For the treatment of malignancy, many therapeutic agents, including small molecules, photosensitizers, immunomodulators, proteins and genes, and so forth, have been loaded into nanocarriers for controllable cancer therapy. Among these nanocarriers, polymeric micelles have been considered as one of the most promising nanocarriers, some of which have already been applied in different stages of clinical trials. The successful advantages of polymeric micelles from bench to bedside are due to their special core/shell structures, which can carry specific drugs in certain disease conditions. Particularly, poly(ethylene glycol)−polylactide (PEG−PLA) micelles have been considered as one of the most promising platforms for drug delivery. The PEG shell effectively prevents the adsorption of proteins and phagocytes, thereby evidently extending the blood circulation period. Meanwhile, the hydrophobic PLA core can effectively encapsulate many therapeutic agents. This review summarizes recent advances in PEG−PLA micelles for the treatment of malignancy. In addition, future perspectives for the development of PEG−PLA micelles as drug delivery systems are also presented.
Lung ischemia–reperfusion injury (LIRI) is a common clinical concern. As the injury occurs, the pulmonary afferent nerves play a key role in regulating respiratory functions under pathophysiological conditions. The present study was to examine the effects of inhibiting microRNA‐155 on the levels of proinflammatory cytokines and products of oxidative stress in the pulmonary vagal afferent nerves and the commissural nucleus of the solitary tract (cNTS) after LIRI. A rat model of LIRI was used. ELISA method was employed to examine proinflammatory cytokines, namely, IL‐1β, IL‐6 and TNF‐α; and key biomarkers of oxidative stress, 8‐isoprostaglandin F2α (8‐iso PGF2α) and 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG). In results, in the process of LIRI, the levels of microRNA‐155 were amplified in the vagal afferent nerves and cNTS, and this was accompanied with increases of IL‐1β, IL‐6 and TNF‐α; and 8‐iso PGF2α and 8‐OHdG. Application of microRNA‐155 inhibitor, but not its scramble, attenuated the elevation of proinflammatory cytokines and amplification of 8‐iso PGF2α and 8‐OHdG in those nerve tissues. In conclusion, we observed the abnormalities in the pulmonary afferent pathways at the levels of the peripheral nerves and brainstem, which is likely to affect respiratory functions as LIRI occurs. Our data suggest that blocking microRNA‐155 signal pathways plays a beneficial role in regulating LIRI via inhibiting responses of neuroinflammation and oxidative stress signal pathways to LIRI.
Background Given the high mortality of bacterial bloodstream infections (BSI), blood culture results do not meet clinical needs timely due to being time-consuming and having low positive rate. Whether we can identify the severity and type of bacterial infections by cytokines is a controversial issue. Objective To investigate the dynamic change of cytokines in BSI. Methods 55 patients with Gram-positive (GP) BSI, 64 patients with Gram-negative (GN) BSI and 52 healthy controls were enrolled. We quantitatively detected the cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) by flow cytometry in the sera. The levels of procalcitonin, C-reactive protein, leukocytes and neutrophils were also detected simultaneously. Results There were significantly up-regulated IL-6 and IL-10 expression in BSI patients, particularly in the GN-BSI, for instance Escherichia coli and Klebsiella pneumoniae infections; following the treatment, IL-6 and IL-10 decreased by 10-23 and 4-27 times, respectively. Additionally, IL-2, TNF-α and IFN-γ expression increased slightly in BSI patients and IFN-γ expression declined as GN-BSI progressed. Conclusion IL-6 and IL-10 are closely associated with the severity and treatment efficacy of BSI, and can help to distinguish between GP-BSI and GN-BSI at an early stage.
Objective: The objective of this study was to examine whether plasma transferrin levels are associated with longitudinal changes in cognitive performance in older individuals with normal cognition (CN), mild cognitive impairment (MCI), and mild Alzheimer's disease (AD). Methods: At baseline, there were a total of 358 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, including 58 older individuals with CN, 198 older individuals with MCI, and 102 patients with AD. Linear mixed models were utilized to examine the associations of plasma transferrin levels with changes in cognitive performance over time after adjustment of several potential covariates. The Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) were used to examine the global cognition of participants. Results: First, no significant differences in the plasma transferrin levels were observed across three diagnostic groups. Second, in the cross-sectional analyses, the baseline plasma transferrin levels were negatively associated with the MMSE scores in the CN group, but not in the MCI or the AD group. Third, in the longitudinal analyses, we found that a higher plasma transferrin was associated with a steeper cognitive decline in the MCI and AD groups, but not in the CN group. Conclusion: Higher plasma transferrin levels were associated with a steeper cognitive decline in participants with MCI and AD.
