Eukaryotic translation initiation factor 4B (eIF4B) plays an important role in mRNA translation initiation, cell survival and proliferation in vitro, but the in vivo function is poorly understood. In this study, via various experimental techniques such as hematoxylin-eosin (HE) staining, flow cytometry, Western blotting, and immunohistochemistry, we investigated the role of eIF4B in mouse embryo development using an eIF4B knockout (KO) mouse model and explored the mechanism. We found that the livers, but not lungs, brain, stomach, or pancreas, derived from eIF4B KO mouse embryos displayed severe pathological changes characterized by enhanced apoptosis and necrosis. Accordingly, high expression of cleaved-caspase 3, and excessive activation of mTOR signaling as evidenced by increased expression and phosphorylation of p70S6K and enhanced phosphorylation of 4EBP1, were observed in mouse embryonic fibroblasts and fetal livers from eIF4B KO mice. These results uncover a critical role of eIF4B in mouse embryo development and provide important insights into the biological functions of eIF4B in vivo.
Animals ; Apoptosis/genetics* ; Caspase 3 ; Eosine Yellowish-(YS) ; Eukaryotic Initiation Factors/metabolism* ; Fibroblasts ; Hematoxylin ; Liver/metabolism* ; Mice ; Ribosomal Protein S6 Kinases, 70-kDa/genetics* ; TOR Serine-Threonine Kinases

Objective To identify the potential prognostic biomarkers of the immune-related genes signature for patients with hepatocellular carcinoma (HCC). Methods Original HCC data were downloaded from TCGA, and the immune activity of each sample was calculated by ssGSEA. HCC samples were divided into high and low immune cell infiltration groups by "GSVA" package and "hclust" package. The ESTIMATE algorithm scored the tumor microenvironment in each HCC sample. The "limma" package and Venn diagram identified effective immune-related genes. Univariate Cox, Lasso regression and multivariate Cox regression analyses were used to explore key genes. The "rms" package was used to create nomograms and draw calibration curves. Results Compared with the high immune cell infiltration group, the tumor purity of the samples in the low immune cell infiltration group was higher, the immune score, ESTIMATE score and stromal score were lower. In the high immune cell infiltration group, the immune components were more abundant, and the expression levels of TIGIT, PD-L1, PD-1, LAG3, TIM-3, CTLA4 and HLA family were higher. Multivariate Cox regression analysis showed that four immune-related genes (S100A9, HMOX1, IL18RAP and FCER1G) were used to construct the prognosis model. Compared with other clinical features, the risk score of this prognostic model was recognized as an independent prognostic factor. Conclusion This study identified the immune-related core genes which may be used in targeted therapy and immunotherapy of HCC.

0bjective To study the angular dependence of optically stimulated luminescent dosimeter (OSLD) with solid phantoms under SSDL radiation level ⁶⁰Co radiation field, and to discuss the possibility of OSLD in volumetric modulated arc therapy (VMAT) and other rotating irradiation dose audit. Methods OSLDs were embedded in the two phantoms with the same size and material, respectively. The phantom 1 was set to make the first OSLD perpendicular to the beam, and the phantom 2 was set to make the second OSLD parallel to the beam. The OSLDs were irradiated at 8 angles: 0°, 45°, 90°, 135°, 180°, −45°, −90, −135°. The counts of the OSLSs were read and the response of each angle which normalized to 0° were calculated. Results When the OSLDs are perpendicular to the beam, the angular response is between −6.76% ～ +1.5%, with the maximum angular dependence at 90° and −90°. When the OSLDs are parallel to the beam, the angular response is between −1.74%～+1.67%, below 2%. Conclusion It is better to correct the sensitivity of dosimeters by Element Correction Factors (ECF) for dose audit. Under the condition of rotating irradiation, OSLD shoud be set parallel to the beam, which can better reduce the influence of angular dependence and facilitate further application research of VMAT dose audit.

