Objective: To investigate the effect and mechanisms of spleen in up-regulating the expressions of inflammatory cytokines by macrophages and activating hepatic stellate cells (HSCs). Methods: Mice with liver fibrosis were randomly divided into two groups, and received splenectomy (spx) or sham operation (sham) respectively. Expressions of IL-1β, IL-13, TGF-β, TNF-α, PDGF-β and VEGF in the liver homogenates and hepatic macrophages of each group were detected by Luminex or RT-qPCR. The macrophage cell line RAW264.7 treated with different liver homogenates were conducted for analysis of glutamine metabolist-related molecules and cytokines, or transwell co-cultured with HSC cell line JS1. After co-culture, the cell activity, anti-apoptosis ability, and expression levels of α-SMA and collagens of JS1 were analyzed. SPSS statistical software was used to analyze the measurement data. Results: IL-13, TGF-β and TNF-α showed significant higher expressions in the sham liver homogenate, but IL-1β and TNF-α showed higher expression in the sham macrophages. RAW264.7 treated with sham liver homogenate (sham-RAW264.7) had increased expressions of IL-1β, TGF-β and TNF-α compared with the spx group. JS1 co-cultured with sham-RAW264.7 had higher expressions of α-SMA and collagens, but showed no significant difference in cell activity or anti-apoptotic ability. Moreover, Glutaminase, which is responsible for glutamine hydrolysis, was significantly higher expressed in sham hepatic macrophages, while glutamine-depletion increased the expression of TNF-α in RAW264.7 cells. Conclusion: Spleen is involved in the progression of liver fibrosis by promoting glutamine catabolism in hepatic macrophages, reducing the level of glutamine, and upregulating the expression of TNF-α to activate the HSCs.

High temperature vulcanized silicone rubber (HTV) is one of the most extensively used insulating polymers in power transmission cables (including its accessories) due to its preferable dielectric properties. However, complex of environmental conditions during its service time could lead to its dielectric degradation and then results in its dielectric failure, which would endanger the safety of power grid operation. Therefore, it is crucial to improve the flashover voltage of HTV for its better performance in insulating cables. In this research, room temperature vulcanized silicone rubber (RTV-II) doped with micron BN was prepared using constant temperature magnetic stirring approach and the HTV was then modified by these prepared micron coatings in order to improve its dielectric properties. The scanning electron microscopy (SEM) test showed that the micron-BN in RTV-II matrix was evenly distributed, then, the test results show that HTV films with micron-BN RTV-II coating has better qualities of dielectric and corrosion resistance compared with raw HTV film. Furthermore, find BN micron coating films with different proportions of micron fillers that improves the electrical properties of the composite the most. The addition of micron BN decreased the BN/HTV relative permittivity and increased its flashover voltage. When the micron BN particle size was 1 μm and the mass fraction was 5%, the micron BN had better dispersion in the matrix material, flashover voltage reaches the highest and the dielectric constant was relatively low.

AIM:To establish an ultrasound-based radiomics model through machine learning methods and then to assess the ability of the model to differentiate infected focal liver lesions from malignant mimickers. MATERIALS AND METHODS:A total of 104 patients with infected focal liver lesions and 485 patients with malignant hepatic tumours were included, consisting of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), combined hepatocellular-cholangiocarcinoma (cHCC-CC), and liver metastasis. Radiomics features were extracted from grey-scale ultrasound images. Feature selection and predictive modelling were carried out by dimensionality reduction methods and classifiers. The diagnostic effect of the prediction mode was assessed by receiver operating characteristic (ROC) curve analysis. RESULTS:In total, 5,234 radiomics features were extracted from grey-scale ultrasound image of every focal liver lesion. The ultrasound-based radiomics model had a favourable predictive value for differentiating infected focal liver lesions from malignant hepatic tumours, with an area under the curve (AUC) of 0.887 and 0.836 (HCC group), 0.896 and 0.766 (CC group), 0.944 and 0.754 (cHCC-CC group), 0.918 and 0.808 (liver metastasis group), and 0.949 and 0.745 (malignant hepatic tumour group) for the training set and validation set, respectively. CONCLUSIONS:Ultrasound-based radiomics is helpful in differentiating infected focal liver lesions from malignant mimickers and has the potential for use as a supplement to conventional grey-scale ultrasound and contrast-enhanced ultrasound (CEUS).

