Arsenic Removal via the Biomineralization of Iron-Oxidizing Bacteria Pseudarthrobacter sp. Fe7.

Arsenic (As) is a highly toxic metalloid, and its widespread contamination of water is a serious threat to human health. This study explored As removal using Fe(II)-oxidizing bacteria. The strain Fe7 isolated from iron mine soil was classified as the genus Pseudarthrobacter based on 16S rRNA gene sequence similarities and phylogenetic analyses. The strain Fe7 was identified as a strain of Gram-positive, rod-shaped, aerobic bacteria that can oxidize Fe(II) and produce iron mineral precipitates. X-ray diffraction, X-ray photoelectron spectroscopy, and energy-dispersive X-ray spectroscopy patterns showed that the iron mineral precipitates with poor crystallinity consisted of Fe(III) and numerous biological impurities. In the co-cultivation of the strain Fe7 with arsenite (As(III)), 100% of the total Fe and 99.9% of the total As were removed after 72 h. During the co-cultivation of the strain Fe7 with arsenate (As(V)), 98.4% of the total Fe and 96.9% of the total As were removed after 72 h. Additionally, the iron precipitates produced by the strain Fe7 removed 100% of the total As after 3 h in both the As(III) and As(V) pollution systems. Furthermore, enzyme activity experiments revealed that the strain Fe7 oxidized Fe(II) by producing extracellular enzymes. When 2% (v/v) extracellular enzyme liquid of the strain Fe7 was added to the As(III) or As(V) pollution system, the total As removal rates were 98.6% and 99.4%, respectively, after 2 h, which increased to 100% when 5% (v/v) and 10% (v/v) extracellular enzyme liquid of the strain Fe7 were, respectively, added to the As(III) and As(V) pollution systems. Therefore, iron biomineralized using a co-culture of the strain Fe7 and As, iron precipitates produced by the strain Fe7, and the extracellular enzymes of the strain Fe7 could remove As(III) and As(V) efficiently. This study provides new insights and strategies for the efficient remediation of arsenic pollution in aquatic environments.

Endogenous FGF1 Deficiency Aggravates Doxorubicin-Induced Hepatotoxicity.

Doxorubicin (DOX) is a broad-spectrum antineoplastic agent that widely used in clinic. However, its application is largely limited by its toxicity in multiple organs. Fibroblast growth factor 1 (FGF1) showed protective potential in various liver diseases, but the role of endogenous FGF1 in DOX-induced liver damage is currently unknown. Both wild-type (WT) and FGF1 knockout (FGF1-KO) mice were treated with DOX. DOX induced loss of body weight and liver weight and elevation of ALT and AST in WT mice, which were aggravated by FGF1 deletion. FGF1 deletion exacerbated hepatic oxidative stress mirrored by further elevated 3-nitrosative modification of multiple proteins and malondialdehyde content. These were accompanied by blunted compensatively antioxidative responses indicated by impaired upregulation of nuclear factor erythroid 2-related factor 2 and its downstream antioxidant gene expression. The aggravated oxidative stress was coincided with exacerbated cell apoptosis in DOX-treated FGF1-KO mice reflected by further increased TUNEL positive cell staining and BCL-2-associated X expression and caspase 3 cleavage. These detrimental changes in DOX-treated FGF1-KO mice were associated with worsened intestinal fibrosis and increased upregulation fibrotic marker connective tissue growth factor and α-smooth muscle actin expression. However, DOX-induced hepatic inflammatory responses were not further affected by FGF1 deletion. These results demonstrate that endogenous FGF1 deficiency aggravates DOX-induced liver damage and FGF1 is a potential therapeutic target for treatment of DOX-associated hepatoxicity.

Protective effect of ethyl ferulate against hypoxic injury in retinal cells and retinal neovascularization in an oxygen-induced retinopathy model.

