When Machine Learning Meets 2D Materials: A Review.

The availability of an ever-expanding portfolio of 2D materials with rich internal degrees of freedom (spin, excitonic, valley, sublattice, and layer pseudospin) together with the unique ability to tailor heterostructures made layer by layer in a precisely chosen stacking sequence and relative crystallographic alignments, offers an unprecedented platform for realizing materials by design. However, the breadth of multi-dimensional parameter space and massive data sets involved is emblematic of complex, resource-intensive experimentation, which not only challenges the current state of the art but also renders exhaustive sampling untenable. To this end, machine learning, a very powerful data-driven approach and subset of artificial intelligence, is a potential game-changer, enabling a cheaper - yet more efficient - alternative to traditional computational strategies. It is also a new paradigm for autonomous experimentation for accelerated discovery and machine-assisted design of functional 2D materials and heterostructures. Here, the study reviews the recent progress and challenges of such endeavors, and highlight various emerging opportunities in this frontier research area.

Associations of starchy and non-starchy vegetables with risk of metabolic syndrome: evidence from the NHANES 1999-2018.

BACKGROUND: Higher dietary quality, including increased vegetable consumption, was associated with a reduced risk of metabolic syndrome (MetS). However, specific vegetable consumption in the development of MetS remains obscure. Our study aimed to investigate the correlation between starchy and non-starchy vegetables and MetS. METHODS: Secondary data analysis from the National Health and Nutrition Examination Survey (NHANES 1999-2018). MetS was defined by National Cholesterol Education Program-Adult treatment Panel III (NCEP ATPIII) and dietary consumption was assessed by trained staff using two 24-h diet recall methods. Weighted logistic regression analysis was carried out to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses and restricted cubic spline (RCS) regression were performed to further investigate specific vegetable subtypes and MetS. RESULTS: This research enrolled 24,646 individuals (11,725 females and 12,921 males), with an average age of 45.84 ± 0.23 years. Approximately 15,828(64.22%) participants were defined to be with non-MetS and 8818(35.78%) were with MetS. Both total starchy vegetables and potatoes were associated with increased MetS risk, with the corresponding OR per standard deviation (SD) (95%CI, p-trend) being 1.06(1.02-1.11, p-trend = 0.028) and 1.08(1.04-1.13, p-trend = 0.011), respectively. However, an inverse correlation was found between dark-green vegetables and MetS, and the OR per SD (95%CI, p-trend) was 0.93(0.90-0.97, p-trend = 0.010). Subgroup analyses showed that the positive associations of starchy vegetables and potatoes on MetS risk were stronger in non-Hispanic White participants (p for interaction < 0.050). CONCLUSION: Total starchy vegetables and white potatoes were both associated with an increased risk of MetS, while consumption of dark-green vegetables was negatively associated with MetS risk. These findings might provide a promising and healthy dietary strategy for preventing MetS.

Nomogram analysis of the influencing factors of rapid renal decline in patients with biopsy-proven diabetic nephropathy in type 2 diabetes.

BACKGROUND: HbA1c variability may be related to risk of poor prognoses in chronic kidney disease patients with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether HbA1c variability is associated with rapid renal function decline and the related risk factors in type 2 diabetic nephropathy (DN). MATERIALS AND METHODS: An observational analysis was performed on 387 DN patients who were diagnosed by kidney biopsy from January 2006 through January 2016 at the Department of Nephrology, Jinling Hospital Affiliated to Nanjing University. The rapid decliners were defined as an estimated glomerular filtration rate (eGFR) decline slope ≥ 5 mL/min/1.73m2/year. HbA1c variability and 24 baseline clinicopathologic parameters was evaluated using the least absolute shrinkage and selection operator regression (LASSO) and multivariate logistic regression. The nomogram method was applied to score the factors, and a scoring model was constructed. RESULTS: HbA1c variability positively correlated with the rate of renal function decline (r = 0.277; p < 0.001). Higher baseline eGFR, lower serum calcium concentration, glomerular lesions, arteriosclerosis, and interstitial fibrosis and tubular atrophy (IFTA) were selected into the nomogram. The calibration curve for the probability of survival showed good agreement between the prediction by nomogram and actual observation. The C-index for predicting survival was 0.811 (95% confidence interval (CI) 0.680 - 0.785). CONCLUSION: The proposed nomogram and score provide a useful risk estimate of fast renal function decline in patients with type 2 diabetic nephropathy.