AIM:To investigate the effect of radiomics in the assessment of alterations in canonical cancer pathways in breast cancer. MATERIALS AND METHODS:Eighty-eight biopsy-proven breast cancer cases were included in the present study. Radiomics features were extracted from T1-weighted sagittal dynamic contrast-enhanced magnetic resonance imaging (MRI) images. Radiomics signatures were developed to predict genetic alterations in the cell cycle, Myc, PI3K, RTK/RAS, and p53 signalling pathways by using hypothesis testing combined with least absolute shrinkage and selection operator (LASSO) regression analysis. The predictive powers of the models were examined by the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS:A total of 5,234 radiomics features were obtained from MRI images based on the tumour region of interest. Hypothesis tests screened 250, 229, 156, 785, and 319 radiomics features that were differentially displayed between cell cycle, Myc, PI3K, RTK/RAS, and p53 alterations and no alteration status. According to the LASSO algorithm, 11, 12, 12, 15, and 13 features were identified for the construction of the radiomics signatures to predict cell cycle, Myc, PI3K, RTK/RAS, and p53 alterations, with AUC values of 0.933, 0.926, 0.956, 0.940, and 0.886, respectively. The cell cycle radiomics score correlated closely with the RTK/RAS and p53 radiomics scores. These signatures were also dysregulated in patients with different oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 statuses. CONCLUSION:MRI-based radiogenomics analysis exhibits excellent performance in predicting genetic pathways alterations, thus providing a novel approach for non-invasively obtaining genetic-level molecular characteristics of tumours.

Background:Relapse is a major cause of treatment failure for high‐risk acute leukemia after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Prognosis is considered dismal but data about risk factors associated with disease recurrence have not been elucidated.Aims:We aim to explore the pre‐ and post‐transplantation risk factors on relapse and survival in order to formulate individualized prophylaxis and treatment protocol for primary reoccurrence in high‐risk patients before and after transplantation.Methods:We retrospectively analyzed the outcomes of 321 high‐risk acute leukemia patients who underwent allogeneic hematopoietic stem cell transplantation (allo‐HSCT) who were diagnosed and treated at Union Hospital, and further evaluated the impact of pre‐ and post‐transplantation risk factors on relapse and survival by multivariate analysis.Results:Overall, 104 patients relapsed after allo‐HSCT with relapse cumulative incidence of 31 ± 2%. The median time of relapse was 4 (1.5‐26) months. With a median follow‐up of 50 months, the 3‐year overall survival (OS) and disease‐free survival (DFS) were 70%, 60%, respectively. Multivariate analysis showed that conditioning regimen (HR, 0.309; 95% CI, 0.119‐0.806, p = 0.016), type of disease (HR, 0.335; 95% CI, 0.125‐0.896, p = 0.029), and disease status at transplantation (HR, 1.964; 95% CI, 1.156‐3.338, p = 0.013) were independent factors influencing relapse for high‐risk acute leukemia patients following allo‐HSCT.Summary/Conclusion:Since the prognosis of patients with acute leukemia who experienced relapse after allo‐HSCT was poor, we emphasize the urgent need for formulating individualized prophylaxis and treatment protocol for primary reoccurrence in high‐risk patients before and after transplantation.

Background:Acute myeloid leukemia (AML) is a biologically heterogeneous disease with many different cytogenetic disorders and gene mutations. The advances of the next‐generation sequence (NGS) made it more practical for the clinical research to explore the cytogenetic analysis and mutation testing for the classification and risk assessment of AML patients.Aims:In this study, we sought to investigate the differences in molecular gene mutations between different type of AML patients and the response from those newly diagnosed AML patients to induction chemotherapy.Methods:We retrospectively evaluated 274 hospitalized non‐M3 AML patients. A next‐generation sequencing assay covering 43 genes was used to investigate recurrently mutated genes. The mutational status of fusion genes was determined by real time PCR. Clinical follow up was based on the patients recent clinic visits. Correlation analysis was done based different groups classified by different categories.Results:The median age at diagnosis was 45 year‐old (range 16–81 years). 231 patients were 59 years or younger with the median age of 41 years. Forty‐three patients were 60 years or older with a median age of 69 years (range 60–81 years). At least one non‐synonymous gene mutation was detected in 233 patients (85%). The median number of gene mutations was two (range 0–8). Comparing to the 59 years or younger patients, there was a significantly higher incidence of gene mutation in 60 years and older patients (p <0.01). The mean number of molecular gene mutations at diagnosis was higher in older patients than younger patients (2.92 vs 1.48, p < 0.05). Older patients had significantly higher frequency of ASXL1 (23.3% vs 13.9%, p <0.05), TP53 (11.6% vs 1.7%, p <0.05), IDH2 (18.6% vs 4.3%, p < 0.05) mutations, higher frequency of CEBPA (21.2% vs 14%, p < 0.05). Among 11 patients with no gene mutation received DA (daunorubicin 80 mg/m2 per day on days 1–3 and cytarabine 100 mg/m2 twice per day on days 1–7) as the induction therapy, 8 patients (73%) achieved CR after 1 course induction treatment. Meanwhile, among 21 patients with one or more gene mutations received DA induction therapy, only 12 patients (57%) achieved CR after 1 course induction treatment. More data need to be collected regarding the significance of each individual gene fusion correlating with induction chemotherapy.Summary/Conclusion:A higher incidence of cytogenetic disorders was found in older AML patients with higher burdens of molecular mutations, comparing to younger patients. Also, significantly higher frequency of ASXL1, TP53, IDH2 and CEBPA had been found with older patients. Patients with fewer gene fusion had a better chance of achieving CR when treated with cytarabine and daunorubicin induction chemotherapy.

