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Background: Lactate dehydrogenase (LDH) is a nonspecific inflammatory biomarker and has been reported to be useful in predicting community-acquired pneumonia and Mycoplasma pneumoniae pneumonia. The connection between LDH level and postoperative pneumonia (POP) in patients with aneurysmal subarachnoid hemorrhage (aSAH) is still unclear. The aim of this study was to assess feasibility of predicting POP in patients with aSAH using LDH., Methods: Admission serum LDH level was obtained in 647 patients with aSAH enrolled in a prospective observational study. The relationship between LDH level and POP was analyzed., Results: POP occurred in 187 patients (28.90%). Patients with POP had significantly higher LDH levels than patients without POP (261.26 ± 126.51 U/L vs. 189.00 ± 69.20 U/L, P < 0.001). Multivariate analysis showed that LDH level remained a significant independent factor associated with POP in patients with aSAH, even after adjusting for possible confounding factors. Receiver operating characteristic curve analysis showed that LDH level had a sensitivity of 63.6% and a specificity of 71.3% for predicting POP based on best threshold of 203.5 U/L. There were additive interactions between elevated LDH level and World Federation of Neurosurgical Societies grade or mechanical ventilator use. When patients were classified by World Federation of Neurosurgical Societies grade or mechanical ventilator use, regardless of World Federation of Neurosurgical Societies grade (

The skin microbiome plays important roles in the pathogenesis and development of acne. We aimed to investigate the facial skin microbiome of acne and microbiome differences related to different grades of acne. Skin swabs from nine healthy controls and 67 acne patients were collected, and the skin microbiomes were analyzed using 16S rRNA gene sequencing. Compared with healthy controls, acne patients harbored significantly altered skin microbiomes. The skin microbiomes of patients with grade 1-3 acne were similar, but patients with grade 4 acne showed a significantly different skin microbiome compared with grade 1-3 acne, including increased alpha diversity and increased proportions of four Gram-negative bacteria (Faecalibacterium, Klebsiella, Odoribacter and Bacteroides). In conclusion, acne patients harbored an altered skin microbiome, and more significant dysbiosis was found in patients with grade 4 acne (severe acne). Our findings may provide evidence for the pathogenic mechanisms of acne and microbial-based strategies to avoid and treat acne, especially grade 4 acne., (© 2019 Japanese Dermatological Association.)

In the current study, we present a universal method to preserve DNA-templated silver nanoclusters (DNA AgNCs) in the solid-state. Our results show that DNA AgNCs must be precipitated before drying. By drying the ethanol precipitated DNA AgNCs, we have successfully prepared solid DNA AgNCs with superior stability in aerobic and high-temperature environments. Although the fluorescence lifetime measurements show that the emission of DNA AgNCs is drastically quenched in the solid-state, the emission can be fully recovered in solution. To our knowledge, this is the first attempt to prepare DNA AgNCs in solid-state, and this finding provides an ideal solution for the transportation and long-term preservation of DNA AgNCs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Treatment of blast-induced traumatic brain injury (bTBI) has been hindered. Previous studies have demonstrated that oxidative stress may contribute to the pathophysiological process. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway exhibits a protective effect after traumatic brain injury (TBI). This study explored whether the Nrf2-ARE pathway was activated in a modified bTBI mouse model. Method: Mice were randomly divided into six groups: the 6 h, 1 d, 3 d, 7 d and 14 d after bTBI groups and a sham group. The protein levels of nuclear Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) were detected using western blot, and HO-1 and NQO1 mRNA levels were determined by real-time quantitative polymerase chain reaction. Moreover, HO-1 and Nrf2 were localized using histological staining. Results: The protein level of the Nrf2-ARE pathway in the frontal lobe increased significantly in the 3 d after bTBI. The HO-1 and NQO1 mRNA levels also reached a peak in the frontal lobe 3 d after bTBI. The histological staining demonstrated higher expression of HO-1 in the frontal lobe and hippocampus 3 d after bTBI, when nuclear import of Nrf2 reached a peak in the frontal lobe. Conclusions: bTBI activated the Nrf2-ARE signaling pathway in the brain. The peak activation time in the frontal lobe may be 3 d after injury, and activating the Nrf2 pathway could be a new direction for treatment.

Cellular immunotherapeutics aim to employ immune cells as anticancer agents. Ex vivo engineering of dendritic cells (DCs), the initial role of an immune response, benefits tumor elimination by boosting specific antitumor responses. However, directly activating DCs in vivo is less efficient and therefore quite challenging. Here, we designed a nanoactivator that manufactures DCs through autophagy upregulating in vivo directly, which lead to a high-efficiency antigen presention of DCs and antigen-specific T cells generation. The nanoactivator significantly enhances tumor antigen cross-presentation and subsequent T cell priming. Consequently, in vivo experiments show that the nanoactivators successfully reduce tumor growth and prolong murine survival. Taken together, these results indicate in situ DCs manipulation by autophagy induction is a promising strategy for antigen presentation enhancement and tumor elimination.

Successful seed germination depends on the rapid repair of cell membrane damaged by dry storage. However, little is known about the reorganization of lipids during this process. In this study, the changes of intracellular redox environment, cell membrane integrity, lipid composition, and expression of genes related to phospholipid metabolism were assessed during imbibition of Brassica napus seeds. A total number of 443 lipids belonging to 7 categories were detected by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). In the 24 h-imbibed seeds, the relative content of triacylglycerol was lower than in dry seeds, while the relative content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS), especially PC (36:2, number of carbons in the acyl chains: number of double bonds), PC (36:3), and PE (36:3) were higher than those in dry seeds. Meanwhile, the content and unsaturation levels of phospholipids increased, indicating membrane lipids remodeling during seed imbibition. The plasma membrane integrity, which was measured by the relative electrolyte leakage (REL) of the membrane and FM4-64 fluorescent dye, was improved upon imbibition, confirming that cell membrane was repaired after 24 h-imbibition. The reduction of H 2 O 2 content, redox potential, and malondialdehyde (MDA) content indicated that the degree of membrane lipid peroxidation was significantly decreased upon imbibition. Gene expression analysis showed that the differential expression of genes for key enzymes occurred in the plateau phase of the imbibition curve, i.e. after 8 h-to 24 h-imbibition. Moreover, the differential expression of genes such as those encoding phospholipase C (PLC), phospholipase D (PLD), triacylglycerol lipase (TAG lipase), choline/ethanolamine phosphotransferase (CEPT), and phosphatidylserine synthase (PTDSS2) during imbibition indicated that membrane lipid remodeling was related to complex metabolic pathways, among which the degradation of triacylglycerol and the synthesis of phospholipids using diacylglycerol might play an important role during membrane remodeling., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This study presents a systematic analysis of the functional differences between two genes that encode phytoene desaturase (PDS) in Chinese kale. The promoter sequences of both BaPDS1 and BaPDS2 were amplified and cloned, and their lengths were 2005 bp and 2000 bp, respectively. The mining of cis -acting elements in the promoters showed that the two BaPDS genes are mainly associated with light and phytohormone responsiveness. Light quality, light intensity and plant hormone treatments were conducted in seedlings of Chinese kale, and the results indicated that the response of the two genes to different factors differed. Among them, BaPDSs collectively respond to the treatment with salicylic acid and abscisic acid. With regard to response differences, BaPDS1 is sensitive to red and blue light, blue light, and strong light, while BaPDS2 responds to blue light, weak light, darkness, gibberellin and methyl jasmonate. In addition, both BaPDS1 and BaPDS2 are likely targeted to the chloroplast. Furthermore, single and double mutants of BaPDSs were generated via CRISPR/Cas9 technology. Phenotypic analysis showed that the double mutant with edited PDS1 and PDS2 was a pure albino, while the single mutants with edited PDS1 or PDS2 were partly whitened. In summary, BaPDS1 and BaPDS2 genes played different and indispensable roles in Chinese kale, and their functions were partially complementary., Competing Interests: We declare we have no competing interests.

