1.Next-generation clinically relevant antibody detection: Unlocking electrochemical biosensors for critical disease management.
Zheng ZHAO ; Zhiwei CHEN ; Jacques CROMMEN ; Shengfeng HUANG ; Qiqin WANG ; Zhengjin JIANG
Acta Pharmaceutica Sinica B 2025;15(11):5632-5662
Autoimmune diseases, cancers, and viral infections pose significant global health threats, characterized by chronic pathology, unregulated cellular proliferation, and rapid transmission, respectively, requiring urgent early warning and treatment strategies. Antibodies, primarily classified into autoantibodies and therapeutic antibodies based on their clinical roles, provide essential information and show considerable value in the precise diagnosis and treatment of these serious diseases. Among the technologies utilized in bioanalysis, electrochemical biosensors, with their unique advantages of rapid response, high sensitivity, miniaturization, cost-effectiveness and user-friendly operation, have been developed as a trending technology for precise diagnostic and therapeutic drug monitoring. This review systematically summarizes the relationships and roles of clinically relevant antibodies in autoimmune diseases, cancers, and viral infections, while detailing the composition, strategies, development, and application trends of relevant electrochemical biosensors. Furthermore, it highlights the remaining challenges and opportunities for the advancement and prospects of electrochemical sensors in the context of clinically relevant antibodies.
2.Multiepitope recognition technology promotes the in-depth analysis of antibody‒drug conjugates.
Yutian LEI ; Yuan SHEN ; Feng CHEN ; Rui HE ; Zhang ZHANG ; Ying ZHOU ; Jin-Chen YU ; Jacques CROMMEN ; Zhengjin JIANG ; Qiqin WANG
Acta Pharmaceutica Sinica B 2024;14(11):4962-4976
The dynamic tracking of antibody‒drug conjugates (ADCs) in serum is crucial. However, a versatile bioanalytical platform is lacking due to serious matrix interferences, the heterogeneity and complex biotransformation of ADCs, and the recognition deficiencies of traditional affinity technologies. To overcome this, a multiepitope recognition technology (MERT) was developed by simultaneously immobilizing CDR and non-CDR ligands onto MOF@AuNPs. MERT's excellent specificity, ultrahigh ligand density, and potential synergistic recognition ability enable it to target the different key regions of ADCs to overcome the deficiencies of traditional technologies. The binding capacity of MERT for antibodies is ten to hundred times higher than that of the mono-epitope or Fc-specific affinity technologies. Since MERT can efficiently capture target ADCs from serum, a novel bioanalytical platform based on MERT and RPLC‒QTOF-MS has been developed to monitor the dynamic changes of ADCs in serum, including the fast changes of drug-to-antibody ratio from 3.67 to 0.22, the loss of payloads (maytansinol), and the unexpected hydrolysis of the succinimide ring of the linker, which will contribute to clarify the fate of ADCs and provide a theoretical basis for future design. In summary, the MERT-based versatile platform will open a new avenue for in-depth studies of ADCs in biological fluids.
3.Comparative study of trastuzumab modification analysis using mono/multi-epitope affinity technology with LC-QTOF-MS.
Chengyi ZUO ; Jingwei ZHOU ; Sumin BIAN ; Qing ZHANG ; Yutian LEI ; Yuan SHEN ; Zhiwei CHEN ; Peijun YE ; Leying SHI ; Mao MU ; Jia-Huan QU ; Zhengjin JIANG ; Qiqin WANG
Journal of Pharmaceutical Analysis 2024;14(11):101015-101015
Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.
4.Phosphatidylethanolamine functionalized biomimetic monolith for immobilized artificial membrane chromatography
Peijie ZHU ; Weijia CHEN ; Qiqin WANG ; Huihui WU ; Meng RUAN ; Hongwu WANG ; Zhengjin JIANG
Journal of Pharmaceutical Analysis 2022;12(2):332-338
In this research,a new phospholipid based monolith was fabricated by in situ co-polymerization of 1-dodecanoyl-2-(11-methacrylamidoundecanoyl)-sn-glycero-3-phosphoethanolamine and ethylene dimethacrylate to mimick bio-membrane environment.Excellent physicochemical properties of this novel monolith that were achieved included column efficiency,stability,and permeability.Moreover,the biomimetic monolith showed outstanding separation capability for a series of intact proteins and small molecules.In particular,it exhibited good potential as an alternative to the commercial immobilized artificial membrane(IAM)column(IAM.PC.DD2)for studying drug-membrane interactions.This study not only enriched the types of IAM stationary phases,but also provided a simple model for the prediction of phosphatidylethanolamine related properties of drug candidates.
