Caspase-1/-11 participates in LPS-induced sepsis-associated acute kidney injury by cleaving GSDMD / 生理学报

The present study was aimed to investigate whether Gasdermin D (GSDMD)-mediated pyroptosis participated in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (AKI), and to explore the role of caspase-1 and caspase-11 pyroptosis pathways in this process. The mice were divided into four groups: wild type (WT), WT-LPS, GSDMD knockout (KO) and KO-LPS. The sepsis-associated AKI was induced by intraperitoneal injection of LPS (40 mg/kg). Blood samples were taken to determine the concentration of creatinine and urea nitrogen. The pathological changes of renal tissue were observed via HE staining. Western blot was used to investigate the expression of pyroptosis-associated proteins. The results showed that the concentrations of serum creatinine and urea nitrogen in the WT-LPS group were significantly increased, compared with those in the WT group (P < 0.01); whereas serum creatinine and urea nitrogen in the KO-LPS group were significantly decreased, compared with those in the WT-LPS group (P < 0.01). HE staining results showed that LPS-induced renal tubular dilatation was mitigated in GSDMD KO mice. Western blot results showed that LPS up-regulated the protein expression levels of interleukin-1β (IL-1β), GSDMD and GSDMD-N in WT mice. GSDMD KO significantly down-regulated the protein levels of IL-1β, caspase-11, pro-caspase-1, caspase-1(p22) induced by LPS. These results suggest that GSDMD-mediated pyroptosis is involved in LPS-induced sepsis-associated AKI. Caspase-1 and caspase-11 may be involved in GSDMD cleavage.

Inhibitory Effect of Sangsuyin on Airway Inflammation in Asthmatic Rats by Regulating TLR4 Pathway / 中国实验方剂学杂志

Objective:To investigate the inhibitory effect of Sangsuyin on airway inflammation in asthmatic rats by regulating the Toll-like receptor 4 （TLR4） pathway. Method:Forty-eight SD rats were randomly divided into a normal group （<italic>n</italic>=8） and an experimental group （<italic>n</italic>=40）. Asthma model was induced in the rats of the experimental group which were further divided into the following five groups according to a random number table： a model group， a dexamethasone group （0.005 g·kg^-1），and low- （2.1 g·kg^-1）， medium- （4.2 g·kg^-1）， and high-dose （8.4 g·kg^-1） Sangsuyin groups. The drugs were all dissolved in normal saline at 0.01 L·kg^-1. The rats in the model group and the normal group received normal saline （<italic>ig</italic>） at 0.01 L·kg^-1. The drug treatment was carried out once per day， for a total of 7 days. The grades of allergic reactions were compared among the groups after intervention. The levels of interleukin-1<italic>β</italic> （IL-1<italic>β</italic>），tumor necrosis factor-<italic>α</italic>（TNF-<italic>α</italic>）， and interferon-<italic>γ</italic>（IFN-<italic>γ</italic>） in serum and bronchoalveolar lavage fluid （BALF） were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of lung tissues，and the inflammatory cell infiltration scores of lung tissues were compared. The mRNA expression of TLR4 and nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） was detected by quantitative real-time fluorescence-based reverse-transcription polymerase chain reaction （Real-time PCR）. The expression of TLR4，NF-<italic>κ</italic>B， and the level of phosphorylated NF-<italic>κ</italic>B （p-NF-<italic>κ</italic>B） were detected by Western blot. Result:The success rate of modeling was 95.00%. Compared with the normal group， the model group showed a higher grade of allergic reaction and more severe pathological changes of lung tissues，and the groups with drug intervention exhibited relieved conditions. The levels of IL-1<italic>β</italic> and TNF-<italic>α</italic> in the serum and BALF were higher in the model group than in the normal group，and lower in the groups with drug intervention than in the model group （<italic>P</italic><0.01）. The level of IFN-<italic>γ</italic> in the serum and BALF was lower in the model group than in the normal group，and higher in the groups with drug intervention than in the model group （<italic>P</italic><0.05，<italic>P</italic><0.01）. The inflammatory cell infiltration score，mRNA and protein expression of TLR4 and NF-<italic>κ</italic>B，and the mRNA level of p-NF-<italic>κ</italic>B were higher in the model group than in the normal group，and lower in the groups with drug intervention than in the model group （<italic>P</italic><0.01）. Conclusion:Sangsuyin could inhibit allergic reactions，lung tissue lesions， and airway inflammation in asthmatic rats. It is speculated that this effect is achieved by inhibiting the TLR4 pathway，down-regulating the mRNA and protein expression of TLR4 and NF-<italic>κ</italic>B，and reducing the level of p-NF-<italic>κ</italic>B.angsuyin can inhibit allergic reaction，lung tissue lesions and airway inflammation in asthmatic rats. It is speculated that this effect is achieved by inhibiting TLR4 pathway，down regulating the mRNA and protein expression of TLR4，NF-<italic>κ</italic>B，and reducing the levels of p-NF-<italic>κ</italic>B.