RAGE inhibition alleviates lipopolysaccharides-induced lung injury via directly suppressing autophagic apoptosis of type II alveolar epithelial cells.

BACKGROUND: Advanced glycation end product receptor (RAGE) acts as a receptor of pro-inflammatory ligands and is highly expressed in alveolar epithelial cells (AECs). Autophagy in AECs has received much attention recently. However, the roles of autophagy and RAGE in the pathogenesis of acute lung injury remain unclear. Therefore, this study aimed to explore whether RAGE activation signals take part in the dysfunction of alveolar epithelial barrier through autophagic death. METHODS: Acute lung injury animal models were established using C57BL/6 and Ager gene knockout (Ager -/- mice) mice in this study. A549 cells and primary type II alveolar epithelial (ATII) cells were treated with siRNA to reduce Ager gene expression. Autophagy was inhibited by 3-methyladenine (3-MA). Lung injury was assessed by histopathological examination. Cell viability was estimated by cell counting kit-8 (CCK-8) assay. The serum and bronchoalveolar lavage fluid (BALF) levels of interleukin (IL)-6, IL-8 and soluble RAGE (sRAGE) were evaluated by Enzyme-linked immunosorbent assay (ELISA). The involvement of RAGE signals, autophagy and apoptosis was assessed using western blots, immunohistochemistry, immunofluorescence, transmission electron microscopy and TUNEL test. RESULTS: The expression of RAGE was promoted by lipopolysaccharide (LPS), which was associated with activation of autophagy both in mice lung tissues and A549 cells as well as primary ATII cells. sRAGE in BALF was positively correlated with IL-6 and IL-8 levels. Compared with the wild-type mice, inflammation and apoptosis in lung tissues were alleviated in Ager-/- mice. Persistently activated autophagy contributed to cell apoptosis, whereas the inhibition of autophagy by 3-MA protected lungs from damage. In addition, Ager knockdown inhibited LPS-induced autophagy activation and attenuated lung injury. In vitro, knockdown of RAGE significantly suppressed the activation of LPS-induced autophagy and apoptosis of A549 and primary ATII cells. Furthermore, RAGE activated the downstream STAT3 signaling pathway. CONCLUSION: RAGE plays an essential role in the pathogenesis of ATII cells injury. Our results suggested that RAGE inhibition alleviated LPS-induced lung injury by directly suppressing autophagic apoptosis of alveolar epithelial cells.

Neuroprotective effects of neural stem cells pretreated with neuregulin1ß on PC12 cells exposed to oxygen-glucose deprivation/reoxygenation.

Studies on ischemia/reperfusion (I/R) injury suggest that exogenous neural stem cells (NSCs) are ideal candidates for stem cell therapy reperfusion injury. However, NSCs are difficult to obtain owing to ethical limitations. In addition, the survival, differentiation, and proliferation rates of transplanted exogenous NSCs are low, which limit their clinical application. Our previous study showed that neuregulin1ß (NRG1ß) alleviated cerebral I/R injury in rats. In this study, we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1ß on PC12 cells injured by oxygen-glucose deprivation/reoxygenation (OGD/R). Our results found that 5 and 10 nM NRG1ß promoted the generation and proliferation of NSCs. Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1ß improved the level of reactive oxygen species, malondialdehyde, glutathione, superoxide dismutase, nicotinamide adenine dinucleotide phosphate, and nuclear factor erythroid 2-related factor 2 (Nrf2) and mitochondrial damage in injured PC12 cells; these indexes are related to ferroptosis. Research has reported that p53 and solute carrier family 7 member 11 (SLC7A11) play vital roles in ferroptosis caused by cerebral I/R injury. Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4 (GPX4) was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells, but this change was alleviated after co-culturing NSCs with damaged PC12 cells. These findings suggest that NSCs pretreated with NRG1ß exhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.

