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The test time of impulse tunnels is short, and the heat flux transducers can be easily interfered in the test time. Thus the aerothermal test data analysis of impulse tunnels is complex and usually carried out manually, which leads to low efficiency and nonuniform standards. In this paper, the signals of heat transducers used in the 1 m gun/shock dual-mode impulse tunnel at the China Academy of Aerospace Aerodynamics were investigated. A series of key parameters, e.g., the FFT voltage profile, the correlation profile of nozzle total pressure and transducer heat flux, as well as the time derivative of the heat flux profile, were determined. The characterization capabilities of these parameters with respect to significant features, e.g., the start/end time of the nozzle flow, the time boundary of different operation modes and the effectiveness of the transducer profiles, were certified. Moreover, a profile effectiveness estimation model, a test time interval selection algorithm and a transducer valid time selection algorithm were developed based on convolutional neural networks and density-based clustering algorithms. Thereby the aerothermal test data of impulse tunnels can be analyzed automatically with these data-driven methods. The results show that the accuracy of the profile effectiveness estimation model is as high as 98%. According to the comparison between algorithm and manual results in dealing with 3 568 profiles, about 91% of the results show a difference of less than 10%, which implies that the data-driven method has the value of application to wind tunnel tests.

Abstract Background Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and the key inflammatory mediators of synovium induced by different types of meniscal tears remain unclear. Methods Magnetic resonance imaging (MRI) was employed to identify the type of meniscus tear, and the quantification of synovial inflammation was assessed through H&E staining assay. Transcription and expression levels of IL-1β and IL-6 were evaluated using bioinformatics, ELISA, RT-qPCR, and IHC of CD68 staining assays. The therapeutic potential of Docosapentaenoic Acid (DPA) was determined through network pharmacology, ELISA, and RT-qPCR assays. The safety of DPA was assessed using colony formation and EdU staining assays. Results The results indicate that both IL-1β and IL-6 play pivotal roles in synovitis pathogenesis, with distinct expression levels across various subtypes. Among tested meniscus tears, oblique tear and bucket handle tear induced the most severe inflammation, followed by radial tear and longitudinal tear, while horizontal tear resulted in the least inflammation. Furthermore, in synovial inflammation induced by specific meniscus tears, the anterior medial tissues exhibited significantly higher local inflammation than the anterior lateral and suprapatellar regions, highlighting the clinical relevance and practical guidance of anterior medial tissues’ inflammatory levels. Additionally, we identified the essential omega-3 fatty acid DPA as a potential therapeutic agent for synovitis, demonstrating efficacy in blocking the transcription and expression of IL-1β and IL-6 with minimal side effects. Conclusion These findings provide valuable insights into the nuanced nature of synovial inflammation induced by various meniscal tear classifications and contribute to the development of new adjunctive therapeutic agents in the management of synovitis.

Purpose of Review: IgA vasculitis (IgAV), formerly Henoch–Schonlein purpura, is the most common systemic vasculitis in childhood. In adults, however, this condition is poorly understood, yet associated with more severe disease and poorer outcomes. This necessitates the need for early diagnosis and management. Scope of Review: We describe the pathophysiology, clinical manifestations, and diagnosis of IgAV in adults. Poor outcomes are often due to the high frequency of glomerulonephritis in IgAV-IgA vasculitis-associated nephritis (IgAVN). We hence also aim to summarize the latest clinical data regarding treatment strategies in IgAVN. The diagnosis and differentiation in histology between IgAVN and IgA nephropathy (IgAN) remain a challenge. Review of treatment therapies: Pathological mechanisms between IgAVN and IgAN appear to be consistent between the two, and data from IgAN are often extrapolated to IgAVN. The role of various immunosuppression therapies remains controversial, and in this review, we will discuss immunosuppression use and highlight evidence surrounding emerging and promising novel therapies in IgAVN/IgAN. Our aim for this review is to guide future treatment strategies and direct future studies.

The hair follicle is the basis of hair regeneration, and the dermal papilla is one of the most important structures in hair regeneration. New intervention and reversal strategies for hair loss may arise due to the prevention of oxidative stress. GC/MS analysis was used to determine the compounds contained in NSO. Then, NSO was applied to DPC for cell proliferation and oxidative stress experiments. RNA-seq was performed in cells treated with NSO and minoxidil. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify the gene expression. The effects of NSO on hair length, weight, the number and depth of hair follicles, and the dermal thickness were also studied. GC/MS analysis showed that the main components of NSO were eicosapentaenoic acid, palmitic acid, and linoleic acid. NSO promotes DPC proliferation and reduces H2O2-mediated oxidative damage. NSO can also activate hair growth-related pathways and upregulate antioxidant-related genes analyzed by gene profiling. The topical application of NSO significantly promotes hair growth and increases hair length and weight in mice. NSO extract promotes hair growth and effectively inhibits oxidative stress, which is beneficial for the prevention and treatment of hair loss.

Summary: Rhizosphere dwelling microorganism such as Bacillus spp. are helpful for crop growth. However, these functions are adversely affected by long-term synthetic fertilizer application. We developed a modified CRISPR/Cas9 system using non-specific single-guide RNAs to disrupt the genome-wide cis-acting catabolite-responsive elements (cres) in a wild-type Bacillus pumilus strain, which conferred dual plant-benefit properties. Most of the mutations occurred around imperfectly matched cis-acting elements (cre-like sites) in genes that are mainly involved in carbon and secondary metabolism pathways. The comparative metabolomics and transcriptome results revealed that carbon is likely transferred to some pigments, such as riboflavin, carotenoid, and lycopene, or non-ribosomal peptides, such as siderophore, surfactin, myxochelin, and bacilysin, through the pentose phosphate and amino acid metabolism pathways. Collectively, these findings suggested that the mutation of global cre-like sequences in the genome might alter carbon flow, thereby allowing beneficial biological interactions between the rhizobacteria and plants.

Piriformospora indica, a plant root-colonizing basidiomycete fungus, exhibits strong growth-promoting activity in symbiosis with a broad range of plants. Here, we report the potential of P. indica to improve growth, yield, and disease resistance in wheat in the field. In the present study, P. indica successfully colonized wheat through chlamydospores and formed dense mycelial networks that covered roots. Plants subjected to the seed soaking (SS) treatment with P. indica chlamydospore suspensions enhanced tillering 2.28-fold compared to the non-inoculated wheat in the tillering stage. In addition, P. indica colonization promoted vegetative growth significantly during the three-leaf, tillering, and jointing stages. Moreover, the P. indica-SS-treatment enhanced wheat yield by 16.37 ± 1.63%, by increasing grains per ear and panicle weight and decreased damage to wheat shoot and root architecture markedly, with high field control effects against Fusarium pseudograminearum (81.59 ± 1.32%), Bipolaris sorokiniana (82.19 ± 1.59%), and Rhizoctonia cerealis (75.98 ± 1.36%). Most of the primary metabolites, such as amino acids, nucleotides, and lipids, involved in vegetative reproduction were increased in P. indica-SS-treatment plants, whereas secondary metabolites, such as terpenoids, polyketides, and alkaloids, decreased following P. indica inoculation. The up-regulated processes of protein, carbohydrate, and lipid metabolism indicated that P. indica colonization increased growth, yield, and disease resistance via the acceleration of plant primary metabolism. In conclusion, P. indica improved morphological, physiological, and metabolic substance levels, and further promoted its growth, yield, and disease resistance in wheat.

