ cervical cancer cells had more potent tumorigenicity than that of parental cervical cancer cells. CONCLUSIONS: CD44+/CD24+ cervical cancer resist cell apoptosis induced by irradiation therapy and possessed the characteristics of stem cells.

Cervical cytology ASCUS patients with HPV detection and clinical value.

OBJECTIVE: Patients whose cervical cytological exams produced a result of atypical squamous cells of undetermined significance (ASCUS) were asked to undergo human papillomavirus (HPV DNA) genotyping detection to assess the role of HPV infection in ASCUS. MATERIALS AND METHODS: This study included 1,219 patients with ASCUS that were randomly divided into two groups. The first group contained 618 patients. These participants underwent colposcopy with cervical biopsy. The remaining 601 underwent colposcopy and biopsy with HPV DNA detection. RESULTS: Out of the 56,000 patients with ASCUS who underwent ThinPrep cytology test (TCT) de- tection in the authors' hospitals' gynecological outpatient clinics, 1,604 were diagnosed with ASCUS (2.86%). Among the 1,219 patients with ASCUS, the rate of detection of cervical intraepithelial neoplasia (CIN) and cancerization was 22.89% (279/1,219). Among the 601 patients who underwent HPV testing, 182 were positive for high-risk HPV (30.28%). Among HPV-positive samples, the most common high-risk types were HPV16, and HPV58. The most common low-risk types were HPV6 and HPV 11. The rate of detection among high- risk patients who were positive for HPV and cervical carcinoma with intraepithelial neoplasia was 70.88% (129/182). The rate of detection for HPV-negative patients with cervical cancer with intraepithelial neoplasia was 11.55% (47/407). The rate of detection of high-risk HPV was higher than among patients who had not undergone HPV detection and among patients who were negative for HPV (p < 0.05). CONCLUSION: The results of cervical cytological examination showed that the manner of progression from inflammation to cancer could differ considerably. HPV DNA examination is an effective means of categorizing and managing ASCUS.

TRIM24 promotes glioma progression and enhances chemoresistance through activation of the PI3K/Akt signaling pathway.

The tripartite motif protein TRIM24 (tripartite motif-containing 24) has been found to play distinct roles in tumor development and progression, according to different tumor contexts. However, it remains elusive whether TRIM24 plays a role in malignant gliomas that are the most common and deadly primary brain tumors in adults. We report here that TRIM24 expression is positively correlated with glioma malignancy and is negatively associated with prognosis of patients with newly diagnosed glioblastoma, which is the most malignant form of gliomas but displays highly heterogeneous clinical outcome. The multivariate Cox regression analysis demonstrates the independent predictive value of TRIM24 expression level for overall and progression-free survival. Knockdown of TRIM24 suppresses cell proliferation, cell cycle progression, clone formation and in vivo tumor development, whereas overexpression of TRIM24 promotes cell growth. Chromatin immunoprecipitation, real-time reverse transcription-PCR and mutation analyses demonstrate that TRIM24 binds to the PIK3CA promoter via its PHD-Bromo domain to activate the transcription of PIK3CA gene, thus enhancing phosphatidylinositide 3-kinase (PI3K)/Akt signaling. The pan-PI3K inhibitor LY294002 and small interfering RNA targeting PIK3CA both abrogate the growth-promoting effect of TRIM24. Moreover, TRIM24 regulates the expression of DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) through PI3K/Akt/nuclear factor-κB signaling transduction and enhances resistance to temozolomide, the standard chemotherapeutic agent for glioblastoma. Finally, glioblastoma patients with low TRIM24 expression benefit from chemotherapy, whereas those with high TRIM24 expression do not have such benefit. Our results suggest that TRIM24 might serve as a potential prognostic marker and therapeutic target for the management of malignant gliomas.

Quantitative analysis of P16 gene CpG methylation in Uyghur patients with cervical squamous cell carcinoma and its relationship with HPV16 infection.

The methylation of CpG sites in the promoter region of the P16 gene in Uyghur patients with cervical squamous cell carcinoma (CSCC) was quantitatively analyzed and its relationship with human papillomavirus 16 (HPV16) infection was explored. Cervical samples were collected from 20 Uyghur patients with CSCC and 20 Uyghur controls. Matrix-assisted laser desorption ionization-time of flight mass spectrometry was applied to detect methylation of CpG sites in the promoter region of the P16 gene; polymerase chain reaction was performed to assess HPV16 infection in the 2 groups. Among the 16 CpG sites in the P16 gene promoter region, the methylation level of the CpG1-2 and CpG 6 sites, as well as the HPV16 infection rate, was higher in the CSCC group than in the control group (P<0.05). There was no significant correlation between P16 CpG methylation and HPV16 infection in Uyghur patients with CSCC. The P16 gene CpG1-2 and CpG 6 hypermethylation and HPV16 infection, which are independent of each other, play an important role in cervical squamous cell carcinogenesis in Uyghur patients.

Genome-wide profiling reveals epigenetic inactivation of the PU.1 pathway by histone H3 lysine 27 trimethylation in cytogenetically normal myelodysplastic syndrome.