Background and Purpose- Hypoxic-ischemic brain damage is a well-recognized physiopathologic mechanism after aneurysmal subarachnoid hemorrhage (aSAH). The Ngb (neuroglobin) is a hemoprotein predominantly expressed in the brain with a high affinity for oxygen. Relationship between serum Ngb level and brain metabolism in aSAH patients has not been investigated previously. Methods- Thirty-six consecutive severe aSAH patients (Glasgow Coma Scale score ≤8 on admission) with multimodal neuromonitoring and 36 matched healthy subjects were included. Serum Ngb level was analyzed in combination with other time-matched cerebral microdialysis parameters, brain tissue oxygen tension, and 12-month neurological outcomes. Results- Serum Ngb level was correlated positively with cerebral microdialysis parameters and brain tissue oxygen tension ( P<0.001). Poor functional outcome (modified Rankin Scale score >3) 12 months after aSAH was associated with higher Ngb level but independent of age, sex, and disease severity ( P<0.001). A similar association was found between high Ngb level and neuropsychological test results indicative of impairments in cognition, visual conceptualization, and frontal executive functions ( P<0.001). Conclusions- Ngb may be a potential biomarker for reflecting brain tissue oxygen tension, brain metabolism, and functional outcome in severe aSAH patients and merits further study in the context of aSAH.

Objective: We tested the hypothesis that low hemoglobin levels are associated with acute seizures after aneurysmal subarachnoid hemorrhage (aSAH)., Methods: Patients with ruptured intracranial aneurysms were enrolled in the observational cohort study that prospectively collected age, sex, symptom onset, history of diabetes and hypertension, history of coronary artery disease, temperature, Hunt-Hess grade, Fisher grade, aneurysm location, hemoglobin, hematocrit, serum potassium, sodium, calcium, phosphorus, iron, and modified Rankin Scale. Acute seizures were determined as seizures within 1 week after aSAH., Results: We included 554 patients with requisite data for analysis in the prospective study. Incidence of acute seizures following aSAH was 3.61%. In the univariate analysis, significant differences were detected in admission Hunt-Hess grade, Fisher grade, hemoglobin, and serum iron between epilepsy and nonepilepsy groups. Furthermore, acute seizures were associated with higher modified Rankin Scale score and poor outcome (P = 0.004). Serum hemoglobin levels were 114.30 ± 20.08 g/L in the epilepsy group, which were lower than those in the nonepilepsy group (128.64 ± 17.94 mmol/L, P = 0.001). Serum iron levels were 8.89 ± 5.03 g/L in the epilepsy group, which were also lower than those in the nonepilepsy group (13.71 ± 6.70 mmol/L, P = 0.002). The hemoglobin level was positively correlated with serum iron on admission (ρ = 0.321, P = 0.000). In the multivariate logistic regression model, lower hemoglobin was considered as an independent risk factor of acute seizures (odds ratio 4.286, 95% confidence interval 1.492-12.315, P = 0.007). The optimal cutoff value for hemoglobin level as a predictor for acute epilepsy after aSAH was determined as 119 g/L in the receiver operating characteristic curve (sensitivity was 75.00%, and specificity was 69.48%)., Conclusions: These data support the hypothesis that hemoglobin was inversely associated with acute seizures following aSAH., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The tumor-suppressor function of p53 makes it an attractive drug target. Efforts were mostly put on stabilization of the functional p53 or reactivation of mutated p53. Previous studies have shown that small molecules targeting Loop1/Sheet3 (L1/S3) can reactivate the R175H-p53 and stabilize p53 in vitro. Since the L1/S3 pocket is shared by the mutate and the wild type (WT) p53, virtual screening is introduced to identify natural products targeting the L1/S3 of WT p53. Considering the high flexibility of Loop1, ensemble docking method is utilized for different clusters of the L1/S3. Seven conformations were chosen for docking. As one of the 181 selected candidates, torilin not only improved p53 activity, but also increased p21 protein expression level, which lies downstream of p53, therefore suppressing HCT116 cancer cell growth. Torilin may covalently bind to Cys124 of p53 by 2-methyl-2-butenal (2M2B) group, as torilin derivatives, which do not contain the 2M2B group, were not able to increase the p53 transcription activity. In conclusion, this study demonstrated that L1/S3 of WT-p53 is a druggable pocket, and torilin has a potential cytotoxicity through activating the p53 pathway., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

Cisplatin-based chemotherapy is a widely used first-line strategy for numerous cancers. However, drug resistances are often inevitable accompanied by the long-term use of cisplatin in vivo, significantly hampering its therapeutic efficacy and clinical outcomes. Among others, autophagy induction is one of the most common causes of tumor resistance to cisplatin. Herein, a self-assembled nanoprodrug platform was developed with the synergistic effect of cisplatin and RNAi to fight against cisplatin-resistant lung cancer. The nanoprodrug platform consists of three molecular modules, including prodrug complex of Pt(IV)-peptide-bis(pyrene), DSPE-PEG, and cRGD-modified DSPE-PEG. The Pt(IV) is immobilized with peptide via amide bonds, allowing the Pt(IV) to be loaded with a loading efficiency of >95% and rapid-release active platinum ions (Pt(II)) in the presence of glutathione (GSH). Meanwhile, the peptide of the prodrug complex could efficiently deliver Beclin1 siRNA ( Beclin1 is an autophagy initiation factor) to the cytoplasm, thereby leading to autophagy inhibition. In addition, incorporation of DSPE-PEG and cRGD-modified DSPE-PEG molecules improves the biocompatibility and cellular uptake of the nanoprodrug platform. In vivo results also indicate that the nanoprodrug platform significantly inhibits the growth of a cisplatin-resistant tumor on xenograft mice models with a remarkable inhibition rate, up to 84% after intravenous injection.

We described an effective way to generate a Co 3 O 4 mesocrystal array with well-developed porosity, simply by uniting a coupled interface with hydrazine treatment. Due to the fast electron transfer and sufficient active sites, the Ti mesh-supported Co 3 O 4 nanoneedles electrode could provide a current density of 49.9 mA cm -2 at 570 mV OER overpotential and has exceptionally high stability.