BACKGROUND: Pathological neovascularization is a major cause of visual impairment in hypoxia-induced retinopathy. Ethyl ferulate (EF), the natural ester derivative of ferulic acid commonly found in Ferula and Angelica Sinensis, has been shown to exert antioxidant, neuroprotective, and anti-inflammatory properties. However, whether EF exerts a protective effect on retinal neovascularization and the underlying mechanisms are not well known. PURPOSE: The aim of the study was to investigate the effect of EF on retinal neovascularization and explore its underlying molecular mechanisms. STUDY-DESIGN/METHODS: We constructed hypoxia models induced by cobalt chloride (CoCl2) in ARPE-19 cells and Rhesus choroid-retinal vascular endothelial (RF/6A) cells in vitro, as well as a retinal neovascularization model in oxygen-induced retinopathy (OIR) mice in vivo. RESULTS: In this work, we demonstrated that EF treatment inhibited hypoxia-induced vascular endothelial growth factor A (VEGFA) expression in ARPE-19 cells and abrogated hypoxia-induced tube formation in RF/6A cells. As expected, intravitreal injection of EF significantly suppressed retinal neovascularization in a dose-dependent manner in OIR retinas. We also found that hypoxia increased VEGFA expression by blocking autophagic flux, whereas EF treatment enhanced autophagic flux, thereby reducing VEGFA expression. Furthermore, EF activated the sequestosome 1 (p62) / nuclear factor E2-related factor 2 (Nrf-2) pathway via upregulating oxidative stress-induced growth inhibitor 1 (OSGIN1) expression, thus alleviating oxidative stress and reducing VEGFA expression. CONCLUSION: As a result of our findings, EF has an inhibitory effect on retinal neovascularization, implying a potential therapeutic strategy for hypoxia-induced retinopathy.

Preliminary Experience with Continuous Submucosal Anastomosis in Small-Diameter Hepaticojejunostomy during Single-Port Laparoscopic Choledochal Cyst Surgery in Children.

PURPOSE: Hepaticojejunostomy anastomosis (HJA) is the most challenging aspect in single-port laparoscopic choledochal cystectomy and Roux-en-Y hepaticojejunostomy (SPCH) in children, especially in small-diameter anastomoses (diameters less than 5 mm), which are more susceptible to anastomotic stricture. We developed the continuous submucosal technique for HJA (CS-HJA) to lessen postoperative complications. The purpose of this study is to introduce our preliminary experiences with CS-HJA. METHODS: We retrospectively analyzed all available clinical data of children who underwent SPCH surgery between March 2020 and October 2022. We operated with CS-HJA on 10 children who were diagnosed with small-diameter hepaticojejunostomy (diameter less than 5 mm). Data collection mainly included demographic information, imaging data, perioperative details, and postoperative outcomes. Ten patients were included in this study. The average patient age was 55.2 months; the age range was 3 to 120 months, and the average weight was 11.6 kg; male-female ratio was 1:9. The choledocho had fusiform dilatation in five cases and cystic dilatation in five cases. There was no dilatation of the left and right hepatic ducts or intrahepatic bile ducts in all patients. All patients had no dilatation of the left and right hepatic ducts or intrahepatic bile ducts. All patients underwent a single-port laparoscopic bile-intestinal anastomosis using a submucosal jejunal anastomosis technique. Analysis of the duration of the bile-intestinal anastomosis, the length of the child's stay in the hospital after surgery, the intraoperative complications, and the postoperative complications was performed. RESULTS: All the 10 patients underwent successful SPCH by CS-HJA technique. The average length of time for hepaticojejunostomy ranged from 22 to 40 minutes, and the postoperative hospital stay was 5.2 to 9.2 days. There were no instances of bile leakage following the operation. At 17 to 30 months of follow-up, there was no abdominal pain or jaundice, and the reexamination of transaminases, bilirubin, and amylase were normal. Ultrasonography showed no bile duct stricture or dilated bile ducts, and the incision is elegant, and the families of the patients were satisfied. CONCLUSION: In SPCH surgery in children, the CS-HJA technique is safe and feasible for small-diameter hepaticojejunostomy.

Developing a nomogram for predicting surgical intervention in pediatric intussusception after hydrostatic reduction.

Purpose: The aim of this study was to develop and validate a nomogram for predicting surgical intervention in pediatric intussusception after hydrostatic reduction. Methods: Children with intussusception who had treated with sonographically guided saline hydrostatic reduction as an initial treatment were enrolled in this study. The enrolled patients were randomly selected for training and validation sets, and the split ratio was 7:3. The medical records of enrolled patients were retrospectively reviewed. The patients were divided into a surgery and a non-surgery group according to the results of the nonsurgical reduction. A model for predicting the risk of surgical treatment was virtualized by the nomogram using logistic regression analysis. Results: The training set consisted of 139 patients and the validation set included 74. After logistic regression analysis using training set, duration of symptoms, bloody stools, white blood cells (WBCs), creatine kinase isoenzyme (CK-MB), long-axis diameter, poor prognostic signs by ultrasound and mental state were identified as the independent predictors of surgical intervention for intussusception. A model that incorporated the above independent predictors was developed and presented as a nomogram. The C-index of the nomogram in the validation set was 0.948 (95% CI, 0.888-1.000). The calibration curve demonstrated a good agreement between prediction and observation. The decision curve analysis (DCA) curve showed that the model achieved a net benefit across all threshold probabilities. Conclusion: Based on the predictors of duration of symptoms, bloody stools, WBCs, CK-MB, long-axis diameter, poor prognostic signs by ultrasound and mental state, we developed a nomogram for predicting surgical intervention after hydrostatic reduction. This nomogram could be applied directly to facilitate pre-surgery decision for pediatric intussusception.

