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To investigate the performance of synthetic relaxometry, three-dimensional pseudo-continuous arterial spin labelling (pCASL) and diffusion-weighted imaging (DWI) in differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs) and to compare with the conventional MRI.Seventy-two patients with gliomas (including 27 LGGs and 45 HGGs) were studied using synthetic magnetic resonance imaging (sy-MRI), pCASL, and DWI with a 3.0 T MR scanner. T1 relaxometry (T1), T2 relaxometry (T2), as well as proton density (PD) from sy-MRI, cerebral blood flow (CBF) from pCASL, apparent diffusion coefficient (ADC) from DWI and enhancement quality (EQ), proportion enhancing (PE) from conventional contrast enhanced image based Visually-Accessible-Rembrandt-Images (VASARI) scoring system, were all analyzed by two radiologists. The Student's t-test, Mann-Whitney U test or Fisher's exact test was used to compare the parameters between LGGs and HGGs. The diagnostic performance of each parameter and their combination for glioma grading were analyzed.Significant statistical differences in T1, PD, CBF, ADC, EQ and PE are observed between LGGs and HGGs (all P 0.001). The ADC values have higher discrimination abilities compared with other univariable parameters, with the AUC of 0.905. AUC values for conventional contrast-enhanced method, EQ and PE from VASARI, and conventional contrast-free method, CBF + ADC, are 0.873 and 0.912 respectively. The combined T1, PD, CBF and ADC model had the best performance for differentiating LGGs and HGGs with AUC, sensitivity and specificity of 0.993, 95.5%, 100%, respectively.Relaxometry parameters derived from synthetic MRI contributed to the discrimination of low-grade gliomas from high-grade gliomas. Proposed contrast-free approach combining T1, PD, CBF and ADC showed a strong discriminative power, and outperformed conventional approaches.

Background and aims Fecal calprotectin (FC) is a non-invasive biomarker used in inflammatory bowel disease (IBD) management and risk stratification of non-specific gastrointestinal symptoms. Leukocyte esterase is an inexpensive and widely available point-of-care inflammatory marker present on urinalysis test strips. We aim to assess the diagnostic accuracy of fecal leukocyte esterase (FLE) relative to FC and endoscopy and demonstrate its use as an alternative biomarker for IBD. Methods In this prospective cohort study, 70 patients who had FC ordered as part of standard clinical care also received FLE testing. FLE levels were compared to various FC cut-off values and endoscopy and pathology findings as gold standard. Results As the FC cut-off increased from 50 to 500 μg/g, FLE sensitivity increased from 67% to 95% while the specificity decreased from 86% to 76%. The area under the receiver operating characteristic (AUROC) increased from 0.79 to 0.90. An FLE of ≥1+ had the best test characteristics. Amongst patients who underwent endoscopic evaluation, FLE demonstrated an identical sensitivity (75%) and specificity (86%) to FC in predicting endoscopic inflammation. AUROC was 0.80 for FLE and 0.85 for FC with an optimal cut-off of ≥2+ and 301 μg/g, respectively. When used to distinguish between active IBD and no/inactive IBD patients, FLE had a sensitivity of 84% and specificity of 90%, comparable to the 84% and 83%, respectively, of FC. AUROC was 0.88 for FLE and 0.91 for FC with an optimal cut-off of ≥2+ and 145 μg/g, respectively. Conclusion FLE demonstrates adequate correlation and comparable accuracy to FC in predicting endoscopic inflammation and distinguishing between patients with active versus inactive IBD.

Postrepair mitral stenosis is an important complication but associated with less-than-optimal surgical management. Reoperative mitral valve replacement is challenging due to the narrowness of the mitral annulus. We here present a minimally invasive bio-chimney technique for the first time, performed in an elderly patient with postrepair mitral stenosis, in whom a composite of bioprosthetic valve and vascular graft was sutured on the extremely narrow mitral annulus.

Developing electrode materials to apply in anodes and cathodes with superior kinetics and high specific capacity still remains a serious challenge for potassium-ion hybrid capacitors (PIHCs). Herei...

Aortic aneurysm (AA) remains one of the primary causes of death worldwide. Of the major treatments, prophylactic operative repair is used for AA to avoid potential aortic dissection or rupture. To halt the development of AA and alleviate its progression into aortic dissection, pharmacological treatment has been investigated for years. Currently, β-adrenergic blocking agents, losartan, irbesartan, angiotensin-converting-enzyme inhibitors, statins, antiplatelet agents, doxycycline, and metformin have been investigated as potential candidates for preventing AA progression. However, the paradox between preclinical successes and clinical failures still exists, with no medical therapy currently available for ideally negating the disease progression. This review describes the current drugs used for pharmacological management of AA and their individual potential mechanisms. Preclinical models for drug screening and evaluation are also discussed to gain a better understanding of the underlying pathophysiology and ultimately find new therapeutic targets for AA.

