Multilevel synergically controlling wavefront correction of a high-power slab laser system.

We present a multilevel synergically controlling wavefront correction method that can apply in a slab laser system. To fully utilize the response frequency and the stroke of actuators of the single deformable mirror (DM), we design a set of multilevel wavefront correction devices to reduce the root-mean square of wavefront aberration before the DM. As the wavefront of slab geometry solid-state lasers mainly consists of fourth and longitudinally distributed aberration, such as 5th, 9th, and 14th orders of Legendre polynomials. We design a precompensating level of the aberration with a slow-drift mirror, fast-steer mirror, one-dimensional adjustable slab-aberration compensator, and beam-shaping system to reduce these orders of wavefront aberration with low spatial resolution and large stroke. As the controlling bandwidth of different devices is diverse, the coupling oscillation between the precompensating level and adaptive optics (AO) level occurs, then we develop the multilevel synergically control to address the coupling. With the precompensating level, the experimental result shows the residual wavefront aberration of the slab laser is compensated well by the AO level effectively within the compensating capability. We clean up a 9.8 kW slab laser system with the beam quality ß of far-field focus spots improved from 17.71 to 2.24 times the diffraction limit.

Mitofusin-2 mediates cannabidiol-induced neuroprotection against cerebral ischemia in rats.

Cannabidiol (CBD) reportedly exerts protective effects against many psychiatric disorders and neurodegenerative diseases, but the mechanisms are poorly understood. In this study, we explored the molecular mechanism of CBD against cerebral ischemia. HT-22 cells or primary cortical neurons were subjected to oxygen-glucose deprivation insult followed by reoxygenation (OGD/R). In both HT-22 cells and primary cortical neurons, CBD pretreatment (0.1, 0.3, 1 µM) dose-dependently attenuated OGD/R-induced cell death and mitochondrial dysfunction, ameliorated OGD/R-induced endoplasmic reticulum (ER) stress, and increased the mitofusin-2 (MFN2) protein level in HT-22 cells and primary cortical neurons. Knockdown of MFN2 abolished the protective effects of CBD. CBD pretreatment also suppressed OGD/R-induced binding of Parkin to MFN2 and subsequent ubiquitination of MFN2. Overexpression of Parkin blocked the effects of CBD in reducing MFN2 ubiquitination and reduced cell viability, whereas overexpressing MFN2 abolished Parkin's detrimental effects. In vivo experiments were conducted on male rats subjected to middle cerebral artery occlusion (MCAO) insult, and administration of CBD (2.5, 5 mg · kg-1, i.p.) dose-dependently reduced the infarct volume and ER stress in the brains. Moreover, the level of MFN2 within the ischemic penumbra of rats was increased by CBD treatment, while the binding of Parkin to MFN2 and the ubiquitination of MFN2 was decreased. Finally, short hairpin RNA against MFN2 reversed CBD's protective effects. Together, these results demonstrate that CBD protects brain neurons against cerebral ischemia by reducing MFN2 degradation via disrupting Parkin's binding to MFN2, indicating that MFN2 is a potential target for the treatment of cerebral ischemia.

Construction of MicroRNA-Target Interaction Networks Based on MicroRNA Expression Profiles of HRV16-infected H1-HeLa Cells.

In the present study we investigated the changes in miRNA levels inhuman rhinovirus 16 (HRV16)-infected cells. A small RNA deep sequencing experiment was performed through next-generation sequencing. In total, 53 differentially expressed miRNAs were confirmed by RT-qPCR, including 37 known miRNAs and 16 novel miRNAs. Interaction networks between differentially expressed miRNAs and their targets were established by mirDIP and Navigator. The prediction results showed that QKI, NFAT5, BNC2, CELF2, LCOR, MBNL2, MTMR3, NFIB, PPARGC1A, RSBN1, TRPS1, WDR26, and ZNF148, which are associated with cellular differentiation and transcriptional regulation, were recognized by 12, 11, or 9 miRNAs. Many correlations were observed between transcriptional or post-transcriptional regulation of an miRNA and the expression levels of its target genes in HRV16-infected H1-HeLa cells.