Midkine inhibition enhances anti-PD-1 immunotherapy in sorafenib-treated hepatocellular carcinoma via preventing immunosuppressive MDSCs infiltration.

Sorafenib, a multiple-target tyrosine kinase inhibitor, is the standard of care for patients with advanced hepatocellular carcinoma (HCC), but provides limited benefits. Emerging evidences suggest that prolonged sorafenib treatment induces an immunosuppressive HCC microenvironment, but the underling mechanism is undetermined. In the present study, the potential function of midkine, a heparin-binding growth factor/cytokine, was evaluated in sorafenib-treated HCC tumors. Infiltrating immune cells of orthotopic HCC tumors were measured by flow cytometry. Differentially expressed genes in sorafenib-treated HCC tumors were evaluated by transcriptome RNA sequencing. The potential function of midkine were evaluated by western blot, T cell suppression assay, immunohistochemistry (IHC) staining and tumor xenograft model. We found that sorafenib treatment increased intratumoral hypoxia and altered HCC microenvironment towards an immune-resistant state in orthotopic HCC tumors. Sorafenib treatment promoted midkine expression and secretion by HCC cells. Moreover, forced midkine expression stimulated immunosuppressive myeloid-derived suppressor cells (MDSCs) accumulation in HCC microenvironment, while knockdown of midkine exhibited opposite effects. Furthermore, midkine overexpression promoted CD11b+CD33+HLA-DR- MDSCs expansion from human PBMCs, while midkine depletion suppressed this effect. PD-1 blockade showed no obvious inhibition on tumor growth of sorafenib-treated HCC tumors, but the inhibitory effect was greatly enhanced by midkine knockdown. Besides, midkine overexpression promoted multiple pathways activation and IL-10 production by MDSCs. Our data elucidated a novel role of midkine in the immunosuppressive microenvironment of sorafenib-treated HCC tumors. Mikdine might be a potential target for the combination of anti-PD-1 immunotherapy in HCC patients.

CXCR7 Agonist TC14012 Improves Angiogenic Function of Endothelial Progenitor Cells via Activating Akt/eNOS Pathway and Promotes Ischemic Angiogenesis in Diabetic Limb Ischemia.

PURPOSE: Endothelial progenitor cells (EPCs) play a critical role in repairing damaged vessels and triggering ischemic angiogenesis, but their number is reduced and function is impaired under diabetic conditions. Improving EPC function has been considered a promising strategy to ameliorate diabetic vascular complications. In the present study, we aim to investigate whether and how CXCR7 agonist TC14012 promotes the angiogenic function of diabetic EPCs. METHODS: High glucose (HG) treatment was used to mimic the hyperglycemia in diabetes. Tube formation, cell scratch recovery and transwell assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and cleaved-caspase3 expression were used to evaluate the angiogenic capability, cell migration, and apoptosis of EPCs, respectively. Hind limb ischemia (HLI) model was used to appraise the ability of TC14012 in promoting diabetic ischemic angiogenesis in vivo. RESULTS: HG treatment impaired EPC tube formation and migration, and induced EPC apoptosis and oxidative damage, while TC14012 rescued tube formation and migration, and prevented HG-induced apoptosis and oxidative damage of EPCs. Furthermore, these beneficial effects of TC14012 on EPCs were attenuated by specific siRNAs against CXCR7, validating that CXCR7 is a functional target of TC14012 in EPCs. Mechanistic studies demonstrated that HG treatment reduced CXCR7 expression in EPCs, and impaired Akt and endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production; similarly, these signal impairments in HG-exposed EPCs could be rescued by TC14012. However, the protective effects of TC14012 on tube formation and migration, Akt and eNOS phosphorylation, and NO production in HG-treated EPCs were almost completely abolished by siRNAs against CXCR7 or Akt specific inhibitor wortmannin. More importantly, in vivo study showed that TC14012 administration enhanced blood perfusion recovery and angiogenesis in the ischemic hind limb and increased the EPC number in peripheral circulation of db/db mice, demonstrating the capability of TC14012 in promoting EPC mobilization and ischemia angiogenic function. CONCLUSION: TC14012 can prevent EPCs from HG-induced dysfunction and apoptosis, improve eNOS activity and NO production via CXCR7/Akt signal pathway, and promote EPC mobilization and diabetic ischemia angiogenesis.