Research progress in signal bias of G protein-coupled receptor and its mechanism / 生理学报

G protein-coupled receptors (GPCRs) mediate signal transduction via G protein or β-arrestin. Several biased ligands and receptors that preferentially signal through either G protein- or β-arrestin-mediated pathways have been identified. These discoveries have redefined the classical GPCR signaling paradigm. Distinct ligand-receptor binding sites might be one of the main reasons for biased signal transduction. It is posited that multiple active conformations of receptors lead to distinct kinase phosphorylation patterns on C terminus of receptors. Phosphorylation patterns decide which signal pathway will be transduced. The biased signal pathway transduction has been found in more than 40 GPCRs till now. A few of them have been found involved in fine-regulation of physiological processes. However, most others still need further investigation. The biased ligands may be developed as tools for understanding the basic physiology of GPCR, and, potentially and most importantly, as fine-tuned therapeutics that maximize beneficial effects and minimize adverse or unwanted effects. These studies will provide new insights into new drug discovery.

Measurement and comparison of corneal flap thickness between Wavelight FS200 femtosecond laser and Moria 90 microkeratome LASIK by OCT / 中华实验眼科杂志

Background Lasein situ keratomileusi(LASIK) imainstream surgery forefractive correction,and femtosecond laseimuch often used to create thin corneal flap.The measuremenof OPTOVUE RTVue-100 OCto flap and stromal bed thicknesseofferuseful basifoLASIK.Ican be used in measuring the thicknesand shape of the corneal flap.Buthe study on the comparison of flap thicknesbetween WavelighFS200 femtosecond laseand MoriM2 microkeratome 90 μm-knife (Mori90 microkeratome) LASIK by OCilack.Objective The aim of thitrial wato compare the featureof corneal flapcreated by the WavelighFS200 femtosecond laseand Mori90 microkeratome.Methodpiloand prospective study wadesigned.Written informed consenwaobtained from each patienprioto LASIK.Sixty righeyeof 60 patientwith myopiomyopiastigmatism were enrolled in thiclinical trial.The patientwere randomized into the FS200 femtosecond lasegroup and Mori90 microkeratome group with matching demography.RTVue OCwaused to measure flap thicknesusing 10 settingon the 60 eye1 month afteoperation.The featureof the LASIK flapwere analyzed based on the measuring outcomes.ResultThe central flap thickneswa(112±3) μm and the mean flap thickneswa(112 ±3) μm in the FS200 femtosecond lasegroup,which wasignificanlowethan the central flap thicknesa(121±7) μm and the mean flap thicknesa(128±11) μm in the Mori90 microkeratome group respectively (P=0.031,0.030).Corneal flapin the FS200 femtosecond lasegroup showed flashape and thain the Mori90 microkeratome group wameniscushape.The central flap thickneswanoevidently differenfrom thaof peripheral thicknesin the FS200 femtosecond lasegroup (P =0.320).However,in the Mori90 microkeratome group,the central flap thickneswaobviously thinnethan thain the peripheral thicknes(P=0.038).The mean deviation between the actual and predicted flap thicknes(110 μm) wa(3±4)μm in the FS200 femtosecond lasegroup and (17±10) μm in the Mori90 microkeratome group,showing significandifference between them (P =0.009).ConclusionRTVue OCdeterminethathe shape of flapcreated by the FS200 femtosecond laseimore uniform and closeto the expected thicknesof 110 μm than the onecreated by the Mori90 microkeratome.OPTOVUE RTVue-100 OCiuseful tool to evaluate the flap shape and thicknesafteLASIK.