Purpose: We compared the efficacies of intravitreal ranibizumab (IVR) and intravitreal conbercept (IVC) as the adjuvant pretreatments for vitrectomy with silicone oil infusion for tractional retinal detachment (TRD) secondary to proliferative diabetic retinopathy., Methods: This retrospective study comprised 74 patients (79 eyes) who underwent vitrectomy with silicone oil tamponade for diabetic TRD. They received IVC (37 eyes) or IVR (42 eyes) at standard doses 3-5 days preoperatively and were followed up for ∼6 months. Anatomic success rate, intra- and postoperative complications, and visual outcomes were compared between both groups., Results: Initial (IVC vs. IVR: 97% vs. 98%) and final anatomic success rates (100% in each group) and mean visual acuity changes were not significantly different (P = 0.46). Intraoperative complications [iatrogenic retinal breaks (P = 0.58) and intraoperative bleeding (P = 0.66)], postoperative complications [fibrin formation (P = 0.51), postoperative preretinal bleeding (P = 0.88), progressing or persistent neovascular glaucoma (P = 0.63), progressive fibrovascular proliferation (P = 0.93), and recurrent retinal detachment (P = 0.93)], and surgical variables [surgical time (P = 0.53)] were similar between both groups., Conclusions: Conbercept and ranibizumab are equally effective surgical adjuvants for vitrectomy with silicone oil infusion in patients with diabetic TRD.

Background: Reactive oxygen species (ROS) overproduction is highly related to some human chronic diseases. There are approximately 400 metric tons of chalazae produced yearly after the processing of the liquid-egg production, which are disposed of as waste. The objectives of this study were to look for the optimal production condition of antioxidant crude chalaza hydrolysates and evaluate the in vivo antioxidant capacity via a chronic alcohol consumption mouse model., Results: Antioxidant crude chalaza hydrolysates (CCH-As) could be produced by protease A at 1:100 ratio (w/w) and 0.5 h hydrolytic period. After our analyses, CCH-As were rich in leucine, arginine, phenylalanine, valine, lysine and antioxidant dipeptides (anserine and carnosine), and the major molecular masses were lower than 15 kDa. Regarding protective effects of CCH-As against oxidative damage in alcoholic-liquid-diet-fed mice, alcohol-fed mice had lower (P < 0.05) liver antioxidant capacities, and higher (P < 0.05) liver lipid contents, serum lipid/liver damage indices and IL-1β/IL-6 values. CCH-A supplementation reversed (P < 0.05) liver antioxidant capacities and reduced (P < 0.05) serum/liver lipids in alcohol-fed mice, which may result from increased (P < 0.05) fecal lipid output, upregulated (P < 0.05) fatty acid β-oxidation and downregulated (P < 0.05) lipogenesis in the liver., Conclusion: Taken together, this CCH-A should benefit the liquid-egg industry, while also offering consumers a choice of healthy ingredients from animal sources. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

The incidence of metabolic syndrome gradually multiplied with the change of dietary structure of high fat- high sugar in the population, bringing it as independent risk factors for tumors. Liver is an important organ of lipid metabolism. The main manifestations of metabolic syndrome are obesity and abnormal lipid metabolism, which are closely related to hepatocellular carcinoma occurrence. MicroRNA (miRNA) is an endogenous non-coding RNA that participates in the post-transcriptional regulation of target genes by binding to the 3'-UTR of mRNA. Research studies have found that abnormal miRNA expression can influence the pathogenesis of hepatocellular carcinoma via regulating lipid metabolism-related proteins in the liver. This article reviews and discusses the characteristics and pathogenesis of lipid metabolism disorder in hepatocellular carcinoma, and the mechanism by which miRNA regulates the occurrence and development of hepatocellular carcinoma through lipid metabolism-related proteins. Furthermore, it also provides a reliable theoretical foundation for the study of the pathogenesis of hepatocellular carcinoma.

Objective: Glutamate excitotoxicity and neuronal apoptosis are suggested to contribute to early brain injury after subarachnoid hemorrhage (SAH). Annexin A7 (ANXA7) has been shown to regulate glutamate release. However, the role of ANXA7 in early brain injury after SAH has not been illustrated. In this study, we aimed to investigate the effect of ANXA7 knockdown in reducing the severity of early brain injury after SAH, and determine the underlying mechanisms., Methods: Endovascular perforation was performed to induce SAH in male Sprague-Dawley rats. ANXA7-siRNA was administered via intraventricular injection 5 days before SAH induction. Neurological test, evaluation of SAH grade, assessment of blood-brain barrier (BBB) permeability, measurement of brain water content, Western blot, double immunofluorescence staining, TUNEL staining, and enzyme-linked immunosorbent assay (ELISA) were performed at 24 hours of SAH induction., Results: ANXA7 protein expression increased significantly after SAH induction and was seen mainly in neurons. High expression of ANXA7 was associated with poor neurological status. ANXA7 knockdown dramatically ameliorated early brain injury through alleviating BBB disruption and brain edema. Further investigation of the mechanism showed that inhibiting ANXA7 expression can rescue neuronal apoptosis. In addition, ANXA7 knockdown also significantly reduced glutamate release, which was consistent with a significant increase of Bcl-2 expression and decreases of Bax and cleaved caspase-3 expression., Conclusions: ANXA7 can induce neuronal apoptosis by affecting glutamate release in rats with SAH. Downregulating the expression of ANXA7 can significantly attenuate early brain injury after SAH. Future therapy targeting ANXA7 may be a promising new choice.