Effects of variety and origin on the metabolic and texture characteristics of quinoa seeds based on ultrahigh-performance liquid chromatography coupled with high-field quadrupole-orbitrap high-resolution mass spectrometry.

The nutrition and functionality of Chenopodium quinoa Willd are closely related to its components; however, these properties vary widely in different varieties of C. quinoa Willd from different origins. Using ultrahigh-performance liquid chromatography coupled with high-field quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-QE HF HRMS) for metabolomics analysis, we performed nontargeted metabolomics analysis of C. quinoa Willd of different color varieties and origins and evaluated the texture characteristics after cooking. Both the variety and origin significantly affected the metabolic characteristics of C. quinoa Willd. The differences in the composition and texture properties were closely related to the lipid, amino acid, and polyphenol contents. The contents of kaempferol, catechol, myricetin 7-(6'-galloside), tyrosine, prostaglandin I2, and glutathione in white, red, and black quinoa significantly differed, and the variety had a greater effect on the lipid content than on the polyphenol and amino acid contents. At the same processing level, the texture properties of white and red quinoa were better than those of black quinoa. Furthermore, the contents of differential polyphenols and amino acids in Gansu white quinoa were higher than those in quinoa from the other three producing areas. The contents of differential polyphenols and terpenoids in Inner Mongolia white quinoa were relatively low, whereas in Shanxi white quinoa, the contents of differential amino acids were relatively low and those of differential terpenoids were relatively high. The levels of quercetin and its derivatives, kaempferol and its derivatives, 9-HODE, azelaic acid, sebacic acid, elaidic acid, linoleic acid, prostaglandin H2, glutathione, 5-aminovaleric acid, and other compounds significantly differed in quinoa from different origins; thus, these compounds can be used as metabolic markers to identify the origin of quinoa. The texture properties of white quinoa from Qinghai and Inner Mongolia were better than those of white quinoa from Gansu and Shanxi. Although C. quinoa Willd can tolerate harsh environments, its grain quality varies widely. Cultivating C. quinoa Willd varieties according to local conditions is important for improving their yield and quality.

Liraglutide Improves the Angiogenic Capability of EPC and Promotes Ischemic Angiogenesis in Mice under Diabetic Conditions through an Nrf2-Dependent Mechanism.

The impairment in endothelial progenitor cell (EPC) functions results in dysregulation of vascular homeostasis and dysfunction of the endothelium under diabetic conditions. Improving EPC function has been considered as a promising strategy for ameliorating diabetic vascular complications. Liraglutide has been widely used as a therapeutic agent for diabetes. However, the effects and mechanisms of liraglutide on EPC dysfunction remain unclear. The capability of liraglutide in promoting blood perfusion and angiogenesis under diabetic conditions was evaluated in the hind limb ischemia model of diabetic mice. The effect of liraglutide on the angiogenic function of EPC was evaluated by cell scratch recovery assay, tube formation assay, and nitric oxide production. RNA sequencing was performed to assess the underlying mechanisms. Liraglutide enhanced blood perfusion and angiogenesis in the ischemic hindlimb of db/db mice and streptozotocin-induced type 1 diabetic mice. Additionally, liraglutide improved tube formation, cell migration, and nitric oxide production of high glucose (HG)-treated EPC. Assessment of liraglutide target pathways revealed a network of genes involved in antioxidant activity. Further mechanism study showed that liraglutide decreased the production of reactive oxygen species and increased the activity of nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 deficiency attenuated the beneficial effects of liraglutide on improving EPC function and promoting ischemic angiogenesis under diabetic conditions. Moreover, liraglutide activates Nrf2 through an AKT/GSK3ß/Fyn pathway, and inhibiting this pathway abolished liraglutide-induced Nrf2 activation and EPC function improvement. Overall, these results suggest that Liraglutide represents therapeutic potential in promoting EPC function and ameliorating ischemic angiogenesis under diabetic conditions, and these beneficial effects relied on Nrf2 activation.

Nrf2 transcriptional upregulation of IDH2 to tune mitochondrial dynamics and rescue angiogenic function of diabetic EPCs.

