Icariin alleviates renal inflammation and tubulointerstitial fibrosis via Nrf2-mediated attenuation of mitochondrial damage.

Tubulointerstitial fibrosis is an inevitable consequence of all progressive chronic kidney disease (CKD) and contributes to a substantial health burden worldwide. Icariin, an active flavonoid glycoside obtained from Epimedium species, exerts potential antifibrotic effect. The study aimed to explore the protective effects of icariin against tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO)-induced CKD mice and TGF-ß1-treated HK-2 cells, and furthermore, to elucidate the underlying mechanisms. The results demonstrated that icariin significantly improved renal function, alleviated tubular injuries, and reduced fibrotic lesions in UUO mice. Furthermore, icariin suppressed renal inflammation, reduced oxidative stress as evidenced by elevated superoxide dismutase activity and decreased malondialdehyde level. Additionally, TOMM20 immunofluorescence staining and transmission electron microscope revealed that mitochondrial mass and morphology of tubular epithelial cells in UUO mice was restored by icariin. In HK-2 cells treated with TGF-ß1, icariin markedly decreased profibrotic proteins expression, inhibited inflammatory factors, and protected mitochondria along with preserving mitochondrial morphology, reducing reactive oxygen species (ROS) and mitochondrial ROS (mtROS) overproduction, and preserving membrane potential. Further investigations demonstrated that icariin could activate nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway both in vivo and in vitro, whereas inhibition of Nrf2 by ML385 counteracted the protective effects of icariin on TGF-ß1-induced HK-2 cells. In conclusion, icariin protects against renal inflammation and tubulointerstitial fibrosis at least partly through Nrf2-mediated attenuation of mitochondrial dysfunction, which suggests that icariin could be developed as a promising therapeutic candidate for the treatment of CKD.

Room-Temperature Phosphorescence Materials Featuring Triplet Hybrid Local Charge Transfer Emission.

Room-temperature phosphorescence materials have found important applications in dissolved oxygen sensing, temperature monitoring, anticounterfeiting, etc., because of their prolonged phosphorescence lifetime. However, the known systems mainly utilize the triplet local excited state emission, which is generally less sensitive to microenvironment perturbation. In this work, we designed a series of 4-phenyl-1,8-naphthalimide (NMI) derivatives containing different numbers of carbazole (Cz) units (denoted as NMI-Cz, NMI-2Cz, and NMI-3Cz). Steady state and time-resolved spectroscopy studies determined that the compounds undergo intramolecular through-space charge transfer in solution, yielding a triplet hybrid local charge transfer state. Room-temperature phosphorescence emission was observed in compound-doped poly(methyl methacrylate) thin films upon ammonia treatment. Interestingly, emission from different films exhibited different persistence times. We believe a film-based, time-resolved luminescent ammonia sensor could be developed by making a device of the emissive films as fabricated.

Effects of Peripherally inserted Central Catheter (PICC) materials and designs on reduction of PICC-related complications: A systematic review and meta-analysis.

Studies showed that integrating coating or valve into Peripherally Inserted Central (PICC) can prevent related complications. However, data regarding efficiency were controversial. Therefore, a systematic review was needed to analyse the effect of PICC materials and designs on reduction of PICC-related complications. We searched PubMed, Cochrane library, EMbase, grey literature and referent literature from inception to 5 August 2022. Randomized controlled trials (RCTs) and case-control study were included. Two authors extracted data independently, using a predesigned Excel form, and assessed the quality of included RCTs according to the Cochrane Handbook for Systematic Reviews (V5.1.0), case-control study was assessed by the Newcastle-Ottawa Scale. Data were analysed using Review Manager (v5.3.0). A total of 10 RCTs and one case-control study were included. Meta-analysis results showed that PICC designs reduce the incidence of obstruction, and at the critical value of PICC-associated bloodstream infection, but may have no effects on other complications. Based on the literature reviewed, we can only say PICC new materials did not reflect significant reduction on complications, what's more, the result needs more multicentre, large RCTs to support. We suggested clinicians combine descriptive research and cost-effect analysis to select appropriate PICC materials and designs for patients.

