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Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check

Amy Lee, Fa-Chyi Lee

《医学前沿（英文）》 2020年 第14卷 第3期   页码 273-283 doi: 10.1007/s11684-019-0728-2

摘要： In terms of global cancer-related deaths, hepatocellular carcinoma (HCC) has the fourth highest mortality rate. Up until 2017, treatment of advanced HCC was largely limited to sorafenib, an oral tyrosine kinase inhibitor, with little to no success in the development of alternative treatment options. However, in the past two years, there has been an unprecedented increase in both the number and type of treatment options available for HCC. As of 2019, the US FDA has approved four oral tyrosine kinase inhibitors, two immune checkpoint inhibitors, and one anti-angiogenesis antibody for the treatment of HCC. Even with this new variety, systemic treatment of advanced HCC remains largely unsatisfactory, and the median survival rate stands at approximately one year. The expected breakthrough of using immune checkpoint inhibitors in advanced HCC did not materialize in 2019. The use of immune checkpoint inhibitors in conjunction with oral tyrosine kinase inhibitors or anti-angiogenesis medications is the current clinical research trend, the results of which are eagerly anticipated. Despite limited progress in survival, HCC research is currently experiencing a period of growth and innovation, and there is hope for significant advances in the treatment of advanced HCC as the field continues to develop.

关键词： hepatocellular carcinoma     tyrosine kinase inhibitor     check point inhibitor     anti-angiogenesis    

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Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease

Xiaojing Jiao, Dong Zhang, Quan Hong, Lei Yan, Qiuxia Han, Fengmin Shao, Guangyan Cai, Xiangmei Chen, Hanyu Zhu

《医学前沿（英文）》 2020年 第14卷 第3期   页码 293-304 doi: 10.1007/s11684-019-0715-7

摘要： Netrin-1, an axon guidance factor, and its receptor UNC5B play important roles in axonal development and angiogenesis. This study examined netrin-1 and UNC5B expression in kidneys with diabetic kidney disease (DKD) and investigated their roles in angiogenesis. Netrin-1 and UNC5B were upregulated in streptozotocin-induced DKD Wistar rats, and their expression was compared with that in healthy controls. However, exogenous netrin-1 in UNC5B-depleted human renal glomerular endothelial cells (HRGECs) inhibited cell migration and tubulogenesis. This effect was likely associated with SRC pathway deactivation. Netrin-1 treatment also eliminated the pro-angiogenic effects of exogenous VEGF-165 on UNC5B-silenced HRGECs. These results indicate that UNC5B antagonizes netrin-1 and that UNC5B upregulation contributes partly to enhancing angiogenesis in DKD. Therefore, introducing exogenous netrin-1 and depleting endogenous UNC5B are potential strategies for reducing the incidence of early angiogenesis and mitigating kidney injury in DKD.

关键词： netrin-1     VEGF-165     UNC5B     angiogenesis     diabetic kidney disease    

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Correlative investigation of copper/low-density polyethylene nanocomposite on the endometrial angiogenesis

LI Jianxiong, LIU Zilong, DUAN Yonggang, YU Jing, ZHU Changhong, LI Shuang, XIE Changsheng