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts' clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases. © 2019 The Author(s).

Iron-deficiency anemia is a public health concern that frequently occurs in pregnant mammals and neonatal offspring. Ferrous N-carbamylglycinate chelate (Fe-CGly) is a newly designed iron fortifier with proven effects in iron-deficient rats and weanling piglets. However, the effects of this new compound on pregnant mammals are unknown. Therefore, this experiment was conducted to evaluate the effects of Fe-CGly on sow reproductive performance and iron status of both sows and neonatal piglets. A total of 40 large-white sows after second parity were randomly assigned to two groups (n=20). They were receiving a diet including 80 mg Fe/kg as FeSO4 or Fe-CGly, respectively, from day 85 of gestation to parturition. The serum (day 110 of pregnancy) and placentas of sows were sampled. Litter size, mean weight of live born piglets, birth (live) litter weight, number of live born piglets, and the number of still-born piglets, mummies, and weak-born piglets were recorded. Once delivered, eight litters were randomly selected from the 20 litters per treatment, and one new-born male piglet (1.503±0.142 kg) from each selected litter was slaughtered within 3 h after birth from the selected litters, without colostrum ingestion. The serum, longissimus muscle, liver and kidneys of the piglets were collected. The iron status of the serum samples and the messenger RNA level of iron-related genes in the placenta, liver and kidney were analyzed. The results showed that litter weight of live born piglets was higher (P=0.030) in the Fe-CGly group (19.86 kg) than in the FeSO4 group (17.34 kg). Fe-CGly significantly increased placental iron concentration (P<0.05) of sows. It also significantly increased iron saturation and reduced the total iron-binding capacity of piglets (P<0.05) at birth. However, the results revealed that supplementation of Fe-CGly in sows reduced liver and kidney iron concentration of neonatal piglets (P<0.05), indicating decreased iron storage. In addition, the concentration of iron in the colostrum was not significantly changed. Therefore, the present results suggested that replacement of maternal FeSO4 supplement with Fe-CGly in the late-gestating period for sows could improve litter birth weight, probably via enhanced iron transportation in the placenta.

This study was conducted to investigate effects of dynamic feeding low and high methionine (MET) diets on performance, egg quality traits, and serum metabolites in laying hens. A total of 180 laying hens (Brown Hy-line, 41 wk old) were allocated into 3 equal groups with 6 replicates each. The average egg production (EP) of each group was around 87% during one-week statistics before the formal experiment (P = 0.989). The control group (CON) received the control diet (contained 0.30% MET) at both 07:30 h and 15:30 hours. The low-high group (LH) received a low MET diet (containing 0.27% MET) at 07:30 h and high MET diet (containing 0.33% MET) at 15:30 hours. The high-low group (HL) received a high MET diet at 07:30 h and low MET diet at 15:30 hours. After 10 wk, blood samples were collected at 4-hour intervals in a daily cycle initially starting at 07:30 h before feeding. Results showed that the MET intake of a d was not influenced by the treatments (P > 0.05), respectively. The EP of the LH and HL group increased by 2.28 and 2.45% when compared with the CON group (P > 0.05). The hens in the LH group had a lower albumen ratio and thicker eggshell thickness than both CON and HL groups. Egg yolk ratio of the LH group was higher than the HL group (P < 0.05). The serum total cholesterol (TC), total triglyceride (TG), total protein (TP), and calcium (Ca) of the LH group was significantly lower at 07:30 h than the CON and HL groups, and the serum TG of the HL group was lower at 07:30 h than the CON group (P < 0.05). Meanwhile, the LH group also had the lowest value of serum TP at 23:30 h and 03:30 h (P < 0.05). These results demonstrated that dynamic feeding low and high MET diets might alter the circadian variation of serum TC, TG, TP, and Ca, which is consistent with the change of component ratio of egg albumen and yolk and eggshell thickness.