Microbial modifications with Lycium barbarum L. oligosaccharides decrease hepatic fibrosis and mitochondrial abnormalities in mice.

BACKGROUND: Lycium barbarum L. is a typical Chinese herbal and edible plant and are now consumed globally. Low molecular weight L. barbarum L. oligosaccharides (LBO) exhibit better antioxidant activity and gastrointestinal digestibility in vitro than high molecular weight polysaccharides. However, the LBO on the treatment of liver disease is not studied. PURPOSE: Modification of the gut microbial ecosystem by LBO is a promising treatment for liver fibrosis. STUDY DESIGN AND METHODS: Herein, LBO were prepared and characterized. CCl4-treated mice were orally gavaged with LBO and the effects on hepatic fibrosis and mitochondrial abnormalities were evaluated according to relevant indicators (gut microbiota, faecal metabolites, and physiological and biochemical indices). RESULTS: The results revealed that LBO, a potential prebiotic source, is a pyranose cyclic oligosaccharide possessing α-glycosidic and ß-glycosidic bonds. Moreover, LBO supplementation restored the configuration of the bacterial community, enhanced the proliferation of beneficial species in the gastrointestinal tract (e.g., Bacillus, Tyzzerella, Fournierella and Coriobacteriaceae UCG-002), improved microbial metabolic alterations (i.e., carbohydrate metabolism, vitamin metabolism and entero-hepatic circulation), and increased antioxidants, including doxepin, in mice. Finally, LBO administration reduced serum inflammatory cytokine and hepatic hydroxyproline levels, improved intestinal and hepatic mitochondrial functions, and ameliorated mouse liver fibrosis. CONCLUSION: These findings indicate that LBO can be utilized as a prebiotic and has a remarkable ability to mitigate liver fibrosis.

Vascular calcification in CKD: New insights into its mechanisms.

Vascular calcification (VC) is a common complication of chronic kidney disease (CKD) and contributes to an increased risk of cardiovascular morbidity and mortality. However, effective therapies are still unavailable at present. It has been well established that VC associated with CKD is not a passive process of calcium phosphate deposition, but an actively regulated and cell-mediated process that shares many similarities with bone formation. Additionally, numerous studies have suggested that CKD patients have specific risk factors and contributors to the development of VC, such as hyperphosphatemia, uremic toxins, oxidative stress and inflammation. Although research efforts in the past decade have greatly improved our knowledge of the multiple factors and mechanisms involved in CKD-related VC, many questions remain unanswered. Moreover, studies from the past decade have demonstrated that epigenetic modifications abnormalities, such as DNA methylation, histone modifications and noncoding RNAs, play an important role in the regulation of VC. This review seeks to provide an overview of the pathophysiological and molecular mechanisms of VC associated with CKD, mainly focusing on the involvement of epigenetic modifications in the initiation and progression of uremic VC, with the aim to develop promising therapies for CKD-related cardiovascular events in the future.

Fluorescent Waveguide Lattices for Enhanced Light Harvesting and Solar Cell Performance.

We present the properties and performance of fluorescent waveguide lattices as coatings for solar cells, designed to address the significant mismatch between the solar cell's spectral response range and the solar spectrum. Using arrays of microscale visible light optical beams transmitted through photoreactive polymer resins comprising acrylate and silicone monomers and fluorescein o,o'-dimethacrylate comonomer, we photopolymerize well-structured films with single and multiple waveguide lattices. The materials exhibited bright green-yellow fluorescence emission through down-conversion of blue-UV excitation and light redirection from the dye emission and waveguide lattice structure. This enables the films to collect a broader spectrum of light, spanning UV-vis-NIR over an exceptionally wide angular range of ±70°. When employed as encapsulant coatings on commercial silicon solar cells, the polymer waveguide lattices exhibited significant enhancements in solar cell current density. Below 400 nm, the primary mode of enhancement is through down-conversion and light redirection from the dye emission and collection by the waveguides. Above 400 nm, the primary modes of enhancement were a combination of down-conversion, wide-angle light collection, and light redirection from the dye emission and collection by the waveguides. Waveguide lattices with higher dye concentrations produced more well-defined structures better suited for current generation in encapsulated solar cells. Under standard AM 1.5 G irradiation, we observed nominal average current density increases of 0.7 and 1.87 mA/cm2 for single waveguide lattices and two intersecting lattices, respectively, across the full ±70° range and reveal optimal dye concentrations and suitable lattice structures for solar cell performance. Our findings demonstrate the significant potential of incorporating down-converting fluorescent dyes in polymer waveguide lattices for improving the current spectral and angular response of solar cell technologies toward increasing clean energy in the energy grid.