《医学前沿（英文）》 2007年 第1卷 第4期   页码 401-404 doi: 10.1007/s11684-007-0078-3

摘要： The purpose of this study was to investigate the effects of copper/low-density polyethylene nanocomposite (nano-Cu/LDPE) on the endometrial angiogenesis in rats, and 100 sexual mature female SD rats were randomly divided into five groups: sham-operation groups (SO group, = 20), bulk copper groups (Cu group, = 20), LDPE groups ( = 20), nano-Cu/LDPE groups I ( = 20) and II ( = 20). The levels of angiopoietin-2 (Ang-2), its receptor (Tie-2) and CD34 of the rats endometria in each group were examined by using the S-P method of the immunohistochemistry 30 and 180 days after insertion, respectively. Compared with those in the SO group, the expression of Ang-2 and Tie-2 in all the experimental groups was obviously increased 30 days after insertion, and these parameters in nano-Cu/LDPE groups, except for Ang-2 level in nano-Cu/LDPE group II, were significantly lower in comparison with those in Cu group (<0.05). On the 180th day after insertion, Ang-2 and Tie-2 levels were still higher in Cu group and LDPE group, but there was no difference of Ang-2 and Tie-2 levels between nano-Cu/LDPE groups and the SO group (>0.05). Compared with those in the SO group, the significant increases in microvessel density (MVD) were observed on the 30th and the 180th day after the insertion of the bulk copper (<0.05). There was no significant difference in MVD counts before and after the insertion of nano-Cu/LDPE (>0.05). The results show that Nano-Cu/LDPE have slighter influence on the endometrial angiogenesis than bulk copper.

关键词： significant difference     female     endometrial angiogenesis     nano-Cu/LDPE     CD34    

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tumor-targeted delivery of tumstatin (54-132) significantly suppresses tumor growth in mouse model by inhibiting angiogenesis

《医学前沿（英文）》 2022年 第16卷 第6期   页码 873-882 doi: 10.1007/s11684-022-0925-2

摘要： Tumor growth is an angiogenesis-dependent process and accompanied by the formation of hypoxic areas. Tumstatin is a tumor-specific angiogenesis inhibitor that suppresses the proliferation and induces the apoptosis of tumorous vascular endothelial cells. VNP20009, an attenuated Salmonella typhimurium strain, preferentially accumulates in the hypoxic areas of solid tumors. In this study, a novel Salmonella-mediated targeted expression system of tumstatin (VNP-Tum5) was developed under the control of the hypoxia-induced J23100 promoter to obtain anti-tumor efficacy in mice. Treatment with VNP-Tum5 effectively suppressed tumor growth and prolonged survival in the mouse model of B16F10 melanoma. VNP-Tum5 exhibited a higher efficacy in inhibiting the proliferation and inducing the necrosis and apoptosis of B16F10 cells in vitro and in vivo compared with VNP (control). VNP-Tum5 significantly inhibited the proliferation and migration of mouse umbilical vascular endothelial cells to impede angiogenesis. VNP-Tum5 downregulated the expression of anti-vascular endothelial growth factor A, platelet endothelial cell adhesion molecule-1, phosphorylated phosphoinositide 3 kinase, and phosphorylated protein kinase B and upregulated the expression of cleaved-caspase 3 in tumor tissues. This study is the first to use tumstatin-transformed VNP20009 as a tumor-targeted system for treatment of melanoma by combining anti-tumor and anti-angiogenic effects.

关键词： Salmonella VNP20009     tumstatin     B16F10     melanoma     apoptosis     angiogenesis    

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The relationship between platelet-derived growth factor expression and angiogenesis/lymphangiogenesis

Guocheng LIU MD, Shouhua YANG MD, Zehua WANG MD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 447-451 doi: 10.1007/s11684-009-0082-x

摘要： This paper is aimed to examine if changes in platelet-derived growth factor (PDGF) expression at different stages of cervical cancer are related to the variation in blood vessel density (BVD) and lymphatic vessel density (LVD) to evaluate the relationship between PDGF expression and stages and metastasis of cervical cancer. Polymerase chain reaction (PCR) and RT-PCR were used to detect the expression levels of PDGF in 45 cervical cancer tissue samples (the experimental group). The samples were immunohistochemically stained with monoclonal antibodies D2-40 and CD34, and BVD and LVD were measured. The expressions of PDGF-A, -B, and- D were all higher in the experimental group than in the control group (<0.05); no significant difference was found in the expression of PDGF-C between the experimental group and the control group (>0.05). PDGF-A and -B expression was positively related with BVD and LVD (<0.01, R= 0.49, 0.527, 0.327, 0.68). The expression levels of PDGF-C and -D were not significantly related with BVD and LVD. At the early stage of cervical cancer, BVD and LVD were significantly higher than in the controls (<0.01). The BVD and LVD in tissues in the surrounding areas of cervical cancer were significantly higher than in tissues at cancer center, and LVD was related to lymph node metastasis (<0.001). BVD and LVD were not associated with the differentiation and pathological stages of cervical cancer. The expressions of PDGF-A, -B, and -D in cervical cancer were closely related with the clinical stages of cervical cancer. PDGF-A and -B were intimately associated with the lymph node metastasis and prognosis of cervical cancer.