Objective:To investigate the application value of three-dimensional visualization technology in management of middle hepatic vein (MHV) processing in associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).Methods:The retrospective and descriptive study was conducted. The clinical data of 40 patients with right massive liver cancer or multiple right liver lesions who underwent ALPPS in the First Affiliated Hospital of Guangxi Medical University from November 2017 to August 2019 were collected. There were 34 males and 6 females, aged (44±9)years, with a range from 26 to 64 years. All patients underwent multi-slice computed tomography (CT) plain and enhanced scan of superior abdominal region before operation, and the data were transmitted to the liver visualization analysis software IQQA system with 1.5 mm thin-layer images to complete the three-dimensional reconstruction of the liver and its blood vessels. Patients were performed ALPPS based on results of three-dimensional reconstruction and intraoperative findings. Observation indicators: (1) results of preoperative three-dimensional reconstruction; (2) surgical situations; (3) follow-up. Follow-up was conducted using outpatient examinations and telephone interview to detect postopeartive survival of patients up to March 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were described as M (range). Count data were represented as absolute numbers. Results:(1) Results of preoperative three-dimensional reconstruction: 40 patients underwent three-dimensional reconstruction successfully, of which 37 clearly showed MHV, tumor location and relationship between them, 3 patients showed unclearly MHV and were classified based on two-dimensional images. Of the 40 patients, 12 had MHV classified as type A, 13 as type B, 9 as type C, and 6 as type D. Three-dimensional reconstruction of vessels showed 22 with umbilical veins and 9 with anterior veins. Of the 40 patients, 35 were predicted to preserve MHV, and 5 were predicted to resect MHV. Total estimated liver volume, tumor volume, and reserved liver volume were (1 012±119)cm 3, 600 cm 3(8-2 055 cm 3), (346±80)cm 3. The ratio of future liver remnant to standard liver volume was 34%±8%. (2) Surgical situations : 40 patients underwent the first-stage ALPPS, including 35 with preservation of MHV and 5 with resection of MHV, which was accorded with preoperative prediction. Thirty-four patients underwent the second-stage ALPPS, and 6 patients had failure to receive the second-stage ALPPS due to undificiency future liver remnant. The operation time and volume of intraoperative blood loss for 40 patients undergoing first-stage ALPPS were (350±79)minutes and 300 mL(range, 100-2 600 mL). Three patients received blood transfusion and no perioperative death occurred. There were 24 patients with grade A heptic insufficiency according to criteria of International StudyGroup of Liver Surgery (ISGLS) and 16 patients with grade B heptic insufficiency after the first-stage ALPPS. Twenty-eight patients had grade Ⅰ complications of Clavien-Dindo classification, including 17 with a small pleural effusion, 10 with a small pleural and abdominal effusion, 1 with hypoproteinemia; 8 patients had grade Ⅱ complications of Clavien-Dindo classification, including 5 with pneumonia, 1 with pneumonia combined with pleural and abdominal effusion, 1 with coagulation disorders, 1 with biliary fistula; 3 patients had grade Ⅲ complications of Clavien-Dindo classification, including 2 with pneumothorax and pneumonia, 1 with pneumothorax, pneumonia and coagulation disorders; 1 patient had grade Ⅳ complications of Clavien-Dindo classification as systemic inflammatory response syndrome. All patients with complications were improved after symptomatic treatment, anti infection, transfusion of fresh frozen plasma or drainage. For the 34 patients undergoing the second-stage ALPPS, the operation time and volume of intraoperative blood loss were (320±83)minutes and 500 mL(range, 200-6 000 mL). Twelve patients received blood transfusion. There were 12 patients with grade A heptic insufficiency according to criteria of ISGLS and 22 with grade B heptic insufficiency after the second-stage ALPPS. Eighteen patients had grade Ⅰ complications of Clavien-Dindo classification, including 11 with a small pleural effusion, 7 with a small pleural and abdominal effusion; 12 patients had grade Ⅱ complications of Clavien-Dindo classification, including 4 with pneumonia, 4 with coagulation disorders, 3 with massive abdominal effusion, 1 with biliary fistula; 3 patients had grade Ⅲ complications of Clavien-Dindo classification, including 1 with pneumothorax and pneumonia, 1 with massive pleural effusion, 1 with obstructive jaundice; 1 patient had grade Ⅳ complications of Clavien-Dindo classification as pneumonia and anemia. All patients with complications were improved after symptomatic treatment, anti infection, transfusion of fresh frozen plasma or drainage. (3) Follow-up: 40 patients were followed up for 2-35 months, with a median follow-up time of 17 months. The 6-month, 1-, and 2-year survival cases were 35, 26, 21 cases. Conclusion:Three-dimensional visualization technology can clearly show the MHV classification and its relationship with tumor location, which has an important guiding significance in the decision-making of MHV management in ALPPS.