Development and Validation of a Questionnaire to Measure ICU Nurses' Knowledge, Attitudes, and Practices Related to Central Line Bloodstream Infection Practices.

BACKGROUND: Currently, there is no instrument available to assess intensive care unit (ICU) nurses' knowledge, attitudes, and practices (KAP) of central line-associated bloodstream infection (CLABSI) prevention practices. PURPOSE: To develop and validate a CLABSI questionnaire to measure ICU nurses' KAP (CLABSI-KAP-Q). METHODS: Data were collected from 255 nurses at 4 hospitals in Gansu Province, China. Questions on the CLABSI-KAP-Q were generated through a review of the literature, interviews with nurses, and multiple rounds of content validity evaluation by experts. The validity and reliability of the CLABSI-KAP-Q were assessed with exploratory factor analysis, confirmatory factor analysis, internal consistency, and correlation coefficients. RESULTS: The final version of the CLABSI-KAP-Q consisted of 32 items. The reliability was represented by a Cronbach α of 0.946, while the test-retest reliability was 0.945. The overall content validity was 0.95. CONCLUSIONS: The CLABSI-KAP-Q is shown to be valid and reliable and recommended for use in clinical practice.

Fast and Selective Detection of Trace Chemical Warfare Agents Enabled by an ESIPT-Based Fluorescent Film Sensor.

Reliable detection of airborne chemical warfare agents (CWAs) at the site and in real-time remains a challenge due to the rarity of miniaturized analytical tools. Herein, an o-carborane-functionalized benzothiazole derivative (PCBO) with excited-state intramolecular proton transfer (ESIPT) and AIE characteristics was synthesized. The PCBO-based film sensor showed a highly sensitive response to representative simulants of CWAs, and detection limits were found to be 1.0 mg·m-3 for triphosgene, 6.0 mg·m-3 for chloroethyl ethyl sulfide, and 0.2 mg·m-3 for diethyl chlorophosphite. Moreover, the sensor showed great reusability (>100 cycles) and unprecedented response speed (<0.5 s). The excellent sensing performance was ascribed to the microenvironmental sensitivity of the sensing fluorophore, the porous adlayer structure of the film, and the specific binding of the fluorophore to the analytes. Furthermore, discrimination and identification of the examined CWA simulants were realized via the introduction of another fluorophore (HCBO)-based film. Importantly, a portable fluorescent CWA detector was built with the sensor as the key component, and its applicability was demonstrated by the successful detection of a typical CWA sample (Sarin). The present study indicates that fluorescent film sensors could satisfy reliable onsite and real-time detection of harmful chemicals.

Multidirectional Polymer Waveguide Lattices for Enhanced Ultrawide-Angle Light Capture in Silicon Solar Cells.

We report the synthesis and characterization of a polymer thin-film structure consisting of two intersecting broadband optical waveguide lattices, and its performance in wide-angle optical energy collection and conversion in silicon solar cells. The structures are synthetically organized via the concurrent irradiation of photoreactive polymer blends by two arrays of intersecting, microscale optical beams transmitted through the medium. Through optical beam-induced photopolymerization and photopolymerization-induced phase separation, well-organized lattices are produced comprising of cylindrical core-cladding waveguide architectures that intersect one another. The optical waveguide properties of the lattices transform the transmission characteristics of the polymer film so that incident optical energy is collected and transmitted along the waveguide axes, rather than their natural directions dictated by refraction, thereby creating efficient light-collecting capability. The embedded structures collectively impart their wide-angle acceptance ranges to enable the film to efficiently collect and interact with light over a large angular range (±70°). When employed as the encapsulant material for a commercial silicon solar cell, the novel light collection and transmission properties result in greater wide-angle conversion efficiency and electrical current density, compared to a single vertically aligned waveguide array. The sustained and greater conversion of light afforded by the encapsulating optical material promises to increase solar cell performance by enabling ultrawide-angle solar energy conversion.