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.

Serum vimentin predicts mortality in pediatric severe sepsis: A prospective observational study.

OBJECTIVES: Vascular hyperpermeability by loss of endothelial barrier integrity is a hallmark of sepsis. Vimentin is involved in the regulation of the endothelial function and inflammatory response. However, the serum level of vimentin and its clinical relevance in pediatric severe sepsis (PSS) remain unknown. METHODS: We conducted a prospective study of PSS cases who were admitted to the pediatric intensive care unit (PICU) from January 2018 to December 2020. RESULTS: A total of 108 patients with PSS with a median age of 19.5 month were enrolled. The hospital mortality rate was 19.44% (21/108). Comparing with healthy controls, serum vimentin levels on PICU admission were significantly higher in patients with PSS (P < 0.001). The area under the ROC curve for vimentin to predict the hospital mortality was 0.712 (95% CI: 0.578-846) with a sensitivity of 71.43% and a specificity of 70.11%. Moreover, hospital mortality was significantly higher in patients with vimentin level over the cutoff value of 24.53 ng/ml than in patients with vimentin level below 24.53 ng/ml (P < 0.001). CONCLUSIONS: Serum vimentin level as an indicator of endothelial injury is associated with the prognosis of PSS, and serum vimentin level ≥24.53 ng/ml on PICU admission predicts high risk for hospital mortality in PSS.

Transplantation of Human Umbilical Cord Mesenchymal Stem Cells-Derived Neural Stem Cells Pretreated with Neuregulin1ß Ameliorate Cerebral Ischemic Reperfusion Injury in Rats.

Ischemic stroke is a common cerebrovascular disease and recovering blood flow as early as possible is essential to reduce ischemic damage and maintain neuronal viability, but the reperfusion process usually causes additional damage to the brain tissue in the ischemic area, namely ischemia reperfusion injury. The accumulated studies have revealed that transplantation of exogenous neural stem cells (NSCs) is an ideal choice for the treatment of ischemia reperfusion injury. At present, the source and efficacy of exogenous NSCs after transplantation is still one of the key issues that need to be resolved. In this study, human umbilical cord mesenchymal stem cells (hUC-MSCs) were obtained and induced into NSCs byadding growth factor and neuregulin1ß (NRG1ß) was introduced during the differentiation process of NSCs. Then, the rat middle cerebral artery occlusion/reperfusion (MCAO/R) models were established, and the therapeutic effects were evaluated among groups treated by NRG1ß, NSCs and NSCs pretreated with 10 nM NRG1ß (NSCs-10 nM NRG1ß) achieved through intra-arterial injection. Our data show that the NSCs-10 nM NRG1ß group significantly improves neurobehavioral function and infarct volume after MCAO/R, as well as cerebral cortical neuron injury, ferroptosis-related indexes and mitochondrial injury. Additionally, NSCs-10 nM NRG1ß intervention may function through regulating the p53/GPX4/SLC7A11 pathway, and reducing the level of ferroptosis in cells, further enhance the neuroprotective effect on injured cells.

Neuroprotective effects of salidroside on ageing hippocampal neurons and naturally ageing mice via the PI3K/Akt/TERT pathway.