Tumor-associated macrophages (TAMs) are of great interest in cancer immunology as they play an important role in the tumor microenvironment as cancer stromal cells recruited from circulating monocytes. TAMs are closely associated with tumor progression, including initiation, trophic growth, metabolism, angiogenesis, and metastasis; moreover, in clinical practice, their quantity can be related to poor prognosis. Fundamental and translational studies imply that TAMs are one of the most promising targets in tumor therapy. Herein, the biological origination and classification of TAMs, which correspond to their functions and differentiations, are reviewed in detail. In addition, recent basic research and clinical preprocess of TAMs in tumor immunotherapy are also discussed. Finally, the advances in the use of nanotechnology and TAMs for tumor therapy are discussed. This review focuses on the background and status of basic research and clinical significance of TAMs, points out the potential of TAMs in tumor immunological therapy, and clarifies the possibility of translation TAM-targeting therapies in medicine., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: We tested the hypothesis that cerebellopontine angle (CPA) tumors are associated with a greater incidence of unruptured intracranial aneurysms (IAs)., Methods: Patients with intracranial tumors (ITs) undergoing computed tomography angiography and magnetic resonance imaging were enrolled in an observational cohort study that prospectively collected age, sex, hypertension, diabetes, cerebral arteriosclerosis, tumor type, tumor location, hydrocephalus, smoking, alcohol intake, CPA tumor size, cerebral aneurysms, and cerebral arteriosclerosis. Patients with the coexistence of IA and ITwere classified as group II, whereas the others with IT as group I., Results: We included 1218 patients with IT for analysis. The incidence of IA was 7.1% (86/1218). A total of 31% of patients with aneurysms had CPA tumors. In a multivariate logistic regression model, a greater incidence of IA was found in female patients (odds ratio [OR] 1.726, 95% confidence interval [CI] 1.050-2.836, P=0.031) and in patients with CPA tumors (OR 3.002, 95% CI 1.822-4.947, P=0.000) after adjustment for tumor type, cerebral arteriosclerosis, and age. In female patients, CPA tumors were a unique independent risk factor of a greater incidence of IA (OR 2.270, 95% CI 1.194-4.317, P=0.012). Furthermore, cerebral arteriosclerosis was a unique independent risk factor of IA in patients with CPA tumors (OR 7.626, 95% CI 2.928-19.860, P=0.000)., Conclusions: These data support the hypothesis that CPA tumors are associated with a greater incidence of unruptured IAs, especially in female patients. Cerebral arteriosclerosis contributed to elevated risk of IA in patients with CPA tumors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and various cardiovascular and cerebrovascular diseases is inconsistent. However, the connection between Lp-PLA2 level and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. The objective of this study was to investigate the relationships between the Lp-PLA2 levels in the early stages of aSAH and the occurrence of DCI., Methods: The authors evaluated 114 patients with aSAH who were enrolled into a prospective observational cohort study. Serum Lp-PLA2 level at admission (D0), on the first morning (D1), and on the second morning of hospitalization (D2) were determined using commercial enzyme-linked immunosorbent assay kits. The relationship between Lp-PLA2 levels and DCI was analyzed., Results: Forty-three patients with aSAH (37.72%) experienced DCI. Mean serum Lp-PLA2 level decreased from 183.06 ± 61.36 μg/L at D0 (D0 vs D1, p = 0.303), to 175.32 ± 51.49 μg/L at D1 and 167.24 ± 54.10 μg/L at D2 (D0 vs D2, p = 0.040). The Lp-PLA2 level changes (D0-D1 and D0-D2) were comparable between patients with and without DCI. Multivariate model analysis revealed Lp-PLA2 level (D0) > 200 μg/L was a more significant factor of DCI compared with Lp-PLA2 (D1) and Lp-PLA2 (D2), and was a strong predictor of DCI (odds ratio [OR] 6.24, 95% confidence interval [CI] 2.05-18.94, p = 0.001) after controlling for World Federation of Neurosurgical Societies (WFNS) grade (OR 3.35, 95% CI 1.18-9.51, p = 0.023) and modified Fisher grade (OR 6.07, 95% CI 2.03-18.14, p = 0.001). WFNS grade (area under the curve [AUC] = 0.792), modified Fisher grade (AUC = 0.731), and Lp-PLA2 level (D0; AUC = 0.710) were all strong predictors of DCI. The predictive powers of WFNS grade, modified Fisher grade, and Lp-PLA2 (D0) were comparable (WFNS grade vs Lp-PLA2: p = 0.233; modified Fisher grade vs Lp-PLA2: p = 0.771). The poor-grade patients with Lp-PLA2 (D0) > 200 μg/L had significantly worse DCI survival rate than poor-grade patients with Lp-PLA2 (D0) ≤ 200 μg/L (p < 0.001)., Conclusions: The serum level of Lp-PLA2 was significantly elevated in patients with DCI, and decreased within the first 2 days after admission. Lp-PLA2 in the early stages of aSAH might be a novel predictive biomarker for the occurrence of DCI.

Objective: To observe the effects of Shenmai injection(SM) on p38MAPK and the apoptosis-related genes in lung injury induced by intestinal ischemia reperfusion (I/R) in rats and to investigate the protective mechanism of SM., Methods: Rat model of intestinal I/R injury was established with clamping of the superior mesenteric artery (SMA) for 60 min and then clamping was relieved for 60 min. Twenty-four SD rats were randomly divided into three groups with eight rats in each: control group, intestinal ischemia/reperfusion group(I/R group), Shenmai injection treated group (SM+I/R group). Lung wet/dry weight ratio(W/D), the contents of phosphatidylcholine (PC) and total phospholipid(TPL) which are the major ingredients of pulmonary surfactant were measured, as well as the expression levels of p38MAPK, Bcl-2 and Bax proteins in lung tissue were examined by using immunohistochemical method., Results: Compared with control group, lung W/D was significantly increased, the contents of PC and TPL were significantly decreased, the protein expression levels of p38MAPK, Bcl-2 and Bax were significantly increased in I/R group (all P＜0.01). But Bax protein expression was much greater than Bcl-2 protein expression, the ratio of Bcl-2 to Bax were significantly decreased in I/R group than that in control group (P＜0.01). Compared with I/R group, lung W/D was significantly decreased, while the contents of PC and TPL were significantly increased, the p38MAPK and Bax protein expression levels were significantly decreased in SM+I/R group (all P＜0.01); both Bcl-2 protein expression and the ratio of Bcl-2 to Bax were significantly increased in SM+I/R group than those in I/R group (P＜0.01). The correlation analysis indicated that the expression level of p38MAPK protein in lung tissue was negatively correlated with the contents of PC and the ratio of Bcl-2 to Bax (r is -0.787 and -0.731, all P＜0.01)., Conclusion: SM can protect the lung injury induced by intestinal I/R injury, which may be mediated by inhibiting the activation of p38MAPK, improving the ratio of Bcl-2 to Bax to inhibit lung apoptosis.

Objective: The current research was conducted to test the prediction that children who have hearing loss and are developing spoken language can perform at the same level as hearing children in an auditory memory span task if actual production of speech is excluded from task requirement. Method: A listen-and-point digit span task and two sub-tests of Wechsler Intelligence Scale for Children-IV (Verbal Digit Span and Matrix Reasoning) were administered to thirty hearing children and thirty-three children with hearing loss. A language assessment instrument for Mandarin-speaking preschool children was also administered to the participants with hearing loss. Results: The listen-and-point task not only correlated with the Verbal Digit Span sub-test, but also correlated with the comprehension sub-test of the language assessment instrument. The size of auditory memory span was similar in both groups of participants in the listen-and-point task. Moreover, the memory span estimated in the listen-and-point task was smaller than that estimated in the Verbal Digit Span task. The correlation coefficients between chronological age and the listen-and-point task were also similar in both groups of children. Conclusions: When speech processes are not required in an auditory working memory task, demand for the phonological loop is reduced and the children with hearing loss are able to perform as well as the hearing children. Moreover, the auditory memory span develops at the same rate for the children with hearing loss as for the hearing children.

Background: There is associating with incidence of unfavorable outcomes compared to microsurgical clippings. We are in order to investigate the outcomes of microsurgical clipping for intracranial aneurysms and determine the ideal clipping methods for different aneurysm subtypes., Method: Retrospectively analyzed the clinical characteristics and follow-up data (completely recorded) of 123 patients with 128 aneurysms were treated. 20 cases were treated as control group from October 2013 to December 2013. Since January 2014, aneurysms were classified base on the 20 cases of aneurysm imaging data. 103 patients were treated as experimental group, the classification of aneurysms previously proposed was used to estimate the way of surgery, and the guiding value of the genotype was verified according to the intraoperative findings. The proposed aneurysm classification is based on the virtual surface of the aneurysm and the parent artery, the aneurysm neck was classified as follows: subtype I, the curved surface of the neck is a single curved surface; subtype II, the neck is hyperboloid; subtype III, neck is a three-curved surface. Aneurysms were divided into further subtypes according to the ratio of the width of the aneurysm neck surface and the length of the artery circumference: subtype A, the ratio of the aneurysm neck surface to the parent artery was not more than 0.5; subtype B, more than 0.5. There are some clamping methods include simple, sliding, interlocking and hybrid., Results: In the control group, patients did not undergo a suitable clipping scheme without classification of aneurysm neck (unclassed clipping). While causing the occurrence of occlusion adverse events, including neck residual, Tumor artery stenosis, electrophysiological changes, the lack of blood supply and so on. The experimental[page1image12073600]group was analyzed by using a predetermined clipping scheme (classed clipping), and the use of aneurysms clamps was approximately the same as expected. Compared the preoperative assessment with the actual situation, the consistency of the control group was 50% and the experimental group was 96%. Adverse events of classed clipping is 2%, another is 60%. There is a significant difference between the two groups ( P  < 0.05).Classed clipping of subject IA and IB are simple (mean 1.2 and 1.3 clips); classed clipping of subject IIA is simple and interlocking(mean 1.2 clips); classed clipping of subject IIB is sliding and hybrid(mean 2.05 clips); classed clipping of subject IIIA and IIIB are hybrid(mean 2.3 clips)., Conclusion: There is a higher consistency in surgery through the above classification of preoperative assessment of clipping. There was no adverse event of intracranial aneurysm clipping in the clipping mode selected by the above classification, and satisfactory surgical clipping rate was achieved and no recurrence was found., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2018.)