Human M1 macrophages express unique innate immune response genes after mycobacterial infection to defend against tuberculosis.

Mycobacterium tuberculosis (Mtb) is responsible for approximately 1.5 million deaths each year. Though 10% of patients develop tuberculosis (TB) after infection, 90% of these infections are latent. Further, mice are nearly uniformly susceptible to Mtb but their M1-polarized macrophages (M1-MΦs) can inhibit Mtb in vitro, suggesting that M1-MΦs may be able to regulate anti-TB immunity. We sought to determine whether human MΦ heterogeneity contributes to TB immunity. Here we show that IFN-γ-programmed M1-MΦs degrade Mtb through increased expression of innate immunity regulatory genes (Inregs). In contrast, IL-4-programmed M2-polarized MΦs (M2-MΦs) are permissive for Mtb proliferation and exhibit reduced Inregs expression. M1-MΦs and M2-MΦs express pro- and anti-inflammatory cytokine-chemokines, respectively, and M1-MΦs show nitric oxide and autophagy-dependent degradation of Mtb, leading to increased antigen presentation to T cells through an ATG-RAB7-cathepsin pathway. Despite Mtb infection, M1-MΦs show increased histone acetylation at the ATG5 promoter and pro-autophagy phenotypes, while increased histone deacetylases lead to decreased autophagy in M2-MΦs. Finally, Mtb-infected neonatal macaques express human Inregs in their lymph nodes and macrophages, suggesting that M1 and M2 phenotypes can mediate immunity to TB in both humans and macaques. We conclude that human MФ subsets show unique patterns of gene expression that enable differential control of TB after infection. These genes could serve as targets for diagnosis and immunotherapy of TB.

Different molecular weight hyaluronic acid alleviates inflammation response in DNFB-induced mice atopic dermatitis and LPS-induced RAW 264.7 cells.

AIMS: Atopic dermatitis (AD) is an inflammatory chronic disease which severely interferes the life of patients. Hence, there is a great need for new therapies. Hyaluronic acid (HA) is an effective potential inflammation modifier; however, there is limited information about their implementation in inflammation therapies. This study aimed to evaluate the anti-inflammatory activities of HA and the influence of its molecular weight. MAIN METHODS: Male C57BL/6 J mice were stimulated by 2,4-dinitrofluorobenzene to induce AD-like symptoms and immune response. The skin lesions and histopathological change, as well as levels of inflammatory factors were evaluated. RAW 264.7 mouse macrophages were treated with lipopolysaccharides (LPS) to induce inflammation. NO, IL-6, and TNF-α levels were detected through ELISA kits. KEY FINDINGS: DNFB challenge induced mice AD symptoms including epidermal thickening, mast cell infiltration, Th2/Th1 immune response, skin lesions IL-4 and IFN-γ, and serum IgE elevation. HA treatment ameliorated such symptoms through the inhibition of PI3K/Akt signaling pathway. LPS induction stimulated the secretion of NO, IL-6, and TNF-α in RAW 264.7 cells, while HA pre-treatment reduced the concentration of the cytokines in cell supernatants. SIGNIFICANCE: These findings give clear insight into the interaction between HA and inflammatory response, which can help guiding the utilization of HA in the AD therapies.

Exploration of IRES Elements within the ORF of the Coxsackievirus B3 Genome.

Objective: This study aimed to identify internal ribosome entry sites (IRESs) in the open reading frame (ORF) of the Coxsackievirus B3 (CVB3) genome. Methods: The sequences of P1, P2, or P3 of the CVB3 genome or the truncated sequences from each antithymocyte globulin (ATG) to the end of the P1, P2, or P3 gene were inserted into the pEGFP-N1 vector. After transfection, possible IRES-dependent green fluorescent protein (GFP)-fused proteins were detected by anti-GFP western blotting. The sequences of possible IRESs were inserted into specific Fluc/Rluc bicistronic vectors, in which the potential IRESs were determined according to the Fluc/Rluc activity ratio. Expression of Fluc and Rluc mRNA of the bicistronic vector was detected by RT-qPCR. Results: After transfection of full length or truncated sequences of the P1, P2, or P3 plasmids, six GFP-fused protein bands in P1, six bands in P2 and nine bands in P3 were detected through western blotting. Two IRESs in VP2 (1461-1646 nt) and VP1 (2784-2983 nt) of P1; one IRES in 2C (4119-4564 nt) of P2; and two IRESs in 3C (5634-5834 nt) and 3D (6870-7087 nt) of P3 were identified according to Fluc/Rluc activity ratio. The cryptic promoter was also excluded by RT-qPCR. Conclusion: Five IRESs are present in the CVB3 coding region.