Simulations of Structure and Morphology in Photoreactive Polymer Blends under Multibeam Irradiation.

We present a theoretical study of the organization of photoreactive polymer blends under irradiation by multiple arrays of intersecting optical beams. In a simulated medium possessing an integrated intensity-dependent refractive index, optical beams undergo self-focusing and reduced divergence. A corresponding intensity-dependent increase in molecular weight induces polymer blend instability and consequent phase separation, whereby the medium can evolve into an intersecting waveguide lattice structure, comprising high refractive index cylindrical cores and a surrounding low refractive index medium (cladding). We conduct simulations for two propagation angles and a range of thermodynamic, kinetic, and polymer blend parameters to establish correlations to structure and morphology. We show that spatially correlated structures, namely, those that have a similar intersecting three-dimensional (3D) pattern as the arrays of intersecting optical beams, are achieved via a balance between the competitive processes of photopolymerization rate and phase separation dynamics. A greater intersection angle of the optical beams leads to higher correlations between structures and the optical beam pattern and a wider parameter space that achieves correlated structures. This work demonstrates the potential to employ complex propagating light patterns to create 3D organized structures in multicomponent photoreactive soft systems.

Knockdown long non-coding RNA HCP5 enhances the radiosensitivity of esophageal carcinoma by modulating AKT signaling activation.

Recently, long noncoding RNAs (lncRNAs) have been revealed to participate in cancer therapy. Especial in tumor radiotherapy, lncRNAs usually could enhance or restrict the radiosensitivity in different ways. LncRNA HCP5 is highly expressed in esophageal cancer and influenced the malignant behaviors of esophageal cancer cells. However, this study dedicates to clarify if lncRNA HCP5 affects the radiosensitivity of esophageal carcinoma. The expression levels of HCP5 in esophageal cancer and adjacent noncancerous tissue were first analyzed on the TCGA database and then detected by qRT-PCR. The related functional experiments were used to investigate whether the radiosensitivity of esophageal squamous cell carcinoma was affected by the inhibition of HCP5. The expression results showed HCP5 is upregulated in esophageal cancers compared to the normal tissues. Meanwhile, knockdown HCP5 further suppressed the proliferation and promoted the apoptosis of esophageal cancer cells treated with a 2 Gy dose of radiotherapy. Moreover, we uncovered that knockdown HCP5 eliminated radiotherapy resistance by modulating the miR-216a-3p/PDK1 axis to inhibit the AKT activation. Finally, rescue experiments pointed that lowering the miR-216a-3p expression weakened the inhibition effect of knockdown HCP5 on cells treated with radiotherapy. To summary, our results indicate that HCP5 is involved in esophageal carcinoma radiotherapy and knockdown HCP5 enhances the radiosensitivity of esophageal carcinoma by modulating AKT signaling activation.

[Meta-analysis of effects of neuromuscular electrical stimulation of lower limbs on patients with mechanical ventilation in intensive care unit].