Cytogenetically normal myelodysplastic syndrome (CN-MDS) can pose diagnostic challenges and its pathogenetic mechanism remains elusive. By focusing on cytogenetically normal refractory cytopenia with multilineage dysplasia (CN-RCMD), a subtype of MDS, our genome-wide profiling showed ∼4600 annotated gene promoters with increased Histone H3 lysine 27 trimethylation (H3K27me3) in CN-RCMD, when compared with normal controls. Computational analysis revealed a statistically significant enrichment of the PU.1-binding DNA motif (PU-box) in the regions with increased H3K27me3. An inverse relationship between the levels of H3K27me3 and the levels of PU.1 binding and its downstream myeloid gene expressions was observed. Whole-exome sequencing analysis and Sanger sequencing analysis revealed some recurrent mutations, but no mutations in the PU.1 regulatory regions or in the EZH1/2, H3K27 methytransferase encoding genes. Using an MDS-derived erythroid/myeloid line and primary MDS bone marrow cells, we demonstrated that H3K27me3 inhibitors can increase the expression of PU.1 and its downstream genes and also promote cell differentiation via reducing H3K27me3 at the PU.1 gene locus. Finally, ectopic expression of PU.1 significantly inhibited proliferation of the MDS-derived cell line. Based on these data, we propose a hypothetical model of epigenetic inactivation of the PU.1 pathway due to increased H3K27me3 in some cases of CN-RCMD.

In vivo coherent anti-Stokes Raman scattering imaging of sciatic nerve tissue.

We report in vivo nonlinear optical imaging of mouse sciatic nerve tissue by epidetected coherent anti-Stokes Raman scattering and second harmonic generation microscopy. Following a minimally invasive surgery to open the skin, coherent anti-Stokes Raman scattering imaging of myelinated axons and second harmonic generation imaging of the surrounding collagen fibres were demonstrated with high signal-to-background ratio, three-dimensional spatial resolution, and no need for labelling. The underlying contrast mechanisms of in vivo coherent anti-Stokes Raman scattering were explored by three-dimensional imaging of fat cells that surround the nerve. The epidetected coherent anti-Stokes Raman scattering signals from the nerve tissues were found to arise from interfaces as well as back reflection of forward coherent anti-Stokes Raman scattering.

Dynamics of fracture in drying suspensions.

We investigate the dynamics of fracture in drying films of colloidal silica. Water loss quenches the nanoparticle dispersions to form a liquid-saturated elastic network of particles that relieves drying-induced strain by cracking. These cracks display intriguing intermittent motion originating from the deformation of arrested crack tips and aging of the elastic network. The dynamics of a single crack exhibits a universal evolution, described by a balance of the driving elastic power with the sum of interfacial power and the viscous dissipation rate of flowing interstitial fluid.

Flow and fracture in drying nanoparticle suspensions.

Drying aqueous suspensions of monodisperse silica nanoparticles can fracture in remarkable patterns. As the material solidifies, evenly spaced cracks invade from the drying surface, with individual cracks undergoing intermittent motion. We show that the growth of cracks is limited by the advancement of the compaction front, which is governed by a balance of evaporation and flow of fluid at the drying surface. Surprisingly, the macroscopic dynamics of drying show signatures of molecular-scale fluid effects.

High-sensitivity coherent anti-Stokes Raman scattering microscopy with two tightly synchronized picosecond lasers.

We demonstrate a significant improvement in signal-to-noise ratio in coherent anti-Stokes Raman scattering (CARS) spectroscopy/microscopy, using two highly synchronized picosecond Ti:sapphire lasers. A temporal jitter between the pulse trains from the two independent commercial lasers is reduced from a few picoseconds to ~21 fs , maintained over several hours. The tight synchronization brings the fluctuation of the CARS signal down to the shot-noise limit, leading to enhanced CARS vibrational images of living cells and polymer beads.

Polarization coherent anti-Stokes Raman scattering microscopy.

We report polarization coherent anti-Stokes Raman scattering (P-CARS) microscopy that allows vibrational imaging with high sensitivity and spectral selectivity. The nonresonant background signals from both Raman scatterers and the solvent are efficiently suppressed in P-CARS microscopy. We demonstrate P-CARS imaging of unstained cells based on the contrast of the protein amide I band.

Characterization of cytosolic phospholipases C from porcine aortic endothelial cells.

Phospholipases C (PLCs) are ubiquitous enzymes which play key roles in the response of cells to extracellular agonists. Endothelial cells are involved in myriad normal and pathophysiologic functions. Although it is known that agonists activate PLCs in endothelial cells, second messengers form, and cellular responses ensue, more knowledge is needed about the specific types of PLCs in these cells. To this end, cytosolic PLCs from porcine aortic endothelial cells were partially purified by ammonium sulfate fractionation and column chromatography on DEAE-Sepharose CL-6B and heparin-agarose. Three PLC isozymes immunologically similar to bovine brain PLC-beta, PLC-gamma, and PLC-delta were identified. The relative levels of PLC activities in the cytosol were: PLC-beta, 50%; PLC-gamma, 44%; PLC-delta, 6%. The level of PLC-beta activity in porcine endothelial cells appeared higher than the levels reported for several established cell lines, suggesting that this enzyme may play a specific role in endothelial cell function. Elution profiles of PLC activity with phosphatidylinositol 4,5-bisphosphate (Ptdlns(4,5)P2) as substrate were similar to those with phosphatidylinositol (Ptdlns) as substrate, indicating that cytosolic PLCs hydrolyze both Ptdlns and Ptdlns(4,5)P2 and no Ptdlns(4,5)P2-specific PLC was present in the cytosol. The catalytic properties of the partially purified PLC isozymes from porcine endothelial cells were similar to their counterparts from bovine brain. These include the dependence of hydrolysis of Ptdlns on Ca2+, the optimal Ca2+ concentrations for the hydrolysis of Ptdlns and Ptdlns(4,5)P2, the pH optima, and the stimulatory effects of deoxycholate.