Studies have found that salidroside, isolated from Rhodiola rosea L, has various pharmacological activities, but there have been no studies on the effects of salidroside on brain hippocampal senescence. The purpose of this study was to investigate the mechanistic role of salidroside in hippocampal neuron senescence and injury. In this study, long-term cultured primary rat hippocampal neurons and naturally aged C57 mice were treated with salidroside. The results showed that salidroside increased the viability and MAP2 expression, reduced ß-galactosidase (ß-gal) levels of rat primary hippocampal neurons. Salidroside also improved cognition dysfunction in ageing mice and alleviated neuronal degeneration in the ageing mice CA1 region. Moreover, salidroside decreased the levels of oxidative stress and p21, p16 protein expressions of hippocampal neurons and ageing mice. Salidroside promoted telomerase reverse transcriptase (TERT) protein expression via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway. In conclusion, our findings suggest that salidroside has the potential to be used as a therapeutic strategy for anti-ageing and ageing-related disease treatment.

Cerebroprotein Hydrolysate-I Inhibits Hippocampal Neuronal Apoptosis by Activating PI3K/Akt Signaling Pathway in Vascular Dementia Mice.

INTRODUCTION: Vascular dementia (VaD), one of the brain injuries, is difficult to be cured, so it is important to take active neuroprotective treatment after its occurrence. Many studies have shown that apoptosis serves an important role in VaD occurrence; therefore, inhibition of apoptosis may contribute to the recovery of neurological function after VaD occurrence. Cerebroprotein hydrolysate-I (CH-I), a neuropeptide preparation which consists of several amino acids and small molecular peptides as the main active constituent, is extracted using a method similar to cerebrolysin (CBL) which has neuroprotective and neurotrophic effects. METHODS: In the present study, a VaD model which was constructed using bilateral common carotid artery occlusion (BCCAO) in Kunming mice was applied to examine the neuroprotective effects of CH-I. RESULTS: The results show that CH-I treatment could attenuate the decrease of learning and memory ability, cell apoptosis in the hippocampal CA1 region and inhibit the activation of caspase-3 and caspase-9 in VaD mice. Furthermore, CH-I treatment could also upregulate Bcl-2 protein levels and activate PI3K and Akt. DISCUSSION: We speculate that CH-I may induce a neuroprotective effect activating PI3K/Akt signaling pathway in VaD mice.

The Cerebroprotein Hydrolysate-I Plays a Neuroprotective Effect on Cerebral Ischemic Stroke by Inhibiting MEK/ERK1/2 Signaling Pathway in Rats.

OBJECTIVE: To investigate the neuroprotective effect and mechanism of cerebroprotein hydrolysate-I (CH-I) on cerebral ischemia/reperfusion injury in rats. METHODS: A total of 100 adult healthy male SD rats were randomly divided into a sham group, model group, CH-I treated group, and cerebrolysin (CBL) positive group, consisting of 20 rats in each group. The middle cerebral artery occlusion/reperfusion (MCAO/R) model of rats was built by inserting a suture into the left external carotid artery (ECA) through the internal carotid artery (ICA). Treatment was performed by intraperitoneal injection of CH-I (20 mg/kg). The neurobehavioral function of rats was evaluated by modified neurological severity scores (mNSS). TTC staining was used to detect the cerebral infarction volume (CIV) of rats. The morphological and structural changes of nerve cells were observed by HE staining and the neuronal apoptosis was counted by TUNEL assay. Immunohistochemical (IHC) analysis was used to detect BDNF and pMEK1/2 expressions. The expressions of BDNF, pMEK1/2, pERK1/2, and pCREB were determined with Western blotting. RESULTS: After treatment with CH-I, the mNSS and CIV of rats were improved (P<0.05). And the CH-I can reduce the degeneration and apoptosis of nerve cells in rats (P<0.01). Western blotting showed that the expressions of pMEK1/2, pERK1/2, and pCREB in rats were increased, while the expression of BDNF was decreased after modeling (P<0.05). After treatment, the expressions of pMEK1/2, pERK1/2, and pCREB in the CH-I group were decreased (P<0.05), while the expression of BDNF was significantly increased (P<0.05) compared with the model group. IHC showed that the expression of BDNF and pMEK1/2 was consistent with Western blotting. CONCLUSION: It is suggested that the CH-I might play a neuroprotective role by inhibiting the expression of MEK-ERK-CREB and enhancing the expression of BDNF after cerebral ischemia/reperfusion injury, thus improving the neurobehavioral function of MCAO/R rats.