Inhibition of Ciliogenesis Enhances the Cellular Sensitivity to Temozolomide and Ionizing Radiation in Human Glioblastoma Cells / 生物医学与环境科学（英文）

Objective@#To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM).@*Methods@#GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay.@*Results@#Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation.@*Conclusion@#Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.

Exploration of IRES Elements within the ORF of the Coxsackievirus B3 Genome / 生物医学与环境科学（英文）

Objective@#This study aimed to identify internal ribosome entry sites (IRESs) in the open reading frame (ORF) of the Coxsackievirus B3 (CVB3) genome.@*Methods@#The sequences of P1, P2, or P3 of the CVB3 genome or the truncated sequences from each antithymocyte globulin (ATG) to the end of the P1, P2, or P3 gene were inserted into the pEGFP-N1 vector. After transfection, possible IRES-dependent green fluorescent protein (GFP)-fused proteins were detected by anti-GFP western blotting. The sequences of possible IRESs were inserted into specific Fluc/Rluc bicistronic vectors, in which the potential IRESs were determined according to the Fluc/Rluc activity ratio. Expression of Fluc and Rluc mRNA of the bicistronic vector was detected by RT-qPCR.@*Results@#After transfection of full length or truncated sequences of the P1, P2, or P3 plasmids, six GFP-fused protein bands in P1, six bands in P2 and nine bands in P3 were detected through western blotting. Two IRESs in VP2 (1461-1646 nt) and VP1 (2784-2983 nt) of P1; one IRES in 2C (4119-4564 nt) of P2; and two IRESs in 3C (5634-5834 nt) and 3D (6870-7087 nt) of P3 were identified according to Fluc/Rluc activity ratio. The cryptic promoter was also excluded by RT-qPCR.@*Conclusion@#Five IRESs are present in the CVB3 coding region.

Assessment of liver fibrosis with liver and spleen stiffness measured by sound touch elastography, serum fibrosis markers in patients with chronic hepatitis B.

OBJECTIVES: To evaluate the performance of liver stiffness (LS) and spleen stiffness (SS) by using the sound touch elastography (STE) technique and compare with those of the splenic index, aspartate transaminase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) index, King's score and combined models for diagnosing and staging fibrosis in chronic hepatitis B (CHB). METHODS: One hundred patients with CHB underwent STE and serological tests. LS and SS values were measured with STE technique, and splenic index was calculated. Staging of fibrosis was determined with liver biopsy. Correlations between the individual parameters and the stage of fibrosis were evaluated with the Spearman correlation analysis. The area under the receiver operating characteristic curve (AUROC) was calculated to analyze the performance of all methods. RESULTS: Among all individual parameters, LS showed the highest AUROC for diagnosing fibrosis of ≥S2, ≥S3, and S4 stages (AUROC: 0.70, 0.86, and 0.96, respectively; all P < 0.05). The AUROC of combined model 1 (LS and SS) and 2 (LS, SS, APRI, FIB-4 index, King's score) for diagnosing ≥S2, ≥S3, and S4 fibrosis were 0.70, 0.86, 0.97, and 0.70, 0.86, 0.96, respectively, which were higher than those of APRI, FIB-4 index and the King's score (P < 0.05). No significant differences were found between two combined models and LS for staging fibrosis (P > 0.05). CONCLUSIONS: LS measurement is reliable for diagnosing and staging fibrosis in CHB, with a better performance than SS, splenic index and serum biomarkers. It is also comparable with the performance of combined models.

An innovative role for luteolin as a natural quorum sensing inhibitor in Pseudomonas aeruginosa.

