Background Urethroplasty of complex urethral stricture is a difficult procedure, and there is no widely accepted standard approach described in the published literature. We evaluated the efficacy and ...safety of urethroplasty using lingual mucosa grafts （LMGs） for the repair of urethral strictures. Methods Between August 2006 and April 2009, 92 cases of urethral strictures （length ranging from 2.5 cm to 18 cm, mean 6.5 cm） were treated using LMGs. Of the 92 patients, 38 with long-segment urethral strictures （9-18 cm） underwent dual LMG or LMG combined with foreskin flap or buccal mucosal graft urethroplasty. Results Follow-up was obtained for 3-33 months （mean 17.2 months） postoperatively. Complications occurred in 8 patients, including urinary fistulas in 4 patients; recurrent strictures developed in 4 patients at 3-4 months post-operatively. The remaining patients voided well postoperatively, with peak flows between 14.3 ml/s and 54.6 ml/s （mean 28.4 ml/s）. Conclusions The tongue is an excellent source of graft material for the repair of anterior mucosal strictures. Dual LMG substitution urethroplasty can successfully treat longer, more complex urethral strictures.
Logic flaws within web applications will allow malicious operations to be triggered towards back-end database. Existing approaches to identifying logic flaws of database accesses are strongly tied to ...structured query language （SQL） statement construction and cannot be applied to the new generation of web applications that use not only structured query language （NoSQL） databases as the storage tier. In this paper, we present Lom, a black-box approach for discovering many categories of logic flaws within MongoDB- based web applications. Our approach introduces a MongoDB operation model to support new features of MongoDB and models the application logic as a mealy finite state machine. During the testing phase, test inputs which emulate state violation attacks are constructed for identifying logic flaws at each application state. We apply Lom to several MongoDB-based web applications and demonstrate its effectiveness.
Ultra-fine fibrous mats with magnolol entrapped have been prepared by electrospinning biodegradable copolymer poly（ethylene glycol） blocked poly（L-lactide）.Drug entrapment was perfect which was ...confirmed by scanning electron microscopy and differential scanning calorimetry.According to in vitro drug release investigation by high performance liquid chromatography,it was found that fibers with 10%,20%and 30%drug entrapped respect to polymer（mass ratio） presented dramatically different drug release behavior and degradation behavior under the effect of proteinase K.The reason may be that fibers with 10%drug entrapped was more easily affected by enzyme while,to some degree,magnolol in fibers with 20% and 30%entrapped prevented polymer from being degraded by enzyme.
This paper presents a method for analysis of stress and strain of gas pipelines under the effect of horizontal catastrophic landslides. A soil spring model was used to analyze the nonlinear ...characteristics concerning the mutual effects between the pipeline and the soil. The Ramberg–Osgood model was used to describe the constitutive relations of pipeline materials. This paper also constructed a finite element analysis model using ABAQUS finite element software and studied the distribution of the maximum stress and strain of the pipeline and the axial stress and strain along the pipeline by referencing some typical accident cases. The calculation results indicated that the maximum stress and strain increased gradually with the displacement of landslide.The limit values of pipeline axial stress strain appeared at the junction of the landslide area and non-landslide area. The stress failure criterion was relatively more conservative than the strain failure criterion. The research results of this paper may be used as a technical reference concerning the design and safety management of large-diameter gas pipelines under the effects of catastrophic landslides.
2,3,5,4＇-Tetrahydroxystilbene-2-O-β-D-glucoside （TSG） is a water-soluble active component extracted from Polygonum multiflorum Thunb. A number of studies demonstrate that TSG exerts cardioprotective ...effects. Since endoplasmic reticulum （ER） stress plays a key role in myocardial ischemia/reperfusion （MI/R）-induced cell apoptosis, we sought to determine whether modulation of the ER stress during MI/R injury was involved in the cardioprotective action of TSG. Male mice were treated with TSG （60 mg.kg^-1.d^-1, ig） for 2 weeks and then were subjected to MI/R surgery. Pre-administration of TSG significantly improved post-operative cardiac function, and suppressed MI/R-induced myocardial apoptosJs, evidenced by the reduction in the myocardial apoptotic index, serum levels of LDH and CK after 6 h of reperfusion. TSG （0.1-1000 pmoi/L） did not affect the viability of cultured H9c2 cardiomyoblasts in vitro, but pretreatment with TSG dose-dependently decreased simulated ischemia/reperfusion （SlR）-induced cell apoptosis. Furthermore, both in vivo and in vitro studies revealed that TSG treatment activated the Notchl/Hesl signaling pathway and suppressed ER stress, as evidenced by increasing Notch1, Notch1 intracellular domain （NICD）, Hesl, and Bcl-2 expression levels and by decreasing p-PERK/ PERK ratio, p-elF2~/elF2（x ratio, and ATF4, CHOP, Bax, and caspase-3 expression levels. Moreover, the protective effects conferred by TSG on SIR-treated H9c2 cardiomyoblasts were abolished by co-administration of DAPT （the Notch1 signaling inhibitor）. In summary, TSG ameliorates MI/R injury in vivo and in vitro by activating the Notchl/Hesl signaling pathway and attenuating ER stress-induced apoptosis.
Background and Purpose
Disruption of intestinal barriers plays a vital role in the pathogenesis of colitis. The aryl hydrocarbon receptor (AhR) is a recognition sensor that mediates intestinal immune ...homeostasis and minimizes intestinal inflammation. Astragalus polysaccharide (APS) exerts pharmacological actions in colitis; however, the mechanism has not been elucidated. We investigated whether APS protects through AhR‐dependent autophagy.