Comparison of the flaps made by femtosecond laser and automated keratomes for sub-bowman keratomileusis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Thin-flap laser in situ keratomileusis (LASIK) is the new trend of refractive error correction surgery, the formation of corneal flap is crucial for a success of LASIK surgery. This study aimed to assess and compare the variations of LASIK flap created by the IntraLase femtosecond laser, Moria One Use-Plus SBK and Moria M2 Single-Use 90 µm-head microkeratome using Anterior segment optical coherence tomography (Visante OCT).</p><p><b>METHODS</b>One hundred and sixty-one eyes of 81 consecutive patients were enrolled in this prospective study and randomly divided into three groups depending on the flap creation method: flap creation with the the IntraLase femtosecond laser (IntraLase group, 59 eyes), flap creation with the Moria One Use-Plus SBK (SBK group, 44 eyes), and flap creation with the Moria M2 Single-Use 90 µm-head microkeratome (M2SU90 group, 58 eyes). The nominal flap thickness was 110 µm for all patients and for the three devices. One month after surgery, Visante OCT was used to measure the flap thickness at 20 locations on each cornea and the results were assessed for uniformity, regularity, and accuracy.</p><p><b>RESULTS</b>At 1 month after surgery, the mean central flap thickness was (111 ± 3) µm in the IntraLase group, (114 ± 8) µm in the SBK group, and (118 ± 13) µm in the M2SU90 group respectively. The flaps in the IntraLase group and the SBK group were more regular, showing an almost planar configuration, than the meniscus-shaped flaps in the M2SU90 group. The maximum deviation from the intended flap thickness (110 µm) was 6 µm in the IntraLase group, 10 µm in the SBK group, and 20 µm in the M2SU90 group respectively. A difference greater than 20 µm was observed in 0.42% of measurements in the IntraLase group; 2.95% of the measurements in the SBK group and 21.12% of measurements in the M2SU90 group.</p><p><b>CONCLUSIONS</b>The flaps created by the IntraLase femtosecond laser and Moria One Use-Plus SBK are more uniform; more regular, and more accurate than those created by the Moria M2 Single-Use 90 µm-head microkeratome. The first two methods can make precise flaps for Sub-Bowman Keratomileusis.</p>

The protective effects of SB203580 against mortality and radiation induced intestinal injury of mice / 药学学报

This study is to investigate the protective effects of the SB203580 against radiation induced mortality and intestinal injury of mice. A total of 67 male C57BL/6 mice (20.0-22.0 g) were matched according to body weight and randomly assigned to one of three groups: control, total body irradiation exposure (IR, 7.2 Gy) only, and IR (7.2 Gy) + SB203580 (15 mg x kg(-1)). 30 days survival rate was observed in the experiment. In intestinal injury experiment, the expression levels of caspase-3, Ki67, p53 and p-p38 were assayed in the mice intestine crypts. The results showed that the 30 days survival rate was 100% (control), 0 (IR) and 40% (IR+ SB203580), separately. Compared to the IR groups, the positive cells of caspase-3, p53 and p-p38 in crypt cells decreased 33.00%, 21.78% and 34.63%, respectively. The rate of positive cells of Ki67 increased 37.96%. Significant difference was found between all of them (P < 0.01). SB203580 potently protected against radiation-induced lethal and intestinal injury in mice, and it may be a potential radio protector.