AIMS: The emergence of antibiotic tolerance was a tricky problem in the treatment of chronic Pseudomonas aeruginosa-infected cystic fibrosis and burn victims. The quorum sensing (QS) inhibitor may serve as a new tactic for the bacterial resistance by inhibiting the biofilm formation and the production of virulence factors. This study explored the potential of luteolin as a QS inhibitor against P. aeruginosa and the molecular mechanism involved. MAIN METHODS: Crystal violet staining, CLSM observation, and SEM analysis were carried out to assess the effect of luteolin on biofilm formation. The motility assays and the production of virulence factors were determined to evaluate the QS-inhibitory activity of luteolin. Acyl-homoserine lactone, RT-PCR, and molecular docking assays were conducted to explain its anti-QS mechanisms. KEY FINDINGS: The biofilm formation, the production of virulence factors, and the motility of P. aeruginosa could be efficiently inhibited by luteolin. Luteolin could also attenuate the accumulation of the QS-signaling molecules N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) and N-butanoyl-L-homoserine lactone (BHL) (P < 0.01) and downregulate the transcription levels of QS genes (lasR, lasI, rhlR, and rhlI) (P < 0.01). Molecular docking analysis indicated that luteolin had a greater docking affinity with LasR regulator protein compared with OdDHL. SIGNIFICANCE: This study is important as it reports the molecular mechanisms involved in the anti-biofilm formation activity of luteolin against P. aeruginosa. This study also indicated that luteolin could be helpful when used for the treatment of clinical drug-resistant infections of P. aeruginosa.

Nutrition status of primary and middle school students in poor rural areas of Ningxia during 2013 to 2017 / 中国学校卫生

Objective@#To investigate the nutritional status of the rural compulsory education students from "Rural Compulsory Education Students Nutrition Improvement Program"(hereinafter referred to "plan") in Ningxia, to provide a scientific basis for future targeted nutrition education and interventions.@*Methods@#The survey was conducted in 27 732 students aged 6 to 15 years selected by stratified samplings in 7 counties of Ningxia.@*Results@#In the 5 years of the "plan" implementation, trend in decreasing malnutrition rates across the 5 years(18.16%, 18.77%, 17.08%, 14.38%, 14.93%), with statistically significant difference(Chi-square for trend was 47.02, P<0.01). Overnutrition rate significantly increased(5.21%, 4.89%, 5.51%, 5.68%, 6.83%, Chi-square for trend was 6.66, P<0.01).@*Conclusion@#Improved nutritional status of rural primary and middle school students in Ningxia has been observed, Co-occurring of malnutrition in boys and overnutrition requires further attention.

Establishment of a scoring model based on ultrasonic characteristics for predicting the restenosis after superficial femoral artery stenting / 中华超声影像学杂志

Objective:To establish a comprehensive and effective scoring model based on ultrasonic characteristics for predicting the restenosis risk after superficial femoral artery stenting, in order to assess the possibility of in-stent restenosis and to provide guidance for the selection of therapeutic strategies.Methods:A retrospective review of a database of 328 patients (381 limbs) undergoing superficial femoral artery stents in Xuanwu Hospital, Capital Medical University from January 2016 to January 2018 was made as a modeling group.In the modeling cohort, the multivariate logistic regression analysis was performed to screen independent risk factors for in-stent restenosis. A predictive scoring model of restenosis risk was established with weighted score of independent risk factors according to the odd ratio values. Based on the best cut-off value of the receiver operating characteristic (ROC) curves, the scoring table was divided into low-risk and high-risk groups of restenosis.Results:Multivariate logistic regression analysis showed that 8 factors were included in the score system to establish the scoring model of in-stent restenosis risk prediction including calcified plaque, peak systolic velocity of popliteal artery<40 cm/s, runoff scores≥4, ankle-brachial index<0.5, female (1 point each); complicated stroke, complicated chronic renal disease, total lesion length 15.0-24.9 cm (2 points each); total lesion length≥25.0 cm (3 points), a total of 12 points in the model. The validation indicated that the scoring system had good predictive value(AUC=0.775, 95% CI=0.727-0.824, P<0.001) and goodness of fit (Hosmer-Lemeshow χ 2=4.921, P=0.766). The agreement with digital subtraction angiography(DSA) was good (Kappa value=0.609). The scoring system was further divided into the low-risk restenosis (0-5 points) and high-risk restenosis (6-12 points) according to the best cut-off value of 5.5, with a sensitivity of 68.1%, a specificity of 74.6%, and the accuracy of 72.7%. Conclusions:The superficial femoral artery in-stent restenosis risk predicting score model based on ultrasonic characteristics may accurately predict the restenosis preoperatively. It provides a theoretical basis for the precise surgical plans.

