Synergistic Engineering of CoO/MnO Heterostructures Integrated with Nitrogen-Doped Carbon Nanofibers for Lithium-Ion Batteries.

The integration of heterostructures within electrode materials is pivotal for enhancing electron and Li-ion diffusion kinetics. In this study, we synthesized CoO/MnO heterostructures to enhance the electrochemical performance of MnO using a straightforward electrostatic spinning technique followed by a meticulously controlled carbonization process, which results in embedding heterostructured CoO/MnO nanoparticles within porous nitrogen-doped carbon nanofibers (CoO/MnO/NC). As confirmed by density functional theory calculations and experimental results, CoO/MnO heterostructures play a significant role in promoting Li+ ion and charge transfer, improving electronic conductivity, and reducing the adsorption energy. The accelerated electron and Li-ion diffusion kinetics, coupled with the porous nitrogen-doped carbon nanofiber structure, contribute to the exceptional electrochemical performance of the CoO/MnO/NC electrode. Specifically, the as-prepared CoO/MnO/NC exhibits a high reversible specific capacity of 936 mA h g-1 at 0.1 A g-1 after 200 cycles and an excellent high-rate capacity of 560 mA h g-1 at 5 A g-1, positioning it as a competitive anode material for lithium-ion batteries. This study underscores the critical role of electronic and Li-ion regulation facilitated by heterostructures, offering a promising pathway for designing transition metal oxide-based anode materials with high performances for lithium-ion batteries.

Constructing Abundant Oxygen-Containing Functional Groups in Hard Carbon Derived from Anthracite for High-Performance Sodium-Ion Batteries.

Hard carbon is regarded as one of the greatest potential anode materials for sodium-ion batteries (SIBs) because of its affordable price and large layer spacing. However, its poor initial coulombic efficiency (ICE) and low specific capacity severely restrict its practical commercialization in SIBs. In this work, we successfully constructed abundant oxygen-containing functional groups in hard carbon by using pre-oxidation anthracite as the precursor combined with controlling the carbonization temperature. The oxygen-containing functional groups in hard carbon can increase the reversible Na+ adsorption in the slope region, and the closed micropores can be conducive to Na+ storage in the low-voltage platform region. As a result, the optimal sample exhibits a high initial reversible sodium storage capacity of 304 mAh g-1 at 0.03 A g-1, with an ICE of 67.29% and high capacitance retention of 95.17% after 100 cycles. This synergistic strategy can provide ideas for the design of high-performance SIB anode materials with the intent to regulate the oxygen content in the precursor.

Pediatric intensive care unit treatment alters the diversity and composition of the gut microbiota and antimicrobial resistance gene expression in critically ill children.

Introduction: Common critical illnesses are a growing economic burden on healthcare worldwide. However, therapies targeting the gut microbiota for critical illnesses have not been developed on a large scale. This study aimed to investigate the changes in the characteristics of the gut microbiota in critically ill children after short-term pediatric intensive care unit (PICU) treatments. Methods: Anal swab samples were prospectively collected from March 2021 to March 2022 from children admitted to the PICU of Xinhua Hospital who received broad-spectrum antibiotics on days 1 (the D1 group) and 7 (the D7 group) of the PICU treatment. The structural and functional characteristics of the gut microbiota of critically ill children were explored using metagenomic next-generation sequencing (mNGS) technology, and a comparative analysis of samples from D1 and D7 was conducted. Results: After 7 days of PICU admission, a significant decrease was noted in the richness of the gut microbiota in critically ill children, while the bacterial diversity and the community structure between groups remained stable to some extent. The relative abundance of Bacilli and Lactobacillales was significantly higher, and that of Campylobacter hominis was significantly lower in the D7 group than in the D1 group. The random forest model revealed that Prevotella coporis and Enterobacter cloacae were bacterial biomarkers between groups. LEfSe revealed that two Gene Ontology entries, GO:0071555 (cell wall organization) and GO:005508 (transmembrane transport), changed significantly after the short-term treatment in the PICU. In addition, 30 KEGG pathways were mainly related to the activity of enzymes and proteins during the processes of metabolism, DNA catabolism and repair, and substance transport. Finally, 31 antimicrobial resistance genes had significantly different levels between the D7 and D1 groups. The top 10 up-regulated genes were Erm(A), ErmX, LptD, eptB, SAT-4, tetO, adeJ, adeF, APH(3')-IIIa, and tetM. Conclusion: The composition, gene function, and resistance genes of gut microbiota of critically ill children can change significantly after short PICU treatments. Our findings provide a substantial basis for a better understanding of the structure and function of gut microbiota and their role in critical illnesses.