To explore the role of microRNA-155 (miR-155) in pathogenesis of immune thrombocytopenia (ITP) through investigate the relevance between the expression of miR-155 in CD19(+) B cells in peripheral blood and the function of B lymphocytes in patients with ITP.A total of 55 ITP patients (30 newly diagnosed and 25 in remission) were collected from December 2014 to October 2015 in Tianjin Medical University General Hospital, and 25 healthy volunteers were recruited as controls. The CD19(+) B cells were extracted by immunomagnetic microbeads. The expression of miR-155 in CD19(+) B cells were detected by real-time fluorescent quantitative PCR. The levels of IgG, IgM and SH2 domain-containing inositol 5'-phosphatase 1 (SHIP-1) in CD19(+) B cells were measured by flow cytometry (FCM). Correlation between miR-155 and clinical parameters of ITP patients was analyzed.(1) The expression of miR-155 in CD19(+) B cells in newly diagnosed ITP patients (4.57±1.03) was significantly higher than that in remitted ITP patients (0.79±0.13) and controls (1.74±0.32), and that in the remitted ITP patients was lower than in the controls (all P<0.05). In addition, the level of miR-155 at initial diagnosis in the patients responding to treatment (3.85±0.71) was lower than that in the refractory patients (6.67±1.05) (P<0.05). (2) The levels of IgG and IgM in CD19(+) B cells in newly diagnosed ITP patients (35.20%±6.19%, 26.87%±5.01%) were significantly higher than those in remitted ITP patients (7.51%±1.91%, 5.93%±2.23%) and controls (8.23%±0.68%, 8.21%±1.08%) (all P<0.05). (3) The expression of SHIP-1 in CD19(+) B cells in newly diagnosed ITP patients (44.33%±3.95%) was significantly lower than that in remitted ITP patients (83.13%±3.24%) and controls (67.26%±3.73%), and that in the remitted ITP patients was higher than in controls (all P<0.05). (4) The expression level of miR-155 in CD19(+) B cells in ITP patients was positively correlated with CD19(+) CD5(+) B cell count (r=0.576, P<0.05), and negatively correlated with the level of SHIP-1 and peripheral platelet count (r=-0.445, -0.402, all P<0.05).There is abnormally high expression of miR-155 in CD19(+) B cells in peripheral blood of ITP patients, which is related with the dysfunction of B lymphocytes and ntracellular antibody production, suggesting that miR-155 might be involved in the pathogenesis of ITP.
Objective To investigate the affection of negative life and events coping style to youthful breast cancer patients and their psychological stress state preoperation. Methods 60 youthful breast cancer patients preoperation were investigated with Life Events Scale (LES) and somatization, depression and anxiety in Self-reporting Inventory Symptom Checklist 90 (SCL-90). Results The score of somatization, depression and anxiety were (1.89 ±0.31), (2.28 ± 0.56) and (1.99 ± 0.63). the anxiety and depression were obvious in patients who had lower education level (P < 0. 05). Sematization, depression and anxiety were more severe in patients who was single, divorced and widowed than married (P < 0. 05). The levels of depression and anxiety were higher in patients who had higher income (P < 0. 05). Conclusions The youthful breast cancer patients have severe psychic trauma, and they need humanistic care.
Key words:
Youthful breast cancer patient; Diagnostic period; Psychological stress
Abstract To improve the compatibility and flame retardance of kaolinite (Kaol) in polymeric materials, ammonium dihydrogen phosphate (ADP) was intercalated into kaolinite to obtain a novel intercalated kaolinite (K‐ADP) for enhancing thermal stability, flame retardance, smoke suppression, and mechanical performance of epoxy resins (EPs). The results show that the presence of K‐ADP exerts a more positive effect on reducing the heat release and smoke generation of EPs than the same addition of Kaol. Condensed phase analysis shows that EP/K‐ADP composite generates more aromatic cross‐links in the condensed phase to reinforce the compactness and intumescence of char compared to EP/Kaol composite. Especially, 5 wt% K‐ADP confers a 43.7% reduction in peak heat release rate value and a 36.3% reduction in peak smoke production rate value to EP. Toxic gases analysis shows that K‐ADP conduces to inhibiting the release of combustible gases including isocyanates and aromatic volatiles, and generating incombustible gases including ammonia and carbon dioxide to reduce the intensity of EP combustion. The mechanical test shows that K‐ADP imparts less adverse impact on mechanical behavior to EP composites than Kaol due to the good dispersion and compatibility between K‐ADP with EP matrix.
To observe the expression differences of the plasma miRNA-1, miRNA-21 between patients with coronary heart disease (CHD) and without coronary artery lesions, between patients with in-stent restenosis (ISR) and none in-stent restenosis (NISR), and to study their predictive value for ISR occurred after percutaneous coronary intervention (PCI) in patients with CHD and diabetes mellitus (DM).The selected subjects were divided into CHD group in which patients were implemented stenting (n=187), and control group in which patients were without coronary artery lesions (n=195). According to the guidelines, the control group was divided into normal group (n=150), simple-DM group (n=45); the CHD group was divided into simple-CHD group (n=119) and CHD-DM group (n=68), the CHD group was also divided into ISR group (n=48), NISR group (n=139), and the ISR group was divided into simple-ISR group (n=26) and ISR-DM group (n=22) again. Plasma was collected from each group, and total RNA was extracted, the level of blood miRNA-1, miRNA-21 of each group was detected, and their level differences were analyzed.Compared with control group, the level of miRNA-1 and miRNA-21 of CHD group was increased (P<0.05); compared with NISR group, the level of miRNA-1 and miRNA-21 of ISR group was increased (P<0.05). The incidence of ISR of CHD-DM group was obviously higher than that of simple-CHD group, ISR-DM group's level of miRNA-21 was higher than that of simple-ISR group (P<0.05), and there was no difference of miRNA-1 level between ISR and ISR-DM group (P<0.05). In Logistics, for CHD patents, the OR of DM, miRNA-1, miRNA-21 were 2.132, 3.066, 1.924 respectively (P<0.05); for CHD patents with ISR, the OR of DM, miRNA-21 were 2.123, 3.066 respectively (P<0.05); especially for CHD and DM patents with ISR, the OR of miRNA-21 was 9.148 (P<0.05). In ROC curve, for CHD patients with ISR, the AUC of miRNA-1, miRNA-21 were 0.854, 0.857 respectively; for CHD-DM patients with ISR, the AUC of miRNA-21 was 0.783.To predict the occurrence of ISR for CHD patients, the plasma miRNA-1 and miRNA-21 have a relatively high specificity and sensitivity, for CHD patients with DM, miRNA-21 may have a higher clinical value.
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