OBJECTIVE: To evaluate the effect of lower limb neuromuscular electrical stimulation (NMES) on mechanical ventilation patients in intensive care unit (ICU). METHODS: Databases including the Cochrane Library, PubMed, Web of Science, Embase, SinoMed, CNKI, VIP and Wanfang database were searched from inception to May 2021. Randomized controlled trails (RCT) about the influence of NMES of lower limbs in patients with mechanical ventilation in ICU were collected. Routine rehabilitation measures were implemented in the control group, while the combination of routine rehabilitation and NMES on the lower limbs was implemented in the observation group. The literature screening, data extracting, and bias risk assessment of included studies were conducted independently by two reviewers. RevMan 5.3 software was used to perform Meta-analysis. Funnel plot was used to test publication bias. RESULTS: A total of 8 RCT were eventually enrolled. The literature quality evaluation results showed that 1 study was grade A and 7 studies were grade B, suggesting that the quality of the included literature was relatively high. The Meta-analysis results showed that NMES in the lower extremities could effectively shorten the duration of mechanical ventilation in ICU patients [standardized mean difference (SMD) = -0.51, 95% confidence interval (95%CI) was -0.72 to -0.31, P < 0.000 01], increase the maximum inspiratory pressure [MIP; mean difference (MD) = 14.19, 95%CI was 9.30 to 19.09, P < 0.000 01], and improve the functional status of critically ill patients [functional status score for ICU (FSS-ICU); MD = 10.44, 95%CI was 3.12 to 17.77, P = 0.005] with statistically significances. However, there were no significant advantages in increasing the Medical Research Council (MRC) score (MD = 2.13, 95%CI was -1.38 to 5.63, P = 0.23), reducing ICU mortality [relative risk (RR) = 0.80, 95%CI was 0.51 to 1.24, P = 0.31], shortening length of ICU stay (MD = -0.54, 95%CI was -3.67 to 2.59, P = 0.74), and the combined effect was not statistically significant. Funnel plot based on the duration of mechanical ventilation showed that the distribution of included articles was basically symmetrical, and no publication bias was detected. CONCLUSIONS: NMES of the lower limbs can not only shorten the ventilation duration effectively, but also improve the MIP and functional status of mechanically ventilated patients in ICU. However, it has no significant effect on the MRC score, ICU mortality and length of ICU stay of patients with mechanical ventilation. In the future, high-quality, large sample size and multi-center RCT are needed to verify the effects of NMES.

High-Performance NMHC Detection Enabled by a Perylene Bisimide-Cored Metallacycle Complex-Based Fluorescent Film Sensor.

Non-methane hydrocarbons (NMHCs) can serve as precursors of ozone and photochemical smog, and hence their highly efficient detection is of great importance for air quality monitoring. Here, we synthesized a new fluorescent perylene bisimide (PBI)-cored metallacycle complex through coordination-driven self-assembly and used it for the production of a fluorescent film sensor. The unique rectangular structure of the developed fluorophore endows the sensor with enhanced sensing performance and discriminability to n-alkanes (C5-10). Specifically, the experimental detection limits for n-pentane, n-hexane, and n-decane are 39, 7, and 1.4 mg/m3, respectively, and the corresponding linear ranges are from 39 to 2546, 7 to 1745, and 1.4 to 85 mg/m3, respectively. Moreover, the sensing is fully reversible. In tandem with a gas chromatographic separation system, the film sensor showed comparable detection ability for the n-alkanes with a commercial flame ionization detector (FID), while the film sensor needs no hydrogen; it occupies a much smaller size (30 × 30 × 44 mm3) and consumes less energy (0.215 W). Further studies demonstrated that the developed sensor can be used for on-site and real-time quantification of NHMCs, laying the foundation for developing into a portable detector.

DCPNet: A Densely Connected Pyramid Network for Monocular Depth Estimation.

Pyramid architecture is a useful strategy to fuse multi-scale features in deep monocular depth estimation approaches. However, most pyramid networks fuse features only within the adjacent stages in a pyramid structure. To take full advantage of the pyramid structure, inspired by the success of DenseNet, this paper presents DCPNet, a densely connected pyramid network that fuses multi-scale features from multiple stages of the pyramid structure. DCPNet not only performs feature fusion between the adjacent stages, but also non-adjacent stages. To fuse these features, we design a simple and effective dense connection module (DCM). In addition, we offer a new consideration of the common upscale operation in our approach. We believe DCPNet offers a more efficient way to fuse features from multiple scales in a pyramid-like network. We perform extensive experiments using both outdoor and indoor benchmark datasets (i.e., the KITTI and the NYU Depth V2 datasets) and DCPNet achieves the state-of-the-art results.