Differences in pathologic characteristics between ductal carcinoma in situ (DCIS), DCIS with microinvasion and DCIS with invasive ductal carcinoma.

In order to further our understanding of pathologic features in various ductal carcinoma in situ (DCIS) related breast ductal cancers, including DCIS, DCIS with microinvasion (DCIS-Mi) and DCIS with invasive ductal carcinoma (DCIS-IDC), a retrospective study including 453 cases of DCIS, 88 cases of DCIS-Mi, and 269 cases of DCIS-IDC was conducted. Statistical analysis showed significant pathological differences were found in DCIS, DCIS-Mi, and DCIS-IDC. Compared with DCIS, DCIS-IDC was significantly more associated with high nuclear grade, large tumor size, high Ki67 index, and lymph node metastasis (all P<0.05). Higher expression of steroid receptors was shown in DCIS-IDC than in DCIS (all P<0.05), but the status of HER2 between the two groups was similar (P=0.269). Compared with DCIS, DCIS-Mi was significantly more associated with high nuclear grade, large tumor size, comedonecrosis, absence of steroid receptors, HER2 overexpression, and high Ki67 index (all P<0.05). These features remain consistently even when compared with DCIS-IDC. According to the immunohistochemistry surrogate classification, the dominant types of DCIS and DCIS-IDC were luminal types (luminal A and luminal B, respectively), while the dominant type of DCIS-Mi was HER2 overexpression. These findings suggest that DCIS-Mi represents a distinct entity, and DCIS with features including high nuclear grade, large tumor size, comedonecrosis, steroid receptors negativity, HER2 positivity, and high Ki67 expression was more likely to have microinvasion than DCIS without these features.

The Gap of Semantic Parsing: A Survey on Automatic Math Word Problem Solvers.

Solving mathematical word problems (MWPs) automatically is challenging, primarily due to the semantic gap between human-readable words and machine-understandable logics. Despite the long history dated back to the 1960s, MWPs have regained intensive attention in the past few years with the advancement of Artificial Intelligence (AI). Solving MWPs successfully is considered as a milestone towards general AI. Many systems have claimed promising results in self-crafted and small-scale datasets. However, when applied on large and diverse datasets, none of the proposed methods in the literature achieves high precision, revealing that current MWP solvers still have much room for improvement. This motivated us to present a comprehensive survey to deliver a clear and complete picture of automatic math problem solvers. In this survey, we emphasize on algebraic word problems, summarize their extracted features and proposed techniques to bridge the semantic gap, and compare their performance in the publicly accessible datasets. We also cover automatic solvers for other types of math problems such as geometric problems that require the understanding of diagrams. Finally, we identify several emerging research directions for the readers with interests in MWPs.

Clinical effect of artificial liver support system in treatment of drug-induced liver failure: A Meta-analysis / 临床肝胆病杂志

