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131I标记的人源化抗B7-H3抗体用于胶质母细胞瘤放射免疫疗法的治疗特性 Article

傅丰庆, Meng Zheng, Shandong Zhao, Yan Wang, Minzhou Huang, Hanqing Chen, Ziyi Huang, Kaijie Zhang, 缪丽燕, 张学光

《工程（英文）》 2023年 第30卷 第11期   页码 190-202 doi: 10.1016/j.eng.2023.05.011

摘要：

B7 homolog 3 (B7-H3) has attracted much attention in glioblastoma (GBM) radioimmunotherapy (RIT) due to its abnormally high expression on tumor cells. In this study, we report that two specific humanized anti-human B7-H3 antibodies (hu4G4 and hu4H12) derived from mouse anti-human B7-H3 antibodies that were generated by computer-aided design and exclusively recognize membrane expression of B7-H3 by human glioma cells. Hu4G4 and hu4H12 were radiolabeled with 89Zr for RIT antibody screening. Micro-positron emission tomography (PET) imaging, biodistribution and pharmacokinetic (PK) analyses of 89Zr-labeled antibodies were performed in U87-xenografted models. 125I labelling of the antibodies for single-photon emission computed tomography (SPECT) imaging was also used to investigate the biological behavior of the antibodies in vivo. Furthermore, the pharmacodynamic (PD) of the 131Ilabeled antibodies were evaluated in U87-xenografted mice and GL261 Red-FLuc-B7-H3 in situ glioma tumor models. Micro-PET imaging and biodistribution analysis with a gamma counter showed that 89Zr-deferoxamine (DFO)-hu4G4 had higher tumor targeting performance with lower liver uptake than 89Zr-DFO (hu4H12, immunoglobulin G (IgG)). The biodistribution results of 125I-SPECT imaging were similar to those of 89Zr-PET imaging, though the biodistribution in long bone joints and the thyroid varied. The PD analysis results indicated that 131I-hu4G4 had an excellent therapeutic effect and high safety with no apparent toxicity. Interestingly, 131I-hu4G4 improved the tumor vasculature in tissues with higher expression of collagen type IV and platelet-derived growth factor receptor b (PDGFR-b) compared with control treatment, as determined by immunofluorescence (IF), which contributed to inhibiting tumor growth. Taken together, our data indicate that hu4G4 exhibits good tumor targeting and specificity, achieves low nonspecific concentrations in normal tissues, and has acceptable PK characteristics. 131I-hu4G4 also exerts effective antitumor effects with an ideal safety profile. Therefore, we expect hu4G4 to be an excellent antibody for the development of GBM RIT.

关键词： B7-H3     Radioimmunotherapy     Glioblastoma     Pharmacokinetics     Pharmacodynamics    

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Research progress on human infection with avian influenza H7N9

Xiaoxin Wu, Lanlan Xiao, Lanjuan Li

《医学前沿（英文）》 2020年 第14卷 第1期   页码 8-20 doi: 10.1007/s11684-020-0739-z

摘要： Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. Meanwhile, the H7N9 virus continues to accumulate mutations, and its affinity for the human respiratory epithelial sialic acid 2-6 receptor has increased. Therefore, a pandemic is still possible. In the past 6 years, we have accumulated rich experience in dealing with H7N9, especially in terms of virus tracing, epidemiological research, key site mutation monitoring, critical disease mechanisms, clinical treatment, and vaccine development. In the research fields above, significant progress has been made to effectively control the spread of the epidemic and reduce the fatality rate. To fully document the research progress concerning H7N9, we reviewed the clinical and epidemiological characteristics of H7N9, the key gene mutations of the virus, and H7N9 vaccine, thus providing a scientific basis for further monitoring and prevention of H7N9 influenza epidemics.

关键词： H7N9     pandemic     epidemiology     mutations     vaccine     influenza    

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Universal influenza virus vaccines: what can we learn from the human immune response following exposure to H7

null

《医学前沿（英文）》 2017年 第11卷 第4期   页码 471-479 doi: 10.1007/s11684-017-0602-z

摘要：

Several universal influenza virus vaccine candidates based on eliciting antibodies against the hemagglutinin stalk domain are in development. Typically, these vaccines induce responses that target group 1 or group 2 hemagglutinins with little to no cross-group reactivity and protection. Similarly, the majority of human anti-stalk monoclonal antibodies that have been isolated are directed against group 1 or group 2 hemagglutinins with very few that bind to hemagglutinins of both groups. Here we review what is known about the human humoral immune response to vaccination and infection with H7 subtype influenza viruses on a polyclonal and monoclonal level. It seems that unlike vaccination with H5 hemagglutinin, which induces antibody responses mostly restricted to the group 1 stalk domain, H7 exposure induces both group 2 and cross-group antibody responses. A better understanding of this phenomenon and the underlying mechanisms might help to develop future universal influenza virus vaccine candidates.