Endothelial progenitor cells (EPCs) are reduced in number and impaired in function in diabetic patients. Whether and how Nrf2 regulates the function of diabetic EPCs remains unclear. In this study, we found that the expression of Nrf2 and its downstream genes were decreased in EPCs from both diabetic patients and db/db mice. Survival ability and angiogenic function of EPCs from diabetic patients and db/db mice also were impaired. Gain- and loss-of-function studies, respectively, showed that knockdown of Nrf2 increased apoptosis and impaired tube formation in EPCs from healthy donors and wild-type mice, while Nrf2 overexpression decreased apoptosis and rescued tube formation in EPCs from diabetic patients and db/db mice. Additionally, proangiogenic function of Nrf2-manipulated mouse EPCs was validated in db/db mice with hind limb ischemia. Mechanistic studies demonstrated that diabetes induced mitochondrial fragmentation and dysfunction of EPCs by dysregulating the abundance of proteins controlling mitochondrial dynamics; upregulating Nrf2 expression attenuated diabetes-induced mitochondrial fragmentation and dysfunction and rectified the abundance of proteins controlling mitochondrial dynamics. Further RNA-sequencing analysis demonstrated that Nrf2 specifically upregulated the transcription of isocitrate dehydrogenase 2 (IDH2), a key enzyme regulating tricarboxylic acid cycle and mitochondrial function. Overexpression of IDH2 rectified Nrf2 knockdown- or diabetes-induced mitochondrial fragmentation and EPC dysfunction. In a therapeutic approach, supplementation of an Nrf2 activator sulforaphane enhanced angiogenesis and blood perfusion recovery in db/db mice with hind limb ischemia. Collectively, these findings indicate that Nrf2 is a potential therapeutic target for improving diabetic EPC function. Thus, elevating Nrf2 expression enhances EPC resistance to diabetes-induced oxidative damage and improves therapeutic efficacy of EPCs in treating diabetic limb ischemia likely via transcriptional upregulating IDH2 expression and improving mitochondrial function of diabetic EPCs.

Effect of Thermal Processing on the Metabolic Components of Black Beans on Ultra-High-Performance Liquid Chromatography Coupled with High-Field Quadrupole-Orbitrap High-Resolution Mass Spectrometry.

An ultra-high-performance liquid chromatography coupled with high-field quadrupole-orbitrap mass spectrometry (UHPLC-QE-MS) histological platform was used to analyze the effects of two thermal processing methods (cooking and steaming) on the nutritional metabolic components of black beans. Black beans had the most amino acids, followed by lipids and polyphenols, and more sugars. Multivariate statistical analysis indicated that heat processing significantly affected the metabolic component content in black beans, with effects varying among different components. Polyphenols, especially flavonoids and isoflavones, were highly susceptible. A total of 197 and 210 differential metabolites were identified in both raw black beans and cooked and steamed black beans, respectively. Cooking reduced the cumulative content of amino acids, lipids, polyphenols, sugars, and nucleosides, whereas steaming reduced amino acid and lipid content, slightly increased polyphenol content, and significantly increased sugar and nucleoside content. Our results indicated that metabolic components were better retained during steaming than cooking. Heat treatment had the greatest impact on amino acids, followed by polyphenols, fatty acids, sugars, and vitamins, indicating that cooking promotes the transformation of most substances and the synthesis of a few. The results of this study provide a basis for further research and development of nutritional products using black beans.

(-)-5-O-(3-O-ß-d-Glucopyranosylcaffeoyl)-quinic acid from the fruits of Lycium barbarum L. var. auranticarpum K. F. Ching: Purification, identification and in vitro bioactivities.

Chlorogenic acids are important phenolics in the fruits of wolfberry, but little attention has been paid on their glucosylated forms. In the present study, a glucosylated form of chlorogenic acid was isolated from the fruits of Lycium barbarum L. var. auranticarpum K. F. Ching (also called yellow wolfberry) and identified to be (-)-5-O-(3-O-ß-d-glucopyranosylcaffeoyl)-quinic acid (5-CQA-3'ßG) by high resolution mass spectrometry and nuclear magnetic resonance spectrometry. The content of 5-CQA-3'ßG in the dried fruit was determined as 0.0293 ± 0.0015% by HPLC. In addition, 5-CQA-3'ßG showed a good scavenging capacity for 2,2'-azino-bis-(3-ethylben-zothiazoline-6-sulphonate) free radicals but had a relatively low reducing power and scavenging capacity for 2,2-diphenyl-1-picrylhydrazyl free radical. Moreover, the secretion of nitric oxide, tumor necrosis factor-α and interleukin-6 as well as related mRNA expression were reduced in lipopolysaccharide-stimulated RAW264.7 macrophage cells treated with 5-CQA-3'ßG. This is the first report describing purification, identification and bioactivity of glucosylated CQA from yellow wolfberry.