Analysis of microRNA expression in rat kidneys after VEGF inhibitor treatment under different degrees of hypoxia.

Previously, we found that the incidence of kidney injury in patients with chronic hypoxia was related to the partial pressure of arterial oxygen. However, at oxygen concentrations that contribute to kidney injury, the changes in the relationship between microRNAs (miRNAs) and the hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) axis and the key miRNAs involved in this process have not been elucidated. Therefore, we elucidated the relationship between VEGF and kidney injury at different oxygen concentrations and the mechanisms mediated by miRNAs. Sprague-Dawley rats were exposed to normobaric hypoxia and categorized into six groups based on the concentration of the oxygen inhaled and injection of the angiogenesis inhibitor bevacizumab, a humanized anti-VEGF monoclonal antibody. Renal tissue samples were processed to determine pathological and morphological changes and HIF-1α, VEGF, and miRNA expression. We performed a clustering analysis of high-risk pathways and key hub genes. The results were validated using two Gene Expression Omnibus datasets (GSE94717 and GSE30718). As inhaled oxygen concentration decreased, destructive changes in the kidney tissues became more severe. Although the kidney possesses a self-protective mechanism under an intermediate degree of hypoxia (10% O2), bevacizumab injections disrupted this mechanism, and VEGF expression was associated with the ability of the kidney to repair itself. rno-miR-124-3p was identified as a crucial miRNA; a key gene target, Mapk14, was identified during this process. VEGF plays an important role in kidney protection from injury under different hypoxia levels. Specific miRNAs and their target genes may serve as biomarkers that provide new insights into kidney injury treatment.NEW & NOTEWORTHY Renal tolerance to hypoxic environments is limited, and the degree of hypoxia does not show a linear relationship with angiogenesis. VEGF plays an important role in the kidney's self-protective mechanism under different levels of hypoxia. miR-124-3p may be particularly important in kidney repair, and it may modulate VEGF expression through the miR-124-3p/Mapk14 signaling pathway. These microRNAs may serve as biomarkers that provide new insights into kidney injury treatment.

Boosting the Initial Coulomb Efficiency of Sisal Fiber-Derived Carbon Anode for Sodium Ion Batteries by Microstructure Controlling.

As anode material for sodium ion batteries (SIBs), biomass-derived hard carbon has attracted a great deal of attention from researchers because of its renewable nature and low cost. However, its application is greatly limited due to its low initial Coulomb efficiency (ICE). In this work, we employed a simple two-step method to prepare three different structures of hard carbon materials from sisal fibers and explored the structural effects on the ICE. It was determined that the obtained carbon material, with hollow and tubular structure (TSFC), exhibits the best electrochemical performance, with a high ICE of 76.7%, possessing a large layer spacing, a moderate specific surface area, and a hierarchical porous structure. In order to better understand the sodium storage behavior in this special structural material, exhaustive testing was performed. Combining the experimental and theoretical results, an "adsorption-intercalation" model for the sodium storage mechanism of the TSFC is proposed.

[Features of unintentional injury in children under the impact of coronavirus disease 2019]. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žç–«æƒ ä¸‹å„¿ç«¥æ„å¤–ä¼¤å®³çš„ç‰¹å¾.