Numerous studies have shown that microRNA (miRNA) serves as key regulatory factors in the origin and development of cancers. However, the biological mechanisms of miRNAs in kidney renal clear cell carcinoma (KIRC) are still unknown. It is necessary to construct an effective miRNA‐clinical model to predict the prognosis of KIRC. In this study, 94 differentially expressed miRNAs were found between para‐tumor and tumor tissues based on the Cancer Genome Atlas (TCGA) database. Seven miRNAs (hsa‐miR‐21‐5p, hsa‐miR‐3613‐5p, hsa‐miR‐144‐5p, hsa‐miR‐376a‐5p, hsa‐miR‐5588‐3p, hsa‐miR‐1269a, and hsa‐miR‐137‐3p) were selected as prognostic indicators. According to their cox coefficient, a risk score formula was constructed. Patients with risk scores were divided into high‐ and low‐risk groups based on the median score. Kaplan–Meier curves analysis showed that the low‐risk group had a better survival probability compared to the high‐risk group. The area under the ROC curve (AUC) value of the miRNA model was 0.744. In comparison with clinical features, the miRNA model risk score was considered as an independent prognosis factor in multivariate Cox regression analysis. In addition, we built a nomogram including age, metastasis, and miRNA prognostic model based on the results of multivariate Cox regression analysis. The decision curve analysis (DCA) revealed the clinical net benefit of the prognostic model. Gene set enrichment analysis (GSEA) results suggested that several important pathways may be the potential pathways for KIRC. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for the target genes of 7 miRNAs revealed that miRNAs may participate in KIRC progression via many specific pathways. Additionally, the levels of seven prognostic miRNAs showed a significant difference between KIRC tissues and adjacent non‐tumorous tissues. In conclusion, the miRNA‐clinical model provides an effective and accurate way to predict the prognosis of KIRC., In this study, we constructed a novel 7‐miRNA risk model for KIRC, which may be an independent predictor for KIRC. Moreover, a nomogram including the above risk model and clinical features could provide a better way to evaluate the prognosis of KIRC patients.

Hyperactive signal transducer and activator of transcription 3 (STAT3) signaling is frequently detected in human triple-negative breast cancer (TNBC) and gastric cancer, leading to uncontrolled tumor growth, resistance to chemotherapy, and poor prognosis. Thus, inhibition of STAT3 signaling is a promising therapeutic approach for both TNBC and gastric cancer, which have high incidences and mortality and limited effective therapeutic approaches. Here, we report a small molecule, WZ-2-033, capable of inhibiting STAT3 activation and dimerization and STAT3-related malignant transformation. We present in vitro evidence from surface plasmon resonance analysis that WZ-2-033 interacts with the STAT3 protein and from confocal imaging that WZ-2-033 disrupts HA-STAT3 and Flag-STAT3 dimerization in intact cells. WZ-2-033 suppresses STAT3-DNA-binding activity but has no effect on STAT5-DNA binding. WZ-2-033 inhibits the phosphorylation and nuclear accumulation of pY705-STAT3 and consequently suppresses STAT3-dependent transcriptional activity and the expression of STAT3 downstream genes. Moreover, WZ-2-033 significantly inhibited the proliferation, colony survival, migration, and invasion of TNBC cells and gastric cancer cells with aberrant STAT3 activation. Furthermore, administration of WZ-2-033 in vivo induced a significant antitumor response in mouse models of TNBC and gastric cancer that correlated with the inhibition of constitutively active STAT3 and the suppression of known STAT3 downstream genes. Thus, our study provides a novel STAT3 inhibitor with significant antitumor activity in human TNBC and gastric cancer harboring persistently active STAT3.

Arsenic is a well-known environmental toxicant and carcinogen, which has been epidemiologically proved related to the increased hepatic disorders. Researches have shown that aseptic inflammation and abnormal immune response are associated with arsenic-induced liver injury. However, the immunotoxic effects of liver have not been extensively characterized. Ginkgo biloba extract (GBE), a natural products of G. biloba leaves with proven anti-inflammatory and potential immunoregulatory activities, was used as intervention agent to explore its protective effects on arsenic-induced hepatotoxicity. Thus, the underlying mechanism of the immunotoxic effects on arsenic-induced liver injury were investigated in 2.5, 5.0, and 10.0 mg/kg NaAsO2 of Wistar rats for 16 weeks. Subsequently, GBE was used as intervention agent in 50 mg/kg for 6 weeks after cessation of arsenic exposure. The ratio of Th17 to Treg cells in peripheral blood as well as the secretion of inflammatory cytokines IL-17A, IL-6, TGF-β1, and IL-10 in serum and liver were detected. Meanwhile, the notable activation of aseptic inflammation-related molecule TLR4 and its downstream targets MyD88 and NF-κB in the liver were observed. In this work, we confirmed that subchronic exposed to arsenic triggered the infiltration of inflammatory cells in rat liver, coupled with obvious histopathological changes and aberrant hepatic serum biochemical parameters. Meanwhile, imbalanced immune response was verified by the notable abnormal ratio of Th17 to Treg cells in peripheral blood as well as the secretion of inflammatory cytokines IL-17A, IL-6, TGF-β1, and IL-10 in serum and liver of arsenic exposed rats. Further, the level of TLR4, MyD88, and NF-κB in liver both transcription and translation activity were raised. Subsequently, GBE markedly mitigated arsenic-induced liver injury, most impressively, post treatment with GBE prominently suppressed the overactivated inflammatory-related TLR4-MyD88-NF-κB pathway and evidently decreased the secretion of inflammation cytokines. Meanwhile, the disturbance of pro- and anti-inflammatory response was reversed. We concluded that the disruption of pro- and anti-inflammatory T-cells balance caused by cytokines mediated cell–cell interactions may be one of the mechanisms underlying arsenic-induced liver injury and that GBE intervention exerts an evidence protective effects, which might be closely associated with the suppression of inflammatory-related TLR4 pathway.