5.Efficacy of aminophylline and methylprednisolone in the treatment of bronchial asthma
Chinese Journal of Biochemical Pharmaceutics 2017;37(9):244-246
Objective To investigate the clinical effect of methylprednisolone and aminophylline on bronchial asthma patients, so as to improve the level of clinical treatment. Methods Selected form August 2014 to June 2016 in our hospital diagnosed with bronchial asthma in 90 patients as the research object, for the normal group and the treatment group in accordance with the double blind method standard for sharing, the former the latter with aminophylline treatment; Methylprednisolone Treatment on the basis of the former treatment. After treatment, the statistical comparison of two groups and the clinical symptoms and quality of life to improve the situation. Results the total efficiency of the treatment group was 97.8%, significantly higher than that of the control group 77.8%(P<0.05). The treatment group of clinical symptoms and signs scores were lower than those of the reference group; improving the quality of life was better than the reference group, there were significant differences between groups of data comparison, statistical significance was established(P<0.05). Conclusion Patients with bronchial asthma by aminophylline combined with methylprednisolone treatment, the effect is considerable, not only can improve the treatment effect, rapidly relieve symptoms, improve the quality of life of patients, suggest further promotion.
6.Salivary duct carcinoma associated with giant cell tumor: A case report.
Zhengjin LIU ; Ping YIN ; Yong-Gang CHEN ; Hongfeng LIAO ; Yan LÜ
West China Journal of Stomatology 2013;31(3):317-329
Primary salivary duct carcinoma(SDC) featured with giant cell tumor(GCT) is a extremely rare, relatively new understanding lesion and its histogenesis has not been fully defined. This paper reported a case of SDC associated with GCT, its clinical, histopathologic features and histological origin were discussed in combination with literature review.
Carcinoma, Ductal
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Carcinoma, Squamous Cell
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Giant Cell Tumors
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Head and Neck Neoplasms
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Humans
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Salivary Ducts
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Salivary Gland Neoplasms
7.Visualization of the first Chinese visible human male and female
Shaoxiang ZHANG ; Pingan WANG ; Zhengjin LIU ; Liwen TAN ; Mingguo QIU ; Qiyu LI ; Kai LI ; Gaoyu CUI ; Yanli GUO ; Guangjiu LIU ; Jinlu SHAN ; Jijun LIU ; Weiguo ZHANG ; Jinhua CHEN ; Jian WANG ; Wei CHEN ; Ming LU ; Jian YOU
Journal of Third Military Medical University 2003;0(07):-
Objective To achieve computer visualization of the first Chinese visible male and female Methods After acquisition of the dataset of the first Chinese visible male and female (2 518 cross sections were obtained from the visible male, the complete data files take up 90 468 GBs; while 3 640 cross sections from the female, the complete data files take up 131 04 GBs ), we processed 2 D images in an SGI Workstation and on P4 computer respectively Then, image registration was performed through reserved scaling point Reconstruction was achieved by two approaches: volume rendering reconstruction and surface rendering reconstruction Results We visualized the whole body and special parts of Chinese visible male and female on an SGI Workstation and a personal computer respectively Furthermore, by optimizing 3 D reconstruction and data processing technique, interactive 3 D visualization of the dataset was achieved Conclusions ①The dataset of the first Chinese visible male and female proves to be eligible for 3 D visualization research ②The platform setup of interactive 3 D visualization of Chinese visible male and female dataset provides foundation for digital human anatomy and virtual surgery ③The models of human organs and parts built through data segmentation, classification, registration and drawing lay basis for rendering complex structures of the whole human body delicately
8.The third Chinese visible human dataset produced
Shaoxiang ZHANG ; Zhengjin LIU ; Liwen TAN ; Mingguo QIU ; Qiyu LI ; Kai LI ; Gaoyu CUI ; Yanli GUO ; Guangjiu LIU ; Jinlu SHAN ; Jijun LIU ; Weiguo ZHANG ; Jinhua CHEN ; Jian WANG ; Wei CHEN ; Ming LU ; Jian YOU ; Xueli PANG ;
Journal of Third Military Medical University 2003;0(15):-
Objective To establish more detailed dataset of Chinese visible human male. Methods After undergoing macroscopical, CT and MRI examinations to exclude organic lesion, a young aged, middle sized male cadaver was selected as the subject. First, morphological measurement and vascular perfusion were performed. Second, after embedding with 5% gelatin, the cadaver was put in ice house and frozen to -30 ℃ for 1 week. Third, TK 6350 numerical control milling machine (milling accuracy of 0.001 mm) was used to shave off slices of the body layer by layer from head to foot at -25 ℃ in low temperature laboratory. Fourth, the successive cross sections were photographed with high resolution digital camera and scanned into an animation computer. Thus, data acquisition from cadaver model was completed to obtain structural dataset of the human body. Results The selected sample was a 21 year old, 1 820 mm in height, 66 kg in weight male died due to non organic disease. CT with 1.0 mm slice thickness for the head and neck and 2.0 mm for the rest of the body was performed. MRI with 1.5 mm slice thickness for the head and neck and 3.0 mm for the rest of the body was also performed. A total of 18 398 serial cross sections with the thickness of 0.1 mm of each section were obtained. The digital photographs were sampled at a resolution of 10 989 056 (4 064?2 704) pixels. The data file of each section occupies 62.9 MB. The complete data files occupy 1 157.23 GB. The research results are issued simultaneously on the Internet (http://www.chinese visiblehuman.Conclusion ① Review of the related literatures reveals that the thinnest thickness of the reported cross section of the visible human dataset is 0.2 mm(the thickness of the sections of the skull base of the first case of Chinese visible human reported by our research group is 0.1 mm.), and the slices consist of several thousands of serial cross sections with several millions of pixels. The data files occupy several tens of GB or more than 100 GB. However, the thickness of the cross sections of the whole body of the dataset achieved in our research is 0.1 mm. The total slices consist of 18 398 serial cross sections with the photographic resolution of 11 million pixels and the total data file reaches 1 157.23 GB. The three indexes mentioned above are elevated by 1 log unit. ② We have solved the key technical problems in data acquisition of visible human such as super thin serial cross sectioning, enormous quantity of data storing and display of tiny blood vessels.