OBJECTIVES: To study the features of unintentional injury in children under the impact of coronavirus disease 2019 (COVID-19). METHODS: A retrospective analysis was performed on the medical data of 2 526 children with unintentional injury in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2019 to June 2022. The study period was divided into 5 stages: before the epidemic (July to December, 2019), the Wuhan epidemic period (January to April, 2020), the epidemic remission period in China (May 2020 to February 2022), the Shanghai epidemic period (March to May, 2022), and the epidemic remission period in Shanghai (June 2022). The incidences of unintentional injury in children at different time stages and different ages were compared. A questionnaire survey was conducted on 107 children of the 2 526 children to explore the features of unintentional injury. RESULTS: There were significant differences in gender composition, age, age distribution and proportion of many types of unintentional injuries among the five time stages (P<0.05). There was a reduction in the number of children who attended the emergency department due to unintentional injury during the Wuhan epidemic and the Shanghai epidemic. The proportion of children with trauma-related unintentional injuries in each stage reached more than 50%, and the proportion of children with trauma-related unintentional injuries reached 63.9% and 82.0%, respectively during the Wuhan epidemic and the Shanghai epidemic. Most children suffering from unintentional injury were mainly school-aged and preschool children (1 823 children, 72.17%). Compared with the same period of Shanghai epidemic in 2021, the age of children with unintentional injury was younger (median 7 years vs 11 years), and the proportion of children with trauma-related unintentional injuries increased (97% vs 69%) during the Shanghai epidemic (P<0.05). CONCLUSIONS: Under the COVID-19 epidemic, there is a reduction in the number of children with unintentional injury, while there is an increase in the proportion of children with trauma-related unintentional injuries. Unintentional injury is more common among school-aged and preschool children.

Value of Central Venous Pressure Monitoring in the Patients with Sepsis-Associated Acute Kidney Injury.

Background: Although the measurement of central venous pressure (CVP) is a common clinical tool, the role of CVP monitoring in the outcome of sepsis is controversial because threshold values of CVP are uncertain, and there are only limited data on short-term survival of patients with septic acute kidney injury (AKI). Methods: This retrospective cohort study was based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (source of the training dataset). Multivariate regression analysis was performed to clarify the relation between CVP measurement and clinical outcomes, and a univariate regression model after propensity score matching was utilized to validate our findings. A mortality prediction model for septic AKI and a risk stratification scoring approach were developed, and the emergency intensive care unit (eICU) database was used for external validation. Results: Of the 9170 patients in the training set, 2446 (26.7%) underwent CVP measurement. No significant association was found between CVP monitoring and 28-day mortality among patients with septic AKI (odds ratio = 0.479; 95% confidence interval 0.213-1.076, P = 0.075), even after adjustments (propensity score matching; P = 0.178). Length of ICU stay and hospital stay was markedly reduced in patients undergoing CVP measurement within 3 hours (median 6.2 and 10.9 days, respectively, P < 0.001). The addition of the mean perfusion pressure initial, CVP, and the magnitude of the CVP change within 48 hours to the model significantly increased model discrimination (area under the receiver operating characteristic curve: 0.867 and 0.780, respectively, P < 0.001). Conclusions: These findings suggest that CVP measurement alone has little effect on the outcome of septic AKI. Nonetheless, initial CVP levels and the dynamic changes in CVP within the first 48 hours after ICU admission and the mean perfusion pressure initial can improve the accuracy of outcome prediction models.

Contribution of gut microbiota toward renal function in sepsis.

Sepsis most often involves the kidney and is one of the most common causes of acute kidney injury. The prevalence of septic acute kidney injury has increased significantly in recent years. The gut microbiota plays an important role in sepsis. It interacts with the kidney in a complex and multifactorial process, which is not fully understood. Sepsis may lead to gut microbiota alteration, orchestrate gut mucosal injury, and cause gut barrier failure, which further alters the host immunological and metabolic homeostasis. The pattern of gut microbiota alteration also varies with sepsis progression. Changes in intestinal microecology have double-edged effects on renal function, which also affects intestinal homeostasis. This review aimed to clarify the interaction between gut microbiota and renal function during the onset and progression of sepsis. The mechanism of gut-kidney crosstalk may provide potential insights for the development of novel therapeutic strategies for sepsis.

Fibroblast Growth Factor 19 Improves LPS-Induced Lipid Disorder and Organ Injury by Regulating Metabolomic Characteristics in Mice.

