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Expression and clinical implication of PRL-1 and PRL-3 in transitional cell carcinoma of bladder

Bin HAO, Changwei LIU, Huixiang LI

《医学前沿（英文）》 2009年第3卷第2期页码 197-203 doi: 10.1007/s11684-009-0036-3

摘要： The mRNA and protein expression of phosphatase of regenerating liver 1 (PRL-1) and phosphatase of regenerating liver 3 (PRL-3) in transitional cell carcinoma of bladder (BTCC) and normal epithelia of bladder was investigated, and the relationship between the BTCC and pathological changes was clarified. The expression of PRL-1 and PRL-3 mRNA was detected by using reverse transcription polymerase chain reaction (RT-PCR) in 30 cases of BTCC and 10 cases of normal bladder, and the expression of PRL-1 and PRL-3 protein was checked by using immunohistochemistry in 30 cases of BTCC and 15 cases of normal bladder. The expression levels of PRL-1 and PRL-3 mRNA and protein were higher in BTCC than those in normal bladder epithelia ( <0.05). The increased expression of PRL-1 and PRL-3 mRNA and protein was detectable in deep invasion and metastasis of BTCC ( <0.05). There was no correlation between the expression of PRL-1 and PRL-3 and gender, age or recurrence of BTCC (all >0.05). A significantly positive correlation was found between PRL-1 and PRL-3 in BTCC ( <0.05). PRL-1 and PRL-3 are expressed consistently and may contribute to the growth, differentiation, invasion and metastasis of BTCC.

关键词： transitional cell carcinoma of bladder phosphatase of regenerating liver 1 phosphatase of regenerating liver 3 reverse transcription polymerase chain reaction immunohistochemistry

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Protein phosphatase magnesium-dependent 1δ is a novel tumor marker and target in hepatocellular carcinoma

null

《医学前沿（英文）》 2016年第10卷第1期页码 52-60 doi: 10.1007/s11684-016-0433-3

摘要：

Hepatocellular carcinoma (HCC) is a lethal liver malignancy worldwide. In this study, we reported that protein phosphatase magnesium-dependent 1δ (PPM1D) was highly expressed in the majority of HCC cases (approximately 59%) and significantly associated with high serum α-fetoprotein (AFP) level (P= 0.044). Kaplan-Meier and Cox regression data indicated that PPM1D overexpression was an independent predictor of HCC-specific overall survival (HR, 2.799; 95% CI, 1.346–5.818, P = 0.006). Overexpressing PPM1D promoted cell viability and invasion, whereas RNA interference-mediated knockdown of PPM1D inhibited proliferation, invasion, and migration of cultured HCC cells. In addition, PPM1D suppression by small interfering RNA decreased the tumorigenicity of HCC cells in vivo. Overall, results suggest that PPM1D is a potential prognostic marker and therapeutic target for HCC.

关键词： PPM1D hepatocellular carcinoma prognosis target therapy

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Loss of liver kinase B1 causes planar polarity defects in cochlear hair cells in mice

null

《医学前沿（英文）》 2016年第10卷第4期页码 481-489 doi: 10.1007/s11684-016-0494-3

摘要：

The tumor suppressor gene liver kinase B1 (LKB1), also called STK11, encodes a serine/threonine kinase. LKB1 plays crucial roles in cell differentiation, proliferation, and polarity. In this study, LKB1 conditional knockout mice (LKB1^Pax2 CKO mice) were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1^Pax2 CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1^Pax2 CKO mice were clustered and misoriented, respectively. Moreover, ectopic distribution of kinocilium bundles resulting from abnormal migration of kinocilium was observed in the mutant mice. The orientation of stereociliary bundles and the migration of kinocilia are critical indicators of planar cell polarity (PCP) of hair cells. LKB1 deficiency in LKB1^Pax2 CKO mice thus disrupted hair cell planar polarity during embryonic development. Our results suggest that LKB1 is required in PCP formation in cochlear hair cells in mice.