Incidence and influencing factors of post-intensive care cognitive impairment.

OBJECTIVE: To evaluate the incidence and risks factors of short-term post-intensive care (ICU) cognitive impairment. DESIGN: Prospective, observational study. SETTING: Closed university-affiliated intensive care unit. PATIENTS: We enrolled consecutive patients >18 yrs of age expected to be in intensive care unit for ≥24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The score of Montreal Cognitive Assessment (MoCA) less than 26 was defined as cognitive impairment at hospital discharge and short-term post-ICU cognitive impairment was diagnosed in 185 of 409 assessed patients (45.2%). According to univariate analysis, age, years of education, occupation, past medical history, main ICU diagnosis, Acute Physiology and Chronic Evaluation Scoring System (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, Charlson comorbidity index, ICU length-of-stay (LOS), total hospital LOS, sedation, vasoactive agents, muscle relaxants, mechanical ventilation and duration of mechanical ventilation, constraints, early active mobilisation, hypoxemia, frequency and severity of delirium, blood pressure, rescue experience, and infection were significant predictors of post-ICU cognitive impairment. Multivariate analysis results showed that the frequency and severity of delirium, and advanced age were risk factors of post-ICU cognitive impairment; high years of education and early active mobilisation were protective factors. CONCLUSIONS: Incidence of post-ICU cognitive impairment is at a high level, which is similar to former researches' results; the frequency and severity of delirium, and advanced age were risk factors of post-ICU cognitive impairment; high years of education and early active mobilisation were protective factors of post-ICU cognitive impairment.

Chinesisation, adaptation and validation of the Chelsea Critical Care Physical Assessment Tool in critically ill patients: a cross-sectional observational study.

PURPOSE: To translate and adapt the Chelsea Critical Care Physical Assessment Tool (CPAx) into Chinese version ('CPAx-Chi'), test the reliability and validity of CPAx-Chi, and verify the cut-off point for the diagnosis of intensive care unit-acquired weakness (ICU-AW). STUDY DESIGN: Cross-sectional observational study. METHODS: Forward and back translation, cross-cultural adaptation and pretesting of CPAx into CPAx-Chi were based on the Brislin model. Participants were recruited from the general ICU of five third-grade class-A hospitals in western China. Two hundred critically ill adult patients (median age: 53 years; 64% men) with duration of ICU stay ≥48 hours and Glasgow Coma Scale ≥11 were included in this study. Two researchers simultaneously and independently assessed eligible patients using the Medical Research Council Muscle Score (MRC-Score) and CPAx-Chi. RESULTS: The content validity index of items was 0.889. The content validity index of scale was 0.955. Taking the MRC-Score scale as standard, the criterion validity of CPAx-Chi was r=0.758 (p<0.001) for researcher A, and r=0.65 (p<0.001) for researcher B. Cronbach's α was 0.939. The inter-rater reliability was 0.902 (p<0.001). The area under the receiver operating characteristic curves of CPAx-Chi for diagnosing ICU-AW based on MRC-Score ≤48 were 0.899 (95% CI 0.862 to 1.025) and 0.874 (95% CI 0.824 to 0.925) for researcher B. The best cut-off point for CPAx-Chi for the diagnosis of ICU-AW was 31.5. The sensitivity was 87% and specificity was 77% for researcher A, whereas it was 0.621, 31.5, 75% and 87% for researcher B, respectively. The consistency was high when taking CPAx-Chi ≤31 and MRC-Score ≤48 as the cut-off points for the diagnosis of ICU-AW. Cohen's kappa=0.845 (p=0.02) in researcher A and 0.839 (p=0.04) for researcher B. CONCLUSIONS: CPAx-Chi demonstrated content validity, criterion-related validity and reliability. CPAx-Chi showed the best accuracy in assessment of patients at risk of ICU-AW with good sensitivity and specificity at a recommended cut-off of 31.