The DNA origami design algorithm DAEDALUS is modified to design a nanoscale cube with a two-step assembly protocol, assembling 9 modules from three DNA scaffolds and the complementary staples, combined to form the DNA origami cube.

The trends in annual precipitation and wind induced by tropical cyclones (TCs) over Shanghai during the last 40 years are estimated. Results indicate that there is a significant increasing trend in the annual total precipitation induced by TCs, which is related to the significant positive trends in daily precipitation and annual torrential rain days. Meanwhile, a significant decreasing trend shows in maximum sustained wind, which seems to be related to the downward trend in the intensity of TCs when affecting Shanghai. The annual frequencies of affected TCs, TC translation speed and distance from Shanghai when affecting Shanghai have no obvious tendency. The different trends in precipitation and wind suggested that a more comprehensive metric for assessing TCs' influence on society is necessary.

Gas film thickness significantly influences the performance prediction of Gas Foil Thrust Bearings (GFTB). However, the Classical Model (CM) for GFTBs exhibits inaccuracies in describing gas film thickness. In this paper, we explore the differences in the details of gas film thickness modeling and propose a Parallel Segmentation Model (PSM), which fixes the errors of the CM in describing the gas film thickness in the ramp section, and a Full-Ramp Model (FRM), to which a more realistic description of the gas film in the flat section is also added. Comparative analysis, utilizing a publicly available test dataset based on the open-source GFTB structure, establishes that the FRM surpasses the CM and PSM in accurately predicting load capacity. In-depth analysis shows that the location of the minimum gas film thickness for determining the load capacity is located at the innermost circle of the free end of the top foil, whereas the FRM is subjected to the same load with a larger film thickness at this location, which may be due to the unique geometry of the top foil of the FRM. Subsequently, employing the FRM, a parametric study explores load capacity in GFTB, considering variables such as ramp height, top foil thickness, bump foil stiffness, ramp section extent, and top foil area. The results demonstrate that GFTB load capacity exhibits a linear increase with the expansion of the top foil area. Moreover, the load capacity increases with augmented top foil thickness and bump foil stiffness, albeit at a decreasing rate. Additionally, an increase in ramp section extent initially enhances load capacity, reaching a maximum value before declining. Similarly, an increase in ramp height initially augments load capacity, attaining a maximum before subsequent diminution.

The critical speed is a crucial factor that impacts the stability of high-speed compressors. However, limited research has simultaneously considered the influence of gas foil bearings (GFBs), labyrinth seals, and impellers on critical speed. In this study, we develop a rotordynamic model that incorporates the aerodynamic forces of GFBs, labyrinth seals, and impellers to explore the effects of each component on the critical speed. To validate the developed model, experimental tests are conducted on a centrifugal compressor test bed, and the results exhibit a high level of agreement with the model calculations. By comparing the model calculations that include different components, we comprehensively analyze the influence of each component on the critical speed. The findings reveal that, for centrifugal compressors used in fuel cell vehicles, the rotordynamic coefficients resulting from GFBs are significantly larger than those resulting from impellers and labyrinth seals. Thus, it is reasonable to disregard the aerodynamic forces caused by impellers and labyrinth seals when calculating the critical speed. Furthermore, substituting rigid gas bearings for GFBs as a means to simplify the calculations has only a very slight impact on the results. This study aims to optimize the design process of centrifugal compressors for fuel cell vehicles and offers valuable insights for designing compressors of similar sizes.

Abstract Background The association between prothrombin time-international normalized ratio (PT-INR) and long-term prognosis among patients with coronary artery disease (CAD) without atrial fibrillation or anticoagulant therapy was still unclear. We analyzed the association of PT-INR levels and long-term mortality in a large cohort of CAD patients without atrial fibrillation or using of anticoagulant drugs. Methods We obtained data from 44,662 patients who were diagnosed with CAD and had follow-up information from January 2008 to December 2018. The patients were divided into 4 groups (Quartile 1: PT-INR ≤ 0.96; Quartile2: 0.96 1.06). The main endpoint was long-term all-cause death. Kaplan–Meier curve analysis and Cox proportional hazards models were used to investigate the association between quartiles of PT-INR levels and long-term all-cause mortality. Results During a median follow-up of 5.25 years, 5613 (12.57%) patients died. We observed a non-linear shaped association between PT-INR levels and long-term all-cause mortality. Patients in high PT-INR level (Quartile4: PT-INR > 1.06) showed a significantly higher long-term mortality than other groups (Quartile2 or 3 or 4), (Compared with Quartile 1, Quartile 2 [0.96 1.06], aHR = 1.33, 95% CI 1.22–1.45, P

To figure out gas enrichment laws in Permian volcanic rocks, Sichuan Basin, an association among reservoir-forming elements was explored to analyze forming modes and point out exploration prospects in accordance with reservoir characteristics, gas source conditions, and fault elongation in Zhougongshan and Jianyang areas. Results show that there mostly exist porous volcaniclastic rock and lava reservoirs of explosive facies. In Jianyang with Lower Cambrian Qiongzhusi Formation as the principal source rock, early faults offered pathways to assemble ample initial oil and gas. Following an increase of burial depth, oil started cracking vastly to create oil-cracked gas. These elements constitute one reservoir-forming mode of Cambrian hydrocarbon supply–fault transporting–in-situ cracking in Jianyang. While in Zhougongshan with Lower Permian Maokou 1 Member as the main source, active faults during hydrocarbon generation and expulsion acted on trap preservation. Late kerogen-cracked gas gathered at structural highs far from giant faults. Thus, the other mode exhibited in Zhougongshan is Permian hydrocarbon supply–fault adjustment–effective trap accumulation. Reservoir-forming conditions in volcanic rocks present certain disparity among all kinds of tectonic settings inside the basin, giving rise to various volcanic gas reservoirs developed. The Permian volcanic rocks are expected to be a major domain for reserve and production increase in Sichuan Basin.