关键词： universal influenza virus vaccine     hemagglutinin stalk     H7N9    

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Compiling of comprehensive data of human infections with novel influenza A (H7N9) virus

null

《医学前沿（英文）》 2013年 第7卷 第3期   页码 275-276 doi: 10.1007/s11684-013-0285-z

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The first avian influenza A (H7N9) viral infection in humans in Zhejiang Province, China: a death report

null

《医学前沿（英文）》 2013年 第7卷 第3期   页码 333-344 doi: 10.1007/s11684-013-0275-1

摘要：

This study reports the first death caused by a novel avian influenza A (H7N9) virus in Zhejiang Province, China. The patient had chronic hepatitis B and history of exposure to poultry. The patient initially complained of diarrhea and influenza-like symptoms on March 7 and 14 respectively. The disease progressed to severe pneumonia, sustained hypoxia, and coagulation abnormalities. The patient died on March 27 because of respiratory failure, multiple organ failure, and disseminated intravascular coagulation without oseltamivir treatment. This H7N9 virus from Zhejiang is highly similar to isolates obtained from Shanghai, Jiangsu, Anhui, etc. Analysis of hemagglutinin, neuramidinase, and matrix genes indicated that the isolates share the same avian origin, have low virulence, and are sensitive to oseltamivir, but are resistant to adamantine. Only the isolate that caused the fatality exhibited substitution of Q226I in the HA gene, which indicates a potentially enhanced human affinity. The secondary transmission rate was 1.6% (2/125). Only two health workers presented with influenza-like symptoms, and they subsequently tested negative for H7N9 RNA. In conclusion, underlying disease, late diagnosis, and untimely antiviral treatment are possible high-risk factors for infections and death caused by the low-pathogenicity avian influenza A (H7N9). Person-to-person transmission of the H7N9 virus was not detected among close contacts, but such transmission should be investigated in the future. Expanding and enhancing surveillance will help in the early discovery and diagnosis of suspected cases, which will reduce the number of severe cases and deaths.

关键词： avian influenza A (H7N9) virus     epidemiology     contacts     person-to-person transmission    

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Novel variants in LAMA3 and COL7A1 and recurrent variant in KRT5 underlying epidermolysis bullosa in

《医学前沿（英文）》 2022年 第16卷 第5期   页码 808-814 doi: 10.1007/s11684-021-0878-x

摘要： Epidermolysis bullosa (EB) is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation. Here, we investigated five Chinese families with EB, and eight variants including a novel nonsense variant (c.47G>A, p.W16*) in LAMA3, a known recurrent variant (c.74C>T, p.P25L) in KRT5, 2 novel (c.2531T>A, p.V844E; c.6811_6814del, p.R2271fs) and 4 known (c.6187C>T, p.R2063W; c.7097G>A, p.G2366D; c.8569G>T, p.E2857*; c.3625_3635del, p.S1209fs) variants in COL7A1 were detected. Notably, this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay. Our study expands the mutation spectra of Chinese patients with EB.

关键词： epidermolysis bullosa     LAMA3     COL7A1     KRT5     Chinese families    

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RGS16 regulated by let-7c-5p promotes glioma progression by activating PI3K-AKT pathway

《医学前沿（英文）》 2023年 第17卷 第1期   页码 143-155 doi: 10.1007/s11684-022-0929-y

摘要： Gliomas are the most common central nervous system tumours; they are highly aggressive and have a poor prognosis. RGS16 belongs to the regulator of G-protein signalling (RGS) protein family, which plays an important role in promoting various cancers, such as breast cancer, pancreatic cancer, and colorectal cancer. Moreover, previous studies confirmed that let-7c-5p, a well-known microRNA, can act as a tumour suppressor to regulate the progression of various tumours by inhibiting the expression of its target genes. However, whether RGS16 can promote the progression of glioma and whether it is regulated by miR let-7c-5p are still unknown. Here, we confirmed that RGS16 is upregulated in glioma tissues and that high expression of RGS16 is associated with poor survival. Ectopic deletion of RGS16 significantly suppressed glioma cell proliferation and migration both in vitro and in vivo. Moreover, RGS16 was validated as a direct target gene of miR let-7c-5p. The overexpression of miR let-7c-5p obviously downregulated the expression of RGS16, and knocking down miR let-7c-5p had the opposite effect. Thus, we suggest that the suppression of RGS16 by miR let-7c-5p can promote glioma progression and may serve as a potential prognostic biomarker and therapeutic target in glioma.