关键词： cervical cancer     lymphatic vessel density     blood vessel density     platelet-derived growth factor    

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QUANTITATIVE STUDY ON ANTI-PEST ACTIVITY OF NATURAL PRODUCTS BASED ON VISUALIZATION FRAMEWORK OF KNOWLEDGE

《农业科学与工程前沿（英文）》 2023年 第10卷 第2期   页码 306-332 doi: 10.15302/J-FASE-2023488

摘要：

● Using visual analysis to predict the trend of natural product pest resistance.

关键词： anti-pest activity     crop protection     insect pest     natural product     visual analysis    

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Dihydroartemisinin increased the abundance of by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD

《医学前沿（英文）》 2023年 第17卷 第4期   页码 729-746 doi: 10.1007/s11684-022-0978-2

摘要： The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8+ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

关键词： hepatocellular carcinoma     YAP1     Akkermansia muciniphila     anti-PD-1     dihydroartemisinin     bile acid    

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A modular cable-driven humanoid arm with anti-parallelogram mechanisms and Bowden cables

《机械工程前沿（英文）》 2023年 第18卷 第1期 doi: 10.1007/s11465-022-0722-2

摘要： This paper proposes a novel modular cable-driven humanoid arm with anti-parallelogram mechanisms (APMs) and Bowden cables. The lightweight arm realizes the advantage of joint independence and the rational layout of the driving units on the base. First, this paper analyzes the kinematic performance of the APM and uses the rolling motion between two ellipses to approximate a pure-circular-rolling motion. Then, a novel type of one-degree-of-freedom (1-DOF) elbow joint is proposed based on this principle, which is also applied to design the 3-DOF wrist and shoulder joints. Next, Bowden cables are used to connect the joints and their driving units to obtain a modular cable-driven arm with excellent joint independence. After that, both the forward and inverse kinematics of the entire arm are analyzed. Last, a humanoid arm prototype was developed, and the assembly velocity, joint motion performance, joint stiffness, load carrying, typical humanoid arm movements, and repeatability were tested to verify the arm performance.

关键词： modular robotic arm     anti-parallelogram mechanism     Bowden cable     humanoid arm     lightweight joint design    

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Anti-biofouling strategies for implantable biosensors of continuous glucose monitoring systems

《化学科学与工程前沿（英文）》 2023年 第17卷 第12期   页码 1866-1878 doi: 10.1007/s11705-023-2340-x

摘要： Continuous glucose monitoring (CGM) systems play an increasingly vital role in the glycemic control of patients with diabetes mellitus. However, the immune responses triggered by the implantation of poorly biocompatible sensors have a significant impact on the accuracy and lifetime of CGM systems. In this review, research efforts over the past few years to mitigate the immune responses by enhancing the anti-biofouling ability of sensors are summarized. This review divided these works into active immune engaging strategy and passive immune escape strategy based on their respective mechanisms. In each strategy, the various biocompatible layers on the biosensor surface, such as drug-releasing membranes, hydrogels, hydrophilic membranes, anti-biofouling membranes based on zwitterionic polymers, and bio-mimicking membranes, are described in detail. This review, therefore, provides researchers working on implantable biosensors for CGM systems with vital information, which is likely to aid in the research and development of novel CGM systems with profound anti-biofouling properties.