High-Performance Trichloroacetic Acid Sensor Based on the Intramolecular Hydrogen Bond Formation and Disruption of a Specially Designed Fluorescent o-Carborane Derivative in the Film State.

Discriminative and sensitive detection of environmentally important and health-related trichloroacetic acid (TCA) suffers from various problems such as bulky instruments and time-consuming operation as well as complex sample processing. Herein, we present a rapid, sensitive, and specific method for the detection of gaseous TCA using a fluorescent single-molecule array. An o-carborane-based benzothiazole derivative (CB-BT-OCH3) with specific fluorescence properties was specifically designed and utilized to fabricate a film-based single-molecule array. It was revealed that the fluorescent film is photochemically stable and extremely sensitive to TCA vapor, depicting an observable fluorescence color change from green to blue. The experimental detection limit is 0.2 ppm, which is lower than the safety limit (1 ppm) required by the threshold limit values and biological exposure indices. In addition, the film could show detectable intensity change within 0.2 s. On the basis of multiple signal responses, a conceptual two-channel-based fluorescent TCA sensor was developed. Importantly, the proposed conceptual sensor paves a new route to the development of specific fluorescent film-based sensor arrays with a single fluorophore as sensing units.

Chitinase-3-like protein 1 is an independent risk factor for the early failure of forearm autologous arteriovenous fistulas in uremic patients.

Chitinase-3-like protein 1 (CHI3L1) has been introduced as a marker of inflammation in different diseases, which can promote cell proliferation and differentiation. It has also been demonstrated that elevated serum CHI3L1 concentration can independently predict all-cause mortality in uremic patients. However, the impact of CHI3L1 on the early failure of autologous arteriovenous fistulas (AVFs) in uremic patients remains unknown. We conducted a prospective observational cohort study of 109 uremic patients (mean age 53.2 ± 14.7 years, 67.9% males), who received forearm AVF surgery, and were consecutively enrolled with a median follow-up time of 15 months. The early failure was defined as a fistula that never developed adequately for dialysis or that failed within the first 3 months of use. Serum CHI3L1 concentration was determined by the ELISA method. Among 109 uremic patients, 24 patients had AVF failure. The optimal cutoff value based on the receiver operating characteristics analysis of CHI3L1 was 122.6 ng/mL, with the area under the curve of 0.73 (P = 0.001). The Kaplan-Meier survival analysis demonstrated that patients with CHI3L1 < 122.6 ng/mL had better AVF patency than patients with CHI3L1 ≥ 122.6 ng/mL (Log-rank test, P = 0.001). Multivariable Cox proportional hazards regression analysis showed that baseline CHI3L1 level (≥ 122.6 ng/mL vs. < 122.6 ng/mL) was significantly associated with AVF failure after adjustment for confounders (adjusted hazard ratio [HR], 3.67; 95% CI, 1.44-9.36). The study demonstrated that Increased baseline serum level of CHI3L1 is independently associated with higher risk of the early failure of forearm AVFs.

ASK1/p38­mediated NLRP3 inflammasome signaling pathway contributes to aberrant retinal angiogenesis in diabetic retinopathy.

Diabetic retinopathy (DR) is the leading cause of blindness among the working­age population in several countries. Despite the available treatments, some patients are diagnosed at the late stages of the disease when treatment is more difficult. Hence, it is crucial that novel targets are identified in order to improve the clinical therapy of DR. In the present study, an animal model of DR and a cell model using primary human retinal microvascular endothelial cells exposed to high glucose were constructed to examine the association between apoptosis signal­regulating kinase 1 (ASK1)/p38 and NLR family pyrin domain containing 3 (NLRP3) in DR. The results revealed that DR induced inflammatory response and microvascular cell proliferation. NLRP3 contributed to DR­mediated inflammatory development and progression, which promoted the expression of inflammatory­related cytokines. In addition, NLRP3 promoted the tube formation of retinal microvascular endothelial cells and angiogenesis. Moreover, further research indicated that the NLRP3­mediated aberrant retinal angiogenesis in DR was regulated by ASK1 and p38. It was thus suggested that ASK1/p38 may be novel target for the treatment of DR.