关键词： RGS16     let-7c-5p     glioma     proliferation     migration    

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Design, synthesis, and antiviral properties of 2-aryl-1H-benzimidazole-4-carboxamide derivatives

Xianjin LUO, Zhonglü ZHANG, Yutian YANG, Fei XUE, Naiyun XIU, Yuanbin SHE

《化学科学与工程前沿（英文）》 2009年 第3卷 第3期   页码 305-309 doi: 10.1007/s11705-009-0021-z

摘要： A series of new benzimidazole derivatives were designed and synthesized. Their chemical structures were testified by H NMR, infrared spectroscopy (IR), mass spectrography (MS), and elemental analysis. Their potent antiviral properties indicated the prospect of new drugs. Compound , , , , , , and were identified as novel antivirus with much better selective activity and inhibitory activity than the comparable ribavirin against Coxsackie virus B in VERO cells.

关键词： benzimidazole     coxsackie virus B3     antiviral properties    

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A 7-year follow-up study of the features and transformations of elderly male patients with OGTT-1h hyperglycemia

TIAN Hui, LI Chunlin, ZHONG Wenwen, PAN Changyu, LU Juming, CAO Xiutang

《医学前沿（英文）》 2008年 第2卷 第4期   页码 396-399 doi: 10.1007/s11684-008-0076-0

摘要： The aim of this paper is to investigate the clinical features and transformation of elderly male patients with normal blood glucose levels at fasting and 2 hours after glucose intake but with hyperglycemia (≥ 11.1 mmol/L) 1 hour after oral glucose tolerance test (OGTT-1h HG). Seven years of follow-up visits were performed on 189 elderly male outpatients with OGTT-1h HG and data was recorded on their body mass index (BMI), blood pressure, serum cholesterol and triglyceride test results and on their glucose tolerance changes every 1–2 years after taking OGTT; their possible causes were analysed. Follow-up visits revealed that 19 patients with OGTT-1h HG were diagnosed with diabetes (10.1%), 78 patients with impaired glucose tolerance (IGT, 41.3%), 2 patients transformed to normal glucose tolerance (NGT, 1.1%) and the remaining 90 patients (47.6%) remained unchanged. Synchronized comparison with IGT patients showed that the ratio of OGTT-1h HG patients turning to diabetes was lower than that of IGT patients (21.1%, = 13.05, < 0.01), and the ratio of OGTT-1h HG patients transforming to NGT was slightly higher (0.4%, = 2.46, > 0.05). The prevalence of complications of hypertension, coronary heart disease, cerebral vascular diseases and dyslipidemia in patients with OGTT-1h HG were higher than those with NGT ( < 0.05) and were similar to that of IGT patients. As a special phenotype of OGTT and as part of an abnormal glucose tolerance conformation, patients with OGTT-1h HG warrant special attention, since about half of them were found to have developed diabetes or IGT, and their risk of suffering from vascular diseases were also increased.

关键词： special attention     prevalence     unchanged     dyslipidemia     elderly    

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Heat-spreading analysis of a heat sink base embedded with a heat pipe

B. V. BORGMEYER, H. B. MA,

《能源前沿（英文）》 2010年 第4卷 第2期   页码 143-148 doi: 10.1007/s11708-010-0013-1

摘要： A simplified model predicting the heat transfer performance of a heat sink base with a high thermal conductivity was developed. Numerical analysis was performed using the commercial software FLUENT. The investigation indicates that for heat sink bases with a high effective thermal conductivity, such as the base embedded with a typical heat pipe, the entire heat sink can be modeled as a flat plate with a uniform temperature and an effective convection heat transfer coefficient. This simplified model can be used to determine the heat transfer performance of a heat sink embedded with a typical heat pipe or vapor chamber.