Background: In this study, we investigated the impact of concomitant coronary artery bypass grafting (CABG) on operative and midterm mortality in patients with acute type A aortic dissection (ATAAD) undergoing surgical repair. Methods: From January 2012 to December 2014, among 489 patients (mean age: 47.6 ± 10.4 years, 77.1% male) with ATAAD who received surgical repair at our institute, 21 patients (4.3%) underwent concomitant CABG. Isolated aortic repair was performed in the remaining 468 cases (95.7%). Coronary dissection was indicated in 15 patients (Neri classification type B in 2, type C in 13), concomitant coronary artery disease in five and coronary artery compression in one. The follow-up time was 97.3% at 44.1 ± 13.9 months. Results: A total of 44 patients (9%) died from surgery, and operative mortality in the concomitant CABG group was significantly higher than that in the isolated aortic repair group (47.6%, 10/21 vs. 7.3%, 34/468; P

NASICON-type Na3V2(PO4)2F3 (NVPF) is proposed to be a potential cathode material for sodium-ion battery because of its good structural stability, relatively high capacity and voltage platform. Nonetheless, the poor-rate performance, resulting from its low conductivity, has become a massive obstacle to its practical application. In this work, carbon coating together with morphology controlling were introduced to solve the issue of NVPF. This experiment used a hydrothermal method to prepare Na3V2(PO4)2F3@C (NVPF@C) and explored the impact of surfactants (polyvinylpyrrolidone (PVP)) on the positive material performance of sodium-ion battery. Through various characterisation, NVPF@C compared its performance with that of untreated products, and verified that appropriate surfactant modification could enhance the performance of the electron conduction and sodium ion diffusion, thus effectively improved the performance of NVPF. Through comparison, it was found that appropriate surface modification with PVP can achieve the effects of specific crystal surface exposure and clusters of porous micron ball structure, and improve the electrochemical performance of NVPF best. Under the charge and discharge ratio of 0.2C, its initial reversible capacity was 127.8 mA h g−1. After 100 cycles, its discharge capacity was 106.1 mA h g−1, and the cycling retention rate reached 82.8%. Compared to the original NVPF, its performance has been dramatically improved.

Background The efficacy of postoperative treatment of squamous cell carcinoma of the esophagus has not yet been determined. In this retrospective study, we investigated whether postoperative adjuvant chemotherapy (POCT) confers a survival benefit on patients who undergo curative esophagectomy. Methods A total of 782 patients were enrolled in our study. The patients were divided into surgery alone (S) and surgery plus postoperative chemotherapy (S + POCT) groups. Propensity score matching (PSM) was used to eliminate the differences in baseline characteristics. The primary endpoint was overall survival (OS), which was calculated by the Kaplan–Meier method and compared with the log‐rank test. A Cox proportional hazards model was used to identify factors influencing the prognosis. Results Of 782 patients, 343 (43.9%) underwent S alone, and 439 (56.1%) underwent S + POCT before PSM. The five‐year OS rates were 42.3% and 47.8% in the S and S + POCT groups (p = 0.080), respectively. After PSM (296 patients per group), the five‐year OS rates were 48.7% and 56.2% in the S and S + POCT groups (p = 0.025), respectively. For different cycles of POCT, patients with more than three cycles had a better survival than those with less than three cycles. The significant predictive factors for OS were pN stage (HR = 1.861, 95% CI: 1.310–2.645, p = 0.001), number of dissected nodes (HR = 0.621, 95% CI: 0.494–0.781, p, After propensity score‐matched analysis, the OS rates significantly improved in the S + POCT group. We concluded that POCT appears to improve the OS rate of patients with ESCC after R0 resection.