关键词： implantable glucose biosensor     anti-biofouling     continuous glucose monitoring     immune responses    

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Lignin-derived dual-function red light carbon dots for hypochlorite detection and anti-counterfeiting

《化学科学与工程前沿（英文）》 2023年 第17卷 第7期   页码 966-975 doi: 10.1007/s11705-022-2244-1

摘要： The efficient utilization of natural lignin, which is the main by-product of the cellulose industry, is crucial for enhancing its economic value, alleviating the environmental burden, and improving ecological security. By taking advantage of the large sp2 hybrid domain of lignin and introducing amino functional groups, new lignin-derived carbon dots (SPN-CDs) with red fluorescence were successfully synthesized. Compared with green and blue fluorescent materials, red SPN-CDs have desirable anti-interference properties of short-wave background and exhibit superior luminescence stability. The SPN-CDs obtained exhibited sensitive and distinctive visible color with fluorescence-dual responses toward hypochlorite. Considering this feature, a portable, low-cost, and sensitive fluorescence sensing paper with a low limit of detection of 0.249 μmol∙L–1 was fabricated using the SPN-CDs for hypochlorite detection. Furthermore, a new type of visible-light and fluorescence dual-channel information encryption platform was constructed. Low-concentration hypochlorite can be employed as an accessible and efficient information encryption/decryption stimulus, as well as an information “eraser”, facilitating a safe and diversified transmission and convenient decryption of information. This work opens new avenues for high-value-added applications of lignin-based fluorescent materials.

关键词： alkali lignin     red light carbon dots     hypochlorite     encryption and anti-counterfeiting    

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Modulatory effect on dyslipidemia and anti-atherosclerotic function of in newly diagnosed type 2 diabetes

SUN Mingxiao, WANG Yao, CHI Jiamin

《医学前沿（英文）》 2008年 第2卷 第2期   页码 174-177 doi: 10.1007/s11684-008-0032-z

摘要： The modulatory effect of on dyslipidemia and the preventive effect on atherosclerosis in newly diagnosed type 2 diabetic patients were studied. A prospective clinical trial was conducted to test the effectiveness of in selected 201 newly diagnosed type 2 diabetic patients. All patients were randomly divided into two groups: 108 with therapy and 93 without therapy. The mean follow-up period was 22 months. The blood glucose and blood pressure of all patients were under control. Serum levels of total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) were significantly lowered and their decreased percentages were significantly higher in therapy group ( < 0.05). The number of patients with arteria iliaca intima thickening was significantly lower in group of therapy ( = 0.024). With stepwise multivariate logistic regression analysis, the decreased percentage of TG was significantly and independently related with the decreased number of patients with arteria iliaca intima thickening ( = 0.005). The study demonstrates that therapy is effective on modulating dyslipidemia in newly diagnosed type 2 diabetes patients, and may be related with the improvement of early atherosclerosis.
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Preparation of reverse osmosis membrane with high permselectivity and anti-biofouling properties for

《环境科学与工程前沿（英文）》 2022年 第16卷 第7期 doi: 10.1007/s11783-021-1497-0

摘要：

• Nanoparticle incorporation and anti-biofouling grafting were integrated.

关键词： Anti-biofouling grafting     Nanoparticle incorporation     Sterilization rates     Water flux     Water flux recovery    

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Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

《医学前沿（英文）》 doi: 10.1007/s11684-023-1037-3

摘要： The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir–ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir–ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir–ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China’s homegrown anti-COVID-19 drugs.

关键词： COVID-19     antiviral drugs     mindeudesivir    

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Improved dissolution and anti-inflammatory effect of ibuprofen by solid dispersion