关键词： heat pipe     heat sink     microprocessor heat removal    

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间充质干细胞治疗人感染H7N9禽流感病毒所致急性呼吸窘迫综合征的临床研究——为新冠病毒肺炎救治提供新策略 Article

陈佳佳, 胡晨霞, 陈利军, 汤灵玲, 朱一新, 徐小微, 陈露, 高海女, 鲁晓庆, 俞亮, 戴霞红, 项春生, 李兰娟

《工程（英文）》 2020年 第6卷 第10期   页码 1153-1161 doi: 10.1016/j.eng.2020.02.006

摘要：

2013年，H7N9病毒在哺乳动物宿主之间迅速传播，并具有人与人之间传播的风险。间充质干细胞（mesenchymal stem cell, MSC）移植在病毒性肺炎的治疗中有广阔的前景，并于2013年作为应急性治疗方法来治疗H7N9感染的ARDS。根据自愿和知情同意的原则，17例H7N9感染的ARDS患者移植同种异体经血来源的MSC作为治疗组，44例H7N9感染的ARDS患者作为对照组。总体而言，该研究结果表明MSC移植显著提高了H7N9感染的ARDS的存活率，并为开展临床前和临床应用MSC治疗H7N9感染的ARDS的研究提供了理论基础。由于H7N9和2019新型冠状病毒性肺炎（coronavirus disease 2019, COVID-19）临床表现相似（如ARDS和呼吸衰竭），并继发多器官功能障碍，因此基于MSC的疗法可能为COVID

关键词： H7N9     间充质干细胞     甲型流感     急性呼吸窘迫综合征     新型冠状病毒性肺炎     干细胞治疗    

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Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance

《医学前沿（英文）》 2022年 第16卷 第6期   页码 883-895 doi: 10.1007/s11684-022-0919-0

摘要： Metastasis and drug resistance are the leading causes of poor prognosis in patients with osteosarcoma. Identifying the relevant factors that drive metastasis and drug resistance is the key to improving the therapeutic outcome of osteosarcoma. Here, we reported that autophagy was highly activated in metastatic osteosarcoma. We found increased autophagolysosomes in metastatic osteosarcoma cell lines by using electron microscopy, Western blot, and immunofluorescence experiments. We further examined the expression of the autophagy-related genes Beclin1 and LC3B in 82 patients through immunohistochemistry and found that Beclin1 and LC3B were highly related to unfavorable prognosis of osteosarcoma. Knockdown of Beclin1 and LC3B reduced invasion, metastasis, and proliferation in metastatic osteosarcoma cells. In vitro and in vivo studies also demonstrated that inhibiting by 3-MA inhibited cell growth and metastasis. Moreover, we demonstrated that autophagy-related genes were activated by SEs and that the inhibition of SEs by JQ-1 decreased the metastasis of osteosarcoma. Overall, our findings highlighted the association of autophagy with osteosarcoma progression and shed new light on autophagy-targeting therapy for osteosarcoma.

关键词： osteosarcoma     autophagy     metastasis     drug resistance     Beclin1     LC3B    

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Catalytic ozonation of reactive red X-3B in aqueous solution under low pressure: decolorization and OH

Hong SUN,Min SUN,Yaobin ZHANG,Xie QUAN

《环境科学与工程前沿（英文）》 2015年 第9卷 第4期   页码 591-595 doi: 10.1007/s11783-014-0694-5

摘要： Catalytic ozonation of Reactive Red X-3B in aqueous solution had been carried out in an ozone oxidation reactor where Mn-Fe-ceramic honeycomb was used as the catalysts. The presence of Mn-Fe-ceramic honeycomb catalyst could obviously improve the decoloration efficiency of Reactive Red X-3B and the utilization efficiency of ozone compared to the results from non-catalytic ozonation. Adsorption of Reactive Red X-3B had no obviously influence on the degradation efficiency. Addition of tert-butanol significantly decreased the degradation efficiency, indicating that the degradation of Reactive Red X-3B followed the mechanism of hydroxyl radical (OH·) oxidation. The operating variables such as reaction pressure and ozone supply had a positive influence on the degradation efficiency, mainly attributing to facilitate the ozone decomposition and OH· formation.

关键词： catalytic ozonation     reactive red X-3B     ceramic honeycomb     hydroxyl radical (OH·)    

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Single and joint effects of HHCB and cadmium on zebrafish (

Lei ZHANG, Jing AN, Qixing ZHOU

《环境科学与工程前沿（英文）》 2012年 第6卷 第3期   页码 360-372 doi: 10.1007/s11783-011-0353-z

摘要： As an important type of emerging pollutants, ecological toxicity and risk of artificial musks are increasingly concerned. Thus, single and joint toxic effects of 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8- hexamethylcyclopenta-gamma-2-benzopyran (HHCB) as one of the most widely applied artificial musks and cadmium (Cd) as an toxic metal on zebrafish ( ) were investigated by the exposure of zebrafish to various concentrations of HHCB or/and Cd in feculent water containing bedloads. The results indicated that the joint effect of HHCB and Cd changed during different exposure times within 120 h. The index of the antioxidant enzyme system including superoxide dismutase (SOD) and peroxidase (POD), and malondialdehyde (MDA) were sensitive and induced in the zebrafish stressed by Cd, and content of soluble protein (SP) was sensitive to HHCB and could be used as a biomarker for HHCB. Joint effects on antioxidant enzymes depended more on the effect of single Cd in the first one or two days. However, in the rest exposure days, the effect of HHCB began to dominate in the joint effect during the exposure process.

