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γδ T cells in liver diseases

null

《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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Correlation between viral load and liver cirrhosis in chronic hepatitis B patients

Lili LIU MM , Jiyao WANG MD , Weimin SHE MM ,

《医学前沿（英文）》 2009年第3卷第3期页码 271-276 doi: 10.1007/s11684-009-0054-1

摘要： The aim of this paper is to investigate the relationship between hepatitis B virus (HBV) DNA levels during the course and the progression to cirrhosis with chronic hepatitis B. A total of 239 chronic hepatitis B patients confirmed by liver biopsy between 2001 and 2007 were followed up for a median of 28 months. Compared with the patients without cirrhosis, the patients progressed to cirrhosis were older and with higher HBV-DNA levels at end point. However, there was no significant difference in cirrhosis progression between different HBV-DNA groups at baseline ( = 0.531). Kaplan-Meier analysis showed higher HBV-DNA level at endpoint had increasing risk of cirrhosis ( = 0.019). The results of Cox model indicated that HBV-DNA levels at endpoint, stage of fibrosis, negative hepatitis B e antigen, and γ-glutamyl transpeptidase at baseline were independent risk factors of cirrhosis. The relative risk ratios were 1.898, 1.918, 8.976, and 1.006, respectively. Progression to cirrhosis in chronic hepatitis B patients is correlated with HBV-DNA levels during follow-up.

关键词： hepatitis B chronic viral load liver cirrhosis

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Assessment of liver volume variation to evaluate liver function

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《医学前沿（英文）》 2012年第6卷第4期页码 421-427 doi: 10.1007/s11684-012-0223-5

摘要：

In order to assess the value of liver volumetry in cirrhosis and acute liver failure (ALF) patients, we explored the correlation between hepatic volume and severity of the hepatic diseases. The clinical data of 48 cirrhosis patients with 60 normal controls and 39 ALF patients were collected. Computed tomography-derived liver volume (CTLV) and body surface area (BSA) of normal controls were calculated to get a regression formula for standard liver volume (SLV) and BSA. Then CTLV and SLV of all patients were calculated and grouped by Child-Turcotte-Pugh classification for cirrhosis patients and assigned according to prognosis of ALF patients for further comparison. It turned out that the mean liver volume of the control group was 1 058±337 cm³. SLV was correlated with BSA according to the regression formula. The hepatic volume of cirrhosis patients in Child A, B level was not reduced, but in Child C level it was significantly reduced with the lowest liver volume index (CTLV/SLV). Likewise, in the death group of ALF patients, the volume index was significantly lower than that of the survival group. Based on volumetric study, we proposed an ROC (receiver operating characteristic) analysis to predict the prognosis of ALF patients that CTLV/SLV<83.9% indicates a poor prognosis. In conclusion, the CTLV/SLV ratio, which reflects liver volume variations, correlates well with the liver function and progression of cirrhosis and ALF. It is also a very useful marker for predicting the prognosis of ALF.

关键词： liver volume variation cirrhosis acute liver failure (ALF)

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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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肝硬化患者胃黏膜微生物菌群特征及其与胃肠道症状的相关性分析 Article

陈燕飞, 郭静, 陈春雷, 石鼎, 方戴琼, 季峰, 李兰娟

《工程（英文）》 2021年第7卷第4期页码 507-514 doi: 10.1016/j.eng.2020.04.014

摘要：

研究表明，肝硬化患者的口腔和肠道微生物群与健康人群存在差异。胃位于口腔和肠道之间，关于其黏膜微生物群结构所知甚少。本研究采用16S rRNA焦磷酸测序技术分析了肝硬化患者和对照组的胃黏膜微生物群。研究发现，组织学和测序法均证实肝硬化患者幽门螺杆菌感染率显著降低。在幽门螺杆菌阴性人群中，可以按细菌组成结构将胃黏膜微生物群分为4个聚类，其中聚类1和2主要是肝硬化患者，聚类3主要是健康人群，而聚类4中肝硬化患者和健康人群各占一半左右。这些不同聚类间的成分和功能存在显著差异。在属的水平上，聚类1和2分别富集奈瑟菌和链球菌。在功能基因分类上，相对而言，聚类2缺乏涉及遗传信息处理以及与聚糖生物合成和代谢相关的功能基因。胃黏膜菌群结构表现为聚类2的患者胃肠道症状更严重，既往内镜下曲张静脉的治疗率显著高于其他组。我们的研究结果表明，在肝硬化中，幽门螺杆菌和非幽门螺杆菌的定植都受到影响。虽然幽门螺杆菌阴性的胃黏膜微生物结构表现出相当大的异质性，但特定的胃微生物群与临床特征之间仍然存在相关性。既往内镜下静脉曲张治疗会引起胃黏膜菌群结构明显改变，从而加重幽门螺杆菌阴性肝硬化患者的胃肠道症状。

关键词：微生物组肝硬化症状静脉曲张胃镜

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血清N-聚糖生物标志物诊断ALT水平正常慢性乙型肝炎患者显著肝纤维化和肝硬化的临床意义 Article