Objective The aim of the present study was to ascertain the independent risk factors of poor preliminary outcome and to reveal the value of these factors in predicting the postoperative prognosis. Methods A total of 165 patients diagnosed with thoracic myelopathy because of thoracic ossification of the ligamentum flavum (TOLF) were enrolled in this retrospective study. All of them underwent posterior decompressive laminectomy surgery in our hospital from May 2016 to June 2019. The postoperative improvement of symptoms was evaluated using the modified Japanese Orthopaedic Association (mJOA) scoring system. Clinical data, such as age, sex, body mass index (BMI), duration of symptoms, history of hypertension and diabetes, tobacco use, history of drinking, symptoms of incontinence, number of compressed segments, and preoperative mJOA score, were respectively recorded. Radiologic features data included sagittal maximum spinal cord compression (MSCC), axial spinal canal occupation ratio (SCOR), grades and extension of increased signal on sagittal T2‐weighted images (ISST2I), types of increased signal on axial T2‐weighted images (ISAT2I), and the classification of ossification on axial CT scan and sagittal MRI. The t‐test, the χ2‐test, Fisher's exact test, binary logistic regression analyses, receiver operating characteristic (ROC) curves, and subgroup analyses were used to evaluate the effects of individual risk predictors on surgical outcomes. Results A total of 76 men and 89 women were enrolled in this study. The mean age of all patients was 58.53 years. After comparison between two groups, we found some risk factors that may be associated with postoperative outcomes, such as age, preoperative mJOA score, BMI, history of hypertension, MSCC, SCOR, grade and extension of ISST2I, type of ISAT2I, axial type of ossification, and sagittal type of ossification (P, In the present study, four independent risk factors (age, grade of ISST2I, types of ossification on axial CT scan, and number of compressed segments) were identified to be associated with poor preliminary postoperative outcome for TOLF. The obscure and bright intramedullary increased signal intensity on sagittal T2‐weighted MRI had the best predictive ability (AUC = 0.817). In addition, risk factors have different values for predicting the clinical outcome in each subgroup.

Introduction Neuroblastoma (NB) is the most common solid tumor in children. Studies showed that long-chain noncoding RNA (lncRNA) HCP5 played an important role in tumorigenesis, but its role in NB remained unclear. This study aims to determine the role of HCP5 in NB and its possible molecular mechanism. Methods We analyzed the expression levels of miRNA-186-5p and HCP5 in neuroblastoma and neuroblastoma cell lines SHSY-5Y, Kelly, NBL-S and SK-N-AS, and explored their roles. Results We found that the HCP5 expression was up-regulated in NB tissues and cells. The higher the HCP5 expression in NB cells, the stronger the ability of clone formation. Down regulation of the HCP5 expression inhibited the proliferation of NB cells and the growth of subcutaneous transplanted tumor in nude mice. HCP5 could competitively bind miR-186-5p, while miR-186-5p could target the 3′-UTR of MAP3K2. The expression level of miR-186-5p was down regulated while the expression level of MAP3K2 was up-regulated in NB tissues. The expression level of HCP5 and miR-186-5p, the expression level of miR-186-5p and MAP3K2 were negatively correlated. The decreased proliferation of NB cells induced by down-regulation of HCP5 expression can be counteracted by miR-186-5p inhibitor or MAP3K2, and vice versa. Conclusion This study showed that lncRNA HCP5, as ceRNA, regulated MAP3K2 to promote NB progression through competitive binding of miR-186-5p. We revealed a new signaling pathway that mediates NB, which provided a new target for the diagnosis and treatment of NB.

Purpose: To investigate the gastroprotective effect of leaf extract of Aloe barbadensis on ethanolinduced gastric ulcer in rats.Methods: Healthy male Wistar rats (n = 30) weighing 180 - 220 g (mean weight = 200 ± 20 g) were randomly assigned to 6 groups (5 rats/group): control group, gastric ulcer group, two Aloe barbadensis extract groups (250 and 500 mg/kg), cimetidine group and indomethacin group. Gastric ulcer was induced via oral injection of absolute ethanol at a dose of 1 mL/kg after a 24-h fast. Gross evaluation, determination of gastric juice acidity and histological examination of gastric tissue were carried out.Results: Treatment of gastric ulcer rats with Aloe barbadensis extract significantly reduced ulcerated area (UA), ulcer index (UI), and acidity of gastric juice (p < 0.05). Injection of 1 % carrageenan into rat hind paw led to a time-dependent increase in paw volume which peaked 3 h after injection. However, the Aloe barbadensis extract significantly and dose-dependently reduced the volume of inflamed paw, and inhibited edema formation (p < 0.05). It also markedly reduced or completely eliminated edema and leucocyte infiltration. Moreover, treatment of gastric ulcer rats with Aloe barbadensis leaf extract led to significant and dose-dependent reduction in gastric tissue MDA level (p < 0.05). Histological examination of the gastric wall showed that control rats had severe injury in gastric mucosa,accompanied by edema and leucocytes infiltration, relative to rats pretreated with extract which showed marked gastric protection and inhibition of edema and leucocytes infiltration. Moreover, the extract treatment protected the gastric surface against ulceration as indicated by reduced lesions in the treated rat model.Conclusion: These results show that Aloe barbadensis mitigates ethanol-induced gastric injury in rats via inhibition of lipid peroxidation and inflammation. Thus, the extract has potentials for development into a therapeutic agent for the management of gastric ulcer. Keywords: Aloe barbadensis, Gastric ulcer, Gastric mucosa, Inflammation, Lipid peroxidation