Sepsis is extremely heterogeneous pathology characterized by complex metabolic changes. Fibroblast growth factor 19 (FGF19) is a well-known intestine-derived inhibitor of bile acid biosynthesis. However, it is largely unknown about the roles of FGF19 in improving sepsis-associated metabolic disorder and organ injury. In the present study, mice were intravenously injected recombinant human FGF19 daily for 7 days followed by lipopolysaccharide (LPS) administration. At 24 hours after LPS stimuli, sera were collected for metabolomic analysis. Ingenuity pathway analysis (IPA) network based on differential metabolites (DMs) was conducted. Here, metabolomic analysis revealed that FGF19 pretreatment reversed the increase of LPS-induced fatty acids. IPA network indicated that altered linoleic acid (LA) and gamma-linolenic acid (GLA) were involved in the regulation of oxidative stress and mitochondrial function and were closely related to reactive oxygen species (ROS) generation. Further investigation proved that FGF19 pretreatment decreased serum malondialdehyde (MDA) levels and increased serum catalase (CAT) levels. In livers, FGF19 suppressed the expression of inducible NO synthase (iNOS) and enhanced the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and hemeoxygenase-1 (HO-1). Finally, FGF19 pretreatment protected mice against LPS-induced liver, ileum, and kidney injury. Taken together, FGF19 alleviates LPS-induced organ injury associated with improved serum LA and GLA levels and oxidative stress, suggesting that FGF19 might be a promising target for metabolic therapy for sepsis.

Resultados de la ventilación asistida ajustada neuronalmente no invasiva y la presión positiva continua nasal en recién nacidos prematuros: revisión sistemática y metanálisis / Outcomes of noninvasive neurally adjusted ventilatory assist and nasal continuous positive airway pressure in preterm infants: a systematic review and meta-analysis

Introducción: los beneficios de la ventilación asistida ajustada neuronalmente (NAVA) en los recién nacidos prematuros son inciertos. El objetivo de este estudio fue explorar si la NAVA no invasiva (NIV) era más beneficiosa para los recién nacidos prematuros que la presión positiva continua nasal (NCPAP). Diseño del estudio: metanálisis de tres ensayos clínicos: dos ensayos controlados aleatorizados y un estudio de grupos cruzados. Se comparó la NAVA-NIV con la NCPAP y se informó sobre el fracaso del tratamiento, la mortalidad y los eventos adversos como resultados principales. Resultados: tres estudios con 173 pacientes (89 recibieron NAVA-NIV) cumplieron los criterios de inclusión en este metanálisis. No se observaron diferencias en el fracaso del tratamiento entre la NAVA-NIV y la NCPAP (razón de riesgos [RR] = 1,09; intervalo de confianza [IC] del 95 % = 0,65-1,84; diferencia de riesgos = 0,02; IC95% = -0,10-0,14; I2 = 33 %; P = 0,23). De manera similar, no hubo diferencias en la mortalidad (RR = 1,52; IC95% = 0,51-4,52; no aplica heterogeneidad). En comparación con la NCPAP, la NAVA-NIV redujo significativamente el uso de cafeína (RR = 0,85; IC 95% = 0,74-0,98; I2 = 71 %; P = 0,03). Conclusiones: en comparación con la NCPAP, no hay evidencia suficiente para sacar una conclusión sobre los beneficios o daños de la NAVA-NIV en los recién nacidos prematuros. Los hallazgos de esta revisión deben confirmarse en ensayos clínicos con una metodología rigurosa y potencia adecuada

Introduction: The benefits of neurally adjusted ventilatory assist (NAVA) in preterm infants are unclear. This study aimed to explore if noninvasive NAVA is more beneficial for preterm infants than nasal continuous positive airway pressure (NCPAP). Study design: Meta-analysis was performed in three clinical trials comprising two randomized controlled trials and one crossover study. We compared NIV-NAVA and NCPAP and reported treatment failure, mortality, and adverse events as the primary outcomes. Results: Three studies including 173 patients (89 of whom underwent NIV-NAVA) were eligible for this meta-analysis. This review found no difference in treatment failure between NIV-NAVA and NCPAP (RR 1.09, 95% CI 0.65 to 1.84; RD 0.02, 95% CI -0.10-0.14; I2=33%, P=0.23). Similarly, there was no difference in mortality (RR 1.52, 95% CI 0.51-4.52, heterogeneity not applicable). Compared with NCPAP, NIV-NAVA significantly reduced the use of caffeine (RR 0.85, 95% CI 0.74-0.98, I2=71%, P=0.03). Conclusions: Compared with NCPAP, there is insufficient evidence to conclude on the benefits or harm of NIV-NAVA therapy for preterm infants. The findings of this review should be confirmed using methodologically rigorous and adequately powered clinical trials.

Outcomes of noninvasive neurally adjusted ventilatory assist and nasal continuous positive airway pressure in preterm infants: a systematic review and meta-analysis. / Resultados de la ventilación asistida ajustada neuronalmente no invasiva y la presión positiva continua nasal en recién nacidos prematuros: revisión sistemática y metanálisis.