Epidemiological retrospective analysis in major burn patients: single centre medical records from 2009 to 2019.

Burns cause a loss of skin barrier function, rendering it prone to infection. The prevention of infection comprises a focus on the treatment of patients with burns. Therefore, we analysed the results of microbiological tests of patients with severe and extremely severe burns to provide a basis for the prevention and treatment of infection in patients with burns. The results of microbiological tests of patients with severe and extremely severe burns admitted to our burn centre between 2009 and 2019 were retrospectively reviewed. The overall positive rate of microbial detection was 40.67% and did not significantly decline over the 10-year study period. The most common positive sites were wounds, sputum, and urine. The most common bacterial species causing the infections were Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Furthermore, the predictors of a positive detection, overall and at various sites, mainly included the burn area and depth, inhalation injury, and length of the hospital stay. Positive detection was an important predictor of the prognosis. In particular, a positive blood culture and Klebsiella pneumoniae had better predictive strength for mortality than other sites and strains. This study analysed the microbiological testing results at a single burn centre over a period of 10 years. The results provide information regarding the predictors of a positive detection and the influence of a positive detection on prognosis, and can be used as a basis for the development of clinical infection prevention and treatment strategies, as well as the selection of treatment measures.

Feasibility analysis of CT-guided thermal ablation of multiple pulmonary nodules combined with intraoperative biopsy.

Purpose: To analyze the safety and feasibility of computed tomography (CT)-guided thermal ablation of multiple pulmonary nodules combined with intraoperative biopsy. Methods: The data of 431 patients with 540 lung nodules undergoing CT-guided biopsy or ablation were retrospectively analyzed. Biopsy-only group (A): 107 patients (107 lesions) received CT-guided percutaneous lung biopsy only; Ablation-only group (B): 117 cases (117 lesions) only received CT-guided thermal ablation; Single focal ablation combined with biopsy group (C): 103 patients (103 lesions) received CT-guided thermal ablation combined with intraoperative immediate biopsy; Multifocal ablation combined with biopsy group (D): 104 patients (213 lesions) received CT-guided thermal ablation combined with intraoperative biopsy. The success rate of this technique was calculated, the complications were recorded, and the positive rate of pathological diagnosis of the specimens was evaluated (the tissue specimens could be confirmed as positive by pathological diagnosis). Results: All 431 patients with pulmonary nodules successfully completed the operation, and the technical success rate was 100% (431/431). In group A, hemoptysis occurred in seven cases after operation, while no hemoptysis was observed in the other groups. Pneumothorax occurred in 8 cases in group A, 14 cases in group B, 11 cases in group C, and 13 cases in group D. Hydrothorax occurred in 4 cases in group A, 7 cases in group B, 5 cases in group C and 9 cases in group D, and there were no significant differences between the groups. The positive rate of pathological diagnosis was 84.1% (90/107) in group A, 81.5% (84/103) in group C, and 82.6% (176/213) in group D, and there was no significant difference among the groups (P > 0.05). A total of 15 cases in group C and 23 cases in group D underwent gene testing and analysis, and the biopsy tissue samples all met quality control standards. Conclusion: CT-guided thermal ablation of multiple pulmonary nodules combined with intraoperative biopsy does not prolong the length of hospital stay or increase the risk of postoperative complications. It can meet the requirements of clinical, pathological and genetic testing, and is safe and reliable.

Screening of heat stress-regulating active fractions in mung beans.

Introduction: Heat stress caused by high temperatures has important adverse effects on the safety and health status of humans and animals, and dietary interventions to alleviate heat stress in daily life are highly feasible. Methods: In this study, the components of mung bean that have heat stress-regulating effects were characterized by in vitro antioxidant indicators and heat stress cell models. Results: As a result, 15 target monomeric polyphenol fractions were identified based on untargeted analysis on an ultra performance liquid chromatography coupled with high field quadrupole orbit high resolution mass spectrometry (UHPLC-QE-HF-HRMS) platform and available reports. The results of DPPH and ABTS radical scavenging showed that mung bean polyphenols (crude extract) and 15 monomeric polyphenols had better antioxidant activity, followed by oil and mung bean peptides, while protein and polysaccharides had relatively poor antioxidant activity. Qualitative and quantitative assays for 20 polyphenols (15 polyphenols and 5 isomers) were then established based on platform targets. Vitexin, orientin, and caffeic acid were identified as monomeric polyphenols for heat stress control in mung beans based on their content. Finally, mild (39°C), moderate (41°C), and severe (43°C) heat stress models were successfully constructed based on mouse intestinal epithelial Mode-k cells and human colorectal adenocarcinoma Caco-2 cell lines, all with an optimal heat stress modeling time of 6 h. Screening of mung bean fractions using HSP70 mRNA content, a key indicator of heat stress. As a result, HSP70 mRNA content was significantly up-regulated by different levels of heat stress in both cell models. The addition of mung bean polyphenols (crude extract), vitexin, orientin, and caffeic acid resulted in significant down-regulation of HSP70 mRNA content, and the higher the level of heat stress, the more significant the regulation effect, with orientin having the best effect. Mung bean proteins, peptides, polysaccharides, oils and mung bean soup resulted in increased or no change in HSP70 mRNA levels after most heat stresses. Discussion: The polyphenols were shown to be the main heat stress regulating components in mung bean. The results of the validation experiments confirm that the above three monomeric polyphenols may be the main heat stress regulating substances in mung bean. The role of polyphenols in the regulation of heat stress is closely linked to their antioxidant properties.