BackgroundBody mass index (BMI) has been widely recognized as a risk factor for metabolic syndrome (MetS). However, the relationship between the trajectory of BMI and cumulative incident MetS is still unclear. We investigate the associations of long-term measurements of BMI with MetS among young adults in the China Health and Nutrition Survey.MethodsWe enrolled individuals aged 10 to 20 at baseline with recorded BMI at each follow-up interview, and 554 participants were finally included in our study. The assessment and incidence of MetS were evaluated by blood tests and physical examinations in their adulthood. A latent class growth mixed model was used to identify three BMI trajectory patterns: a low baseline BMI with slow development (low-slow, n=438), a low baseline BMI with fast development (low-fast, n=66), and a high baseline BMI with fast development (high-fast, n=50). Logistic regression was used to explore the relationship between different BMI trajectories and the incidence of MetS.ResultDuring a follow-up of 16 years, 61 (11.01%) participants developed MetS. The combination of elevated triglycerides and reduced high-density lipoprotein cholesterol was most frequent in diagnosed MetS. In multivariate adjusted models, the low-fast and high-fast BMI trajectories showed a significantly higher risk of MetS than those with the low-slow BMI trajectory (low-high: OR = 3.40, 95% CI: 1.14-10.13, P < 0.05; high-fast: OR = 5.81, 95% CI: 1.63-20.69, P < 0.05).ConclusionOur study identified three BMI trajectories in young adults and found that long-term measurements of BMI were also associated with cumulative incident MetS.

Enteric viruses are known to be prevalent in municipal wastewater, but information on the health risks arising from wastewater reuse is limited. This study quantified six common enteric viruses in raw wastewater and determined the effectiveness of different secondary and tertiary treatment processes at reducing their abundances in three full-scale wastewater treatment plants in China. In the raw wastewater, polyomavirus BK and norovirus GII (Nov GII) exhibited the highest abundance among the detected DNA and RNA viruses, respectively, with concentrations >5 log10 copies/L. Viruses in the raw wastewater were mainly removed by the secondary treatment processes, with log reduction values ranging from 1 to 2. The tertiary treatment processes of both chlorination and ultraviolet irradiation facilitated the additional reduction of viruses. The quantitative microbial risk assessment was applied to estimate the health risks of adenovirus (Adv) and Nov GII when reusing the treated wastewater for irrigation of public green spaces and crops. Estimated disability-adjusted life years of Adv and Nov GII for both reuses were higher than the risk threshold (10−6) required by the WHO in the actual scenarios. More effective treatment technologies should be implemented to remove viruses for safe reuse of the treated wastewater. HIGHLIGHTS Secondary and tertiary treatment processes can remove viruses from wastewater.; Health risk induced by Adv and Nov GII for the reuse of treated wastewater is higher than the required threshold.; More effective technologies should be applied to remove viruses for safe reuse of the treated wastewater.;

Objective: Previous studies have shown that the relationship between hypertension (HT) and contrast-associated acute kidney injury (CA-AKI) is not clear. We apply a systematic review and meta-analysis to assess the association between HT and CA-AKI. Methods: We searched for articles on the study of risk factors for CA-AKI in the Embase, Medline, and Cochrane Database of Systematic Reviews (by March 25, 2021). Two authors independently performed quality assessment and extracted data such as the studies’ clinical setting, the definition of CA-AKI, and the number of patients. The CA-AKI was defined as a serum creatinine (SCr) increase ≥25% or ≥0.5 mg/dL from baseline within 72 h. We used fixed or random models to pool adjusted OR (aOR) by STATA. Results: A total of 45 studies (2,830,338 patients) were identified, and the average incidence of CA-AKI was 6.48%. There was an increased risk of CA-AKI associated with HT (aOR: 1.378, 95% CI: 1.211–1.567, I2 = 67.9%). In CA-AKI with a SCr increase ≥50% or ≥0.3 mg/dL from baseline within 72 h, an increased risk of CA-AKI was associated with HT (aOR: 1.414, 95% CI: 1.152–1.736, I2 = 0%). In CA-AKI with a Scr increase ≥50% or ≥0.3 mg/dL from baseline within 7 days, HT increases the risk of CA-AKI (aOR: 1.317, 95% CI: 1.049–1.654, I2 = 51.5%). Conclusion: Our meta-analysis confirmed that HT is an independent risk factor for CA-AKI and can be used to identify risk stratification. Physicians should pay more attention toward prevention and treatment of patients with HT in clinical practice.

BackgroundPrevious studies have shown that malnutrition is very common in patients with congestive heart failure (CHF) and is closely related to the occurrence of acute kidney injury. However, the relationship between malnutrition and contrast-associated acute kidney injury (CA-AKI) is unclear.Method and resultsWe obtained data from 842 patients who were diagnosed with CHF following coronary angiography (CAG) or percutaneous coronary angiography (PCI) and had follow-up information from January 2013 to February 2016. The patients were divided into 3 groups according to the Controlling Nutritional Status Score before CAG or PCI procedure (Group 1: Normal; Group 2: Mild Malnutrition; Group 3: Moderate to Severe Malnutrition). The main endpoint was CA-AKI. Univariate and multivariable logistic regression analyses were performed. 556 (60.0%) patients suffered from malnutrition before CAG or PCI. During a median follow-up of 2.1 years, A total of 49 (5.82%) patients developed CA-AKI. Additionally, 5 (1.75%), 26 (6.27%) and 18 (12.77%) events were documented in patients with normal, mild and moderate or severe malnutrition, respectively (p < 0.01). In multivariable-adjusted models, patients with malnutrition showed a significantly higher incidence of CA-AKI than those in the normal group.ConclusionMalnutrition is an independent risk factor for CA-AKI in CHF patients following CAG.

Alopecia has gradually become a problem that puzzles an increasing number of people. Dermal papilla cells (DPCs) play an important role in hair follicle (HF) growth; thus, exploring the effective chemicals or natural extracts that can remediate the growth of DPCs is vital. Our results showed that Schizochytrium sp.-extracted lipids (SEL) significantly promoted proliferation (up to 1.13 times) and survival ratio (up to 2.45 times) under oxidative stress. The treatment with SEL can protect DPCs against oxidative stress damage, reducing the reactive oxygen species (ROS) level by 90.7%. The relative gene transcription and translation were thoroughly analyzed using RNA-Seq, RT-qPCR, and Western blot to explore the mechanism. Results showed that SEL significantly inhibited the ferroptosis pathway and promoted the expression of antioxidant genes (up to 1.55–3.52 times). The in vivo application of SEL improved hair growth, with the length of new hair increasing by 16.7% and the length of new HF increasing by 92.6%, and the period of telogen shortening increased by 40.0%. This study proposes a novel therapeutic option for alopecia, with the effect and regulation mechanism of SEL on DPC systematically clarified.