INTRODUCTION: The benefits of neurally adjusted ventilatory assist (NAVA) in preterm infants are unclear. This study aimed to explore if noninvasive NAVA is more beneficial for preterm infants than nasal continuous positive airway pressure (NCPAP). STUDY DESIGN: Meta-analysis was performed in three clinical trials comprising two randomized controlled trials and one crossover study. We compared NIV-NAVA and NCPAP and reported treatment failure, mortality, and adverse events as the primary outcomes. RESULTS: Three studies including 173 patients (89 of whom underwent NIV-NAVA) were eligible for this meta-analysis. This review found no difference in treatment failure between NIVNAVA and NCPAP (RR 1.09, 95% CI 0.65 to 1.84; RD 0.02, 95% CI -0.10-0.14; I2=33%, P=0.23). Similarly, there was no difference in mortality (RR 1.52, 95% CI 0.51-4.52, heterogeneity not applicable). Compared with NCPAP, NIVNAVA significantly reduced the use of caffeine (RR 0.85, 95% CI 0.74-0.98, I2=71%, P=0.03). CONCLUSIONS: Compared with NCPAP, there is insufficient evidence to conclude on the benefits or harm of NIV-NAVA therapy for preterm infants. The findings of this review should be confirmed using methodologically rigorous and adequately powered clinical trials.

Introducción: los beneficios de la ventilación asistida ajustada neuronalmente (NAVA) en los recién nacidos prematuros son inciertos. El objetivo de este estudio fue explorar si la NAVA no invasiva (NIV) era más beneficiosa para los recién nacidos prematuros que la presión positiva continua nasal (NCPAP). Diseño del estudio: metanálisis de tres ensayos clínicos: dos ensayos controlados aleatorizados y un estudio de grupos cruzados. Se comparó la NAVA-NIV con la NCPAP y se informó sobre el fracaso del tratamiento, la mortalidad y los eventos adversos como resultados principales. Resultados: tres estudios con 173 pacientes (89 recibieron NAVA-NIV) cumplieron los criterios de inclusión en este metanálisis. No se observaron diferencias en el fracaso del tratamiento entre la NAVA-NIV y la NCPAP (razón de riesgos [RR] = 1,09; intervalo de confianza [IC] del 95 % = 0,65-1,84; diferencia de riesgos = 0,02; IC95% = -0,10-0,14; I2 = 33 %; P = 0,23). De manera similar, no hubo diferencias en la mortalidad (RR = 1,52; IC95% = 0,51-4,52; no aplica heterogeneidad). En comparación con la NCPAP, la NAVA-NIV redujo significativamente el uso de cafeína (RR = 0,85; IC 95% = 0,74-0,98; I2 = 71 %; P = 0,03). Conclusiones: en comparación con la NCPAP, no hay evidencia suficiente para sacar una conclusión sobre los beneficios o daños de la NAVA-NIV en los recién nacidos prematuros. Los hallazgos de esta revisión deben confirmarse en ensayos clínicos con una metodología rigurosa y potencia adecuada.

Improvement of Lithium Storage Performance of Silica Anode by Using Ketjen Black as Functional Conductive Agent.

In this paper, SiO2 aerogels were prepared by a sol-gel method. Using Ketjen Black (KB), Super P (SP) and Acetylene Black (AB) as a conductive agent, respectively, the effects of the structure and morphology of the three conductive agents on the electrochemical performance of SiO2 gel anode were systematically investigated and compared. The results show that KB provides far better cycling and rate performance than SP and AB for SiO2 anode electrodes, with a reversible specific capacity of 351.4 mA h g-1 at 0.2 A g-1 after 200 cycles and a stable 311.7 mA h g-1 at 1.0 A g-1 after 500 cycles. The enhanced mechanism of the lithium storage performance of SiO2-KB anode was also proposed.

Early post-operative PV-ACO2/CA-VO2 predicts subsequent acute kidney injury after complete repair of tetralogy of Fallot.