Human acute leukemia (AL) is a clonal malignancy with abnormal hematopoietic stem cells. Clinically, AL is very difficult to cure due to its sudden onset and short course of disease progression. Previous studies have shown that eukaryotic initiation factor 4B (eIF4B) plays a critical role in the development of chronic leukemia. However, the involvement of eIF4B in human acute leukemia is still largely unknown. Therefore, we studied eIF4B function and its regulatory mechanism in human acute leukemia. We found that phosphorylation levels of eIF4B in acute leukemia cells were significantly reduced in response to treatment with either LY294002 (PI3K inhibitor), AKTi (AKT inhibitor) or SMI-4A (Pim inhibitor). Co-treatment with inhibitors targeting JAK/STAT5/Pim and PI3K/AKT/mTOR signaling dramatically promoted apoptosis of acute leukemia cells by downregulating eIF4B phosphorylation. Furthermore, in vitro and in vivo functional experiments showed that eIF4B played an important anti-apoptosis role in the acute leukemia cells by regulating the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL. In contrast, silencing eIF4B inhibited the growth of acute leukemia cells as engrafted tumors in nude mice. Taken together, our results indicate the synergistic role of JAK/STAT5/Pim and PI3K/AKT/mTOR signaling pathways in regulating eIF4B phosphorylation in acute leukemia, and highlight eIF4B as a candidate therapeutic target for treatment of acute leukemia.
Animals ; Apoptosis ; Cell Line, Tumor ; Leukemia ; Mice ; Mice, Nude ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; STAT5 Transcription Factor/metabolism*