Oxidative stress in the lumbar disc leads to the degeneration of nucleus pulposus (NP). However, the molecular mechanisms underlying this process remain unclear. In this study, we delineated a key calcium‐binding protein, S100A9, which was induced by oxidative stress and was highly expressed in the degenerative NP. Immunofluorescence staining and Western blotting revealed that S100A9 induced NP cell apoptosis in vitro by up‐regulating the expression of pro‐apoptotic markers, including cleaved caspase‐3, cytochrome c and Bax. Moreover, RT‐PCR analyses revealed that the expression of S100A9 caused NP matrix degradation by up‐regulating the expression of matrix degradation enzymes and increased the inflammatory response by up‐regulating cytokine expression. Therefore, S100A9 induced NP cell degeneration by exerting pro‐apoptotic, pro‐degradation and pro‐inflammatory effects. The detailed mechanism underlying S100A9‐induced NP degeneration was explored by administering SC75741, a specific NF‐κB inhibitor in vitro. We concluded that S100A9 induced NP cell apoptosis, caused matrix degradation and amplified the inflammatory response through the activation of the NF‐κB signalling pathway. Inhibition of these pro‐apoptotic, pro‐degradation and pro‐inflammatory effects induced by S100A9 in NP may be a favourable therapeutic strategy to slow lumbar disc degeneration.

Induced pluripotent stem cells (iPSCs) offer an effective platform for studies of human physiology and have revealed new possibilities for disease modeling at the cellular level. These cells also have the potential to be leveraged in the practice of precision medicine, including personalized drug testing. Aortic diseases result in significant morbidity and mortality and pose a global burden to healthcare. Their pathogenesis is mostly associated with functional alterations of vascular components, such as endothelial cells and vascular smooth muscle cells. Drugs that have been proven to be effective in animal models often fail to protect patients from adverse aortic events in clinical studies, provoking researchers to develop reliable in vitro models using human cells. In this review, we summarize the patient iPSC‐derived aortic cells that have been utilized to model aortic diseases in vitro. In advanced models, hemodynamic factors, such as blood flow‐induced shear stress and cyclic strain, have been added to the systems to replicate cellular microenvironments in the aortic wall. Examples of the utility of such factors in modeling various aortopathies, such as Marfan syndrome, Loeys‐Dietz syndrome, and bicuspid aortic valve‐related aortopathy, are also described. Overall, the iPSC‐based in vitro cell models have shown the potential to promote the development and practice of precision medicine in the treatment of aortic diseases., Application of iPSCs to establish in vitro models for research of aortic diseases.

Constitutive activation of signal transducer and activator of transcription 3 (STAT3) is a common feature in human non-small cell lung cancer (NSCLC). STAT3 plays an important role in cancer progression as a driver oncogene and acquired resistance of targeted therapies as an alternatively activated pathway. W2014-S with pharmacophore structure of imidazopyridine, which was firstly reported to be utilized in STAT3 inhibitor discovery, was screened out as a potent STAT3 inhibitor from a library of small molecules. The aim of this study is to investigate the antitumor activities and mechanisms of W2014-S in NSCLC and effect on epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) resistance in vitro and in vivo. Methods: SPR analysis, Co-immunoprecipitation, confocal microscope imaging, and luciferase report gene assays were utilized to determine the mechanisms. Cell viability, colonial survival, wound healing, cell invasion assay, human cancer cell xenografts and PDX tumor xenografts were used to determine antitumor activities. Results: W2014-S disrupted STAT3 dimerization and selectively inhibited aberrant STAT3 signaling in NSCLC cell line. W2014-S strongly suppressed proliferation, survival, migration and invasion of lung cancer cells with aberrant STAT3 activation and inhibited the growth of human NSCLC cell xenografts and PDX tumor xenografts in mouse model. Furthermore, W2014-S significantly sensitized resistant NSCLC cell line to gefitinib and erlotinib in vitro and enhances the anti-tumor effect of gefitinib in TKI-resistant lung cancer xenografts in vivo. Conclusions: Our study has provided a novel STAT3 inhibitor with significant anti-tumor activities in NSCLC and suggests that combination of STAT3 inhibitor such as W2014-S with gefitinib could serve as a promising strategy to overcome EGFR-TKIs acquired resistance in NSCLC patients.