Abstract Background Contrast-associated acute kidney injury (CA-AKI) is a common complication with poor prognosis after coronary angiography (CAG). With the prevention methods widely being implemented, the temporal trends of incidence and mortality of CA-AKI are still unknown over the last five years. The study aims to determine the incidence and prognosis of CA-AKI in China. Methods This retrospective cohort study was based on the registry at Guangdong Provincial People’s Hospital in China (ClinicalTrials.gov NCT04407936). We analyzed data from hospitalization patients who underwent CAG and with preoperative and postoperative serum creatinine (Scr) values from January 2013 to December 2017. Results 11,943 patients were included in the study, in which the mean age was 63.01 ± 10.79 years and 8,469 (71.1 %) were male. The overall incidence of CA-AKI was 11.2 %. Compared with 2013, the incidence of CA-AKI in 2017 was significantly increased from 9.7 to 13.0 % (adjusted odds ratios [aOR], 1.38; 95 %CI, 1.13–1.68; P-value

ObjectiveCurrent knowledge on the global burden of infant sepsis is limited to population-level data. We aimed to summarize global case fatality rates (CFRs) of young infants with sepsis, stratified by gross national income (GNI) status and patient-level risk factors.MethodsWe performed a systematic review and meta-analysis on CFRs among young infants < 90 days with sepsis. We searched PubMed, Cochrane Central, Embase, and Web of Science for studies published between January 2010 and September 2019. We obtained pooled CFRs estimates using the random effects model. We performed a univariate analysis at patient-level and a meta-regression to study the associations of gestational age, birth weight, onset of sepsis, GNI, age group and culture-proven sepsis with CFRs.ResultsThe search yielded 6314 publications, of which 240 studies (N = 437,796 patients) from 77 countries were included. Of 240 studies, 99 were conducted in high-income countries, 44 in upper-middle-income countries, 82 in lower-middle-income countries, 6 in low-income countries and 9 in multiple income-level countries. Overall pooled CFR was 18% (95% CI, 17–19%). The CFR was highest for low-income countries [25% (95% CI, 7–43%)], followed by lower-middle [25% (95% CI, 7–43%)], upper-middle [21% (95% CI, 18–24%)] and lowest for high-income countries [12% (95% CI, 11–13%)]. Factors associated with high CFRs included prematurity, low birth weight, age less than 28 days, early onset sepsis, hospital acquired infections and sepsis in middle- and low-income countries. Study setting in middle-income countries was an independent predictor of high CFRs. We found a widening disparity in CFRs between countries of different GNI over time.ConclusionYoung infant sepsis remains a major global health challenge. The widening disparity in young infant sepsis CFRs between GNI groups underscore the need to channel greater resources especially to the lower income regions.Systematic Review Registration[www.crd.york.ac.uk/prospero], identifier [CRD42020164321].

Abstract Background Several studies have found that a low baseline low -density lipoprotein cholesterol (LDL-C) concentration was associated with poor prognosis in patients with acute coronary syndrome (ACS), which is called the “cholesterol paradox”. Low LDL-C concentration may reflect underlying malnutrition, which was strongly associated with increased mortality. The aim of this study was to investigate the cholesterol paradox in patients with CAD and the effects of malnutrition. Method A total of 41,229 CAD patients admitted to Guangdong Provincial People’s Hospital in China were included in this study from January 2007 to December 2018 and divided into two groups (LDL-C

Phenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase (PAH) and can lead to neurotoxicity. Here the authors describe a mouse model of PKU based on a mutation in phenylalanine hydroxylase (R261Q) which replicates traits of this disease and shows a proteostasis defect and oxidative stress, implying a gain-of-function contribution to the disease phenotype.

AIM: To evaluate the inhibitory effect of glycyrrhizin(Gly)on acute alkali burn induced corneal neovascularization(CNV)in mice. METHODS: Corneal neovascularization was established in mice by alkali burn. Sixty mice were then randomly distributed into normal group, Gly group and phosphate buffer solution(PBS)group. The mice were treated with subconjunctival injection of 2g/L Gly solution or vehicle alone every other day for 14d. Corneal inflammation and neovascularization were monitored with a slit lamp microscope. At the end of treatment, the corneas were harvested for hematoxylin-eosin(HE)staining as well as immunohistochemical of CD34 and myeloperoxidase(MPO)staining, microvessel density(MVD), neutrophils were then calculated. RESULTS: At the 7 and 14d, the CNV area of Gly group were 4.16±0.00 and 7.33±0.13mm2 respectively, which were lower than those in PBS group(7.58±0.20 and 9.24±0.08mm2; all PPPCONCLUSION: Gly can eliminate corneal inflammation and inhibit corneal neovascularization in mice with acute corneal alkali burn, which provides a new idea for clinical prevention and treatment of corneal neovascularization.

Corneal neovascularization (CNV) is a sight-threatening condition usually associated with various inflammatory settings including chemical injury. High mobility group box 1 (HMGB1) is identified as an inflammatory alarmin in diverse tissue damage. Here, we evaluate the expression of HMGB1 and the consequences of its inhibition through its selective inhibitor glycyrrhizin (GLY) in alkali burn-induced corneal inflammation and neovascularization. GLY effectively attenuated alkali burn-induced HMGB1 expression at both mRNA and protein levels. Furthermore, slit-lamp analysis, ink perfusion, H&E staining, and CD31 histochemical staining showed that GLY relieved corneal neovascularization, while GLY attenuated VEGF expression via inhibiting HMGB1/NF-κB/HIF-1α signal pathway. In addition, GLY treatment decreased the cytokine expression of CCL2 and CXCL5, accompanied by the reduction of their receptors of CCR2 and CXCR2. GLY diminished the inflammatory cell infiltration of the cornea, as well as reduced the expression of IL-1β, IL-6, and TNF-α. Moreover, treatment with GLY reduced the degree of cornea opacity through inactivating extracellular HMGB1 function, which otherwise induces TGF-β1 release and myofibroblast differentiation. Furthermore, we found that GLY treatment attenuated the upregulation of miR-21 levels in alkali burned cornea; while inhibition of miR-21in keratocytes in vitro, significantly inhibited TGF-β1-induced myofibroblast differentiation. Collectively, our results suggested that targeting HMGB1-NFκb axis and miR-21 by GLY could introduce a therapeutic approach to counter CNV.

BackgroundDifferent definitions of contrast-associated acute kidney injury (CA-AKI) have different predictive effects on prognosis. However, few studies explored the relationship between these definitions and long-term prognosis in patients with congestive heart failure (CHF). Thus, we aimed to evaluate this association and compared the population attributable risks (PAR) of different CA-AKI definitions.MethodsThis study enrolled 2,207 consecutive patients with CHF undergoing coronary angiography (CAG) in Guangdong Provincial People's Hospital. Two different definitions of CA-AKI were used: CA-AKIA was defined as an increase ≥.5 mg/dl or > 25% in serum creatinine (SCr) from baseline within 72 h after CAG, and CA-AKIB was defined as an increase of ≥.3 mg/dl or > 50% in SCr from baseline within 48 h after CAG. Kaplan-Meier methods and Cox regression were applied to evaluate the association between CA-AKI with long-term mortality. Population attributable risk (PAR) of different definitions for long-term prognosis was also calculated.ResultsDuring the 3.8-year median follow-up (interquartile range 2.1-6), the overall long-term mortality was 24.9%, and the long-term mortality in patients with the definitions of CA-AKIA and CA-AKIB were 30.4% and 34.3%, respectively. We found that CA-AKIA (HR: 1.44, 95% CI 1.19-1.74) and CA-AKIB (HR: 1.48, 95% CI 1.21-1.80) were associated with long-term mortality. The PAR was higher for CA-AKIA (9.6% vs. 8%).ConclusionsOur findings suggested that CA-AKI was associated with long-term mortality in patients with CHF irrespective of its definitions. The CA-AKIA was a much better definition of CA-AKI in patients with CHF due to its higher PAR. For these patients, cardiologists should pay more attention to the presence of CA-AKI, especially CA-AKIA.