Cerebroprotein hydrolysate-I protects senescence-induced by D-galactose in PC12 cells and mice.

Cerebroprotein hydrolysate-I (CH-I)，a mixture of peptides extracted from porcine brain tissue，has shown a neuroprotective effect, but its role in brain senescence is unclear. In the present study, we established a senescence model of PC12 cells and mice to investigate the effect of CH-I on brain senescence via JAK2/STAT3 pathway. The results showed that CH-I could improve cell viability, inhibit the apoptosis of cells, and reduce the senescence-positive cells induced by D-galactose. In vivo, CH-I improved the learning ability and memory of aging mice, reduced neuronal damage in mice hippocampus. Mechanism studies showed that CH-I could adjust BDNF protein expressions, activate JAK2/STAT3 pathway, and finally enhance telomerase activity. All these findings indicated that CH-I showed a neuroprotective effect against brain senescence. These results might provide further reference and support for the application of CH-I in delaying aging.

IL-22 ameliorates LPS-induced acute liver injury by autophagy activation through ATF4-ATG7 signaling.

Uncontrollable inflammatory response acts as a driver of sepsis-associated liver injury (SALI). IL-22 plays an important role in regulating inflammatory responses, but its role in SALI remains unknown. The aim of the study was to assess the association of serum IL-22 with SALI in pediatric patients and to enclose the underlying mechanisms of IL-22 involved in lipopolysaccharide (LPS) - induced acute liver injury (ALI) in mice. Serum IL-22 levels in patients with SALI were significantly lower than in septic patients without liver injury, and the area under receiver operating characteristic (ROC) curve of IL-22 for discriminating SALI was 0.765 (95% CI: 0.593-0.937). Pre-administration of recombinant murine IL-22 alleviated LPS-induced ALI in mice, and serum IL-6 levels and the mRNA levels of TNF-α, IL-1ß, and IL-6 in livers were decreased in response to IL-22 pre-treatment in mice. More importantly, IL-22 pre-treatment activated hepatic autophagy mediated by activating transcription factor 4 (ATF4)-autophagy-related gene 7 (ATG7) signaling in vivo and in vitro in response to LPS administration. Moreover, knockdown of ATF4 in mice aggravated LPS-induced ALI, which was associated with suppressed ATG7-related autophagy. In addition, the protective effects of IL-22 on LPS-induced ALI was partially blocked by ATF4 knockdown, which was associated with lower expression of LC3II/I in the livers of ATF4 knockdown (HT or Atf4+/-) mice compared with wild-type mice (WT or Atf4+/+) mice. In conclusion, low serum IL-22 level is associated with SALI occurrence, and IL-22 pre-administration activates autophagy in hepatocytes and protects mice against LPS-induced ALI partially related to ATF4-ATG7 signaling pathway.

CD163 as a valuable diagnostic and prognostic biomarker of sepsis-associated hemophagocytic lymphohistiocytosis in critically ill children.