Numerical computation on the scaffolds models with regular square holes using nonlinear fluid-solid-coupling approaches / 医用生物力学

Objective The influencing parameters of solid and fluid computing fields for the scaffolds models with regular square holes were discussed by nonlinear fluid-solid-coupling approaches.The numerical computational resuits of which the models were regarded as both rigid body and non-linear elasticity were compared as well.Method One direct fluid-solid-coupling approach and two indirect fluid-solid-coupling approaches were adopted,and the calculating reliability of three kinds of fluid-solid coupling methods was verified.Rasults The solid-fluidcoupling computational results are obtained in light of 12 kinds of scaffolds models which are constructed by 3 groups of square side length(50,100 and 150 μm)and 4 groups of porosity(61%,65%,77%and 84%).The field parameters of those solid models including stress,strain and displacement and those fluid models including static pressure,velocity,wall shear stress and strain rate are achieved and compared.Conclusion There appear some difference between the results of porous scaffold models as a rigid body and as non-linear elasticity.The different porosity with the same pore radius or the different pore radius with the same porosity would affect the field parameters of solid models and fluid models in varying degrees.

Numerical computation on the scaffolds models with regular square holes using nonlinear fluid-solid-coupling approaches / 医用生物力学

Objective The influencing parameters of solid and fluid computing fields for the scaffolds models with regular square holes were discussed by nonlinear fluid-solid-coupling approaches.The numerical computational resuits of which the models were regarded as both rigid body and non-linear elasticity were compared as well.Method One direct fluid-solid-coupling approach and two indirect fluid-solid-coupling approaches were adopted,and the calculating reliability of three kinds of fluid-solid coupling methods was verified.Rasults The solid-fluidcoupling computational results are obtained in light of 12 kinds of scaffolds models which are constructed by 3 groups of square side length(50,100 and 150 μm)and 4 groups of porosity(61%,65%,77%and 84%).The field parameters of those solid models including stress,strain and displacement and those fluid models including static pressure,velocity,wall shear stress and strain rate are achieved and compared.Conclusion There appear some difference between the results of porous scaffold models as a rigid body and as non-linear elasticity.The different porosity with the same pore radius or the different pore radius with the same porosity would affect the field parameters of solid models and fluid models in varying degrees.

Efficacy of different LASIK mode for the correction of mixed astigmatism / 眼科

Objective To compare the efficacy and predictability of sphere-cylinder-combined LASIK and two-zone cross-cylinder LASIK for the correction of moderate and high astigmatism.Design Prospective,comparative case series.Participants 40 eyes of 35 patients with mixed astigmatism undergoing LASIK.Methods All patients were treated with Visx Star IV LASIK system.20 eyes of 19 cases were used for sphere-cylinder combined LASIK mode and 20 eyes of 16 cases for two-zone-cross-cylinder LASIK mode.All sub- jects were followed more than 6 months.Main Outcome Measures Uncorrected visual acuity (UCVA),best spectacle-corrected visual acuity (BSCVA),spherical diopter,residual astigmatism and corneal thickness.Results For the patients who received two-zone-cross-cylinder LASIK mode,the UCVA at 6 months after surgery was 0.5 or above,and 13 eyes (65.0%) were 1.0 or above. For the patients who received sphere-cylinder-combined LASIK mode,the UCVA at 6 months after surgery was 0.5 or above,and 11 eyes (55.0%) was 1.0 or above (P=0.683).The residual astigmatism for the patients received sphere-cylinder-combined LASIK mode was (1.15?1.00)D,while for the patients received cross-cylinder LASIK mode was (1.13?0.62)D(P=0.045).The remotion depth of cornea for sphere-cylinder-combined LASIK mode and cross-cylinder LASIK mode was (36.73?13.12)?m and (15.60?6.85)?m,respectively (P= 0.031).Condusion The UCVA,residual astigmatism and corneal thickness after surgery in two-zone-cross-cylinder LASIK mode were better than that in sphere-cylinder-combined LASIK mode for the correction of moderate and high astigmatism.