BackgroundPrevious studies have shown that renal function recovery after acute kidney injury (AKI) was associated with decreased risk of all-cause mortality. However, little is known about the correlation between renal function recovery and long-term prognosis in patients with contrast-associated acute kidney injury (CA-AKI) undergoing coronary angiography (CAG).MethodsWe retrospectively enrolled 5,865 patients who underwent CAG. CA-AKI was defined as an increase in serum creatinine (SCr) ≥ 50% or ≥ 0.3 mg/dl from baseline within 72 h post procedure. Recovered CA-AKI was defined as a decrease in SCr to baseline or no CA-AKI level. The first endpoint was long-term all-cause mortality. Kaplan–Meier analysis and Cox regression analysis were used to investigate the association between kidney function recovery and long-term mortality.ResultsDuring the median follow-up period of 5.25 years, the overall long-term mortality was 20.07%, and the long-term mortality in patients with recovered CA-AKI and non-recovered CA-AKI was 17.46 and 27.44%, respectively. After multivariate Cox hazard regression, non-recovered CA-AKI was significantly associated with long-term mortality, while recovered CA-AKI was not [recovered CA-AKI vs. no CA-AKI, hazard ratio (HR) = 1.06, 95% confidence interval (CI): 0.81–1.39, p = 0.661; non-recovered CA-AKI vs. no CA-AKI, HR = 1.39, 95% CI: 1.21–1.60, p < 0.001]. In the subgroup of CAD, both recovered CA-AKI and non-recovered CA-AKI were associated with increased risk of long-term all-cause mortality. However, in other subgroup analyses, only non-recovered CA-AKI was associated with increased risk of long-term all-cause mortality.ConclusionOur results found that non-recovered CA-AKI is significantly associated with long-term mortality. In patients with CAD, recovered CA-AKI can still increase the risk of all-cause mortality. Clinicians need to pay more attention to patients suffering from CA-AKI, whose kidney function has not recovered. In addition, active prevention treatments should be taken by patients with CAD.

PurposeLeft ventricular end-diastolic diameter (LVEDD) is a common indicator in echocardiogram, and dilated LVEDD was correlated with left ventricular insufficiency. However, it is uncertain whether dilated LVEDD is associated with increasing the risk of contrast-associated acute kidney injury (CA-AKI) in patients with coronary artery disease (CAD).Patients and MethodsWe enrolled 8,189 patients with CAD undergoing coronary angiography (CAG) between January 2007 and December 2018. Patients were divided into two groups according to the LVEDD length (normal LVEDD: men: LVEDD ≤56 mm, women: LVEDD ≤51 mm; dilated LVEDD: men: LVEDD >56 mm, women: LVEDD >51 mm). The endpoints were CA-AKI0350 and CA-AKI0525 (CA-AKI0350: an increase in the serum creatinine (Scr) level by >0.3 mg/dl or >50% within the first 48 h after CAG; CA-AKI0525: an absolute Scr increase ≥ 0.5 mg/dl or a relative increase ≥ 25% within 72 h after contrast medium exposure). In-hospital dialysis, 30-day mortality, and 1-year mortality were contained as well. Univariate and multivariable logistic regressions were used to assess the association between LVEDD and CA-AKI.ResultsAmong 8,189 participants (men: 76.6%, mean age: 64.4 ± 10.7 years), 1,603 (19.6%) presented with dilated LVEDD. In addition, the dilated LVEDD group indicated an elevation of CA-AKI0350 (12.4 vs. 6.2%, p < 0.001) and CA-AKI0525 (15.0 vs. 8.8%; p < 0.001) when compared with the normal group. According to multivariable logistic analysis, dilated LVEDD was an independent predictor of CA-AKI0350 [adjusted odds ratio (aOR): 1.31; 95% confidence interval (CI): 1.06–1.61, p = 0.010) and CA-AKI0525 (aOR: 1.32; 95% CI: 1.04–1.67; p = 0.020).ConclusionIn conclusion, these results demonstrated that the dilated LVEDD was a significant and independent predictor of CA-AKI following CAG in patients with CAD. Further verifications are needed to verify the association between LVEDD and CA-AKI.

Abstract Background The definitions of contrast-associated acute kidney injury (CA-AKI) are diverse and have different predictive effects for prognosis, which are adverse for clinical practice. Few articles have discussed the relationship between these definitions and long-term prognosis in patients with diabetes. Methods A total of 1154 diabetic patients who were undergoing coronary angiography (CAG) were included in this study. Two definitions of CA-AKI were used: CA-AKIA was defined as an increase ≥ 0.3 mg/dl or > 50% in serum creatinine (SCr) from baseline within 72 h after CAG, and CA-AKIB was defined as an increase ≥ 0.5 mg/dl or > 25% in SCr from baseline within 72 h after CAG. We used Cox regression to evaluate the association of these two CA-AKI definitions with long-term mortality and calculate the population attributable risks (PARs) of different definitions for long-term prognosis. Results During the median follow-up period of 7.4 (6.2–8.2) years, the overall long-term mortality was 18.84%, and the long-term mortality in patients with CA-AKI according to both CA-AKIA and CA-AKIB criteria were 36.73% and 28.86%, respectively. We found that CA-AKIA (HR: 2.349, 95% CI 1.570–3.517, p = 0.001) and CA-AKIB (HR: 1.608, 95% CI 1.106–2.339, p = 0.013) were associated with long-term mortality. The PARs were the highest for CA-AKIA (31.14%), followed by CA-AKIB (14.93%). Conclusions CA-AKI is a common complication in diabetic patients receiving CAG. The two CA-AKI definitions are significantly associated with a poor long-term prognosis, and CA-AKIA, with the highest PAR, needs more clinical attention.