This study investigated the changes in metabolisms of membrane lipids and phenolics caused by Phomopsis longanae Chi infection in association with pericarp browning and fruit disease occurrence of postharvest longans. Compared with the uninoculated-longans, the longans inoculated by P. longanae exhibited higher cellular membrane permeability; higher PLD, lipase, and LOX activities; and higher levels of saturated fatty acids (SFAs) and phosphatidic acid but lower levels of phosphatidylinositol, phosphatidylcholine, and unsaturated fatty acids (USFAs). Additionally, the longans inoculated by P. longanae showed higher activities of POD and PPO but a lower amount of total phenolics. These findings suggested that infection of P. longanae enhanced activities of PLD-, lipase-, and LOX- stimulated degradations of membrane lipids and USFAs, which destroyed the integrity of the cell membrane structure, resulting in enzymatic browning by contact of phenolics with POD and PPO, and resulting in reduction of resistance to pathogen infection and accordingly accelerated disease occurrence of postharvest longan fruit.

Background: We tested the hypothesis that high-density lipoprotein (HDL) is associated with intracranial aneurysm growth and rupture., Methods: We used an observational cohort study design. Age, sex, admission systolic blood pressure (SBP), diabetes, hypertension, coronary artery disease, aneurysmal rupture, apolipoprotein (APO)-A1, APO-B, HDL, low-density lipoprotein, triglycerides, cholesterol, and aneurysm location and size were recorded. Aneurysms <8 mm were categorized as small., Results: The data from 581 patients with intracranial aneurysms were analyzed. The predictive factors for small size of aneurysms were female sex (odds ratio [OR], 0.630; 95% confidence interval [CI], 0.428-0.927; P = 0.019) and higher HDL (OR, 0.327; 95% CI, 0.159-0.672; P = 0.0002). In the subgroup of male patients, lower HDL was the only risk factor for large size (P = 0.015). The predictors of aneurysmal rupture were small size (OR, 0.875; 95% CI, 0.842-0.910; P = 0.000), higher HDL (OR, 3.716; 95% CI, 1.623-8.509; P = 0.002), no coronary artery disease (OR, 4.736; 95% CI, 1.528-14.681; P = 0.007), lower APO-A1 (OR, 0.202; 95% CI, 0.064-0.641; P = 0.007), and higher admission SBP (OR, 1.024; 95% CI, 1.015-1.032; P = 0.000). An HDL/aneurysm size ratio >0.31 was associated with a 46.2-fold increased likelihood of aneurysmal rupture (OR, 46.214; 95% CI, 13.386-159.548; P = 0.002)., Conclusions: The HDL level was inversely associated with intracranial aneurysm growth, especially in men. Higher HDL levels and small aneurysm size contributed to a greater risk of aneurysmal rupture. An HDL/size ratio >0.31 was a valuable predictor of intracranial rupture., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Epstein-Barr virus (EBV)-associated epithelial cancers, including nasopharyngeal carcinoma (NPC) and approximately 10% of gastric cancers, termed EBVaGC, represent 80% of all EBV-related malignancies. However, the exact role of EBV in epithelial cancers remains elusive. Here, we report that EBV functions in vasculogenic mimicry (VM). Epithelial cancer cells infected with EBV develop tumor vascular networks that correlate with tumor growth, which is different from endothelial-derived angiogenic vessels and is VEGF-independent. Mechanistically, activation of the PI3K/AKT/mTOR/HIF-1α signaling cascade, which is partly mediated by LMP2A, is responsible for EBV-induced VM formation. Both xenografts and clinical samples of NPC and EBVaGC exhibit VM histologically, which are correlated with AKT and HIF-1α activation. Furthermore, although anti-VEGF monotherapy shows limited effects, potent synergistic antitumor activities are achieved by combination therapy with VEGF and HIF-1α-targeted agents. Our findings suggest that EBV creates plasticity in epithelial cells to express endothelial phenotype and provides a novel EBV-targeted antitumor strategy.

Objective: Percutaneous radiofrequency thermocoagulation (RFT) of the Gasserian ganglion is an effective treatment for refractory trigeminal craniofacial pain.In the present study, we assessed the feasibility of accessing the Gasserian ganglion through the foramen ovale with neuronavigation guidance in the patients of trigeminal craniofacial pain. Method: We retrospectively analyzed forty-four patients with type Ⅰ trigeminal neuralgia who had undergone percutaneous RFT treatment in our hospital from June 2014 to December 2016.The patients were divided into fluoroscopy group and navigation group according to the intraoperative guiding manners for foramen ovale cannulation.We compared groups in terms of the duration of the whole RFT procedure and times of intraoperative fluoroscopy.We also analyzed the immediate and late outcome accessing by Barrow Neurological Institute (BNI) pain scale, as well as the complication rates in groups. Result: There were 32 patients in the fluoroscopy group and 12 in the navigation group.The duration of the surgical procedure in navigation group was less than that in fluoroscopy group (46±12 min versus 67±16 min, P =0.00), and times of intraoperative fluoroscopy was reduced (6.3±2.2 versus 1.3±1.6, P =0.00). The learning curve of navigation-aid RFT was not steep in the present study overall.There was no significant difference between groups regarding pain reduction at the immediate ( P =0.07) or late follow-up ( P =0.400) time points.However, the rate of pain reduction to BNI-Ⅰ grade was greater in navigation group ( P =0.026). No significant difference in the complication rate between both groups, and no serious complications were observed in the both groups. Conclusion: Neuronavigation may be encouraged in trigeminal Gasserian ganglion RFT with better operating efficiency and less radiation exposure.The immediate and late therapeutic effects for craniofacial pain control were positive, whereas further studies are necessary.

Yttrium fluoride (YF₃) films were grown on sapphire substrate by a radio frequency magnetron using a commercial ceramic target in a vacuum chamber. The structure, composition, and plasma etching behavior of the films were systematically investigated. The YF₃ film was deposited at a working pressure of 5 mTorr and an RF power of 150 W. The substrate-heating temperature was increased from 400 to 700 °C in increments of 100 °C. High-resolution transmission electron microscopy (HRTEM) and X-ray diffraction results confirmed an orthorhombic YF₃ structure was obtained at a substrate temperature of 700 °C for 2 h. X-ray photoelectron spectroscopy revealed a strongly fluorinated bond (Y⁻F bond) on the etched surface of the YF₃ films. HRTEM analysis also revealed that the YF₃ films became yttrium-oxyfluorinated after exposure to fluorocarbon plasma. The etching depth was three times lower on YF₃ film than on Al₂O₃ plate. These results showed that the YF₃ films have excellent erosion resistance properties compared to Al₂O₃ plates.