OBJECTIVE: To investigate CD163 as an effective biomarker for identifying and predicting the outcomes of sepsis-associated hemophagocytic lymphohistiocytosis (SAHS) in children. METHODS: We prospectively enrolled presumed sepsis patients who had developed prolonged fever (>7 days), hepatosplenomegaly, cytopenias, and hyperferritinemia (>500 ng/mL) despite antibiotic therapy. Blood samples were collected within 24 hours after enrolment. A nested case-control study was performed. The number of patients who fulfilled the HLH-2004 criteria, 28-day mortality outcomes, and 90-day mortality outcomes were recorded. RESULTS: Sixty-nine patients were enrolled in the study. Significant increases in the levels of ferritin and soluble CD163 (sCD163) and the percentage of CD163-positive peripheral blood mononuclear cells (mCD163) and decreases in fibrinogen levels and the percentage of natural killer cells (NK %) were observed in patients with SAHS (n = 23) compared with those of patients with sepsis (n = 46). The area under the ROC curve (AUC) for ferritin combined with sCD163 was superior to the AUC for either ferritin or sCD163 for distinguishing SAHS from sepsis. Moreover, sCD163 was a prognostic factor for 28-day mortality (0.857 [0.659-1.000]). CONCLUSIONS: sCD163 is a valuable biomarker for the differential diagnosis of SAHS from sepsis and effectively predicts 28-day mortality in children with SAHS.

Continuous hemofiltration improves the prognosis of bacterial sepsis complicated by liver dysfunction in children.

BACKGROUND: Liver dysfunction is an independent risk factor for poor prognosis of patients with sepsis. The aim of this study is to evaluate the effects of continuous hemofiltration in patients with bacterial sepsis complicated by liver dysfunction. METHODS: We retrospectively analyzed the medical records of 27 cases of bacterial sepsis with liver dysfunction admitted to pediatric intensive care unit (PICU) of Shanghai Children's Hospital between January 2013 and December 2016. RESULTS: 28-day mortality and length of PICU stay were significantly reduced in the continuous hemofiltration group (n = 16) compared with the conventional management group (n = 11) (31.3% vs. 72.7%, 9 [4-23] vs. 14 [4-36], respectively, both P < 0.05). The interval time between PICU admission and continuous hemofiltration initiation was (22.06 ± 17.68) h, and the median time of continuous hemofiltration duration was 48 h (31-70 h). After 72 h hemofiltration, the levels of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acids (TBA), ammonia, lactate (Lac), TNF-α and IL-6 were significantly decreased in the continuous hemofiltration group. Moreover, multivariate logistic regression analysis indicated that continuous hemofiltration treatment and the TBIL level were independently associated with 28-day mortality of patients with bacterial sepsis complicated by liver dysfunction. CONCLUSIONS: Continuous hemofiltration significantly decreases the serum levels of TBIL, DBIL, TBA, Lac, ammonia, TNF-α, IL-6, and improves 28-day mortality of patients with bacterial sepsis complicated by liver dysfunction.

Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation.

BACKGROUND: Cholestasis, as a main manifestation, induces liver injury during sepsis. The farnesoid X receptor (FXR) plays an important role in regulating bile acid homeostasis. Whether FXR activation by its agonist obeticholic acid (OCA) is contributed to improve sepsis-induced liver injury remains unknown. OBJECTIVE: The aim of the present study was to investigate the effect of OCA on lipopolysaccharide (LPS)-induced acute liver injury in mice. RESULTS: 8-week old male C57BL/6J mice were randomly divided into control group, LPS group, oral OCA group and LPS plus oral OCA (LPS + OCA) group. The serum and livers were collected for further analysis. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and total bilirubin (TBIL) were measured at indicated time after LPS administration. Liver sections were stained with hematoxylin & eosin (H&E). Orally OCA pretreatment stimulated the expression of FXR and BSEP in livers and protected mice from LPS-induced hepatocyte apoptosis and inflammatory infiltration. Consistently, LPS-induced higher serum levels of ALT, AST, TBA and TBIL were significantly reversed by OCA administration. Meanwhile, the mRNA levels of interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α) and IL-6 were decreased in livers of mice in LPS + OCA group compared with LPS group. Further investigation indicated that the higher expression of ATF4 and LC3II/I were associated with the protective effect of OCA on LPS-induced liver injury. CONCLUSION: Orally OCA pretreatment protects mice from LPS-induced liver injury possibly contributed by improved bile acid homeostasis, decreased inflammatory factors and ATF4-mediated autophagy activity in hepatocytes.