9.Dataset collection and visualization for first visible human female in China
Shaoxiang ZHANG ; Zhengjin LIU ; Liwen TAN ; Mingguo QIU ; Qiyu LI ; Kai LI ; Gaoyu CUI ; Yanli GUO ; Guangjiu LIU ; Jinglu SHAN ; Jijun LIU ; Weiguo ZHANG ; Jinhua CHEN ; Jian WANG ; Wei CHEN ; Ming LU ; Jian YOU ; Xueli PANG ;
Journal of Third Military Medical University 1988;0(05):-
Objective To build the dataset of Chinese visible human female. Methods After undergoing macroscopical, CT and MRI examinations to exclude organic lesions, a young female cadaver of medium height was selected as the subject. After morphological measurement and vascular perfusion, the cadaver was embedded with 5% gelatin and cryopreserved in a -30 ℃ icehouse for 1 week. A digital milling machine TK 6350 (milling accuracy of 0.001 mm) was used to shave off slices of the body layer by layer from head to foot in a laboratory at -25 ℃. The successive cross sections were photographed with a high definition digital camera, and the pictures were put into a computer to establish a dataset of human body. By utilizing the image dataset derived from the successive cross sections, 3D reconstruction and stereodisplay of human structure were finished with a SGI Workstation which was equipped with an independently self developed software package for 3D reconstruction. Results The selected specimen, a 22 year old female native of Chongqing, was 1 620 mm in height, 54 kg in weight and died of non organic disease. CT scans were made in every 1.0 mm for head and neck and every 2.0 mm for rest parts, and the thickness for MRI scans was 1.5 mm for head and 3.0 mm for rest parts. For serial cross sections, the thickness was 0.25 mm for head and 0.5 mm for rest parts. Thus, a total of 3640 slices were obtained, and the photo for every slice was saved as a 36 MB file in a resolution of 6 291 456 pixels (3 072?2 048). Finally, the complete data files reached to 131.04 GB. Conclusion ① This is the first formally reported case of Chinese visible human female, suggesting that China becomes the second country owning visible human female dataset of her population. We set up a website for the purpose of exchanging ideas and information on this subject. So, the results are issued simultaneously on the Internet (http://www.chinesevisiblehuman.com).② According to US Visible Human Project(VHP), the data of the 3 junctional parts of their female cadaver were absent because the body was cut into 4 segments. Taking the age of 59 year old into account, the visible human female's body was not exactly perfect. The sections of 0.33 mm in thickness were saved to pictures at a resolution of 2 490 368 pixels (2 048?1 216). While, the first Chinese visible human female reported here is a young female without organic disease or lesion. No sectional datum is lost for being acquired from successive sections of the whole body. The resolution of cross sectional image reaches to 6 291 456 pixels (3 072?2 048).
10.THE VESSELS OF THE SKIN FLAPS AT GROIN REGION——1. THE MACRO-MICRO-ANATOMY OF THE SUPERFICIAL CIRCUMFLEX ILIAC VESSELS
Eryu CHEN ; Gwangtsi HO ; Gengli CHENG ; Zhengjin LIU
Acta Anatomica Sinica 1957;0(04):-
In many textbooks and literatures the superficial circumflex iliac artery (SCIA) is generally described, but only its superficial main branch (SMB) is referred, Its deep main branch (DMB) is always neglected, though it is present constantly. In 56% of fifty cases we studied the SCIA trunk possesses both these main branches.The SMB is present in 86% of the cases studied. After it originates from the trunk, it usually emerges promptly from the back of deep fascia into the subcutaneous layer. The points of emergence were found in an area around a center located 15 mm lateral and 10 mm below the origin of femoral artery. The course of the SMB can be marked as a line which located between a point 15 mm below the origin of femoral artery and anterior superior iliac spine. The SMB supplies an area along the lateral half of inguinal ligament, and its terminal branch usually turns upwards to the lateral portion of the abdominal wall.The DMB is a constant branch in our cases. It runs parallel to and 15mm beow the inguinal ligament, It supplies the upper lateral portion of the thigh, and its terminal branch usually turns downwards and laterally into the superficial layer of the gluteal region. The site where the DMB penetrates the deep fascia was found in an area around a center located 20 mm below the anterior superior iliac spine.The caliber of each of the two main branches is intimately correlated with the size of the skin which supplies. The course of the(SCIV)is similar to one of the main branches of the SCIA or runs between them (70%) The axes, thickness, size of the groin skin flaps were discussed.

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