关键词： 1     3     4     6     7     8-hexahydro-4     6     6     7     8     8-hexamethylcyclopenta-gamma-2-benzopyran (HHCB)     cadmium (Cd)     antioxidant biomarker     feculent water containing bedloads    

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Oxidative leaching kinetics of molybdenum-uranium ore in H

El-Ahmady, H. B. Hassib, A. S. Helal

《化学科学与工程前沿（英文）》 2013年 第7卷 第1期   页码 95-102 doi: 10.1007/s11705-013-1317-6

摘要： The processing of molybdenum-uranium ore in a sulfuric acid solution using hydrogen peroxide as an oxidant has been investigated. The leaching temperature, hydrogen peroxide concentration, sulfuric acid concentration, leaching time, particle size, liquid-to-solid ratio and agitation speed all have significant effects on the process. The optimum process operating parameters were: temperature: 95°C; H O concentration: 0.5 M; sulfuric acid concentration: 2.5 M; time: 2 h; particle size: 74 μm, liquid-to-solid ratio: 14 ∶ 1 and agitation speed: 600 rpm. Under these experimental conditions, the extraction efficiency of molybdenum was about 98.4%, and the uranium extraction efficiency was about 98.7%. The leaching kinetics of molybdenum showed that the reaction rate of the leaching process is controlled by the chemical reaction at the particle surface. The leaching process follows the kinetic model 1 ? (1? ) = with an apparent activation energy of 40.40 kJ/mole. The temperature, concentrations of H O and H SO and the mesh size are the main factors that influence the leaching rate. The reaction order in H SO was 1.0012 and in H O it was 1.2544.

关键词： leaching of molybdenum     leaching of uranium     kinetics    

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标题 作者 时间 类型 操作

131I标记的人源化抗B7-H3抗体用于胶质母细胞瘤放射免疫疗法的治疗特性

傅丰庆, Meng Zheng, Shandong Zhao, Yan Wang, Minzhou Huang, Hanqing Chen, Ziyi Huang, Kaijie Zhang, 缪丽燕, 张学光

期刊论文

Research progress on human infection with avian influenza H7N9

Xiaoxin Wu, Lanlan Xiao, Lanjuan Li

期刊论文

Universal influenza virus vaccines: what can we learn from the human immune response following exposure to H7

null

期刊论文

Compiling of comprehensive data of human infections with novel influenza A (H7N9) virus

null

期刊论文

The first avian influenza A (H7N9) viral infection in humans in Zhejiang Province, China: a death report

null

期刊论文

Novel variants in LAMA3 and COL7A1 and recurrent variant in KRT5 underlying epidermolysis bullosa in

期刊论文

RGS16 regulated by let-7c-5p promotes glioma progression by activating PI3K-AKT pathway

期刊论文

Design, synthesis, and antiviral properties of 2-aryl-1H-benzimidazole-4-carboxamide derivatives

Xianjin LUO, Zhonglü ZHANG, Yutian YANG, Fei XUE, Naiyun XIU, Yuanbin SHE

期刊论文

A 7-year follow-up study of the features and transformations of elderly male patients with OGTT-1h hyperglycemia

TIAN Hui, LI Chunlin, ZHONG Wenwen, PAN Changyu, LU Juming, CAO Xiutang

期刊论文

Heat-spreading analysis of a heat sink base embedded with a heat pipe

B. V. BORGMEYER, H. B. MA,

期刊论文

间充质干细胞治疗人感染H7N9禽流感病毒所致急性呼吸窘迫综合征的临床研究——为新冠病毒肺炎救治提供新策略

陈佳佳, 胡晨霞, 陈利军, 汤灵玲, 朱一新, 徐小微, 陈露, 高海女, 鲁晓庆, 俞亮, 戴霞红, 项春生, 李兰娟

期刊论文

Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance

期刊论文

Catalytic ozonation of reactive red X-3B in aqueous solution under low pressure: decolorization and OH

Hong SUN,Min SUN,Yaobin ZHANG,Xie QUAN

期刊论文

Single and joint effects of HHCB and cadmium on zebrafish (

Lei ZHANG, Jing AN, Qixing ZHOU

期刊论文

Oxidative leaching kinetics of molybdenum-uranium ore in H

El-Ahmady, H. B. Hassib, A. S. Helal

期刊论文