关键词： LKB1 stereociliary bundles kinocilium planar cell polarity hearing mice

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Protein phosphatase 2A, a key player in Alzheimer’s disease

Rong LIU, Qing TIAN

《医学前沿（英文）》 2009年第3卷第1期页码 8-12 doi: 10.1007/s11684-009-0017-6

摘要： Protein phosphatase 2A (PP2A) is the predominant serine/threonine phosphatase in eukaryotic cells. In the brains of patients with Alzheimer’s disease (AD), decreased PP2A activities were observed, which is suggested to be involved in neurofibrillary tangle (NFT) formation, disturbed amyloid precursor protein (APP) secretion and neurodegeneration in AD brain. Based on our research and other previous findings, decreased PP2Ac level, decreased PP2A holoenzyme composition, increased level of PP2A inhibitors, increased PP2Ac Leu309 demethylation and Tyr307 phosphorylation underlie PP2A inactivation in AD. β-amyloid (Aβ) over-production, estrogen deficiency and impaired homocysteine metabolism are the possible up-stream factors that inactivate PP2A in AD neurons. Further studies are required to disclose the role of PP2A in Alzheimer’s disease.

关键词： protein phosphatase 2A Alzheimer’s disease holoenzyme composition protein phosphatase 2A inhibitors Leu309 demethylation Tyr307 phosphorylation

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Effects of parenteral nutrition with and without GH on the GH/IGF-1 axis after hepatectomy in hepatocellularcarcinoma with liver cirrhosis

CAO Jie, LUO Shimin, LIANG Lijian, LAI Jiaming, CHEN Shanming

《医学前沿（英文）》 2007年第1卷第3期页码 287-293 doi: 10.1007/s11684-007-0055-x

摘要： Postoperative hepatic insulin-like growth factor-1 (IGF-1) production may be severely disturbed in patients with liver cirrhosis. Complex alterations in the GH/IGF-1 axis are thought to play an important role in the protein catabolism that complicates major surgical procedures. The aim of this study was to explore the effects of parenteral nutrition (PN) with and without growth hormone (GH) on the GH/IGF-1 axis after hepatectomy for hepatocellular carcinoma (HCC) with cirrhosis and evaluate the potential roles of recombinant human GH (rhGH) therapy. Twenty-four patients with HCC with cirrhosis who underwent hepatectomy were randomly divided into two groups: a PN group ( = 12) and an rhGH+PN group ( = 12). Liver function, serum GH, IGF-1 and IGFBP-3 were measured before the operation and at postoperative days (POD) 1 and 6. Insulin-like growth factor-1 and IGFBP-3 mRNA in the liver tissue was detected by RT-PCR. The liver Ki67 immunohistochemistry staining was studied. At the same time, 12 patients with cholelithiasis or liver hemangioma who underwent operation served as normal control group. On POD 6, serum prealbumin, GH, IGF-1, IGFBP-3, hepatic IGF-1 mRNA, IGFBP-3 mRNA and liver Ki67 LI were higher in the rhGH+PN group than in the PN group. There was no significant difference in the 6- and 12-month tumor-free survival rate and the median tumor-free survival time between the PN group and the rhGH+PN group (〉0.05). These data indicate that rhGH+PN could ameliorate the changes in the GH/IGF-1 axis after hepatectomy for HCC in the setting of cirrhosis.

关键词： control function production surgical Complex

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Measurement of bone alkaline phosphatase and relative study with osteosarcoma

