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Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease. Keratinocyte dysfunction plays a central role in AD development. MicroRNA is a novel player in many inflammatory and immune skin diseases. In this study, we investigated the potential function and regulatory mechanism of miR‐193b in AD. Inflamed human keratinocytes (HaCaT) were established by tumor necrosis factor (TNF)‐α/interferon (IFN)‐γ stimulation. Cell viability was measured using MTT assay, while the cell cycle was analyzed using flow cytometry. The cytokine levels were examined by enzyme‐linked immunosorbent assay. The interaction between Sp1, miR‐193b, and HMGB1 was analyzed using dual luciferase reporter and/or chromatin immunoprecipitation (ChIP) assays. Our results revealed that miR‐193b upregulation enhanced the proliferation of TNF‐α/IFN‐γ‐treated keratinocytes and repressed inflammatory injury. miR‐193b negatively regulated high mobility group box 1 (HMGB1) expression by directly targeting HMGB1. Furthermore, HMGB1 knockdown promoted keratinocyte proliferation and inhibited inflammatory injury by repressing nuclear factor kappa‐B (NF‐κB) activation. During AD progression, HMGB1 overexpression abrogated increase of keratinocyte proliferation and repression of inflammatory injury caused by miR‐193b overexpression. Moreover, transcription factor Sp1 was identified as the biological partner of the miR‐193b promoter in promoting miR‐193b expression. Therefore, Sp1 upregulation promotes keratinocyte proliferation and represses inflammatory injury during AD development via promoting miR‐193b expression and repressing HMGB1/NF‐κB activation. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic auto-immune inflammation disease with skin lesions and abnormal keratinocyte proliferation. Sunitinib, a multi-targeted tyrosine kinase inhibitor, is known to selectively inhibit several growth factor receptors, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor and stem cell factor. It was reported that a patient with renal cell carcinoma (RCC) whose psoriatic lesion was resolved dramatically during treatment with Sunitinib, however, the mechanism is still unclear. We applied Sunitinib ointment to treat imiquimod-induced mouse model of psoriasis and found that Sunitinib ointment could alleviate imiquimod-induced psoriasis-like inflammation and reduce the Ki67 expression, while Sunitinib ointment couldn’t reduce imiquimod-induced splenomegaly of the mouse model, then we concentrated on studying the effect of Sunitinib on the proliferation and apoptosis of keratinocytes, we cultivated HaCaT cells with epidermal growth factor (HaCaT/E cells) to represent as a state of highly proliferative psoriatic keratinocytes. We found that Sunitinib could inhibit the proliferation of Hacat/E cell in a time and concentration dependent manner by influencing the expression level of cell cycle protein D1, cycle protein E1, in addition, Sunitinib could induce the apoptosis of Hacat/E cell and up-regulate the expression of poly ADP-ribose polymerase (PARP). Sunitinib down-regulated the expression of phosphorylated signal transduction and activator of transcription 3 (p-Stat3) of Hacat/E cells significantly. We conclude that Sunitinib alleviates imiquimod-induced psoriasis-like inflammation by regulating the proliferation and apoptosis of HaCaT cells through inhibiting the expression of p-Stat3. [ABSTRACT FROM AUTHOR]

In Western China, there are some mining areas with complex geological structure and significant hazards of gas, coal and gas outburst. The outburst hazard not only threatens safety of mine gravely, but also makes it difficult to explore coal resources in some regions. Aiming at the characteristics of the complex structure, poor coal seam permeability and multi-seam mining in the mining area, with the purpose of eliminating the danger of outburst and decreasing the gas content of coal seam, this paper made a systematic research on the mining of the lower distant protective layer, the technology of pressure-relieved gas drainage using surface boreholes and eliminating the potential dangers of coal and gas outburst. By constructed the model of similar materials experiments of stope and numerical simulation, the author studied the depressurization effect of protected coal seam under the mining condition of lower distant protective layer: (1) During extraction of the lower distant layer, the stress of protected layer could be reduced sufficiently, and gas permeability coefficient could be increased substantially, providing favorable condition for