Purpose: CD8 + T cells are primarily cytotoxic cells that provide immunological protection against malignant cells. Considerable evidence suggests that the T-cell repertoire is closely associated with the host immune response and the development of cancer. In this study, we explored the characteristics of the circulating CD8 + T-cell repertoire and their potential value in predicting the clinical response of breast cancer patients to chemotherapy., Experimental Design: We applied a high-throughput TCR β-chain sequencing method to characterize the CD8 + T-cell repertoire of the peripheral blood from 26 breast cancer patients. In addition, changes in the circulating CD8 + T-cell repertoire during chemotherapy were analyzed., Results: We found that the HEC ratios of the CD8 + T-cell repertoires from HER2 + breast cancer patients were significantly higher than those of HER2 - patients, suggesting that the HER2 protein is released into circulation where it is targeted by CD8 + T cells. Several Vβ and CDR3 motifs preferentially used in HER2 + patients were identified. Besides, we found that the circulating CD8 + T-cell repertoires evolved during chemotherapy and correlated with patient clinical responses to chemotherapy. Increased CD8 + T-cell repertoire heterogeneity during chemotherapy was associated with a better clinical response., Conclusions: Although functional studies of clonally expanded CD8 + T-cell populations are clearly required, our results suggest that the circulating CD8 + T-cell repertoire reflects the characteristics of the tumor-associated biomolecules released into the blood and correlates with the clinical responses of the patients to chemotherapy which might assist in making treatment decisions.

Clean fuels with extremely low sulfur content are highly desirable due to environmental concerns. Herein, three water-stable and eco-friendly metal-organic frameworks with tunable window diameters, denoted as MOF-808X, have been employed as PTA solid supports. An array of PTA@MOF-808X composites were facilely synthesized via the encapsulation strategy. With tunable window sizes and adjustable PTA loading amounts, the obtained PTA@MOF-808X composites were screened for catalytic oxidative desulfurization (ODS) with H 2 O 2 serving as oxidant. The experiments found that 42%PTA@MOF-808A had the highest catalytic ODS activity and could completely remove dibenzothiophene (DBT) in a model fuel with an initial sulfur content of 1000 ppm within 30 min, which falls far below the acceptable limits for fuel standards (10 ppm). Further investigations revealed that this high catalytic activity could be attributed to the cooperative catalysis of metal clusters in the host framework and the guest PTA molecules. Moreover, 42%PTA@MOF-808A could be facilely recovered and reused for at least five runs without loss of catalytic activity. Having a combination of eco-sustainability, high stability, high catalytic activity, and good recyclability, 42%PTA@MOF-808A therefore represents a new benchmark material for catalytic ODS and provides a new perspective for ultradeep desulfurization.

Background: Although coagulopathy have been proved to be a contributor to a poor outcome of aneurysmal subarachnoid hemorrhage (aSAH), the risk factors for triggering coagulation abnormalities have not been studied after aneurysm clipping., Methods: We investigated risk factors of coagulopathy and analyzed the relationship between acute coagulopathy and outcome after aneurysm clipping. The clinical data of 137 patients with ruptured CA admitted to our institution was collected and retrospectively reviewed. Patient demographic data (age, sex), smoking, alcohol use, hypertension, diabetes, Hunt-Hess grade, Fisher grade, operation time, intraoperative total infusion volume, intraoperative blood loss, intraoperative transfusion, intraoperative hemostatic drug treatment, calcium reduction (preoperative free calcium concentration-postoperative free calcium concentration) were recorded. Coagulation was assessed within 24 h. Postoperative hemorrhage and infarction, deep venous thrombosis (DVT), and mortality were analyzed., Results: Coagulopathy was detected in a total of 51 cases (group I), while not in 86 cases (group II). Univariable analysis demonstrated that age, smoking, alcohol use, intraoperative total infusion volume, intraoperative blood loss, intraoperative transfusion, and calcium reduction (≥ 1.2 mg/dl ) were related to coagulopathy. Non-conditional logistic regression analysis showed that age [OR, 1.037 (95% CI, 1.001-1.074); p  = 0.045] and calcium reduction (≥ 1.2 mg/dl) [OR, 5.509 (95% CI, 1.900-15.971); p  = 0.002] were considered as the risk factors for coagulopathy. Hunt-Hess grade [OR, 2.641 (95% CI, 1.079-6.331); p  = 0.033] and operation time [OR, 0.107 (95% CI, 1.012-0.928); p  = 0.043] were considered as the risk factors for hypocoagulopathy. There were 6 cases (11.7%) with cerebral infarction in group I, while 6 cases (6.98%) in group II ( χ 2  = 0.918, p  = 0.338). There were 4 cases (7.84%) with rebleeding in group I, while 5 cases (5.81%) in group II ( χ 2  = 0.215, p  = 0.643). The mortality was 9.80% (5/51) in group I, while 1.16% (1/86) in group II ( χ 2  = 5.708, p  = 0.017). DVT was not detected in all cases., Conclusions: In conclusion, age (≥ 65 years) and calcium reduction (≥ 1.2 mg/dl) were considered as the risk factors for coagulopathy and have been proved to be associated with higher mortality after aneurysm clipping., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2018.)

The exploitation of metal-free organic polymers as electrodes for water splitting reactions is limited by their presumably low activity and poor stability, especially for the oxygen evolution reaction (OER) under more critical conditions. Now, the thickness of a cheap and robust polymer, poly(p-phenylene pyromellitimide) (PPPI) was rationally engineered by an in situ polymerization method to make the metal-free polymer available for the first time as flexible, tailorable, efficient, and ultra-stable electrodes for water oxidation over a wide pH range. The PPPI electrode with an optimized thickness of about 200 nm provided a current density of 32.8 mA cm -2 at an overpotential of 510 mV in 0.1 mol L -1 KOH, which is even higher than that (31.5 mA cm -2 ) of commercial IrO 2 OER catalyst. The PPPI electrodes are scalable and stable, maintaining 92 % of its activity after a 48-h chronoamperometric stability test., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Seed viability monitoring is very important in ex situ germplasm preservation to detect germplasm deterioration. This requires seed-, time- and labor- saving methods with high precision to assess seed germination as viability. Although the current non-invasive, rapid, sensing methods (NRSs) are time- and labor-saving, they lack the precision and simplicity which are the virtues of traditional germination. Moreover, they consume a considerable amount of seeds to adjust sensed signals to germination percentage, which disregards the seed-saving objective. This becomes particularly severe for rare or endangered species whose seeds are already scarce. Here we propose a new method that is precise, low-invasive, simple, and quick, which involves analyzing the pattern of dehiscence (seed coat rupture), followed by embryonic protrusion., Results: Dehiscence proved simple to identify. After the trial of 20 treatments from 3 rice varieties, we recognized that dehiscence percentage at the 48th hour of germination (D(48)) correlates significantly with germination rate for tested seed lots. In addition, we found that the final germination percentage corresponded to D(48) plus 5. More than 70% of the seeds survived post-dehiscence desiccation for storage. Hydrogen peroxide (1 mM) as the solution for imbibition could further improve the survival. The method also worked quicker than tetrazolium which is honored as a fast, traditional method, in detecting less vigorous but viable seeds., Conclusion: We demonstrated the comprehensive virtues of dehiscence method in assessing rice seed: it is more precise and easier to use than NRSs and is faster and more seed-saving than traditional methods. We anticipate modifications including artificial intelligence to extend our method to increasingly diverse circumstances and species.