Effect of Traditional Chinese Medicine Combined with Bladder Perfusion with Hydroxycamptothecin on Color Ultrasound and Clinical Efficacy in Patients with Bladder Cancer Surgery.

OBJECTIVE: To observe the clinical effect of Xiaozheng Decoction combined with bladder perfusion with hydroxycamptothecin in the treatment of bladder cancer. METHODS: A total of 92 bladder cancer patients admitted to our hospital from January to December 2018 were selected and divided into an observation group and a control group according to the random number table method, with 46 cases in each group. The observation group was given Xiaozheng Decoction combined with bladder perfusion with hydroxycamptothecin, and the control group was given hydroxycamptothecin. The levels of serum-related factors (intercellular adhesion molecule-1 (ICAM-1), E-cadherin, cell adhesion molecules (CAM), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF)), white blood cell (WBC) level, immune function indexes, short-term total response rate, and incidence of adverse reactions were compared between the two groups before and after treatment. RESULTS: After 2 years of postoperative treatment, the levels of ICAM-1, E-cadherin, CAM-1, FGF, and VEGF (a, b, c) in both groups were improved compared with those before treatment and the observation group was better than the control group (p < 0.01). The number of WBCs was significantly higher than in the control group after Traditional Chinese Medicine (TCM) treatment. The observation group was better than the control group in increasing CD3+ and CD4+ levels and decreasing CD8+ level (p < 0.05), indicating that this prescription could improve the immune function of patients. The recurrence rate in the observation group was 6.52% after 2 years of treatment, lower than 17.39% in the control group. Color ultrasound parameters showed that there were no statistically significant differences in arrive time (AT) and time to peak (TTP) between patients with and without recurrence and peak intensity (PI) and washout time (WT) were higher in patients with recurrence than in patients without recurrence (p < 0.01). The incidence of adverse reactions was significantly lower than that of the control group (p < 0.01). CONCLUSION: The clinical effect of Xiaozheng Decoction combined with hydroxycamptothecin on the treatment of bladder cancer was clear and superior to that of hydroxycamptothecin, which could effectively improve the serological indicators of patients with a low incidence of adverse reactions and prolong the survival cycle of patients. Therefore, it is worthy of promotion and application.

lncRNA NEAT1 aggravates sepsis-induced lung injury by regulating the miR-27a/PTEN axis.

Sepsis is an acute inflammatory reaction and a cause of acute respiratory distress syndrome (ARDS). In the present study, we explored the roles and underlying mechanism of the lncRNA Nuclear enriched abundant transcript 1 (NEAT1) in ARDS. The expression levels of genes, proteins and pro-inflammatory cytokines in patients with ARDS, LPS-stimulated cells and septic mouse models were quantified using qPCR, western blotting and ELISA assays, respectively. The molecular targeting relationship was validated by conducting a dual-luciferase reporter assay. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. The cell cycle phase was determined by flow cytometry assay. The expression levels of NEAT1 and pro-inflammatory cytokines were higher in patients with ARDS and septic models than in controls. Knockdown of NEAT1 significantly increased cell proliferation and cycle progression and prolonged mouse survival in vitro and in vivo. Mechanistically, miR-27a was identified as a downstream target of NEAT1 and directly inhibited PTEN expression. Further rescue experiments revealed that inhibition of miR-27a impeded the promoting effects of NEAT1 silence on cell proliferation and cycle progression, whereas inhibition of PTEN markedly weakened the inhibitory effects of NEAT1 overexpression on cell proliferation and cycle progression. Altogether, our study revealed that NEAT1 plays a promoting role in the progression of ARDS via the NEAT1/miR-27a/PTEN regulatory network, providing new insight into the pathologic mechanism behind ARDS.