BACKGROUND: Acute kidney injury is a severe complication following complete repair of tetralogy of Fallot. Anaerobic metabolism is believed to contribute to the development of acute kidney injury. The ratio of central venous to arterial carbon dioxide tension to arterio-venous oxygen content (PV-ACO2/CA-VO2) has been proposed as a surrogate for respiratory quotient and an indicator of tissue oxygenation. We hypothesised that a small increase of PV-ACO2/CA-VO2 might have superior discrimination ability in subsequent acute kidney injury prediction. METHODS: This study is retrospective and single-centre design study. The study population consisted of 61 children with tetralogy of Fallot that underwent a complete surgical repair between July 2017 and January 2021. Baseline characteristics and intra-operative parameters were collected through a retrospective chart review. PV-ACO2/CA-VO2 was collected within 12 hours of surgical completion. Acute kidney injury was defined according to the criteria established by the Kidney Disease: Improving Global Outcomes group. Univariate and logistic regression analyses were performed to determine risk factors for acute kidney injury. RESULTS: Of the 61 patients, 20 (32.8%) developed acute kidney injury. Multivariate logistic analyses showed that age, height, haematocrit, and Pv-aCO2/Ca-vO2 were independently associated with the development of acute kidney injury. The addition of Pv-aCO2/Ca-vO2 to the model significantly increased model discrimination [AUROC 0.939 (95% CI 0.894-0.984) and AUROC 0.922 (95% CI 0.869-0.975), respectively]. CONCLUSIONS: The increase of PV-ACO2/CA-VO2 could improve the predictive ability for subsequent development of acute kidney injury in children with tetralogy of Fallot.

Mild Hypoxia Enhances the Expression of HIF and VEGF and Triggers the Response to Injury in Rat Kidneys.

BACKGROUND: Hypoxia contributes to a cascade of inflammatory response mechanisms in kidneys that result in the development of renal interstitial fibrosis and subsequent chronic renal failure. Nonetheless, the kidney possesses a self-protection mechanism under a certain degree of hypoxia and this mechanism its adaptation to hypoxia. As the hypoxia-inducible factor (HIF)-vascular endothelial growth factor (VEGF) axis is a key pathway for neovascularization, the activation of this axis is a target for renal hypoxia therapies. METHODS: Sprague-Dawley rats were exposed to normobaric hypoxia and subdivided into three groups, namely group A (21% O2), group B (10% O2), and group C (7% O2). Renal tissue samples were processed and analyzed to determine pathological morphological changes, the expression of HIF, VEGF, inflammation factor and vascular density. RESULTS: We found that as the duration of hypoxia increased, destructive changes in the kidney tissues became more severe in group C (7% O2). In contrast, the increased duration of hypoxia did not exacerbate kidney damage in group B (10% O2). As the hypoxia was prolonged and the degree of hypoxia increased, the expression of HIF-1α increased gradually. As hypoxia time increased, the expression of VEGF increased gradually, but VEGF expression in group B (10% O2) was the highest. Group C (7% O2) had higher levels of IL-6, IL-10, and TNF-alpha. Additionally, the highest vascular density was observed in group B. CONCLUSION: These findings suggest that activating the HIF-VEGF signaling pathway to regulate angiogenesis after infliction of hypoxic kidney injury may provide clues for the development of novel CKD treatments.

Serum proteome-wide identified ATP citrate lyase as a novel informative diagnostic and prognostic biomarker in pediatric sepsis: A pilot study.

INTRODUCTION: ATP citrate lyase (ACLY) is involved in lipid metabolism and inflammatory response in immune cells. However, the serum level of ACLY and its clinical relevance in sepsis is totally unknown. METHODS: We conducted a prospective pilot study in patients with sepsis admitted to pediatric intensive care unit (PICU) from January 2018 to December 2018. RESULTS: Higher levels of ACLY were detected in sera of pediatric patients with sepsis than that of healthy children. The area under the receiver operating characteristic curve (AUC) of ACLY for diagnosis of sepsis was 0.855 (95% confidence interval [CI]: 0757-0.952), and an AUC of ACLY for predicting PICU mortality was 0.770 (95% CI: 0.626-0.915). ACLY levels ≤21 ng/ml on PICU admission predicted an unfavorable prognosis among patients with sepsis with a sensitivity of 87.5% and a specificity of 67.6%. Moreover, serum ACLY levels were correlated to platelet count, IL-18 levels, and monocyte counts in pediatric patients with sepsis, implying the potential roles of ACLY in immunometabolic regulation in sepsis. CONCLUSIONS: ACLY is firstly identified in sera of patients with sepsis. Serum ACLY level is an additional diagnostic and prognostic biomarker in pediatric patients with sepsis.