Mixed adenoneuroendocrine carcinoma rarely occurs in the gallbladder. Most cases of cholecystic mixed adenoneuroendocrine carcinoma have been reported from Asia, North American, and Europe; however, there is scarce literature available on this tumor in other populations. Here, we report a case of mixed adenoneuroendocrine carcinoma in a Melanoderm woman who was initially suspected to have gallbladder cancer. No specific symptoms or abnormal blood test results were observed preoperatively. Magnetic resonance imaging revealed a 7-cm hypointense mass in the gallbladder fossa, which invaded the surrounding liver segments. Radical cholecystectomy, partial liver resection, and regional lymphadenectomy were performed. Finally, she was diagnosed as mixed adenoneuroendocrine carcinoma of the gallbladder upon postoperative pathological examination and immunohistochemical staining. She received six cycles of systemic chemotherapy and somatostatin treatment and survived 21 months after surgery. Our case highlights the fact that mixed adenoneuroendocrine carcinoma of the gallbladder can occur in African populations as well. Surgical approach combined with adjuvant chemotherapy and somatostatin treatment may contribute a relatively good survival outcome.

Electrochemical gas evolution and activation reactions are complicated processes, involving not only active electrocatalysts but also the interaction among solid electrodes, electrolyte, and gas-phase products and reactants. In this study, multiphase interfaces of superadsorbing graphene-based electrodes were controlled without changing the active centers to significantly facilitate mass diffusion kinetics for superior performance. The achieved in-depth understanding of how to regulate the interfacial properties to promote the electrochemical performance could provide valuable clues for electrode manufacture and for the design of more active electrocatalysts., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The management of advanced nasopharyngeal carcinoma (NPC) remains a challenge. The ubiquitous nature of Epstein-Barr virus (EBV) infection in nonkeratinizing NPC has forced us to investigate novel drugs for NPC in the presence of EBV. In this study, we performed a small-scale screening of a library of compounds that target epigenetic regulators in paired EBV-positive and EBV-negative NPC cell lines. We found that bromodomain and extra-terminal (BET) inhibitor JQ1 preferentially inhibits the growth of EBV-positive NPC cells. JQ1 induces apoptosis, decreases cell proliferation and enhances the radiosensitivity in NPC cells, especially EBV-positive cells. Significantly, JQ1-induced cell death is c-Myc-dependent. Notably, RNA-seq analysis demonstrated that JQ1 represses TP63, TP53 and their targets. JQ1 also lessens the expression of PD-L1 in NPC. Moreover, the high potency of JQ1 in NPC cells was further confirmed in vivo in CNE2-EBV+ tumor-bearing mice. These findings indicate that JQ1 is a promising therapeutic candidate for advanced NPC.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition that can differ in its clinical manifestation, structural changes and response to treatment., Objective: To identify subgroups of COPD with distinct phenotypes, evaluate the distribution of phenotypes in four related regions and calculate the 1-year change in lung function and quality of life according to subgroup., Methods: Using clinical characteristics, we performed factor analysis and hierarchical cluster analysis in a cohort of 1676 COPD patients from 13 Asian cities. We compared the 1-year change in forced expiratory volume in one second (FEV1), modified Medical Research Council dyspnoea scale score, St George's Respiratory Questionnaire (SGRQ) score and exacerbations according to subgroup derived from cluster analysis., Results: Factor analysis revealed that body mass index, Charlson comorbidity index, SGRQ total score and FEV1 were principal factors. Using these four factors, cluster analysis identified three distinct subgroups with differing disease severity and symptoms. Among the three subgroups, patients in subgroup 2 (severe disease and more symptoms) had the most frequent exacerbations, most rapid FEV1 decline and greatest decline in SGRQ total score., Conclusion: Three subgroups with differing severities and symptoms were identified in Asian COPD subjects.

Genetic susceptibility underlies the pathogenesis of cancer. We and others have previously identified a novel susceptibility gene TNFRSF19 , which encodes an orphan member of the TNF receptor superfamily known to be associated with nasopharyngeal carcinoma (NPC) and lung cancer risk. Here, we show that TNFRSF19 is highly expressed in NPC and is required for cell proliferation and NPC development. However, unlike most of the TNF receptors, TNFRSF19 was not involved in NFκB activation or associated with TRAF proteins. We identified TGFβ receptor type I (TβRI) as a specific binding partner for TNFRSF19. TNFRSF19 bound the kinase domain of TβRI in the cytoplasm, thereby blocking Smad2/3 association with TβRI and subsequent signal transduction. Ectopic expression of TNFRSF19 in normal epithelial cells conferred resistance to the cell-cycle block induced by TGFβ, whereas knockout of TNFRSF19 in NPC cells unleashed a potent TGFβ response characterized by upregulation of Smad2/3 phosphorylation and TGFβ target gene transcription. Furthermore, elevated TNFRSF19 expression correlated with reduced TGFβ activity and poor prognosis in patients with NPC. Our data reveal that gain of function of TNFRSF19 in NPC represents a mechanism by which tumor cells evade the growth-inhibitory action of TGFβ. Significance: TNFRSF19 , a susceptibility gene for nasopharyngeal carcinoma and other cancers, functions as a potent inhibitor of the TGFβ signaling pathway. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3469/F1.large.jpg Cancer Res; 78(13); 3469-83. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Cerebral amyloid β-peptide (Aβ) accumulation resulting from an imbalance between Aβ production and clearance is one of the most important causes in the formation of Alzheimer's disease (AD). In order to preserve the maintenance of Aβ homeostasis and have a notable AD therapy, achieving a method to clear up Aβ plaques becomes an emerging task. Herein, we describe a self-destructive nanosweeper based on multifunctional peptide-polymers that is capable of capturing and clearing Aβ for the effective treatment of AD. The nanosweeper recognize and bind Aβ via co-assembly through hydrogen bonding interactions. The Aβ-loaded nanosweeper enters cells and upregulates autophagy thus promoting the degradation of Aβ. As a result, the nanosweeper decreases the cytotoxicity of Aβ and rescues memory deficits of AD transgenic mice. We believe that this resourceful and synergistic approach has valuable potential as an AD treatment strategy.