Dengue is a rapidly spreading mosquito-borne disease caused by the dengue virus (DENV) and has emerged as a severe public health problem around the world. Guangdong, one of the southern Chinese provinces, experienced a serious outbreak of dengue in 2014, which was believed to be the worst dengue epidemic in China over the last 20 years. To better understand the epidemic, we collected the epidemiological data of the outbreak and analyzed 14,594 clinically suspected dengue patients from 25 hospitals in Guangdong. Dengue cases were then laboratory-confirmed by the detection of DENV non-structural protein 1 (NS1) antigen and/or DENV RNA. Afterwards, clinical manifestations of dengue patients were analyzed and 93 laboratory-positive serum specimens were chosen for the DENV serotyping and molecular analysis. Our data showed that the 2014 dengue outbreak in Guangdong had spread to 20 cities and more than 45 thousand people suffered from dengue fever. Of 14,594 participants, 11,387 were definitively diagnosed. Most manifested with a typical non-severe clinical course, and 1.96 % developed to severe dengue. The strains isolated successfully from the serum samples were identified as DENV-1. Genetic analyses revealed that the strains were classified into genotypes I and V of DENV-1, and the dengue epidemic of Guangdong in 2014 was caused by indigenous cases and imported cases from the neighboring Southeast Asian countries of Malaysia and Singapore. Overall, our study is informative and significant to the 2014 dengue outbreak in Guangdong and will provide crucial implications for dengue prevention and control in China and elsewhere.

The present work is focused on the numerical prediction of ship selfpropulsion in different shallow water conditions: H/T=2.0 and H/T=1.2 (H is the depth of water and T is draft of ship). The KRISO Container Ship (KCS) model is used in the present simulation. Numerical computations are carried out by our own solver naoe-FOAM-SJTU, which is developed on the open source platform OpenFOAM and mainly composed of a dynamic overset grid module and a full 6DoF motion module with a hierarchy of bodies. A proportional-integral (PI) controller is applied to adjust the rotational speed of the propeller to achieve the desired ship speed. The simulated results, i.e. the rate of revolution of propeller n, propulsion coefficients, are compared to the experimental data provided by Flanders Hydraulics Research (FHR) in SIMMAN 2014. Good agreements show that the present approach is applicable for self-propulsive prediction in shallow water.

ABSTRACT Aim: Early tumor shrinkage (ETS) is associated with long-term outcome in patients receiving chemotherapy plus cetuximab, which was investigated in CRYSTAL and OPUS trials. CLIME study (NCT01322178) was designed to observe whether the addition of targeted drug in first line further increases the curative resection rate and improves long-term survival in KRAS wide-type colorectal liver limited metastases patients in China. This retrospective analysis aims to show the impact of ETS on long-term outcome in CLIME study. Methods: Radiologic assessments at week 8 were used to calculate the relative change in the sum of the longest diameters of the target lesions. A 20% decrease cutoff value was selected as a dichotomization threshold for further investigation. Outcome measures were objective response rate (ORR), curative resection rate and progression-free survival (PFS). Cox regression models were used to quantify individual changes in tumor size over time and to relate these changes to PFS. Results: From the ITT cohort (100 cases), 92 patients were available for ETS assessment and 70 pts achieved ETS (76.1%). These data were comparable with quantitative analysis of ETS in CRYSTAL and OPUS trials (table 1). Longer PFS was observed in patients who achieved ETS as compared to patients with no-ETS (10.9m vs. 6.2m, HR 0.203, 95%CI 0.087-0.473, P CLIME n = 92 CRYSTAL n = 299 OPUS n = 78 ETS rate (%) 70 (76.1%) 184 (62%) 54 (69%) mPFS in ETS group 10.9m 14.1m 11.9m mPFS in no-ETS group 6.2m 7.3m 5.7m HR 0.203 0.32 0.22 P value KRAS exon2 wt only Conclusions: Quantitative analyses from CLIME study further revealed the value of the variable ETS as a potential efficacy outcome measure for KRAS wild-type colorectal liver-limited metastases patient in China. Reference:Piessevaux et al., JCO 2013 Disclosure: All authors have declared no conflicts of interest.

OBJECTIVE:To demonstrate the relationship between nm23-H1 loss of heterozygosity (LOH) and clinical pathological characteristics of hepatocellular carcinoma (HCC) from the DNA level.METHOD:Southern blot hybridization was used to analyze genomic DNA in liver cancer and its corresponding liver tissue.RESULT:nm23-H1 has diallelic bands at 7.6 Kb and 2.3 Kb. Allelic loss of heterozygosity in tumour tissues was detected in 31.25% patients (5 patients). LOHs were more common in the tumours with intrahepatic metastasis or portal vein tumour embolism and the tumours poorly differentiated (Edmondson's classification III, IV).CONCLUSION:nm23-H1 LOHs may induce the metastasis potential of HCC and help to predict recurrence and metastasis of HCC.

Two new passive safety systems for a demonstration nuclear heating plant, the residual heat removal system (RHRS) and the boron injection system (BIS), are introduced in this paper. Their common characteristic is that they have no driving equipment, therefore fluid circulation depends only on gravity (in BIS) or natural circulation (in RHRS). The inherent safety and realizability of both systems are illustrated in this paper.