AIM:The dry eye model of rat was induced either by lacrimal gland extirpation or injection of botulinum toxin A into lacrimal gland. The clinical manifestations, pathological features and cytokine changes of these two models were compared, then we discussed their advantages, disadvantages and applicable scope.METHODS:Thirty healthy 8-week-old male Brown Norway rats were randomly assigned into three groups equally. The left eye of group A was blank group, group B was the left lacrimal gland extirpation model, the left tear gland of group C was injected with botulinum toxin A. We compared the data of Schirmer I test, tear break-up time(BUT), and the corneal fluoresceince staining scores at different times(1d before experiment, 3d, 7d, 14d, 28d, and 42d after the surgical process). We observed pathological changes of conjunctiva, cornea and lacrimal gland at 42d, and we used real-time polymerase chain reaction to analyze interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and epithelial growth factor(EGF).RESULTS:At the 3d, compared with group A, the tear secretion of both group B and group C were continuous decrease(PPPP>0.05). The corneal epithelial cells in group A was set as normal morphology, while the corneal epithelial cells in group B and group C showed filamentous separation of surface cells to varying degrees, and the number of conjunctival goblet cells was decreased. The lacrimal gland of group C was obviously atrophic. In conjunctival and corneal tissues, the expression of EGF, TNF-α and IL-6 were significantly increased in group B and group C, which was statistically significant compared with group A(PP>0.05), however, the expression of IL-6 in group B was much higher than that in group C(PCONCLUSION:In this study, we proved that both lacrimal gland extirpation and lacrimal gland injection botulinum toxin A could construct a stable aqueous tear deficiency dry eye rat model. The appropriate animal model should be selected according to the experimental design and research purpose.

This paper assesses published findings on projections of future tropical cyclone (TC) activity in the ESCAP/WMO Typhoon Committee Region under climate change scenarios. This assessment also estimates the projected changes of key TC metrics for a 2 °C anthropogenic global warming scenario for the western North Pacific (WNP) following the approach of a WMO Task Team, together with other reported findings for this region. For projections of TC genesis/frequency, most models suggest a reduction of TC frequency, but an increase in the proportion of very intense TCs over the WNP in the future. However, some individual studies project an increase in WNP TC frequency. Most studies agree on a projected increase of WNP TC intensity over the 21st century. All available projections for TC related precipitation in the WNP indicate an increase in TC related precipitation rate in a warmer climate. Anthropogenic warming may also lead to changes in TC prevailing tracks. A further increase in storm surge risk may result from increases in TC intensity. The most confident aspect of forced anthropogenic change in TC inundation risk derives from the highly confident expectation of further sea level rise, which we expect will exacerbate storm inundation risk in coastal regions, assuming all other factors equal.

Published findings on climate change impacts on tropical cyclones (TCs) in the ESCAP/WMO Typhoon Committee Region are assessed. We focus on observed TC changes in the western North Pacific (WNP) basin, including frequency, intensity, precipitation, track pattern, and storm surge. Results from an updated survey of impacts of past TC activity on various Members of the Typhoon Committee are also reported. Existing TC datasets continue to show substantial interdecadal variations in basin-wide TC frequency and intensity in the WNP. There has been encouraging progress in improving the consensus between different datasets concerning intensity trends. A statistically significant northwestward shift in WNP TC tracks since the 1980s has been documented. There is low-to-medium confidence in a detectable poleward shift since the 1940s in the average latitude where TCs reach their peak intensity in the WNP. A worsening of storm inundation levels is believed to be occurring due to sea level rise-due in part to anthropogenic influence-assuming all other factors equal. However, we are not aware that any TC climate change signal has been convincingly detected in WNP sea level extremes data. We also consider detection and attribution of observed changes based on an alternative Type II error avoidance perspective.

BackgroundThe relationship between malnutrition and the risk of contrast-associated acute kidney injury (CA-AKI) and the resulting prognosis in patients undergoing percutaneous coronary intervention (PCI) is still not well known.MethodsPatients undergoing PCI were consecutively enrolled in a multicenter study in China (NCT01402232), categorized by nutritional status (non-malnutrition, malnutrition) based on two different cut-off values (i.e., traditional threshold and the best cut-off value based on the receiver operating characteristic (ROC) curve) for the controlling nutritional status (CONUT) score. The primary endpoint was CA-AKI, diagnosed as a rise in serum creatinine >0.3 mg/dl or >50% than the baseline level occurring within 48 h after the intervention. The secondary endpoint was all-cause mortality. The relationships of malnutrition, CA-AKI, and all-cause mortality were examined using multivariate-adjusted logistic and Cox regression analyses, respectively.ResultsAmong 2,083 patients undergoing PCI (age: 62.8 ± 11.1 years; 79.0% men), 1,258 (60.4%) were malnourished. During hospitalization, 80 (3.8%) patients developed CA-AKI events. The incidence of CA-AKI in patients who did not have malnutrition (the non-malnutrition group) and those who did have malnutrition (the malnutrition group) was 1.7% and 5.25%, respectively. Patients with malnutrition had a 2-fold increased adjusted risk of CA-AKI compared to those with no malnutrition [adjusted odds ratio (aOR) (95% confidence interval CI): 2.41 (1.22 to 5.22)]. Malnutrition was associated with a 3-fold increased adjusted risk of CA-AKI in patients aged ≤ 75 years [N = 1,791, aOR (95% CI): 3.39 (1.46–9.25)]. Malnourished patients with CA-AKI had a higher risk of all-cause mortality than the others. Similar results were observed in the grouping of Supplemental Analyses based on the optimal cut-off value of the CONUT score identified by the ROC curve.ConclusionsMalnutrition is strongly associated with an increased risk of CA-AKI in both young and old patients undergoing PCI. Malnourished patients with CA-AKI had a significantly higher risk of all-cause mortality. Further studies are needed to prospectively assess the efficacy of nutritional interventions on outcomes in patients undergoing PCI.

Breast cancer is characterized by the uncontrolled proliferation of breast epithelial cells under the action of a variety of carcinogens. Although HER2-inhibitors were currently applied for HER2-positive breast cancer patients, they didn’t work for patients with resistance to HER2-targeted anti-cancer drugs. In this work, we prepared novel CuS@BSA-NB2 nanoparticles (NPs) for breast cancer photothermal therapy (PTT). The NPs had good biocompatibility due to the Bovine Serum Albumin (BSA) encapsulating and excellent targeting to HER2 because of nanobody 2 (NB2). Under 808 nm laser irradiation, CuS@BSA-NB2 NPs had high photothermal conversion efficiency and photothermal stability. Meanwhile, we constructed a stable cell line of MDA-MB-231/HER2 with a high expression of HER2 protein. Immunofluorescence and ICP-MS assays showed that CuS@BSA-NB2 NPs can be specifically enriched and be ingested in MDA-MB-231/HER2 cells. Furthermore, CuS@BSA-NB2 NPs had shown a more significant photothermal treatment effect than CuS@BSA under certain treatment conditions for MDA-MB-231/HER2. In addition, the cytotoxicity assay demonstrated that CuS@BSA-NB2 NPs had a low toxicity for MDA-MB-231/HER2 cells. The above results suggested that CuS@BSA-NB2 NPs were great photothermal therapeutic agents to reduce the malignant proliferation of breast epithelial cells and have potential for breast cancer therapy.