Objective: To investigate the value of 3-dimensional (3D)-printed models with pathologic entities in enhancing the learning curve of surgery of tuberculum sellae meningioma., Methods: We printed 4 models of tuberculum sellae meningiomas based on radiologic data using a 3D printer. Participants were allocated to the 3D group and the atlas group. In the 3D group, participants learned surgery with the assistance of 3D models. In the atlas group, participants used only 2-dimensional materials to assist their learning. All participants undertook a pre-test and post-test. The scores were used to identify the difference in learning efficiency between the 2 groups., Results: A total of 42 new trainees were recruited, of whom 22 were in the 3D group and 20 in the atlas group. The baseline data were not significantly different. The difference of pre-test score was not significant, either. However, the post-test score was significantly greater in the 3D group (P = 0.005), and the change in score was also significantly greater in the 3D group (P < 0.001). In accordance with the objective test, the subjective survey through a questionnaire from participants in the 3D group showed that 3D models significantly promoted the learning curve of this kind of complex skull base surgery., Conclusions: 3D-printed models can assist in improving the learning curve of surgery of tuberculum sellae meningiomas. It particularly aids in memorization and spatial construction, improves understanding of surgical view, and arouses interest on the part of the trainee. We recommend using it in the education of complex skull base surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

It is not fully established whether leukocyte can predict the poor outcome for ruptured cerebral aneurysms (CA) or not. Here, we retrospectively analyzed the clinical data of 428 patients with ruptured CA between 2010 and 2015. Patients' demographic data, including gender, age, history of smoking, alcohol, hypertension, diabetes and hypercholesterolemia, Hunt-Hess and Fisher grade, occurrence of hydrocephalus, aneurysm location, time to surgery, delayed ischemic neurological deficit (DIND) and peak leukocyte of blood test from day 1 to 3 after aneurysmal rupture were recorded and analyzed. In the multivariable analysis model, gender, Fisher grade, time to surgery and hydrocephalus were not relevant to poor outcome. However, Hunt-Hess grade, DIND and preoperative leukocyte count (>13.84 × 10 9 /L) were significantly associated with adverse outcome. The respective increased risks were 5.2- (OR5.24, 95% CI 1.67-16.50, p = 0.005), 6.2-(OR 6.24, 95% CI 3.55-10.99, p < 0.001) and 10.9-fold (OR 9.35, 95% CI 5.98-19.97, p < 0.001). The study revealed that Hunt-Hess grade, DIND and preoperative leukocyte count (>13.84 × 10 9 /L) were independent risk factors for poor outcome of ruptured CA at 3 months. Higher leukocyte count is a convenient and useful marker to predict 3-month poor outcome for ruptured CA.

Paragonimiasis is a parasitic lung infection caused by lung flukes of the genus Paragonimus. Ectopic infection may occur but rarely involves the liver. Here, we report a case of hepatic paragonimiasis in a Chinese man who was initially suspected to have hepatocellular carcinoma. He had been previously diagnosed with chronic hepatitis B. No specific symptoms or abnormal blood test results were observed, except for a significant rise in serum alfa-fetoprotein. Magnetic resonance imaging revealed a 12-cm mass with inhomogeneous signal intensity at the left lobe of the liver. Laparoscopic left hemihepatectomy was performed. He was finally diagnosed as hepatic paragonimiasis upon pathological examination and antibody serology. The postoperative course was uneventful. He received a standard course of praziquantel and recovered well. Our case is unique in its tumor-like characteristic and protrudes the difficulty of differential diagnosis with both benignant and malignant hepatic diseases by imaging studies or non-specific symptoms. Hepatic paragonimiasis is unusual; however, it should be considered in the differential diagnosis of liver malignancy by clinicians.

OBJECTIVE Using intraoperative electrocorticography (ECoG) to identify epileptogenic areas and improve postoperative seizure control in patients with low-grade gliomas (LGGs) remains inconclusive. In this study the authors retrospectively report on a surgery strategy that is based on intraoperative ECoG monitoring. METHODS A total of 108 patients with LGGs presenting at the onset of refractory seizures were included. Patients were divided into 2 groups. In Group I, all patients underwent gross-total resection (GTR) combined with resection of epilepsy areas guided by intraoperative ECoG, while patients in Group II underwent only GTR. Tumor location, tumor side, tumor size, seizure-onset features, seizure frequency, seizure duration, preoperative antiepileptic drug therapy, intraoperative electrophysiological monitoring, postoperative Engel class, and histological tumor type were compared between the 2 groups. RESULTS Univariate analysis demonstrated that tumor location and intraoperative ECoG monitoring correlated with seizure control. There were 30 temporal lobe tumors, 22 frontal lobe tumors, and 2 parietal lobe tumors in Group I, with 18, 24, and 12 tumors in those same lobes, respectively, in Group II (p < 0.05). In Group I, 74.07% of patients were completely seizure free (Engel Class I), while 38.89% in Group II (p < 0.05). In Group I, 96.30% of the patients achieved satisfactory postoperative seizure control (Engel Class I or II), compared with 77.78% in Group II (p < 0.05). Intraoperative ECoG monitoring indicated that in patients with temporal lobe tumors, most of the epileptic discharges (86.7%) were detected at the anterior part of the temporal lobe. In these patients with epilepsy discharges located at the anterior part of the temporal lobe, satisfactory postoperative seizure control (93.3%) was achieved after resection of the tumor and the anterior part of the temporal lobe. CONCLUSIONS Intraoperative ECoG monitoring provided the exact location of epileptogenic areas and significantly improved postoperative seizure control of LGGs. In patients with temporal lobe LGGs, resection of the anterior temporal lobe with epileptic discharges was sufficient to control seizures.

The blockade of PD-1/PD-L1 interaction by peptide antagonists can unleash and enhance pre-existing anti-cancer immune responses of T cells to eradicate cancer cells. However, low proteolytic stability is the "Achilles' Heel" of peptides. Here, we first report a nanoantagonist with a physiological temperature sensitive nanophase-segregated surface that exhibits significantly enhanced blood circulation, peptide stability and PD-L1 immune checkpoint blockade efficacy. Thermosensitive polymers with different phase transition temperatures (Tt) are used to form the nanophase-segregated surface on an Au nanorod core. Importantly, the nanophase-segregated surface aids the nanoantagonist to resist protein adsorption and enhance the systemic stability of the linked peptides. Finally, the as-designed nanoantagonist effectively blocks PD-1/PD-L1 interaction in vitro and in vivo, enhances the pre-existing CD8 + T cell tumor destruction capability and inhibits tumor growth. This study offers a new strategy for designing nano-formulations for cancer immunotherapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In order to develop and commercialize for the regenerative medicinal products, smart biomaterials with biocompatibility must be needed. In this chapter, we introduce collagen and hyaluronic acid (HA) as extracellular matrix as well as deal with the molecular mechanism as microenvironment, mechanistic effects, and gene expression. Application of collagen and HA have been reviewed in the area of orthopedics, orthopedics, ophthalmology, dermatology and plastic surgery. Finally, the ongoing and commercial products of collagen and HA for regenerative medicine have been introduced.

Diabetes has become a global public health problem that seriously threatens human health. Traditional Chinese medicine, the characteristics of the role of multiple targets, has a unique advantage in the prevention and treatment of diabetes mellitus and its complications. Astragaloside-Ⅳ (AS-Ⅳ), one of the main activities of Astragalus membranaceus, has a series of pharmacological effects including improvement in the function of endothelial cells and neovascularization, anti-inflammatory, antioxidant, regulating energy metabolism, protectionnervous, anti-cancer and so on. In this paper, AS-Ⅳ to prevent and treat diabetes and its complications has been reviewed, which has effect on lowering blood sugar, lowering blood pressure, improving insulin resistance, inhibiting inflammatory reaction and oxidative stress. Additionally, it also can improve the diabetic animal and cell model of diabetic vascular disease, diabetic nephropathy, diabetic retinopathy, diabetic peripheral neuropathy, diabetic cardiomyopathy and other pathological damages. AS-Ⅳ may be a potential active substance for the treatment of diabetes and its complications., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)