Expression of IGF-II in early experimental hepatocellular carcinomas and its significance in early diagnosis

AIM: To investigate the serum level and expression of insulin growth factor II (IGF-II) in liver tissues of rats with early experimental hepatocellular carcinomas (HCC) and its significance in early diagnosis.METHODS: Early experimental hepatocellular carcinomas were induced by diethylnitrosamine (DENA) in 180 male SD rats. Another 20 male SD rats served as control. The IGF-IIserum level was measured by ELISA. Immunohistochemistry and electron microscopic immunohistochemistry were usedto observe the expression of IGF-II in normal and tumor liver tissues and its ultrastructural location in malignant hepatocytes. The expressions of IGF-II in human hepatoma cell lines HepG2, SMMC7721 and human embryonic liver cell line L-02 were measured by immunocytochemistry. IGF-II mRNA level was studied by in situ hybridization.RESULTS: IGF-II was expressed in the cytoplasm of both sinusoidal cells in paracancerous cirrhotic liver tissue and malignant hepatocytes in early experimental HCC tissues.Gold particles were seen on the rough endoplasrnic reticulum and the mitochondrion in malignant hepatocytes. IGF-II was expressed in the human hepatoma cell lines. The mRNA level of IGF-II was higher in rat liver tumor tissue than in normal rat liver tissue. The serum IGF-II level of the early experimental HCC group was 34.67±10.53 ng.ml^-1 and that of the control group was 11.75±5.84 ng.ml^-1. The rank sum test was used for statistical analysis. There was a significant difference between the two groups (P<0.01).CONCLUSION: During the induction of early experimental HCC by DENA, IGF-II may promote hepatocytic proliferation via a paracrine mechanism in the pre-cancerous stage. When hepatocytes are transformed into malignant cells, they may secrete IGF-II and promote malignant cell proliferation by an autocrine mechanism. IGF-II may be a possible biological marker in the early diagnosis of HCC.

Estimation of Aleatory Randomness by S_(a)(T_(1))-Based Intensity Measures in Fragility Analysis of Reinforced Concrete Frame Structures

Based on the multiple stripes analysis method,an investigation of the estimation of aleatory randomness by S_(a)(T_(1))-based intensity measures(IMs)in the fragility analysis is carried out for two typical low-and mediumrise reinforced concrete(RC)frame structures with 4 and 8 stories,respectively.The sensitivity of the aleatory randomness estimated in fragility curves to various S_(a)(T_(1))-based IMs is analyzed at three damage limit states,i.e.,immediate occupancy,life safety,and collapse prevention.In addition,the effect of characterization methods of bidirectional ground motion intensity on the record-to-record variability is investigated.It is found that the damage limit state of the structure has an important influence on the applicability of the ground motion IM.The S_(a)(T_(1))-based IMs,considering the effect of softened period,can maintain lower record-to-record variability in the three limit states,and the S_(a)(T_(1))-based IMs,considering the effect of higher modes,do not show their advantage over S_(a)(T_(1)).Furthermore,the optimal multiplier C and exponentαin the dual-parameter ground motion IM are proposed to obtain a lower record-to-record variability in the fragility analysis of different damage limit state.Finally,the improved dual-parameter ground motion IM is applied in the risk assessment of the 8-story frame structure.

Establishment of animal model for potency evaluationof inactivated SARS virus experimental vaccine

The purpose of this study was to test the effectiveness of source virus strain for the manufacture of the inactivated SARS virus vaccine, and establish an experimental method and preliminary standard for potency evaluation. Mice were divided into groups for being immunized with corresponding serially diluted experimental SARS virus inactivated vaccine. And the rabbits were immunized with undiluted vaccine. Challenge assay was conducted with a heterologous SARS virus. And the neutralization antibody was determined with plaque reduction neutralization test (PRNT), to which the neutralization antibody in the convalescent serum of SARS patients was compared. The experimental vaccine viral strains were proved to be suitable for manufacturing the vaccine. Mice immunized by vaccines of serial dilutions were able to elicit neutralizing antibody. The antibody titer from mice immunized with the undiluted vaccine could reach up to 1∶495.2, while those of rabbits immunized with the undiluted vaccine could reach a GMT of 55.0-79.9. The capability of the antibody to neutralize the virus from Guangdong is more efficient than that from Beijing. The GMT of neutralizing antibody in SARS convalescents living in south and north China ranged from 50.12 to 54.95, and the titers of convalescents from north China were higher than those from south China. Mice and rabbits used as the model for evaluation of potency are of sensitivity, and the test is of reproducibility. The candidate challenge viral strains showed a relatively consistent effect on evaluating antibodies produced by various batches and different vaccine-source strains, hence they can be used to evaluate potency of the vaccine. The method for testing the vaccine potency and the evaluation standard was established preliminarily.

Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer(RATICAL):a nationwide multicenter retrospective study

Background:Anaplastic lymphoma kinase(ALK)test in advanced non-small cell lung cancer(NSCLC)can help physicians provide target therapies for patients harboring ALK gene rearrangement.This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC.Methods:In this real-world study(ChiCTR2000030266),patientswith advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1,2018 and December 31,2019 were retrospectively analyzed.Interpretation training was conducted before the study was initiated.Quality controls were performed at participating centers using immunohistochemistry(IHC)-VENTANA-D5F3.The positive ALK gene rearrangement rate and consistency rate were calculated.The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well.Results:The overall ALK gene rearrangement rate was 6.7%in 23,689 patients with advanced NSCLC and 8.2%in 17,436 patients with advanced lung adenocarcinoma.The quality control analysis of IHC-VENTANA-D5F3 revealed an intrahospital consistency rate of 98.2%(879/895)and an inter-hospital consistency rate of 99.2%(646/651).IHC-VENTANA-D5F3 was used in 53.6%,real-time polymerase chain reaction(RT-PCR)in 25.4%,next-generation sequencing(NGS)in 18.3%,and fluorescence in-situ hybridization(FISH)in 15.9%in the adenocarcinoma subgroup.For specimens tested with multiple methods,the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0%(822/839)for FISH,98.7%(1,222/1,238)forNGS,and 91.3%(146/160)for RT-PCR.The overall ALK gene rearrangement rateswere higher in females,patients of≤35 years old,never smokers,tumor cellularity of>50,and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup(all P<0.05).Conclusions:This study highlights the real-world variability and challenges of ALK test in advanced NSCLC,demonstrating a predominant use of IHCVENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients.These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.

Higher levels of circulating monocyte-platelet aggregates are correlated with viremia and increased sCD 163 levels in HIV- 1 infection

Increased levels of monocyte-platelet aggregates （MPAs） are reported to be highly correlated with cardiovascular events. In this study, the MPA levels in different monocyte subsets and the associations between MPA levels, HIV-1 viremia and monocyte activation were evaluated during HIV-1 infection. The results showed that the percentages of MPAs in all three monocyte subsets were higher in HIV-l-infected subjects than in healthy controls, and were associated with the plasma viral load in the non-classical and intermediate monocyte subsets. The plasma levels of sCD14 and sCD163 were upregulated in HIV-1 infection and were positively associated with viral loads and negatively associated with CD4 counts. P-selectin glycoprotein ligand-1 （PSGL-1） was shown to be expressed at significantly lower levels on all three monocyte subsets and was negatively correlated with the sCD163 level. The MPA level was correlated with the levels of plasma sCD163 but negatively correlated with CD163 and PSGL-1 on all three monocyte subsets. An elevated immune activation status was correlated with increased MPA formation, underlying the potential interaction between monocyte activation and MPA formation. This interaction may be related to a higher thromboembolic risk in patients infected with HIV-I.

循环溶剂退火条件下柱状相组成的两嵌段共聚物薄膜自组装行为的模拟研究

采用蒙特卡洛模拟研究了体相形成柱状相的两嵌段共聚物薄膜在循环溶剂退火条件下的自组装行为.结果表明,在循环溶剂退火条件下,溶剂蒸发速率、溶剂选择性和有效薄膜厚度与柱状相周期的匹配性都会影响形成垂直柱状结构的表面选择性窗口(β窗口).当溶剂蒸发速率在一定范围内时,β窗口随蒸发速率的增大而增大.溶剂对长嵌段的选择性越强,形成垂直柱状结构的β窗口越宽.当溶胀比约为1.5时的薄膜厚度与柱状相周期不匹配时更利于形成垂直柱状结构.通过对链节均方位移曲线的分析发现,在循环溶剂退火条件下高分子链节在垂直方向的扩散始终快于平行方向,因此链节优先沿垂直方向聚集,从而促进了垂直柱状结构的形成.循环溶剂退火条件下,β窗口比溶剂退火条件下的宽,同时大幅度减少了退火时间.