ObjectiveTo systematically review the clinical of artificial liver support system (ALSS) in the treatment of drug-induced liver failure. MethodsPubMed, Embase, The Cochrane Library, CMB, CNKI, and VIP databases were searched for related randomized controlled trials or randomized controlled trials on ALSS in the treatment of drug-induced liver failure published up to October 2019, and a statistical analysis was performed. Odds ratio (OR) was the effect size for categorical data, and the difference between groups was the effect size for continuous data. The weighted mean difference (WMD) method was used for the pooled analysis of effect size, and 95% confidence interval (CI) was calculated for each effect size. I2 and P values were used to evaluate the heterogeneity of the articles included in the analysis; a fixed effect model was used when I2＜50% and P＞0.1, otherwise a random effects model was used. ResultsA total of 16 articles with 945 patients were included, with 520 patients in the ALSS+routine medical treatment (RMT) group and 425 in the RMT group. The meta-analysis showed that compared with the RMT group, the ALSS+RMT group had a significantly lower mortality rate of drug-induced liver failure (OR=0.27, 95%CI: 0.20-0.36, P＜0.001), significant improvements in albumin (Alb) (MD=1.21, 95%CI: 0.18-2.25, P=0.02) and prothrombin activity (PTA) (MD=11.84, 95%CI: 6.34-17.35, P＜0.001), and a significant reduction in total bilirubin (TBil) (MD=-104.97, 95%CI: -163.63 to -46.30, P＜0.001). Further analysis of Alb, TBil, and PTA after the withdrawal of ALSS showed that ALSS significantly improved Alb (MD=1.74, 95%CI: 1.20-2.27, P＜0.001) and PTA (MD=4.45, 95%CI: 2.80-6.10, P＜0.001) and significantly reduced TBil (MD=-128.41, 95%CI: -217.22 to -39.59, P=0.005). ConclusionCompared with RMT alone, RMT combined with ALSS can significantly improve the main biochemical indicators of patients with drug-induced liver failure and reduce their mortality rate.

Application of ultrasound elastography in evaluating portal hypertension / 临床肝胆病杂志

Portal hypertension (PH) is a common clinical syndrome, and the main risk factor for death is esophageal variceal bleeding. Therefore, the early and accurate diagnosis of PH can reduce the incidence rate of serious complications and mortality rate. Hepatic venous pressure gradient, as a main method for the diagnosis of PH, has certain limitations in clinical application, and thus it is necessary to explore new noninvasive diagnostic techniques. Up to now, ultrasound elastography has become one of the important methods for the noninvasive assessment of PH. This article elaborates on its current application and prospects in the assessment of PH.

Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer.

BACKGROUND: Preclinical studies suggest synergistic effectiveness of ascorbic acid (AA, vitamin C) and cytotoxic agents in gastrointestinal malignancies. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AA combined with mFOLFOX6 or FOLFIRI regimens in patients with metastatic colorectal cancer (mCRC) or gastric cancer (mGC). METHODS: In the dose-escalation phase, patients received AA (0.2-1.5 g/kg, 3-h infusion, once daily, days 1-3) with mFOLFOX6 or FOLFIRI in a 14-day cycle until the MTD was reached. In the speed-expansion phase, AA was administered at the MTD or at 1.5 g/kg if the MTD was not reached at a fixed rate of 0.6, 0.8 or 1 g/min. Pharmacokinetics and preliminary efficacy were also assessed. RESULTS: Thirty-six patients were enrolled. The MTD was not reached. The RP2D was established as AA at 1.5 g/kg/day, days 1-3, with mFOLFOX6 or FOLFIRI. No dose-limiting toxicity (DLT) was detected during dose escalation. The most common treatment-emergent adverse events (TRAEs) were sensory neuropathy (50%), nausea (38.9%), vomiting (36.1%) and neutropenia (27.8%). Grade 3-4 TRAEs were neutropenia (13.9%), sensory neuropathy (2.8%), vomiting (2.8%), diarrhea (2.8%) and leukopenia (2.8%). AA exposure was dose-proportional. The objective response rate was 58.3%, and the disease control rate was 95.8%. No difference in efficacy was found between mCRC patients with wild-type RAS/BRAF and mutant RAS or BRAF. CONCLUSIONS: The favorable safety profile and preliminary efficacy of AA plus mFOLFOX6/FOLFIRI support further evaluation of this combination in mCRC or mGC. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT02969681 .