Objective To investigate the clinical efficacy of hepatic artery ringed and restriction operation-associating liver partition and portal vein ligation for staged hepatectomy (HARO-ALPPS) in the treatment of giant hepatocellular carcinoma.Methods The retrospective and descriptive study was conducted.Clinical data of a 45-year-old male patient with giant hepatocellular carcinoma who was admitted to the First Affiliated Hospital of Guangxi Medical University in July 2018 were collected.In the first stage operation,right portal vein ligation+ in situ liver partition + right hepatic artery ringed operation was performed on the patient.In the second stage operation,right hemihepatectomy was performed on the patient.Observation indicators:(1) surgical and postoperative situations of the first stage operation;(2) surgical and postoperative situations of the second stage operation;(3) postoperative pathological examination;(4) changes in future liver remnant (FLR) and tumor volume;(5) perioperative hemodynamic changes of right hepatic artery,proper hepatic artery and left hepatic artery;(6) perioperative hemodynamic changes of left-portal vein and main portal vein;(7) follow-up.Follow-up using outpatient examination was performed to detect the prognosis of patients up to February 2019.Count data were described as absolute number.Results (1) Surgical and postoperative situations of the first stage operation:the patient underwent right portal vein ligation+ in situ liver partition+ right hepatic artery ringed operation successfully.The operation time and volume of intraoperative blood loss were 376 minutes and 400 mL.Inflammatory indicators including body temperature,white blood cells (WBC),C-reactive protein,procalcitonin,and liver function indices including total bilirubin (TBil),albumin (Alb),alanine aminotransferase (ALT),aspartate aminotransferase (AST),ascites,indocyanine green retention rate at15 min (ICG R15),score of model for end-stage liver disease (MELD) before the second stage operation were improved after symptomatic supportive treatment.Prothrombin time (PT) was in the normal range after the first stage operation.There was no complication of Clavien-Dindo classification Ⅱ or above.(2) Surgical and postoperative situations of the second stage operation:the patient underwent right hemihepatectomy successfully.The operation time and volume of intraoperative blood loss were 322 minutes and 900 mL.The patient received 300 mL of fresh frozen plasma infusion.Inflammatory indicators including body temperature,C-reactive protein,and liver function indices including Alb,ALT,AST,ascites,were recoved to normal level after symptomatic supportive treatment.WBC,procalcitonin,TBil,and PT were in the normal range.There was no complication of Clavien-Dindo classification Ⅱ or above.(3) Postoperative pathological examination:① Ⅱ stage hepatocellular carcinoma was confirmed,mass-like type,with tissue necrosis and microvascluar invasion.There was no distal metastasis and tumor did not invade liver capsule or surgical margin.Ishak score of surrounding tissues was 3 in the inflammation and 2 in the fibrosis.② Chronic inflammation was detected in the gallbladder mucosa.③ Reactive hyperplasia was found in the 2 lymph nodes of the group 8.④ One in the group 12 lymph nodes showed reactive hyperplasia.Immunohistochemistry showed positive Glypican-3,Hepatocyte,Arginase-1,NM23,weakly positive vascular endothelial growth factor,and negative Ki-67,vascular endothelial cell marker CD34,biliary epithelial marker CK19 and CK 7,tumor suppressor gene P21 and P23.(4) Changes in FLR and tumor volume:FLR was 565 mL and 580 mL at the 5th and 14th day after the first stage operation respectively,accounting for 54％ and 57％ of total liver volume.The FLR to body weight ratio was 0.96 and 0.98,and the growth rate of FLR was 194％ and 202％.Tumor volume was 1 210 mL and 1 297 mL at the 5th and 14th day after the first stage operation respectively.Tumor necrosis volume was 635 mL and 500 mL at the 5th and 14th day after the first stage operation respectively.At the 5th and 14th day after the first stage operation,the liver CT examination showed that HARO was successfully underwent and the blood supply of remnant liver was good.Preoperative CT aothgraphy (CTA) examination showed that the right hepatic tumor had rich arterial blood supply.At the 5th day after the first stage operation,the CTA examination confirmed the ringed site of right hepatic artery,and the blood supply of the tumor gradually decreased.At the 14th day after the first stage operation,CTA examination showed significant decrease in the blood supply of liver tumors.Liver CT examination showed rich supply of the remnant liver and the liver volume of 829 mL at the 7th day after the second stage operation.(5) Perioperative hemodynamic changes of the right hepatic artery,proper hepatic artery and left hepatic artery.① Blood flow of right hepatic artery was 224.3,574.7,827.5,222.7,153.0,282.5,279.1,247.9 and 150.2 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and before right hepatic artery ringed and restriction,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th and 7th day after the first stage operation.Blood flow of right hepatic artery in the second stage operation was 505.0 mL/min.② Blood flow of proper hepatic artery was 399.7,793.5,830.5,1 075.4,784.7.5,821.2,722.8,467.4 and 555.4 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and before right hepatic artery ringed and restriction,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th and 7th day after the first stage operation.Blood flow of proper hepatic artery was 505.0,473.3,158.5,627.0,103.8 and 139.8 mL/min before right hepatectomy in the second stage operation,after right hepatectomy,at the 1st,3th and 5th day after the second operation,respectively.③ Blood flow of left hepatic artery was 147.5,13.8,19.4,16.2,62.1,93.9,67.1,30.8 and 106.1 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and before right hepatic artery ringed and restriction,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th,7th and 10th day after the first stage operation.Blood flow ot left hepatic artery was 52.0,43.2,112.4,103.6,80.7 and 56.1 mL/min before right hepatectomy in the second stage operation,after right hepatectomy,at the 1st,3th and 5th day after the second operation,respectively.(6) Perioperative hemodynamic changes of left-portal vein and main portal vein.① Blood flow of left portal vein was 552.6,181.2,412.2,320.0,1 777.7,1 284.7,749.5 and 484.2 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th,7th and 10th day after the first stage operation,respectively.Blood flow of left portal vein was 793.3,979.0,485.2,1 042.5,803.5 and 548.3 mL/min before right hepatectomy in the second stage operation,after right hepatectomy,at the 1st,3th,5th and 7th day after the second operation respectively.② Blood flow of main portal vein was 1 186.0,696.7,833.7,431.7,1 319.1,668.4,890.7,550.8 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th,7th and 10th day after the first stage operation,respectively.Blood flow of main portal vein was 846.4,937.4,891.2,1 671.0,2 697.8,and 1 230.0 mL/min before right hepatotectomy in the second stage operation,after right hepatectomy,at the 1st,3th,5th and 7th day after the second stage operation,respectively.(7) Follow up:the patient was followed up for 6 months and survived well,with Child A of liver function and normal alpha fetoprotein level.Liver contrast CT examination showed increase in the remnant liver,good blood supply,and no tumor recurrence.The FLR was 727 mL at the 2 months after operation.Conclusion For patients with giant hepatocellular carcinoma,HARO-ALPPS can be performed to decrease blood supply of tumor,increase tumor necrosis area,and reduce the incidence of intrahepatic arteriovenous fistula,which ensure blood supply of remnant liver hyperplasia.