YANG Zhiping, LI Jianmin, LI Xin, HUO Yanqing, SUN Guangzhi

《医学前沿（英文）》 2007年第1卷第1期页码 54-57 doi: 10.1007/s11684-007-0011-9

摘要： The objective of this paper is to explore the value of bone alkaline phosphatase (BALP) for diagnosing osteosarcoma, evaluating the effect of the chemotherapy, judging the prognosis and supervising the relapse and metastasis. The immunoassay was used to check the BALP of the blood serum that was from 42 primary osteosarcoma patients. Alkaline phosphatase (ALP) in blood serum was checked with auto biochemistry equipment. The biopsy tissue and the lesion resected in operation were treated with pathology and histological response was counted. The patients were followed up from five months to 49 months with an average of 24.3 months. Eighteen cases relapsed and transferred, among which, 16 of them were dead, and others were survival to the end of the follow-up. BALP was more sensitive than ALP in diagnosing osteosarcoma ( = 0.015). Fifteen cases decreased to normal value in ALP after preoperative chemotherapy, and 34 cases decreased in BALP. Both ALP and BALP in all cases decreased to normal value in postoperative. There was significant difference in positive correlation between the decrease of BALP and the increase of histological response ( = 0.001, = 0.642). In the followup, there was significant difference in BALP between the group of relapse and transfer and the group of free disease survival ( = 0.000). As a check marker in blood serum, BALP, reflecting the process of ossification, has a higher sensitivity than ALP. It has applied value in the diagnosis of osteosarcoma, reflection of the effect of chemotherapy and forecast the prognosis.

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Rdh13 deficiency weakens carbon tetrachloride-induced liver injury by regulating Spot14 and Cyp2e1 expression

Xiaofang Cui, Benting Ma, Yan Wang, Yan Chen, Chunling Shen, Ying Kuang, Jian Fei, Lungen Lu, Zhugang Wang

《医学前沿（英文）》 2019年第13卷第1期页码 104-111 doi: 10.1007/s11684-017-0568-x

摘要： Mitochondrion-localized retinol dehydrogenase 13 (Rdh13) is a short-chain dehydrogenase/reductase involved in vitamin A metabolism in both humans and mice. We previously generated knockout mice and showed that Rdh13 deficiency causes severe acute retinal light damage. In this study, considering that Rdh13 is highly expressed in mouse liver, we further evaluated the potential effect of Rdh13 on liver injury induced by carbon tetrachloride (CCl ). Although Rdh13 deficiency showed no significant effect on liver histology and physiological functions under regular culture, the mice displayed an attenuated response to CCl -induced liver injury. Their livers also exhibited less histological changes and contained lower levels of liver-related metabolism enzymes compared with the livers of wild-type (WT) mice. Furthermore, the mice had Rdh13 deficiency and thus their liver cells were protected from apoptosis, and the quantity of their proliferative cells became lower than that in WT after CCl exposure. The ablation of gene decreased the expression levels of thyroid hormone-inducible nuclear protein 14 (Spot14) and cytochrome P450 (Cyp2e1) in the liver, especially after CCl treatment for 48 h. These data suggested that the alleviated liver damage induced by CCl in mice was caused by Cyp2e1 enzymes, which promoted reductive CCl metabolism by altering the status of thyroxine metabolism. This result further implicated Rdh13 as a potential drug target in preventing chemically induced liver injury.

关键词： retinol dehydrogenase 13 carbon tetrachloride acute liver injury Cyp2e1 Spot14

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Expression of integrin in hepatic fibrosis and intervention of resveratrol