Methodological comparison of the allele refractory mutation system and direct sequencing for detecting EGFR mutations in NSCLC, and the association of EGFR mutations with patient characteristics.

Gefitinib is effective for patients with non-small cell lung cancer (NSCLC) with a mutation in the epidermal growth factor receptor (EGFR) gene, which makes the detection of EGFR mutations a critical step prior to determining a treatment schedule. Therefore, the present study determined the EGFR mutation status in patients with NSCLC using an allele refractory mutation system (ARMS) and analyzed the detection ratio for different specimen types. A total of 1,596 NSCLS samples were collected and EGFR gene mutations were detected on exons 18-21 using ARMS and direct sequencing. The concordance of two methods reached 89.21%, with a total mutation rate of 45.55% (727/1,596), in which the mutation rate in lung adenocarcinoma samples was markedly increased compared with squamous cell carcinoma (51.77 vs. 8.68%). In patients with lung adenocarcinoma, EGFR mutations were more frequent in female patients than male patients (65.53 vs. 39.80%, P<0.01); there was no observable difference depending on age. Similar results were obtained for squamous cell carcinoma. In the present study, certain rare mutations were also identified; these may be subjects for further study. The impact of different sample types on the consistency between the methods was determined to be insignificant. ARMS is a more applicable approach for large-scale clinical detection than direct sequencing, and we hypothesize that ARMS may replace direct sequencing if the drawbacks of ARMS, including its narrow detection range, can be amended.

Sonic hedgehog-mediated epithelial-mesenchymal transition in renal tubulointerstitial fibrosis.

The sonic hedgehog (SHH) signaling pathway plays a critical role in embryonic development, tissue regeneration and organogenesis. The activation of SHH signaling produces profibrogenic effects in various tissues, such as the liver and the biliary ducts. However, the role of SHH signaling in renal fibrogenesis remains to be elucidated. For this purpose, in the present study, we evaluated the hypothesis that activated SHH signaling promotes the acquisition of a myofibroblastic phenotype through the epithelial-mesenchymal transition (EMT), resulting in renal interstitial fibrosis (RIF). Kidney samples from rats subjected to unilateral or bilateral ureteral obstruction exhibited the enhanced expression of SHH-pathway proteins, mesenchymal markers and the decreased expression of epithelial markers. Overactive SHH signaling as well as tubular EMT and RIF in the obstructed kidneys were inhibited by recanalization of the ureter. In vitro, SHH signaling was activated during EMT induction and extracellular matrix (ECM) deposition was observed in transforming growth factor-ß1 (TGF-ß1)-treated renal tubular epithelial cells [RTECs; NRK-52E cell line]. Exogenous SHH activated SHH signaling and resulted in the upregulated expression of mesenchymal genes, the profibrogenic cytokine TGF-ß1, and the downregulated expression of epithelial markers. The blockade of SHH signaling with cyclopamine abolished SHH-mediated EMT as well as the acquisition of a myofibroblastic phenotype, and decreased TGF-ß1 expression and ECM production. Thus, taken together, these findings demonstrate that the activation of the SHH signaling pathway promotes the induction of EMT and renal tubulointerstitial fibrosis. The pharmacological inhibition of SHH signaling may potentially be of therapeutic value in the management of fibrotic kidney diseases.

Altered bulbocavernosus reflex in patients with multiple system atrophy.