Background: Acute kidney injury (AKI) is a common complication after coronary angiography (CAG) and associated with heart failure (HF). Left ventricular (LV) remodeling is a vital process in the progression of HF. However, few studies investigate the relationship between AKI and LV remodeling.Methods: We included consecutive patients undergoing CAG from January 2007 to December 2018 at Guangdong Provincial People’s Hospital (NCT04407936). AKI was defined as an absolute increase in serum creatinine (Scr) of ≥ 0.3mg/dl or a ≥ 50% increase in Scr from baseline within the first 48–72 h after the procedure. LV remodeling was defined as: (1) an absolute decrease in left ventricular ejection fraction (LVEF) of ≥ 10% compared to baseline, or (2) a follow-up LVEF < 40%. Univariate and multivariate logistical regressions were used to assess the association between AKI and LV remodeling.Results: Of the 1,573 patients (62.2 ± 9.7 years, female 36.7%) included in the study, 231 (14.7%) had AKI. The incidence of LV remodeling was higher in patients with AKI than in those without AKI (24.7% vs. 14.5%). After adjusting for confounding, multivariate logistic regression showed that AKI was associated with a significantly higher risk of LV remodeling [adjusted odds ratio (aOR) 1.87; 95% CI, 1.30–2.66; p < 0.001]. In addition, LV remodeling patients had higher all-cause mortality compared to non-LV remodeling patients (9.7% vs. 19.1%).Conclusion: Our data suggested that AKI is present in up to 15% of patients after CAG and that nearly a quarter of AKI patients suffered LV remodeling and AKI patients have a two-fold risk of developing LV remodeling than non-AKI patients. Our findings suggest that more active measures be taken not only to prevent AKI patient developing into LV remodeling, but to prevent patients undergoing CAG from developing AKI.

Background: Previous studies reported that patients with coronary artery disease (CAD) and well-controlled baseline LDL-C (

CRISPR-associated Cas9 endonuclease (CRISPR/Cas9) systems are widely used to introduce precise mutations, such as knocking in/out at targeted genomic sites. Herein, we successfully disrupted the transcription of multiple genes in Bacillus pumilus LG3145 using a series of unspecific guide RNAs (gRNAs) and UgRNA:Cas9 system-assisted cre-box editing. The bases used as gRNAs shared 30–70% similarity with a consensus sequence, a cis-acting element (cre-box) mediating carbon catabolite repression (CCR) of many genes in Bacillus. This triggers trans-crRNA:Cas9 complex wobble cleavage up/downstream of cre sites in the promoters of multiple genes (up to 7), as confirmed by Sanger sequencing and next-generation sequencing (NGS). LG3145 displayed an obvious CCR release phenotype, including numerous secondary metabolites released into the culture broth, ∼ 1.67 g/L white flocculent protein, pigment overflow causing orange-coloured broth (absorbance = 309 nm), polysaccharide capsules appearing outside cells, improved sugar tolerance, and a two-fold increase in cell density. We assessed the relationship between carbon catabolite pathways and phenotype changes caused by unspecific UgRNA-directed cre site wobble editing. We propose a novel strategy for editing consensus targets at operator sequences that mediates transcriptional regulation in bacteria.

Background: A high level of lipoprotein(a) can lead to a high risk of cardiovascular events or mortality. However, the association of moderately elevated lipoprotein(a) levels (≥15 mg/dL) with long-term prognosis among patients with coronary artery disease (CAD) is still uncertain. Hence, we aim to systematically analyzed the relevance of baseline plasma lipoprotein(a) levels to long-term mortality in a large cohort of CAD patients.Methods: We obtained data from 43,647 patients who were diagnosed with CAD and had follow-up information from January 2007 to December 2018. The patients were divided into two groups (

Background: Although glycated hemoglobin (HbA1c) was considered as a prognostic factor in some subgroup of coronary artery disease (CAD), the specific relationship between HbA1c and the long-term all-cause death remains controversial in patients with CAD.Methods: The study enrolled 37,596 CAD patients and measured HbAlc at admission in Guangdong Provincial People's Hospital. The patients were divided into 4 groups according to HbAlc level (Quartile 1: HbA1c ≤ 5.7%; Quartile 2: 5.7% < HbA1c ≤ 6.1%; Quartile 3: 6.1% < HbA1c ≤ 6.7%; Quartile 4: HbA1c > 6.7%). The study endpoint was all-cause death. The restricted cubic splines and cox proportional hazards models were used to investigate the association between baseline HbAlc levels and long-term all-cause mortality.Results: The median follow-up was 4 years. The cox proportional hazards models revealed that HbAlc is an independent risk factor in the long-term all-cause mortality. We also found an approximate U-shape association between HbA1c and the risk of mortality, including increased risk of mortality when HbA1c ≤ 5.7% and HbA1c > 6.7% [Compared with Quartile 2, Quartile 1 (HbA1c ≤ 5.7), aHR = 1.13, 95% CI:1.01–1.26, P < 0.05; Quartile 3 (6.1% < HbA1c ≤ 6.7%), aHR = 1.04, 95% CI:0.93–1.17, P =0.49; Quartile 4 (HbA1c > 6.7%), aHR = 1.32, 95% CI:1.19–1.47, P < 0.05].Conclusions: Our study indicated a U-shape relationship between HbA1c and long-term all-cause mortality in CAD patients.

Background. Contrast-associated acute kidney injury (CA-AKI) is a major adverse effect of coronary angiography (CAG). Patients with chronic kidney disease (CKD) and coronary artery disease (CAD) are at high risk of CA-AKI. This study aimed to investigate the association between prognostic nutritional index (PNI) and CA-AKI in this high-risk population. Methods. This study enrolled a total of 4,391 patients. CA-AKI was defined as a serum creatinine increase ≥0.3 mg/dL or 50% from baseline within the first 48 hours following CAG. The PNI was calculated upon hospital admission: serum albumin (g/L) + 5 × total lymphocyte count (109/L). PNI was analysed from the high level to low level as a continuous variable and categorical variable which was divided into four groups by quartile. Restricted cubic splines and logistic regression were applied. Results. Overall, 13.09% (575/4391) of patients developed CA-AKI. PNI score was significantly lower in patients with CA-AKI than that in patients without CA-AKI (P

Introduction Neonatal sepsis has a high mortality rate that varies across different populations. We aim to perform a contemporary global evidence synthesis to determine the case fatality rates of neonatal sepsis, in order to better delineate this public health urgency and inform strategies to reduce fatality in this high-risk population.Methods and analysis We will search PubMed, Cochrane Central, Embase and Web of Science for articles in English language published between January 2010 and December 2019. All clinical trials and observational studies involving infants less than 90 days old with a clinical diagnosis of sepsis and reported case fatality rate will be included. Two independent reviewers will screen the studies and extract data on study variables chosen a priori. Quality of evidence and risk of bias will be assessed using Cochrane Collaboration’s tool and ROBINS-I. Results will be synthesised qualitatively and pooled for meta-analysis.Ethics and dissemination No formal ethical approval is required as there is no collection of primary data. This systematic review and meta-analysis will be disseminated through conference meetings and peer-reviewed publications.PROSPERO registration number CRD42020164321.