Increasing number of resistant bacteria have emerged with the overuse of antibiotics, which indicates that the bacterial infection has become a global challenge. Furthermore, the pollution of antibiotics to the environment has become a serious threat to public health. It is known that toxins produced by bacteria are the main cause of bacterial infections. Photothermal therapy is an effective antibacterial approach. However, the photothermal reagents cannot eliminate bacterial toxins, and even some anti-bacterial materials are toxic. Here, we synthesized a biomimetic recycled nanoparticle, red blood cell (RBC) membrane-coated Fe3O4 nanoparticles (RBC@Fe3O4), as an antibacterial agent. The RBC@Fe3O4 nanoparticles act as nano-sponges to trap toxins and then kill them all with a photothermal effect. We can describe this process simply as a battle between two armies. Our strategy is to disarm the "enemy" so that we can easily kill the "enemy" who has no power, which results in enhancing the bactericidal efficacy. The toxin of methicillin-resistant Staphylococcus aureus (MRSA) was absorbed by RBC@Fe3O4in vitro. In addition, in vivo studies proved that the RBC@Fe3O4 nanoparticles confer obvious survival benefits against toxin-induced lethality by absorbing the toxin of MRSA. Furthermore, using a mouse model of MRSA wound infection, the RBC@Fe3O4 nanoparticles with laser irradiation were found to have a superior wound-healing effect. Simultaneously, the RBC@Fe3O4 nanoparticles could be recycled in a simple way without affecting the bactericidal efficacy. The highly biocompatible and recyclable RBC@Fe3O4 biomimetic nanoparticles based on photothermal therapy and bacterial toxin adsorption strategy are promising for treating bacterial infections.

Purpose: The purpose of the present study was to investigate the prognostic value of inflammatory and nutritional-based scores, including the albumin/fibrinogen ratio (AFR) and albumin/globulin ratio (AGR), in patients with esophageal squamous cell carcinoma (ESCC). Methods: The medical records of 641 patients with resectable ESCC from our institution were retrospectively analyzed. The preoperative AFR and AGR were investigated based on serum albumin, globulin and plasma fibrinogen levels. X-tile software, Kaplan-Meier survival curves and Cox proportional hazard models were performed to identify their prognostic value. The predictive accuracy was evaluated by the concordance index (C-index), calibration plots, and decision curve analysis (DCA). Results: The optimal cutoff values were 15.3 and 1.8 for AFR and AGR, respectively. Univariate survival analysis identified age, smoking history, tumor size, pT status, pN status, NLR, PLR, fibrinogen, albumin, AFR, and AGR as factors associated with overall survival. Multivariate analysis indicated that preoperative AFR (HR: 0.690, 95% CI = 0.495~0.960, P = 0.028), rather than other inflammation- and nutrition-based scores, was an independent predictor of overall survival. The C-index of the predicted nomogram containing AFR (C-index = 0.677) was higher than that of the nomogram without AFR (C-index = 0.656). The calibration curves showed that the predictive abilities were consistent with the actual observation results. Moreover, compared with the traditional staging system, the results of DCA showed that the nomogram had superior predictive ability and higher clinical utility. Conclusion: Our preliminary study suggested that a low preoperative AFR might be a novel and valuable predictor of poor prognosis in patients with ESCC, which may be helpful for prognosis assessment, patient counseling, and therapeutic modality selection.

Traditional therapeutic strategies for spinal cord injury (SCI) are insufficient to repair locomotor function because of the failure of axonal reconnection and neuronal regeneration in the injured central nervous system (CNS). Neural stem cell (NSC) transplantation has been considered a potential strategy and is generally feasible for repairing the neural circuit after SCI; however, the most formidable problem is that the neuronal differentiation rate of NSCs is quite limited. Therefore, it is essential to induce the neuronal differentiation of NSCs and improve the differentiation rate of NSCs in spinal cord repair. Our results demonstrate that both Wnt5a and miRNA200b-3p could promote NSC differentiation into neurons and that Wnt5a upregulated miRNA200b-3p expression through MAPK/JNK signaling to promote NSC differentiation into neurons. Wnt5a could reduce RhoA expression by upregulating miRNA200b-3p expression to inhibit activation of the RhoA/Rock signaling pathway, which has been reported to suppress neuronal differentiation. Overexpression of RhoA abolished the neurogenic capacity of Wnt5a and miRNA200b-3p. In vivo, miRNA200b-3p was critical for Wnt5a-induced NSC differentiation into neurons to promote motor functional and histological recovery after SCI by suppressing RhoA/Rock signaling. These findings provide more insight into SCI and help with the identification of novel treatment strategies., Spinal cord injury: Boost for neural stem cell therapies Incorporating key molecules into neural stem cells enhances their ability to differentiate correctly and promote repair following spinal cord injury. Spinal cord injuries can have a debilitating effect on patients’ lives, yet there are no therapies that fully restore movement and sensation. Therapies based on neural stem cells (NSCs) show promise, but initial studies show many NSCs differentiate into astrocytes, supportive cells that do not conduct nerve impulses, instead of neurons, leading to treatment failure. Yong Wan and Le Wang at Sun Yat-sen University in Guangzhou, China, and co-workers demonstrated that adding a protein called Wnt5a and a specific microRNA molecule to NSCs significantly increases differentiation into neurons. Wnt5a suppresses a signalling pathway that otherwise interferes with NSC differentiation. Experiments on rat models showed that the therapy improved locomotor function and tissue repair after injury.