Objective:To comparative Research with MSCT and CAG in the myocardial bridge-wall diagnostic coronary. Methods: Selected 93 patients for the study in January 2011 to the end of December 2013,MB-MCA patients diagnosed in Beijing North Hospital, all patients underwent catheter coronary angiography (CAG) and 64-slice spiral CT (MSCT), comparison of the diagnostic accuracy of the two inspection methods, and the results of the correlation analysis, results processing and analysis using statistical software SPSS17.0. Results:MSCT and CAG were two examination methods in the diagnosis of superficial and deep type MB-MCA, with a high degree of consistency in the diagnosis of MB-MCA average length, average depth comparison with statistical significance(t=3.021, t=3.758;P<0.05), there was not statistically significant comparison in the narrow detection rate. Conclusion:MSCT as a novel, non-invasive means of MB-MCA examination, the diagnosis results are reliable, accurate and capable of providing a richer diagnostic information for clinicians, clinician and patient can be widely applied.

This study was aimed to observe the protective effect of extract from Rhizoma A nemones Raddeanae (RAR) on hepatic fibrosis induced by porcine serum in rats. A total of 68 SD rats were randomly divided into 5 groups, which were the normal group, model group, RAR group, extraction of RAR (EXRAR) group, Fu-Zheng Hua-Y u(FZHY) group. Each rat was intraperitoneally injected with 0.5~0.6 ml of porcine serum twice a week for 15 suc-cessive weeks to establish liver fibrosis model. Intragastric administration was given after the model was successfully established. The FZHY group was given FZHY capsule (0.525 g·kg-1). The RAR group was given RAR decoction (0.7 g·kg-1). The EXRAR group was given EXRAR (0.071 g·kg-1). The model group and normal group were given e-qual amount of physiological saline. The medication was given once a day. And the treatment course was 8 weeks. At the end of the 23th week, rats were sacrificed. Contents of SOD and MDA in blood serum were assayed. The protein expressions of α-SMA and TGF-β1 in liver tissues were detected by SABC. The results showed that compared with the model group, content of MDA decreased in the EXRAR group, RAR group and FZHY group (P<0.05), and content of SOD increased obviously (P<0.05). In the model group, expression of α-SMA and TGF-β1 increased, with dark brown dyeing and diffusion area. Expression area and strength of the FZHY group, RAR group, and EXRAR group were ob-viously weak with tasteless interval dyeing and no formation of typical pseudolobule in comparison with the model group. The color rendering index showed that compared with the model group, the protein expression of α-SMA and TGF-β1 decreased obviously in liver tissues of the FZHY group, EXRAR group, and RAR group (P< 0.05). It was concluded that RAR and its extract had a good antifibrosis effect. And the EXRAR had basically the same antifibrosis effect as RAR. It was assumed that the possible mechanism was related with the inhibiting of hepatic stellate cell (HSC) activation and the expression of TGF-β1 as well as the resisting of lipid peroxidation.

Objective: To discuss the value in the differential diagnosis of benign and malignant in ulmonary ground-glass opacities with multislice spiral CT. Methods: Selected 31 patients in Beijing North hospital with spiral CT examination of the chest as the research object, the lungs differential diagnosis of ground-glass image analysis to pathological findings as diagnostic criteria, analysis Imaging features of benign and malignant grinding glass shadow. Results: Malignant lesions with pleural indentation, spiculation, lobulation, such as performance-based, clear boundary between the two groups in the pleural indentation, spiculation, points Ye Zheng, clear boundary comparing with statistical significance(x2=11.138, x2=6.482, x2=4.306, P<0.05). Meanwhile benign lesions showed a round or oval, and malignant lesions with irregular shape and multi-nodular-like performance-based fusion of the two groups in a round or oval, irregular and more fusion-like nodules difference was significant, the statistical significance (x2=11.138, x2=6.482, x2=4.306, P<0.05). Conclusion:Application of multislice spiral CT examination of the chest can be on the ground glass by special signs and morphological comprehensive analysis, benign and malignant, with a high value.

Objective To verify the reliability of dose parameters of radiotherapy under reference and non-reference conditions by using TLD.Methods Dose parameters were verified by using TLDs under reference and non-reference conditions,including the maximum dose in axel of 5 electron beams with energy of 9 MeV and the variations of dose by depth,source-skin distance,exposure field and 45° wedge for 10 photon beams with energy of 6 MV in 5 hospitals.Results The average relative deviation of 6 MV photon beam measured between TLDs and finger ionization chambers were 4.45％,within ± 7％ as required by IAEA.The average relative deviation of 9 MeV electron beam measured between TLDs and plane parallel chambers were 2.45％,within ± 5％ was required by IAEA.Conclusions Measuring dosimetric parameters by using TLDs under reference and non-reference conditions was reliable and feasible.