王林, 刘艺琪, 顾启馨, 张驰, 徐蕾, 王蕾, 陈翠英, 刘学恩, 赵鸿, 庄辉

《工程（英文）》 2023年第26卷第7期页码 151-158 doi: 10.1016/j.eng.2023.03.008

摘要：血清N-聚糖模型（RF-A和RF-B）的诊断效能优于肝硬度值测量（liver stiffness measurement, LSM）、基于4因子的纤维化指数（fibrosis index

关键词：肝纤维化慢性乙型肝炎血清N-聚糖 N-聚糖模型丙氨酸转移酶

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New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse

《医学前沿（英文）》 2022年第16卷第5期页码 714-722 doi: 10.1007/s11684-021-0888-8

摘要： A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01–1.55) and 1.35 (95% CI 1.07–1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07–2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.

关键词： metabolic dysfunction-associated fatty liver disease non-alcoholic fatty liver disease fibrosis score brachial-ankle pulse wave velocity albuminuria

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beta-elemene on the levels of plasma endotoxin, serum TNF-alpha, and hepatic CD14 expression in rats with liverfibrosis

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《医学前沿（英文）》 2011年第5卷第1期页码 101-105 doi: 10.1007/s11684-011-0111-4

摘要：

It has been demonstrated that β-elemene could protect against carbon tetrachloride (CCl₄)-induced liver fibrosis in our laboratory work, and the aim of this paper is to reveal the protective mechanisms of β-elemene. The hepatic fibrosis experimental model was induced by the hypodermical injection of CCl₄ in Wistar male rats. β-elemene was intraperitoneally administered into rats for 8 weeks (0.1 mL/100 g bodyweight per day), and plasma endotoxin content was assayed by biochemistry. The serum TNF-α level was detected using radioactive immunity. CD14 expression in rat livers was measured by immunohistochemistry and Western blot. The results showed that β-elemene can downregulate the levels of plasma endotoxins, serum TNF-α, and hepatic CD14 expression in rats with liver fibrosis. β-elemene plays an important role in downregulating the lipopolysaccharide signal transduction pathway, a significant pathway in hepatic fibrosis development.

关键词： liver fibrosis beta-elemene endotoxin CD14

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自体骨髓干细胞移植与归元方联用治疗急慢性肝损伤实验研究

吴理茂,李连达,刘红,宁可永,李贻奎

《中国工程科学》 2004年第6卷第7期页码 34-42

摘要：

研究中药归元方与自体骨髓干细胞移植对急慢性肝损伤的治疗作用。研究方法：用肝脏局部注射乙醇的方法复制急性局限性肝损伤模型，复合因素（CCl₄、乙醇、高脂、低蛋白）刺激复制大鼠肝纤维化模型，通过定量组织学、肝功能检查、免疫组化、肝组织羟脯氨酸含量、损伤或纤维区骨髓干细胞观察等综合评价中药、自体骨髓干细胞移植及两者合用的疗效。结果：归元方与自体骨髓干细胞移植可减小肝损伤区域，改善肝功能，使纤维肝组织表达μPA增强，降低血清ALT，AST，PCⅢ，HA和肝组织羟脯氨酸的含量，改善肝组织肝纤维化评分，骨髓干细胞能在肝损伤、肝纤维化形成环境中存活、增殖，并向肝细胞分化，表达肝脏特异的角蛋白CK18。结论：归元方与自体骨髓干细胞移植对急慢性肝损伤有明确的治疗作用，两者合用可优势互补，协同增效。临床上有良好的应用前景。

关键词：归元方骨髓干细胞自体移植肝损伤肝纤维化

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

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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Strategies for preventing peritoneal fibrosis in peritoneal dialysis patients: new insights based on

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《医学前沿（英文）》 2017年第11卷第3期页码 349-358 doi: 10.1007/s11684-017-0571-2

摘要：

Peritoneal dialysis (PD) is an established form of renal replacement therapy. Long-term PD leads to morphologic and functional changes to the peritoneal membrane (PM), which is defined as peritoneal fibrosis, a known cause of loss of peritoneal ultrafiltration capacity. Inflammation and angiogenesis are key events during the pathogenesis of peritoneal fibrosis. This review discusses the pathophysiology of peritoneal fibrosis and recent research progress on key fibrogenic molecular mechanisms in peritoneal inflammation and angiogenesis, including Toll-like receptor ligand-mediated, NOD-like receptor protein 3/interleukin-1β, vascular endothelial growth factor, and angiopoietin-2/Tie2 signaling pathways. Furthermore, novel strategies targeting peritoneal inflammation and angiogenesis to preserve the PM are discussed in depth.