Background Mitral valve (MV) repair has become the gold standard for treating degenerative mitral regurgitation (MR), yet the success rate of MV repair is still low in clinical practice. While studies focused on the learning process of MV repair are scarce, fully understanding the learning curve could provide valuable information for education and the quality control of MV repair, thus benefiting patients. This observational study aimed to evaluate the learning process and performances of individual surgeon for MV repair for degenerative mitral disease using data from a single high-volume center. Methods Profiles of patients who underwent MV repair for degenerative MR at our institution from January 2003 to December 2016 were analyzed retrospectively. Overall and individual learning curves for the repair rate and major adverse events were calculated using sequential probability cumulative sum failure analysis. Average learning curves for major adverse events and operative time were also analyzed, by calculating the average incidence of adverse events and operative time of all operations stratified by accumulated operation numbers of individual surgeon. Altogether, we evaluated 2,482 operations performed by 14 surgeons. Results There was an obvious learning curve for the repair rate at the institution and individual surgeon levels. Altogether, 50 to 200 operations were needed to overcome the repair rate learning curve, yet wide variation was observed among individual surgeons. The learning process for individual surgeons became faster after the turning point in the institutional learning curve appeared. No obvious learning curve was observed at the institution or individual level for major adverse events and in-hospital mortality. Conclusions The number of cases required to overcome the learning curve for repair rate is substantial, although there is marked variation among surgeons. Individuals' learning curves accelerate as the institution accumulates experience. MV repair is safe in experienced high-volume center. Close monitoring is necessary when surgeons begin to practice new techniques.

Background Codonopsis pilosula and C. tangshen are both plants widely used in traditional Chinese medicine. Polysaccharides, which are their primary active components, are thought to be important in their extensive use. In this study, two neutral polysaccharide fractions of C. pilosula (CPPN) and C. tangshen (CTPN) were obtained by fractionation on a DEAE-Sepharose column and characterized. Results It was confirmed that the neutral polymers CPPN and CTPN were β-(2,1)-linked inulin-type fructans with non-reducing terminal glucose, and degree of polymerization (DP) of 19.6 and 25.2, respectively. The antioxidant and prebiotic activities in vitro were assayed based on IPEC-J2 cell lines and five strains of Lactobacillus. Results indicated that the effects of CPPN and CTPN were increased antioxidant defense in intestinal epithelial cells through enhanced cell viability, improved expression of total antioxidant capacity, glutathione peroxidase, superoxide dismutase and catalase, and reduced levels of malondialdehyde and lactic dehydrogenase. The prebiotic activity of CPPN and CTPN was demonstrated by the promoting effect on Lactobacillus proliferation in vitro. The different biological activities obtained between the two fractions are probably due to the different DP and thus molecular weights of CPPN and CTPN. Conclusion The inulin fractions from C. pilosula and C. tangshen were natural sources of potential intestinal antioxidants as well as prebiotics, which will be valuable in further studies and new applications of inulin-containing health products. © 2020 Society of Chemical Industry.

Background Prostate cancer is characterized by aberrant lipid metabolism, including elevated fatty acid oxidation. Carnitine palmitoyltransferase 1B (CPT1B) catalyzes the rate-limiting step of fatty acid oxidation. This study aimed to determine if CPT1B has a critical role in prostate cancer progression and to identify its regulatory mechanism. Methods CPT1B expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases was compared with patient survival data. A tissue microarray was constructed with 60 samples of prostate cancer and immunohistochemically stained for CPT1B. Castration-resistant prostate cancer (CRPC) cell lines 22RV1 and C4-2 in which CPT1B expression had been stably knocked down were established; and cell proliferation, cell cycle distribution, and invasion were investigated by Cell Counting Kit-8 (CCK-8) and colony formation assays, flow cytometry, and Transwell assays, respectively. To examine the impact of androgen receptor (AR) inhibition on CPT1B expression, JASPAR CORE was searched to identify AR-binding sites in CPT1B. Dual luciferase and ChIP assays were performed to confirm CPT1B activity and AR binding, respectively. Differentially expressed genes (DEGs) in prostate cancer underwent gene set enrichment analysis (GSEA). Enzalutamide-resistant C4-2 cells were generated and the mechanism of enzalutamide resistance and downstream signaling pathway changes of CPT1B to C4-2 was explored through CCK-8 test. Results CPT1B expression was upregulated in human prostate cancer compared with normal prostate tissue and was associated with poor disease-free survival and overall survival. Silencing of CPT1B resulted in downregulated cell proliferation, reduced S-phase distribution, and lower invasive ability, whereas the opposite was observed in CRPC cells overexpressing CPTB1. DEGS in prostate cancer were correlated with G-protein-coupled receptor signaling, molecular transducer activity, and calcium ion binding. AR may regulate CPT1B expression and activity via specific binding sites, as confirmed by dual luciferase and ChIP assays. The CCK-8 experiment demonstrated that CPT1B overexpression in C4-2 cells did not significantly increase the ability of enzalutamide resistance. However, overexpression of CPT1B in C4-2R cells significantly increased the enzalutamide resistance. Upregulation of CPT1B expression increased AKT expression and phosphorylation. Conclusions CPT1B is upregulated in prostate cancer and is correlated with poor prognosis, indicating its potential as a biomarker. AR inhibits the transcription of CPT1B. In the CRPC cell line, overexpression of CPT1B alone cannot promote enzalutamide resistance, but in the drug-resistant line C4-2R, overexpression of CPT1B can promote the resistance of C4-2R to enzalutamide.