Tertiary sulphonamide derivatives as dual acting small molecules that inhibit LSD1 and suppress tubulin polymerisation against liver cancer.

A series of tertiary sulphonamide derivatives were synthesised and evaluated for their antiproliferative activity against liver cancer cell lines (SNU-475, HepG-2, and Bel-7402). Among these tertiary sulphonamides, compound 17a displayed the best anti-liver cancer activity against Bel-7402 cells with an IC50 value of 0.32 µM. Compound 17a could effectively inhibit tubulin polymerisation with an IC50 value of 1.27 µM. Meanwhile, it selectively suppressed LSD1 with an IC50 value of 63 nM. It also concentration-dependently inhibited migration against Bel-7402 cells. Importantly, tertiary sulphonamide 17a exhibited the potent antitumor activity in vivo. All these findings revealed that compound 17a might be a tertiary sulphonamide-based dual inhibitor of tubulin polymerisation and LSD1 to treat liver cancer.

Activating Adenosine Monophosphate-Activated Protein Kinase Mediates Fibroblast Growth Factor 1 Protection From Nonalcoholic Fatty Liver Disease in Mice.

BACKGROUND AND AIMS: Fibroblast growth factor (FGF) 1 demonstrated protection against nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic and obese mice by an uncertain mechanism. This study investigated the therapeutic activity and mechanism of a nonmitogenic FGF1 variant carrying 3 substitutions of heparin-binding sites (FGF1△HBS ) against NAFLD. APPROACH AND RESULTS: FGF1△HBS administration was effective in 9-month-old diabetic mice carrying a homozygous mutation in the leptin receptor gene (db/db) with NAFLD; liver weight, lipid deposition, and inflammation declined and liver injury decreased. FGF1△HBS reduced oxidative stress by stimulating nuclear translocation of nuclear erythroid 2 p45-related factor 2 (Nrf2) and elevation of antioxidant protein expression. FGF1△HBS also inhibited activity and/or expression of lipogenic genes, coincident with phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its substrates. Mechanistic studies on palmitate exposed hepatic cells demonstrated that NAFLD-like oxidative damage and lipid accumulation could be reversed by FGF1△HBS . In palmitate-treated hepatic cells, small interfering RNA (siRNA) knockdown of Nrf2 abolished only FGF1△HBS antioxidative actions but not improvement of lipid metabolism. In contrast, AMPK inhibition by pharmacological agent or siRNA abolished FGF1△HBS benefits on both oxidative stress and lipid metabolism that were FGF receptor (FGFR) 4 dependent. Further support of these in vitro findings is that liver-specific AMPK knockout abolished therapeutic effects of FGF1△HBS against high-fat/high-sucrose diet-induced hepatic steatosis. Moreover, FGF1△HBS improved high-fat/high-cholesterol diet-induced steatohepatitis and fibrosis in apolipoprotein E knockout mice. CONCLUSIONS: These findings indicate that FGF1△HBS is effective for preventing and reversing liver steatosis and steatohepatitis and acts by activation of AMPK through hepatocyte FGFR4.

Emergency Management of Acute Late-Presenting Congenital Diaphragmatic Hernia in Infants and Children.

OBJECTIVES: Acute late-presenting congenital diaphragmatic hernia (CDH) might result in mediastinal shift away from the lesion and even sudden cardiopulmonary arrest. This study aimed to discuss the prompt and effective emergency management of acute late-presenting CDH. METHODS: A retrospective review of acute late-presenting CDH cases in West China Hospital of Sichuan University and Guizhou Provincial People's Hospital from October 2010 to June 2016 was conducted. RESULTS: A total of 22 patients were included in this study. All the patients presented with respiratory symptoms. Chest x-ray revealed swollen stomach and mediastinal shift. After nasogastric tube placement, fluid infusion, and nasal oxygen breathing, the symptoms in 8 patients ameliorated, and 14 patients had no signs of obvious relief. Three patients underwent the bedside percutaneous puncture of distensible stomach, and 1 patient died in the process of emergent management for critical condition. The remaining 21 patients underwent emergency surgery. Five thoracotomies and 16 thoracoscopies were performed. Five thoracoscopies that were converted to thoracotomies were required for the difficult reduction of herniated stomach. At follow-up, all patients improved their condition. CONCLUSIONS: Acute late-presenting CDH is a clinical emergency that can be fatal. The sudden and progressive expansion of the stomach is mainly responsible for this emergent condition. The prompt and effective management is key to decrease the mortality and achieve favorable prognosis.