Experimental Approach
The symptoms of dextran sulfate sodium (DSS)‐induced colitis in mice involving intestinal barrier function and inflammatory injury were evaluated after APS administration. Intestinal‐specific Becn1 conditional knockout (Becn1 cKO) mice were constructed and compared with wild‐type mice. Autophagy and the effects of APS were investigated after the deactivation of AhRs. The relationship between APS‐induced AhRs and autophagic Becn1 was investigated using a dual‐luciferase reporter system and chromatin immunoprecipitation (ChIP)‐quantitative polymerase chain reaction assay. Caco‐2 cells were used to investigate inflammatory responses and AhR‐dependent autophagy.
Key Results
APS improved intestinal barrier function in inflammatory injury in colitis mice. APS triggered autophagic flow; however, knockout of Becn1 in the gut increased susceptibility to colitis, leading to diminished epithelial barrier function and severe intestinal inflammation, impairing the protective effects of APS. Mechanistically, APS‐triggered autophagy depends on AhR expression. Activated AhR binds to the promoter Becn1 to operate transcription of genes involved in anti‐inflammation and intestinal barrier repair, while deactivation of AhR correlated with intestinal inflammation and the therapeutic function of APS.
Conclusions and Implications
APS protects colitis mice by targeting autophagy, especially as the AhR stimulates the repair of damaged intestinal barrier functions.
Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate‐induced ...colitis in mice. Based on flow cytometry, colitis‐associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell‐null Rag1−/− mice or upon anti‐IL‐17‐A antibody‐treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA‐driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti‐colitis effect in RAR‐α ‐mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA‐SAA1/2‐Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.
By improving retinoic acid synthesis, a novel probiotic L. intestinalis exerts a protective effect against colitis. Retinoic acid triggers epithelial gene alteration, including SAA1, SAA2, and C/EBPA, to downregulate RORγt+ Th17 cells. L. intestinalis and its associated metabolite, retinoic acid, have potential therapeutic effects for suppressing colonic inflammation.
Abstract
Background
Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether ...these findings translate to epidermal growth factor receptor (EGFR)–mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual.
Methods
Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided.
Results
A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial.
Conclusions
As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.
Polyimide (PI) aerogels have attracted great attention owing to their low density and excellent thermal stability. However, hydrophobic surface modification is required for PI aerogels to improve ...their ability in oil/water separation due to their amphiphilic characteristic. Two-dimensional MXenes (transition metal carbides/nitrides) can be utilized as nanofillers to enhance the properties of polymers because of their unique layered structure and versatile interface chemistry. Herein, the robust, lightweight, and hydrophobic PI/MXene three-dimensional architectures were fabricated via freeze-drying of polyamide acid/MXene suspensions and thermal imidization. Polyamide acid was synthesized using N-N-dimethylacetamide and 4,4′-oxydianiline. MXene (Ti3C2T x ) dispersion was obtained via the etching of Ti3AlC2 and ultrasonic exfoliation. Taking advantage of the strong interaction between PI chains and MXene nanosheets, the interconnected, highly porous, and hydrophobic PI/MXene aerogels with low density were fabricated, resulting in the improved compressive performance, remarkable oil absorption capacity, and efficient separation of oil and water. For the PI/MXene-3 aerogel (weight ratio, 5.2:1) without any surface modification, the water contact angle was 119° with a density of 23 mg/cm3. This aerogel can completely recover to its original height after 50 compression–release cycles, exhibiting superelasticity and exceptional fatigue-resistant ability. It also showed high absorption capacities to various organic liquids ranging from approximately 18 to 58 times of their own weight. This hybrid aerogel can rapidly separate the chloroform, soybean oil, and liquid paraffin from the water–oil system. The thermally stable hybrid aerogel also exhibited excellent fire safety properties and outstanding reusability under an extreme environment.
Due to economic development and population growth, the water shortage in China has gradually become increasingly severe. In this paper, by developing an environmentally expanded input-output (IO) ...model, water footprint in China during 2002–2012 is calculated from the perspective of final demand. Furthermore, a structural decomposition analysis (SDA) model is used to study the driving factors of the water footprint of rural and urban household consumption, gross fixed capital formation and exports. The findings indicate that: 1) the water footprint driven by final demand in China increased by 18.3% during 2002–2012, reaching 617.68 billion m3 in 2012, of which urban household consumption accounts for the highest proportion. 2) Of the different sectors, agricultural commodities have the highest water footprint, accounting for 35% of national water footprint in 2012. 3) In terms of the driving factors, water efficiency inhibits the increase of water footprint regardless of final demand types, while GDP per capita makes a great contribution to its rise. 4) As for rural household consumption, the most important driving factor is the inhibition effects of consumption pattern in water footprint. For urban household consumption, the water footprint is inhibited by consumption pattern but promoted by production structure during 2002–2010. However, it is no longer the case during 2010–2012 that consumption pattern becomes a promoting factor, with production structure being inhibiting one. 5) Regarding gross fixed capital formation, its water footprint increase driven by consumption pattern is only 12.4 billion m3 during 2007–2010. As for exports, consumption pattern causes the decline of water footprint after 2005 and the overall water footprint of exports declines during 2007–2012. Finally, this paper provides policy implications with respect to the promotion of China's water footprint conservation.
Display omitted
•The water footprint of various final demands in China is calculated.•The driving factors of China's water footprint change are explored.•The 39% of the water footprint increment is caused by urban household consumption.•The change of production pattern decreases water footprint of urban consumption.•Water-saving awareness on consumption should be promoted.
PDF