Jianye WU, Chuanyong GUO, Jun LIU, Xuanfu XUAN

《医学前沿（英文）》 2009年第3卷第1期页码 100-107 doi: 10.1007/s11684-009-0013-x

摘要： The aim of this study was to explore the expression of integrin-β1 in different stages of hepatic fibrosis and intervention of resveratrol as well as the way by which integrin-β1 promoted hepatic fibrosis. Hepatic fibrosis models of male Sprague Dawley (SD) rats were created and intragastric administration of resveratrol was given in low (40 mg/kg), middle (120 mg/kg) and high (200 mg/kg) dose groups. The expression of integrin-β1, tumor growth factor-β (TGF-β) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in different stages of hepatic fibrosis was detected by using RT-PCR. The expression of hexadecenoic acid (HA) and precollagen III (pc III) was assayed by radioimmunoassay. The expression of integrin-β1, TGF-β and TIMP-1 was determined in each group. Liver function and pathological sections of each group in different stages of hepatic fibrosis was tested to judge the therapeutic efficacy of resveratrol at different doses. The expression of integrin-β1 in normal control group was low and steady and was not increased as the development of hepatic fibrosis, but it is increased in other groups. The expression levels of integrin-β1 in the model control group (0.878±0.03, <0.01) and low dose group (0.855±0.04, <0.01) were higher than other groups, but there was no difference between model control group and low dose group ( >0.05). The expression levels of integrin-β1 and TGF-β in middle dose group and high dose group were higher than other groups ( <0.01). The expression levels of integrin-β1 and TGF-β in model control group and low dose group were lower than the normal control group ( <0.01). The expression levels of TIMP-1 in the model control and low dose groups were higher than the other groups ( <0.01). The expression levels of TIMP-1 in the middle dose group and the high dose group were lower than the normal control group ( <0.01). The expression of integrin-β1 existed in all stages of hepatic fibrosis of SD rats, and it was increased as the development of hepatic fibrosis. The expression of TGF-β and TIMP-1 was consistent with that of integrin-β1 in different stages of hepatic fibrosis. Resveratrol could improve the degree of hepatic fibrosis of SD rats and decrease the expression of integrin-β1 markedly at a dose of 120 mg/kg.

关键词： liver fibrosis integrin-β1 resveratrol tumor growth factor-β tissue inhibitor of metalloproteinase-1

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Partial liver transplantation

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《医学前沿（英文）》 2011年第5卷第1期页码 1-7 doi: 10.1007/s11684-010-0105-7

摘要：

Partial liver transplantation, including reduced-size liver transplantation, split liver transplantation, and living donor liver transplantation, has been developed with several innovative techniques because of donor shortage. Reduced-size liver transplantation is based on Couinaud’s anatomical classification, benefiting children and small adult recipients but failing to relieve the overall donor shortage. Split liver transplantation provides chances to two or even more recipients when only one liver graft is available. The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situto ensure long-term quality. The first and most important issue involving living donor liver transplantation is donor safety. Before surgery, a series of donor evaluations—including anatomical, liver volume, and liver function evaluations—is indispensable, followed by ethnic agreement. At different recipient conditions, auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation, which employ piggyback techniques, are good alternatives. Partial liver transplantation enriches the practice and knowledge of the transplant society.

关键词： partial liver transplantation reduced-size liver transplantation split liver transplantation living donor liver transplantation

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γδ T cells in liver diseases

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《医学前沿（英文）》 2018年第12卷第3期页码 262-268 doi: 10.1007/s11684-017-0584-x

摘要：

γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and liver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.

关键词： γδT cells liver infection non-alcoholic fatty liver disease autoimmune hepatitis liver fibrosis and cirrhosis liver cancer liver regeneration

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利用CES1和DPP-IV的组织残余活性准确评估和追踪特异性肝损伤过程 Article

潘秋莎, 宋培放, 倪振华, 钱星凯, 王安琪, 邹立伟, 刘勇, 王平, 张卫东, 马红, 杨凌

《工程（英文）》 2022年第19卷第12期页码 153-165 doi: 10.1016/j.eng.2021.09.014

摘要：研究发现羧酸酯酶1（CES1）作为肝内标志物和二肽基肽酶4（DPP-IV）作为肝外标志物可反映肝脏损伤的不同病理生理状态。CES1 和DPP-IV 水平可甄别肝损伤本身和炎症损伤之间的差异。尽管血清与组织中γ-谷氨酰基转肽酶（γ-GT）升降水平的变化方向相反，但其持续时间远短于CES1，并迅速恢复到正常水平。在上述生物标志物中，只有CES1 能够明确排除炎症干扰下的肝细胞损伤。CES1 还能准确评估熊去氧胆酸（UDCA；单成分药物）和清肺排毒汤（QFPDD；多组分药物）的抗胆汁淤积作用。本文数据强调了联合使用CES1（作为肝内肝损伤标志物）和DPP-IV（作为肝外炎症作用标志物）可准确评估和追踪特异性肝损伤，并可区分肝损伤和炎症性肝损伤的差异。