关键词： peritoneal dialysis peritoneal fibrosis inflammation angiogenesis

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Chronic inhibition of cyclic guanosine monophosphate-specific phosphodiesterase 5 prevented cardiac fibrosis

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《医学前沿（英文）》 2014年第8卷第4期页码 445-455 doi: 10.1007/s11684-014-0378-3

摘要：

Recent evidences suggested that cyclic guanosine monophosphate-specific phosphodiesterase 5 (PDE5) inhibitor represents an important therapeutic target for cardiovascular diseases. Whether and how it ameliorates cardiac fibrosis, a major cause of diastolic dysfunction and heart failure, is unknown. The purpose of this study was to investigate the effects of PDE5 inhibitor on cardiac fibrosis. We assessed cardiac fibrosis and pathology in mice subjected to transverse aortic constriction (TAC). Oral sildenafil, a PDE5 inhibitor, was administered in the therapy group. In control mice, 4 weeks of TAC induced significant cardiac dysfunction, cardiac fibrosis, and cardiac fibroblast activation (proliferation and transformation to myofibroblasts). Sildenafil treatment markedly prevented TAC-induced cardiac dysfunction, cardiac fibrosis and cardiac fibroblast activation but did not block TAC-induced transforming growth factor-β1 (TGF-β1) production and phosphorylation of Smad2/3. In isolated cardiac fibroblasts, sildenafil blocked TGF-β1-induced cardiac fibroblast transformation, proliferation and collagen synthesis. Furthermore, we found that sildenafil induced phosphorylated cAMP response element binding protein (CREB) and reduced CREB-binding protein 1 (CBP1) recruitment to Smad transcriptional complexes. PDE5 inhibition prevents cardiac fibrosis by reducing CBP1 recruitment to Smad transcriptional complexes through CREB activation in cardiac fibroblasts.

关键词： PDE5 cardiac fibrosis TGF-β CREB

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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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Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants

Liru Qiu, Fengjie Yang, Yonghua He, Huiqing Yuan, Jianhua Zhou

《医学前沿（英文）》 2018年第12卷第5期页码 550-558 doi: 10.1007/s11684-017-0567-y

摘要：

Cystic fibrosis (CF) is a fatal autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by recurrent pulmonary infection with obstructive pulmonary disease. CF is common in the Caucasian population but is rare in the Chinese population. The symptoms of early-stage CF are often untypical and may sometimes manifest as Bartter syndrome (BS)-like hypokalemic alkalosis. Therefore, the ability of doctors to differentiate CF from BS-like hypokalemic alkalosis in Chinese infants is a great challenge in the timely and accurate diagnosis of CF. In China, sporadic CF has not been diagnosed in children younger than three years of age to date. Three infants, who were initially admitted to our hospital over the period of June 2013 to September 2014 with BS-like hypokalemic alkalosis, were diagnosed with CF through exome sequencing and sweat chloride measurement. The compound heterozygous mutations of the CFTR gene were detected in two infants, and a homozygous missense mutation was found in one infant. Among the six identified mutations, two are novel point mutations (c.1526G>C and c.3062C>T) that are possibly pathogenic. The three infants are the youngest Chinese patients to have been diagnosed with sporadic CF at a very early stage. Follow-up examination showed that all of the cases remained symptom-free after early intervention, indicating the potential benefit of very early diagnosis and timely intervention in children with CF. Our results demonstrate the necessity of distinguishing CF from BS in Chinese infants with hypokalemic alkalosis and the significant diagnostic value of powerful exome sequencing for rare genetic diseases. Furthermore, our findings expand the CFTR mutation spectrum associated with CF.

关键词： cystic fibrosis pseudo-Bartter syndrome hypokalemic alkalosis CFTR gene mutations infants diagnosis

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Observation on therapeutic efficacy of ursodeoxycholic acid in Chinese patients with primary biliary cirrhosis

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《医学前沿（英文）》 2013年第7卷第2期页码 255-263 doi: 10.1007/s11684-012-0227-1

摘要：

The efficacy of ursodeoxycholic acid (UDCA) on long-term outcome of primary biliary cirrhosis (PBC) has been less documented in Chinese cohort. We aimed to assess the therapeutic effect of UDCA on Chinese patients with PBC. In the present study, 67 patients with PBC were treated with UDCA (13–15 mg?kg^-1?day^-1) and followed up for 2 years to evaluate the changes of symptoms, laboratory values and histological features. As the results indicated, fatigue and pruritus were obviously improved by UDCA, particularly in patients with mild or moderate symptoms. The alkaline phosphatase and γ-glutamyl transpetidase levels significantly declined at year 2 comparing to baseline values, with the most profound effects achieved in patients at stage 2. The levels of alanine aminotransferase and aspartate aminotransferase significantly decreased whereas serum bilirubin and immunoglobulin M levels exhibited no significant change. Histological feature was stable in patients at stages 1–2 but still progressed in patients at stages 3–4. The biochemical response of patients at stage 2 was much better than that of patients at stages 3–4. These data suggest that, when treated in earlier stage, patients in long-term administration of UDCA can gain favorable results not only on symptoms and biochemical responses but also on histology. It is also indicated that later histological stage, bad biochemical response and severe symptom may be indicators of poor prognosis for UDCA therapy.

关键词： primary biliary cirrhosis ursodeoxycholic acid Chinese biochemical response therapeutic efficacy