Identification of culprit plaques characteristics of intracranial atherosclerosis: a radiomic study / 国际脑血管病杂志

Objective To investigate the ability of quantitative radiomic method based on highresolution magnetic resonance imaging (HR-MRI) to distinguish between culprit plaques and non-culprit plaques of intracranial atherosclerosis.Methods Patients with middle cerebral artery and basilar artery stenosis underwent HR-MRI in Changhai Hospital Affiliated to the Naval Medical University from September 2013 to October 2016 were analyzed retrospectively.The minimum lumen area,plaque burden,severity of luminal stenosis,intraplaque hemorrhage (IPH),enhancement rate,and 109quantitative radiomic characteristics of the culprit and non-culprit plaques were measured.For clinical features and traditional plaque morphology,multivariate logistic regression models were used to determine independent risk factors for culprit plaque.A random forest-supervised machine learning method was used to determine the radiomic characteristics of distinguishing between symptomatic plaques and asymptomatic plaques.The receiver operating characteristic (ROC) curve was constructed,and the diagnostic efficacy was described by the area under the curve (AUC).Results During the study,158 subjects were enrolled,and they aged (59.42± 11.62) years.The plaques of 75 patients were located in middle cerebral artery,and the plaques of 83 patients were located in basilar artery.There were 111 symptomatic patients and 47 asymptomatic patients.Multivariate logistic regression analysis showed that smoking (odds ratio [OR] 2.724,95％ confidence interval [CI] 1.200-6.183),IPH (OR 11.340,95％ CI 1.441-89.221),and enhancement rate (OR 6.865,95％ CI 1.052-44.802) were the independent risk factors for culprit plaques.The AUC of these three characteristics for predicting symptomatic plaques were 0.605,0.584,and 0.590,respectively.The combination of the three cloud improve the test efficacy for the intracranial atherosclerotic culprit plaques,AUC could reached 0.714.Radiomic analysis showed that 22 radiomic characteristics extracted from T-2 weighted imaging,T1 weighted imaging,and contrast-enhanced T1 weighted imaging were associated with the culprit plaques.Their AUCs were 0.801,0.835,and 0.846,respectively.After the combination of all morphological and radiomic characteristics,AUC could reach 0.976,the accuracy rate was 87.4％.However,the difference was not statistically significant compared to the combined AUC of all radiomic characteristics (0.953) (P=0.275).Conclusion Radiomic analysis could accurately distinguish between the culprit plaques and non-culprit plaques of intracranial atherosclerosis,and is superior to the traditional morphological methods.

Development of Analytical Method and Validation using HPLC/PDA for Discrimination between Artemisiae Argyi Folium and Artemisiae Iwayomogii Herba

In this study, we described the new developed method to simultaneously discriminate two herbal drugs of Artemisiae Argyi Folium and Artemisiae Iwayomogii Herba using eight marker compounds (1 – 8) on an HPLC-PDA system. The developed method was applied to quantify the major components of two herbal drugs. The pattern analysis successfully discriminated and evaluated different components between Artemisiae Argyi Folium and Artemisiae Iwayomogii Herba. Results were used for classification of different species from collected samples.

Quantitation and Radical Scavenging Activity Evaluation of Iridoids and Phenylethanoids from the Roots of Phlomis umbrosa (Turcz.) using DPPH Free Radical and DPPH-HPLC Methods, and their Cytotoxicity

The roots of Phlomis umbrosa (Turcz.) (Phlomidis Radix) have been traditionally used to treat cold, reduce swelling and staunch bleeding. Four iridoids (1 – 3 and 5) and six phenylethanoid derivatives (4, and 6 – 10) were isolated from the roots of P. umbrosa. A simple, sensitive, and reliable analytical HPLC/PDA method was developed, validated, and applied to determine 10 marker compounds in Phlomidis Radix. Furthermore, the isolates were evaluated for cytotoxic and anti-oxidant activities as well as DPPH-HPLC method. Among them, compounds 4 and 6 – 9 displayed potent anti-oxidant capacities using DPPH assay with IC50 values of 27.7 ± 2.4, 10.2 ± 1.1, 18.0 ± 0.8, 19.1 ± 0.3, and 19.9 ± 0.6 µM, and compounds 6, 8, and 9 displayed significant cytotoxic activity against HL-60 with IC50 values of 35.4 ± 3.1, 18.6 ± 2.0, and 42.9 ± 3.0 µM, respectively.