OBJECTIVES: Multiple system atrophy (MSA) is characterized by a combination of symptoms including autonomic dysfunction, parkinsonism, cerebellar ataxia, and cortico-spinal disorders. The disease can have either predominant parkinsonism or cerebellar features (MSA-P and MSA-C, respectively). The measurement of the bulbocavernosus reflex (BCR) and pudendal nerve somatosensory-evoked potentials (PSEPs) was originally developed to diagnose diabetic cystopathy and other neuropathologic diseases that share similar symptoms with MSA. We investigated the relationship between abnormalities of neurophysiological parameters and MSA, and estimated the potential value of BCR. METHODS: Fifty-one MSA patients (28 and 23 MSA-P and 23 MSA-C patients, respectively) and 30 healthy controls who were seen at the Department of Neurology were included in the study. A Keypoint EMG/EP system was used to test BCR and PSEPs, and the latencies and amplitudes were recorded for statistical analyses. RESULTS: The BCR was elicited in 78.4% patients with MSA (22/28 MSA-P, 18/23 MSA-C). Prolonged BCR latencies were found in patients with MSA compared with healthy controls (p < 0.001). BCR amplitudes were significantly lower in the MSA group than the control group (p < 0.001). PSEP P41 amplitudes were not significantly different between the MSA and control groups in males (p = 0.608) or females (p = 0.897). There were no significant differences in PSEP latencies among the MSA-P, MSA-C, and control groups (p = 1.0, p = 0.263, and p = 0.060, respectively). DISCUSSION: MSA patients exhibit prolonged BCR latencies and lower amplitudes, which provides a rough anatomical localization of nervous system lesions in MSA patients.

α-Solanine inhibits vascular endothelial growth factor expression by down-regulating the ERK1/2-HIF-1α and STAT3 signaling pathways.

In tumors, vascular endothelial growth factor (VEGF) contributes to angiogenesis, vascular permeability, and tumorigenesis. In our previous study, we found that α-solanine, which is widespread in solanaceae, has a strong anti-cancer effect under normoxia. However, it is unknown whether α-solanine has a similar effect under hypoxia. We used cobalt chloride (CoCl2) to mimic hypoxia in vitro. HIF-1α, which is almost undetectable under normoxia, was significantly increased. Simultaneously, another regulator of VEGF, STAT3, was also significantly activated by CoCl2. We utilized α-solanine in co-culture with CoCl2. α-solanine decreased the expression of VEGF and loss of E-cadherin. α-solanine also suppressed the activation of phospho-ERK1/2 (p-ERK1/2), HIF-1α, and STAT3 signaling. The results provide new evidence that α-solanine has a strong anti-cancer effect via the ERK1/2-HIF-1α and STAT3 signaling pathways and suggest that it may be a potential new drug.

Roles of iron acquisition systems in virulence of extraintestinal pathogenic Escherichia coli: salmochelin and aerobactin contribute more to virulence than heme in a chicken infection model.

BACKGROUND: Avian pathogenic Escherichia coli (APEC) and uropathogenic E. coli (UPEC) are the two main subsets of extraintestinal pathogenic E. coli (ExPEC). Both types have multiple iron acquisition systems, including heme and siderophores. Although iron transport systems involved in the pathogenesis of APEC or UPEC have been documented individually in corresponding animal models, the contribution of these systems during simultaneous APEC and UPEC infection is not well described. To determine the contribution of each individual iron acquisition system to the virulence of APEC and UPEC, isogenic mutants affecting iron uptake in APEC E058 and UPEC U17 were constructed and compared in a chicken challenge model. RESULTS: Salmochelin-defective mutants E058ΔiroD and U17ΔiroD showed significantly decreased pathogenicity compared to the wild-type strains. Aerobactin defective mutants E058ΔiucD and U17ΔiucD demonstrated reduced colonization in several internal organs, whereas the heme defective mutants E058ΔchuT and U17ΔchuT colonized internal organs to the same extent as their wild-type strains. The triple mutant ΔchuTΔiroDΔiucD in both E058 and U17 showed decreased pathogenicity compared to each of the single mutants. The histopathological lesions in visceral organs of birds challenged with the wild-type strains were more severe than those from birds challenged with ΔiroD, ΔiucD or the triple mutants. Conversely, chickens inoculated with the ΔchuT mutants had lesions comparable to those in chickens inoculated with the wild-type strains. However, no significant differences were observed between the mutants and the wild-type strains in resistance to serum, cellular invasion and intracellular survival in HD-11, and growth in iron-rich or iron-restricted medium. CONCLUSIONS: Results indicated that APEC and UPEC utilize similar iron acquisition mechanisms in chickens. Both salmochelin and aerobactin systems appeared to be important in APEC and UPEC virulence, while salmochelin contributed more to the virulence. Heme bounded by ChuT in the periplasm appeared to be redundant in this model, indicating that other periplasmic binding proteins likely contributed to the observed no phenotype for the heme uptake mutant. No differences were observed between the mutants and their wild-type parents in other phenotypic traits, suggesting that other virulence mechanisms compensate for the effect of the mutations.