null

《医学前沿（英文）》 2012年 第6卷 第2期   页码 195-203 doi: 10.1007/s11684-012-0189-3

摘要：

The purpose of this study was to improve the dissolution rate and anti-inflammatory effect of ibuprofen by a solid dispersion (SD) method. Initial screening was developed based on drug solubility in carriers in the liquid state to select a suitable water-soluble carrier system for the preparation of SDs. The dissolution of ibuprofen in urea was higher than in PEG4000 or mannitol. Thus, urea was selected as the carrier for the preparation of SDs. SDs were characterized in terms of dissolution, differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. Solid dispersion-based (SDBT) and conventional (CT) tablets were prepared by the wet granulation method. The anti-inflammatory effect of SDBT was evaluated using the mouse ear edema test with xylene. In vitro release results indicated that the ibuprofen dissolution rate was improved by the SD. SD characterization results suggested that ibuprofen partly precipitates in crystalline and amorphous forms after SD preparation and that ibuprofen and urea do not interact. SDBT displayed more significant anti-inflammatory effects than CT. The dissolution rate and anti-inflammatory effect of ibuprofen were significantly enhanced by the ibuprofen-urea SD.

关键词： ibuprofen     solid dispersion     physical mixture     dissolution     anti-inflammatory effect    

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Mobile CRISPR-Cas9 based anti-phage system in E. coli

《化学科学与工程前沿（英文）》 2022年 第16卷 第8期   页码 1281-1289 doi: 10.1007/s11705-022-2141-7

摘要： Escherichia coli is one of the most important microbial cell factories, but infection by bacteriophages in the environment may have a huge impact on its application in industrial production. Here, we developed a mobile CRISPR-Cas9 based anti-phage system for bacteriophages defense in E. coli. Two conjugative plasmids pGM1 (phosphoglucomutase 1) and pGM2 carrying one and two guide RNAs, respectively, were designed to defend against a filamentous phage. The results showed that the pGM1 and pGM2 could decrease the phage infection rate to 1.6% and 0.2% respectively in infected cells. For preventing phage infection in E. coli, the pGM2 decreased the phage infection rate to 0.1%, while pGM1 failed to block phage infection. Sequence verification revealed that point mutations in protospacer or protospacer adjacent motif sequences of the phage genome caused loss of the defense function. These results support the potential application of MCBAS in E. coli cell factories to defend against phage infections.

关键词： phage infections     anti-phage     CRISPR-Cas9     conjugative transfer     synthetic biology    

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标题 作者 时间 类型 操作

Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check

Amy Lee, Fa-Chyi Lee

期刊论文

Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease

Xiaojing Jiao, Dong Zhang, Quan Hong, Lei Yan, Qiuxia Han, Fengmin Shao, Guangyan Cai, Xiangmei Chen, Hanyu Zhu

期刊论文

Correlative investigation of copper/low-density polyethylene nanocomposite on the endometrial angiogenesis

LI Jianxiong, LIU Zilong, DUAN Yonggang, YU Jing, ZHU Changhong, LI Shuang, XIE Changsheng

期刊论文

tumor-targeted delivery of tumstatin (54-132) significantly suppresses tumor growth in mouse model by inhibiting angiogenesis

期刊论文

The relationship between platelet-derived growth factor expression and angiogenesis/lymphangiogenesis

Guocheng LIU MD, Shouhua YANG MD, Zehua WANG MD,

期刊论文

QUANTITATIVE STUDY ON ANTI-PEST ACTIVITY OF NATURAL PRODUCTS BASED ON VISUALIZATION FRAMEWORK OF KNOWLEDGE

期刊论文

Dihydroartemisinin increased the abundance of by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD

期刊论文

A modular cable-driven humanoid arm with anti-parallelogram mechanisms and Bowden cables

期刊论文

Anti-biofouling strategies for implantable biosensors of continuous glucose monitoring systems

期刊论文

Lignin-derived dual-function red light carbon dots for hypochlorite detection and anti-counterfeiting

期刊论文

Modulatory effect on dyslipidemia and anti-atherosclerotic function of in newly diagnosed type 2 diabetes

SUN Mingxiao, WANG Yao, CHI Jiamin

期刊论文

Preparation of reverse osmosis membrane with high permselectivity and anti-biofouling properties for

期刊论文

Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

期刊论文

Improved dissolution and anti-inflammatory effect of ibuprofen by solid dispersion

null

期刊论文

Mobile CRISPR-Cas9 based anti-phage system in E. coli

期刊论文