Introduction The effect of neonatal sepsis on the developing brain is not well documented. We aim to perform evidence synthesis to determine the outcome of neurodevelopmental impairment and intellectual disability among survivors of neonatal sepsis. The data gathered will inform on the long-term neurocognitive outcomes of neonates with sepsis and the measures used to document their developmental disability.Methods and analysis We will perform a search based on the following parameters: neonates and infants less than 90 days old diagnosed with sepsis who had neurocognitive outcomes or measures of developmental disability reported. We will search PubMed, Cochrane Central, Embase and Web of Science for articles in English language published between January 2010 and December 2019. Clinical trials and observational studies will be included. Two independent reviewers will screen studies for eligibility. Data extraction will then be performed using a standardised form. The quality of evidence and risk of bias will be assessed using Cochrane Collaboration’s tool and Risk of Bias in Non-randomised Studies of Intervention (ROBINS-I). The results will be synthesised qualitatively and pooled for meta-analysis.Ethics and dissemination No formal ethical approval is required as there is no collection of primary data. This systematic review and meta-analysis will be disseminated through conference meetings and peer-reviewed publications.PROSPERO registration number Registration submitted CRD42020164334

Background: Few studies have demonstrated the association between contrast-induced acute kidney injury (CI-AKI) and long-term mortality and explored which definition of CI-AKI accounts for most long-term deaths among patients with acute myocardial infarction (AMI). Therefore, we aimed to evaluate this association and compared the population attributable risks (PARs) of three CI-AKI definitions. Methods: We analyzed 1300 consecutive AMI patients undergoing angiography in Guangdong Provincial People‘s Hospital. The endpoint was all-cause mortality. CI-AKI was evaluated according to three definitions: (1) CI-AKIA, with a serum creatinine elevation ≥ 50% or ≥ 0.3 mg/dL from baseline in the first 72 h after procedure; (2) CI-AKIB, ≥ 0.5 mg/dL in 72 h; (3) CI-AKIC: ≥ 25% in 72 h; multivariable Cox analysis was conducted to evaluate the association between CI-AKI and long-term mortality. PARs of CI-AKI under different definitions were calculated with their odds ratios and prevalence among our cohort. Results: During the median follow-up period of 7.0 (5.5; 8.7) years, CI-AKI was significantly associated with poorer outcome regardless of the definition (adjusted hazard ratios: 1.417–2.711). Among the three definitions of CI-AKI, the prevalence was the highest for CI-AKIC (18.77%), and PAR was the highest for CI-AKIA (11.62%, 95% CI: 4.99–19.71), followed by CI-AKIB (9.20%, 95% CI: 4.22–16.00) and CI-AKIC (7.26%, 95% CI: 0.21–15.62). Conclusions: Our results suggested that CI-AKI is associated with long-term mortality in patients with AMI irrespective of its definitions. Cardiologists and studies regarding long-term prognosis should pay more attention to the presence of CI-AKI, especially CI-AKIA with the highest PAR.

Abstract Background Pulmonary arterial smooth muscle cell (PASMC) proliferation in response to hypoxia plays an important role in the vascular remodelling that occurs in hypoxic pulmonary hypertension. MicroRNAs (miRs) are emerging as important regulators in the progression of pulmonary hypertension. In this study, we investigated whether the expression of miR-17-5p is modulated by hypoxia and is involved in the hypoxia-induced proliferation of PASMCs. Methods Human PASMCs were cultured under hypoxic conditions. miR-17-5p expression was determined by real-time RT-PCR. A BrdU incorporation assay and time-lapse recording were utilized to determine cell proliferation and migration. Results PASMC proliferation was increased by moderate hypoxia (3% oxygen) but was reduced by severe hypoxia (0.1% oxygen) after 48 h. Moderate hypoxia induced miR-17-5p expression. Overexpression of miR-17-5p by transfection with miR-17-5p enhanced cell proliferation and migration in normoxia, whereas knockdown of miR-17-5p with anti-miR-17-5p inhibitors significantly reduced cell proliferation and migration. The expression of miR-17-5p target genes, specifically phosphatase and tensin homologue (PTEN) and cyclin-dependent kinase inhibitor 1 (p21WAF1/Cip1, p21), was reduced under moderate hypoxia in PASMCs. Under normoxia, overexpression of miR-17-5p in PASMCs reduced the expression of PTEN and p21. Conclusion Our data indicate that miR-17-5p might play a significant role in hypoxia-induced pulmonary vascular smooth muscle cell proliferation by regulating multiple gene targets, including PTEN and p21, and that miR-17-5p could be a novel therapeutic target for the management of hypoxia-induced PH.

AIM: To find a stable, inexpensive, and reliable method to produce a rat meibomian gland dysfunction (MGD) model. METHODS: We inserted slim guidewires into the meibomian gland orifices of twelve Brown Norway rats and fulgurized every guidewire to destroy part of the meibomian gland. We then observed the morphological changes in the eyelid margin, and compared the data of tear breakup time (TBUT), Schirmer I test, and the corneal fluorescence staining scores at different times (1, 2, 4, and 6wk). We observed pathological changes of the cornea, conjunctiva and meibomian gland, and we used real-time polymerase chain reaction to analyze epithelial growth factor (EGF), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and Ki67. RESULTS: In the fourth week, compared with the control group, the TBUT of the model group began to decreased (P0.05). The corneal dots were significantly increased in the fourth week when the fusion stain began to appear (P0.05). CONCLUSION: The MGD rat model, produced via electrocauterization of meibomian gland orifices, matched clinical manifestations and cytokine levels. Our research provides a new method of achieving an MGD animal model.

This research reveals the improved performance of bioelectrodes made with amination-modified glucose oxidase (GOx-NH2) and carboxyl-functionalized mesoporous carbon (OMC-COOH). Results showed that when applied with 10 mM EDC amination, the functional groups of NH2 were successfully added to GOx, according to the analysis of 1H-NMR, elemental composition, and FTIR spectra. Moreover, after the aminated modification, increased enzyme immobilization (124.01 ± 1.49 mg GOx-NH2/g OMC-COOH; 2.77-fold increase) and enzyme activity (1.17-fold increase) were achieved, compared with those of non-modified GOx. Electrochemical analysis showed that aminated modification enhanced the peak current intensity of Nafion/GOx-NH2/OMC-COOH (1.32-fold increase), with increases in the charge transfer coefficient α (0.54), the apparent electron transfer rate constant ks (2.54 s−1), and the surface coverage Γ (2.91 × 10−9 mol·cm−2). Results showed that GOx-NH2/OMC-COOH exhibited impressive electro-activity and a favorable anodic reaction.