Pediatric esophagopleural fistula: Two case reports and a literature review.

Esophagopleural fistula (EPF) is rarely reported in children with a high misdiagnosis rate. This study aimed to reveal the clinical manifestations and managements of EPF in children.Two pediatric cases of EPF in our hospital were reported. A bibliographic search was performed on the PubMed, WANFANG, and CNKI databases for EPF-related reports published between January 1980 and May 2016. The pathogeny, clinical manifestations, diagnosis, treatments, and prognosis of EPF patients were collected and discussed.Based on conservative treatments, 1 pediatric EPF case induced by cervical trauma was cured by longitudinal septum incision-mediated drainage. The other pediatric EPF induced by endoscopic balloon dilation was cured by dual stent implantation. A total of 38 studies of 197 EPF patients (191 adults and 6 children) were reviewed. Latrogenic factor, esophageal foreign body, and infection are considered the main causes of EPF in children. Unilateral pleural effusion accompanied by food residue was the main manifestations of EPF. Chest computed tomography (CT) and contrast esophagography were usually used in the diagnosis of EPF with high accuracy. Surgical treatment in adults with EPF exhibited a significantly higher cure rate and lower mortality rate than conservative treatment (P < .01).Pleural effusion with food residue is a specific finding in EPF. Chest CT exhibited high sensitivity for the diagnosis of EPF. Conservative treatment may be preferable for pediatric patients with EPF.

Inhibition of microRNA-155 alleviates lipopolysaccharide-induced kidney injury in mice.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Accumulated evidences suggest that microRNAs (miRNAs) are related with inflammation-associated diseases.The aim of this study is to investigate whether miR-155 is involved in lipopolysaccharide (LPS)-induced kidney injury, and to explore the underlying mechanisms. Mice were intraperitoneally injected with LPS to construct endotoxemia mice model, and miR-155 inhibitor was injected via tail vein to suppress the expression of miR-155 in kidney. The results indicated that the expression of miR-155 was markedly increased in renal tissues of LPS-treated mice. And miR-155 inhibitor protected mice from LPS-induced kidney injury associated with the lower levels of TNF-α and IL-6 in renal tissues. Furthermore, inhibition of miR-155 increased the expression of suppressor of cytokine signaling 1 (SOCS1), a target gene of miR-155 and a negative regulator of Janus activated kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. Consistently, inhibition of miR-155 suppressed the expression of JAK2, STAT3 and phosphorylated STAT3 (p-STAT3). All these results indicated that inhibition of miR-155 protects mice from LPS-induced kidney injury possibly through regulating SOCS1-JAK2/STAT signaling pathway, which suggested that miR-155 might be an important and potential target in developing therapy for preventing sepsis-associated kidney injury.

High-Volume Hemofiltration in Critically Ill Patients With Secondary Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome: A Prospective Study in the PICU.