gas drainage; (2) As the double protective seam mining,40-50 m area of intake entry and return entry of mining face in protected coal seams is dilated area, which is the proper location of surface boreholes; (3) Repeat depressurization mode is found that the gob of the extracted seam below the gassy one provides a "Buffering Effect" for the overlying coal seam which makes the depressurization of the overlying seam weaken. The results from mechanical model for analysis of the stability of surface borehole are: (1) The greater the difference between the strength of adjacent strata is, the bigger the squeezing and shearing stress in the casing become; (2) Under the condition of leaving the space between the casing and borehole wall, the max shearing stress of casing decreased by 50.8% evenly, and the probability of failure of casing was reduced significantly; (3) The longer the production casing is, the bigger the deflection value is and the greater anti-bending ability the casing gets. Based on the above results, the author designed a structure of surface borehole against shearing and rupturing. There leaves the "buffer spacing" between the cementing casing or borehole wall and the production casing which is whole-tube and screen section was handled by "casing enhancement technology", effectively improving the stability of surface borehole. The law of pressure relief methane drainage using surface borehole is demonstrated: (1) Illustrated the distance from working face to borehole (showing the methane permeability coefficients of overlying coal seam and fractured zone), is the key influencing factor of gas production rate of borehole; (2) Revealed the changing mechanism of "fast increase-slowly decrease" of the gas production rate of borehole during the protective coal seam mining, and determined the best layout parameters of surface boreholes; (3) Built a mathematical model for determining the gas flow rate of overlying coal seam and gob, which can provide a basis of assessment for gas drainage of overlying coal seam; (4) Proposed the method of improving gas drainage form overlying pressure released seams with increasing the lower borehole resistance. The research results mentioned above were carried out in Wulan Coal Mine of Shenhua Group, which show that the effect of eliminating outburst by extracting pressure relieved gas with surface boreholes is remarkable. The pure gas drainage quantity of boreholes in the testing area has totally reached 1 512.96 x 104 m³. The max spacing of borehole near the intake entry and the return entry are 150 m and 169 m respectively. The remaining gas quantities of the protected coal seams are eliminated to 3.63 m³/t and 3.14 m³/t, and the gas drainage rates are 65.8% and 68.0%, respectively, completely eliminating the outburst danger of the coal. [ABSTRACT FROM AUTHOR]

Objective: Cuffless blood-pressure (BP) estimation has attracted widespread interest owing to its potential for long-term, non-invasive BP monitoring. But it is still impractical in clinical settings, mainly owing to ongoing challenges with respect to accuracy in hypertensive patients. To better estimate the BP, the current study proposes a new cuffless estimation method that includes a sympathetic tone, which has been reported with a varied pattern in hypertensive patients., Approach: First, the heart-rate variability of all subjects is investigated, and a new parameter, the heart-rate power spectrum ratio (HPSR), is proposed to indicate BP dynamics under sympathetic regulation. Then, a new BP estimation model is constructed by integrating HPSP with the pulse transit time (PTT) and photoplethysmography intensity ratio. The estimation accuracy is further evaluated by making comparisons with the standard sphygmomanometer BP on 60 subjects (29 hypertensive and 31 normotensive)., Main Results: A significant increase in HPSR was observed in hypertensive patients compared to normotensive subjects. Of the 60 subjects, the estimation accuracy was 0.73  ±  10.04 mmHg for systolic BP (SBP) and 0.90  ±  7.10 mmHg for diastolic BP (DBP) in hypertensive patients, which is comparable to 0.54  ±  7.52 mmHg for SBP and 0.82  ±  6.20 mmHg for DBP in normotensive subjects. Furthermore, the proposed method overperformed the traditional PTT-based algorithm by reducing the 3 mmHg error in the standard deviation in hypertensive patients., Significance: The results of the current study demonstrate that the inclusion of factors associated with autonomic activities in the BP estimation model would improve the BP estimation accuracy, especially for hypertensive subjects.