关键词：羧酸酯酶1 二肽基肽酶4 特异性肝脏损伤标志物来源追溯

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Influence of β-elemene on the secretion of angiotensin II and expression of AT1R in hepatic stellate

Ling YANG, Rui ZHU, Qingjing ZHU, Dan DAN, Jin YE, Keshu XU, Xiaohua HOU

《医学前沿（英文）》 2009年第3卷第1期页码 36-40 doi: 10.1007/s11684-009-0020-y

摘要： This study aims to investigate the influence of β-elemene on the secretion of angiotensin II (ANG II) and the expression of angiotensin receptor type 1 (AT1R) in hepatic stellate cells (HSCs). , HSC-T6 were cultured for 24 hours and then treated with different doses of β-elemene (2.5, 5 and 10 mg/L). A control group was also set up. The secretion of ANG II in the supernatant was detected by radioimmunoassay. The mRNA expression of AT1R at 4, 12 and 24 h after treatment was detected by reverse transcription-polymerase chain reaction (RT-PCR), respectively. The protein expression of AT1R was detected by western blot. At the 4th h, the ANG II secretion in the supernatant was significantly inhibited by 10 mg/L β-elemene compared with the control group ( <0.05), while 5.0 mg/L and 2.5 mg/L β-elemene had no inhibitory effect on the secretion of ANG II ( >0.05). At the time point of the 12th h, the secretion of ANG II in the supernatant treated with 10 mg/L and 5.0 mg/L β-elemene was significantly lower than the control ( <0.01, <0.05). Following the treatment with 5.0 mg/L and 2.5 mg/L β-elemene for 24 h, significant inhibition of ANG II secretion was observed ( <0.05), but 10 mg/L β-elemene had no such effect. β-elemene significantly reduced the amount of AT1R mRNA in HSCs after the treatment for 4, 12, and 24 h in a dose-dependent manner. The expression of AT1R protein also decreased after the treatment with β-elemene for 24 h. β-elemene can inhibit the secretion of ANG II and the gene and protein expression of AT1R, which may be the mechanism by which β-elemene prevents the progress of hepatic fibrosis.

关键词： liver cirrhosis beta-elemene hepatic stellate cells angiotensin II receptor angiotensin type 1

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Effect of inhibiting tyrosine kinase Src expression on protein phosphatase 2A and tau phosphorylation

LIU Rong, ZENG Ji, ZHOU Xinwen, WANG Jianzhi, PEI Jinjing

《医学前沿（英文）》 2008年第2卷第3期页码 235-238 doi: 10.1007/s11684-008-0044-8

摘要： The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307) phosphorylation, protein phosphatase 2A (PP2A) activity, and on tau phosphorylation. Specific Src siRNA was transfected into cultured mouse neuroblastoma N2a cells to inhibit the expression of Src protein, and the phosphorylation levels of PP2A Y307 and tau at different sites, as well as PP2A activity were detected at different time points after siRNA transfection. Twelve hours after siRNA transfection, the protein level of Src was dramatically decreased, with decreased PP2A Y307 phosphorylation. However, the total PP2A protein level was also decreased, together with a decreased PP2A activity. Tau was hyperphosphorylated at the Ser198/199/202 sites. Multiple factors may be involved in the cellular regulation of PP2A activity. Inhibiting Src expression could induce inactivation of PP2A and tau hyperphosphorylation.

关键词： hyperphosphorylation PP2A activity cellular regulation siRNA siRNA transfection

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NKT cells in liver diseases

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《医学前沿（英文）》 2018年第12卷第3期页码 249-261 doi: 10.1007/s11684-018-0622-3

摘要：

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.

关键词： natural killer T cells hepatitis B virus and hepatitis C virus infection autoimmune liver diseases alcoholic liver disease nonalcoholic fatty liver disease hepatocellular carcinoma

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Natural killer cells in liver diseases

null

《医学前沿（英文）》 2018年第12卷第3期页码 269-279 doi: 10.1007/s11684-018-0621-4

摘要：

The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct “killer” functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.

关键词： natural killer cell phenotype immune activation immune tolerance liver diseases