Long non‐coding RNAs (lncRNAs) take various biological effects in clear cell renal cell carcinoma (ccRCC) mostly through sponging with microRNAs (miRNAs). lncRNA MIR4435‐2HG is found to promote tumour progression in gastric cancer, glioblastoma and hepatocellular carcinoma. However, the role of lncRNA MIR4435‐2HG in ccRCC progression remains unknown. The purpose of this research was to investigate the potential molecular mechanism of lncRNA MIR4435‐2HG regarding the regulation of ccRCC initiation and progression. In this study, we found the up‐regulation of MIR4435‐2HG in ccRCC tissues and cell lines. Functionally, overexpression of MIR4435‐2HG promoted the proliferation as well as the metastasis in ccRCC cell lines, whereas knockdown of MIR4435‐2HG inhibited the above changes. Then, bioinformatic analysis and luciferase reporter assays confirmed the negative regulation effect of MIR4435‐2HG on miR‐513a‐5p. And further investigations showed that KLF6, which collected from the intersection of databases, was the potential conjugated mRNAs of miR‐513a‐5p. Finally, the rescue experiments revealed the relation among MIR4435‐2HG and KLF6, which showed that KLF6 could reverse the promoting effect of MIR4435‐2HG on ccRCC in vitro and in vivo. Therefore, our findings provided insight into the mechanisms of MIR4435‐2HG in ccRCC and revealed an alternative target for the clinical diagnosis and treatment of ccRCC.

Clear cell renal cell carcinoma (ccRCC) is the most common and highly malignant pathological type of kidney cancer. We sought to establish a metabolic signature to improve post‐operative risk stratification and identify novel targets in the prediction models for ccRCC patients. A total of 58 metabolic differential expressed genes (MDEGs) were identified with significant prognostic value. LASSO regression analysis constructed 20‐mRNA signatures models, metabolic prediction models (MPMs), in ccRCC patients from two cohorts. Risk score of MPMs significantly predicts prognosis for ccRCC patients in TCGA (P

BACKGROUND: Postoperative unobstructed drainage is an important measure for avoiding hematoma formation and preventing complications from anterior cervical surgery. AIM: To discuss the characteristics and key points of clinical management of two types of commonly used negative pressure drainage systems in clinical settings. METHODS: Two types of commonly used silica gel negative pressure drainage balls and a type of gastrointestinal decompression apparatus were fully emptied and then injected with different amounts of water and air. Following this, the negative pressure values of the three devices were measured. Meanwhile, we undertook a retrospective analysis of the clinical data of 1328 patients who had been treated with different negative pressure drainage apparatuses during their anterior cervical surgery in our department between January 2007 and January 2018. RESULTS: As the amount of injected air or water increased, the negative pressure of the silica gel negative pressure drainage ball decreased rapidly, dropping to zero when 150 mL of water or air was injected. In contrast, the negative pressure of gastrointestinal decompression apparatus decreased slowly, maintaining an ideal value even when 300 mL of water or air was injected. And statistical analysis demonstrated that patients who had been treated with the gastrointestinal decompression apparatus were less likely to develop severe complications than those who had been treated with the silica gel negative pressure drainage ball (P < 0.05). CONCLUSION: This study showed that the gastrointestinal decompression apparatus has the advantages of large suction capacity, long duration of continuous negative pressure, and good drainage effect, all of which are the favorable factors for the use of this apparatus for negative pressure drainage in anterior cervical surgery.

Background Prognosis of hepatocellular carcinoma (HCC) remains poor despite significant recent improvement in therapy. Recent studies have reported that transglutaminase 3 (TGM3) plays an important role in several human cancer types. However, the role of TGM3 in HCC have not been previously elucidated. Methods We evaluated the role of TGM3 in regulating HCC cell proliferation, migration, and invasion. We also investigated the prognostic significance of TGM3 in an HCC cohort. Finally, we explored the signalling pathways that TGM3 regulates in HCC. Results We identified TGM3 to be overexpressed in HCC compared to normal tissues. Higher expression of TGM3 predicts poor prognosis in HCC patients. TGM3 knockdown led to decreased HCC cell proliferation, invasion, and xenograft tumour growth. TGM3 depletion inhibited AKT, extracellular signal–regulated kinase (ERK), p65, and glycogen synthase kinase 3β (GSK3β)/β-catenin activation, but promoted levels of cleaved caspase 3. Moreover, TGM3 knockdown cells had increased E-cadherin levels and decreased vimentin levels, suggesting that TGM3 contributes to epithelial–mesenchymal transition (EMT) in HCC. Conclusion Our results suggest that TGM3 controls multiple oncogenic pathways in HCC, thereby contributing to increased cell proliferation and EMT, and TGM3 potentially enhances HCC metastasis. TGM3 may serve as a novel therapeutic target in HCC.