OBJECTIVES: Hemophagocytic lymphohistiocytosis, which includes primary (familial) and secondary hemophagocytic lymphohistiocytosis, is a fatal disease in children. Macrophage activation syndrome was defined in patients who met secondary hemophagocytic lymphohistiocytosis criteria with an underlying autoimmune disease. High-volume hemofiltration has shown beneficial effects in severe sepsis and multiple organ dysfunction syndrome. Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome shares many pathophysiologic similarities with sepsis. The present study assessed the effects of high-volume hemofiltration in children with secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. DESIGN: A single-center nonrandomized concurrent control trial. SETTING: The PICU of Shanghai Children's Hospital, Shanghai Jiao Tong University. PATIENTS: Thirty-three critically ill secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome patients treated between January 2010 and December 2014. INTERVENTIONS: Thirty-three patients were divided into two groups: high-volume hemofiltration + hemophagocytic lymphohistiocytosis-2004 group (17 cases) or hemophagocytic lymphohistiocytosis-2004 group (16 cases). High-volume hemofiltration was defined as an ultrafiltrate flow rate of 50-70 mL/kg/hr. Clinical and biological variables were assessed before initiation and after 48 and 72 hours of high-volume hemofiltration therapy. MEASUREMENTS AND MAIN RESULTS: The total mortality rate was 42.4% (14/33), but mortality at 28 days was not significantly different between the two groups (high-volume hemofiltration + hemophagocytic lymphohistiocytosis-2004 group: five deaths, 29.4%; hemophagocytic lymphohistiocytosis-2004 group: nine deaths, 56.3%; chi-square, 2.431; p = 0.119). Children received high-volume hemofiltration for 60.2 ± 42.0 hours. After 48 and 72 hours respectively, a significant decrease in serum ferritin (p < 0.001), aspartate aminotransferase (p = 0.037 and p < 0.001), total bilirubin (p = 0.041 and p = 0.037), and serum creatinine (p = 0.006 and p = 0.004) levels were observed. Furthermore, the natural killer-cell activity up-regulated (p = 0.047) after 72 hours. Furthermore, significantly decreased levels of serum tumor necrosis factor-α (from 91.5 ± 44.7 ng/L at 48 hr to 36.7 ± 24.9 ng/L at 72 hr; p = 0.007)) and interleukin-6 (from 46.9 ± 21.1 ng/L at 48 hr to 27.7 ± 14.5 ng/L at 72 hr; p < 0.0001) were observed. After 7 days, patients receiving high-volume hemofiltration had significantly lower bilirubin, creatinine, ferritin, procalcitonin, lactate dehydrogenase level, tumor necrosis factor-α, and interleukin-6 levels, and needed less mechanical ventilation compared with hemophagocytic lymphohistiocytosis-2004 group patients. No serious adverse events were observed. CONCLUSIONS: High-volume hemofiltration may improve organ function by decreasing cytokine levels (tumor necrosis factor-α and interleukin-6). High-volume hemofiltration may be an effective adjunctive treatment in secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome.

Inhibition of microRNA­155 relieves sepsis­induced liver injury through inactivating the JAK/STAT pathway.

The present study aimed to investigate whether the microRNA (miR)­155 inhibitor has an anti­inflammatory effect on sepsis­associated liver injury and whether this effect is associated with the activity of the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. BALB/c mice were randomly divided into three groups (n=40 per group): Control, lipopolysaccharide (LPS) and miR­155 inhibitor plus LPS groups. Liver injury was induced by injection of LPS (20 mg kg­1). In the inhibitor plus LPS group, LPS was administered after injecting the miR­155 inhibitor (80 mg kg­1) for 3 days. Liver tissues were collected at 6, 12, 24 and 48 h after LPS exposure. Hematoxylin and eosin was used to identify the histological changes in the liver. The expression levels of miR­155, suppressor of cytokine signaling 1 (SOCS1) and STAT1 were determined by reverse transcription­quantitative polymerase chain reaction. The protein expression of tumor necrosis factor (TNF)­α and interleukin (IL)­10 were detected by ELISA. miR­155 inhibitor pretreatment alleviated the symptoms of LPS­exposed mice, and reduced LPS­induced mortality and liver injury. Compared with the LPS group, expression of miR­155 was significantly reduced in the miR­155 inhibitor plus LPS group at 6 h (P<0.05). SOCS1 expression was significantly increased in miR­155 inhibitor plus LPS group compared with the control and the LPS group at 12 h (P<0.05). There was a lower level of STAT1 in the miR­155 inhibitor plus LPS group compared with the LPS group (P<0.05). In addition, TNF­α and IL­10 were significantly decreased in the miR­155 inhibitor plus LPS group compared with the LPS group (P<0.05). In conclusion, the miR­155 inhibitor relieves liver injury by enhancing the expression of SOCS1 and inactivating JAK/STAT signaling.