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Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han

《医学前沿（英文）》 2020年 第14卷 第6期   页码 726-745 doi: 10.1007/s11684-020-0746-0

摘要： Chimeric antigen receptor (CAR) T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies. However, CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence, in addition to antigen-negative relapse and an immunosuppressive microenvironment. Various preclinical studies are exploring strategies to overcome the above challenges. Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors. In this review, we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies, especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response. We also explored the sensitizing effects of conventional treatment approaches, such as chemotherapy and radiotherapy, on CAR T cell therapy. Finally, we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.

关键词： CAR T cells     immunoregulatory molecules     endogenous immune response     solid malignancies    

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CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies

《医学前沿（英文）》 2021年 第15卷 第6期   页码 783-804 doi: 10.1007/s11684-021-0904-z

摘要： The current standard of care in hematological malignancies has brought considerable clinical benefits to patients. However, important bottlenecks still limit optimal achievements following a current medical practice. The genetic complexity of the diseases and the heterogeneity of tumor clones cause difficulty in ensuring long-term efficacy of conventional treatments for most hematological disorders. Consequently, new treatment strategies are necessary to improve clinical outcomes. Chimeric antigen receptor T-cell (CAR T) immunotherapy opens a new path for targeted therapy of hematological malignancies. In this review, through a representative case study, we summarize the current experience of CAR T-cell therapy, the management of common side effects, the causative mechanisms of therapy resistance, and new strategies to improve the efficacy of CAR T-cell therapy.

关键词： CAR T cells     hematological malignancies     review    

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cyclophosphamide for allogeneic peripheral stem cell transplantation for adult patients with lymphoid malignancies

Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu

《医学前沿（英文）》 2021年 第15卷 第1期   页码 108-115 doi: 10.1007/s11684-019-0730-8

摘要： Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group ( =0.03 and =0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%–86.7%) and 58.4% (95% CI: 41.9%–81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%–35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%–38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

关键词： post-transplantation cyclophosphamide     allogeneic hematopoietic stem cell transplantation     lymphoid malignancies    

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Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination

null

《医学前沿（英文）》 2017年 第11卷 第1期   页码 20-31 doi: 10.1007/s11684-016-0493-4

摘要：

To date, gastric carcinoma (GC) is one of the common and fatal digestive malignancies worldwide. The prognosis of GC is not always satisfactory because of late diagnosis. Scholars are keen on discovering novel accurate and economical biomarkers in body liquids for GC screening to detect and evaluate the lesion before the results of imaging techniques are obtained. While traditional serum assays have limited sensitivity and specificity, gastrointestinal juice may provide relevant specific biomarkers because of its close contact with the tumor. Herein, the current progress in the relationship between gastrointestinal fluid analyses and GC is systematically and comprehensively reviewed. The detection of gastric juice pH, fluorescence spectrum, cytology, Helicobacter pylori-associated markers, nitrosamines, conventional tumor markers, amino acids, proteomics, microRNAs, long noncoding RNAs, protein-coding genes, vitamin C, etc., and combination tests of different category markers could provide important diagnostic and prognostic clues for gastrointestinal diseases. Particularly, early GC may be efficiently screened using gastric juice. Gastrointestinal fluid examination could also predict the adverse effects of postgastrectomy, such as pancreatic leakage, fistula, and abscess. Gastric fluid markers should be further studied to reveal the early predicators of malignancy and complications. The methods for obtaining the samples of gastrointestinal juice with minimum incision should also be comprehensively investigated.

关键词： gastrointestinal fluid     gastric carcinoma     biomarker     diagnosis     prognosis     gastrectomy     adverse events    

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Clinical characteristics and prognostic factors of patients with mature T-cell lymphoid malignancies:

null

《医学前沿（英文）》 2015年 第9卷 第4期   页码 468-477 doi: 10.1007/s11684-015-0419-6

摘要：

Mature T-cell lymphoid malignancies comprise a group of heterogeneous diseases that vary in clinicopathological features, biological behavior, treatment response, and prognosis. Bone marrow (BM) infiltration is more commonly present in mature T-cell lymphoid malignancies compared with their B-cell counterparts and hence important for differential diagnosis. In this study, clinical characteristics and prognostic factors were analyzed in 225 patients with mature T-cell lymphoid malignancies treated in a single institution. These included 29 cases of T-cell lymphoproliferative disorders (T-LPD, all with BM infiltration) and 196 cases of T-/natural-killer-cell lymphoma (T/NKCL, 56 with BM infiltration and 140 without BM infiltration). The estimated 5-year overall survival (OS) rates of T-LPD and T/NKCL were 96.6% and 37.3%, respectively. T-LPD patients were less likely to exhibit poor performance status, advanced disease stage, presence of B symptoms, or abnormal level of serum β-2 microglobulin. With similar pathological characteristics, T/NKCL patients with BM infiltration showed significantly lower response rates and shorter OS than those without BM infiltration (P = 0.0264 and P<0.0001, respectively). Multivariate analysis indicated that poor performance status, advanced disease stage, elevated serum lactate dehydrogenase level, and BM involvement were independent unfavorable prognostic factors. The Glasgow Prognostic Score may be more efficient than the International Prognostic Index in predicting disease outcome in T/NKCL. In conclusion, clinical characteristics may be useful in more effectively stratifying patients with mature T-cell lymphoid malignancies.

关键词： mature T-cell lymphoid malignancies     clonal T-cell population     bone marrow infiltration     prognostic factors    

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Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies

《医学前沿（英文）》 2022年 第16卷 第3期   页码 459-466 doi: 10.1007/s11684-021-0841-x

摘要： Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.

关键词： Fanconi anemia     aplastic anemia     hematologic malignancy     germline predisposition    

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Clinical risk score for invasive fungal diseases in patients with hematological malignancies undergoing

Ling Wang, Ying Wang, Jiong Hu, Yuqian Sun, He Huang, Jing Chen, Jianyong Li, Jun Ma, Juan Li, Yingmin Liang, Jianmin Wang, Yan Li, Kang Yu, Jianda Hu, Jie Jin, Chun Wang, Depei Wu, Yang Xiao, Xiaojun Huang

《医学前沿（英文）》 2019年 第13卷 第3期   页码 365-377 doi: 10.1007/s11684-018-0641-0

摘要： Invasive fungal disease (IFD) is a major infectious complication in patients with hematological malignancies. In this study, we examined 4889 courses of chemotherapy in patients with hematological diseases to establish a training dataset ( =3500) by simple random sampling to develop a weighted risk score for proven or probable IFD through multivariate regression, which included the following variables: male patients, induction chemotherapy for newly diagnosed or relapsed disease, neutropenia, neutropenia longer than 10 days, hypoalbuminemia, central-venous catheter, and history of IFD. The patients were classified into three groups, which had low (0–10, ~1.2%), intermediate (11–15, 6.4%), and high risk (>15, 17.5%) of IFD. In the validation set ( =1389), the IFD incidences of the groups were ~1.4%, 5.0%, and 21.4%. In addition, we demonstrated that anti-fungal prophylaxis offered no benefits in low-risk patients, whereas benefits were documented in intermediate (2.1% vs. 6.6%, =0.007) and high-risk patients (8.4% vs. 23.3%, =0.007). To make the risk score applicable for clinical settings, a pre-chemo risk score that deleted all unpredictable factors before chemotherapy was established, and it confirmed that anti-fungal prophylaxis was beneficial in patients with intermediate and high risk of IFD. In conclusion, an objective, weighted risk score for IFD was developed, and it may be useful in guiding antifungal prophylaxis.

关键词： invasive fungal diseases     hematological malignancies     chemotherapy     risk score     prophylaxis    

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Plasma spray coating on interconnector toward promoted solid oxide fuel cells and solid oxide electrolysis

《能源前沿（英文）》 doi: 10.1007/s11708-023-0901-9

摘要： Interconnector is a critical component to construct solid oxide cells (SOCs) stack. Oxidation of metallic interconnectors and Cr poisoning caused by oxidation are important factors that lead to long-term performance degradation of SOCs. Coating on the interconnector surface is an important approach to inhibit the oxidation and Cr migration of the interconnector. Herein, (La0.75Sr0.25)0.95MnO3–δ (LSM) and Mn1.5Co1.5O4 (MCO) are used to fabricate the coatings of interconnector. Two advanced thermal spray technology, atmospheric plasma spraying (APS) and low-pressure plasma spray (LPPS), are adopted for the coating preparation. The electrochemical performance, rising and cooling cycle stability, and Cr diffusion inhibition performance of the coatings are tested and evaluated. The result indicates that MCO can generate more uniform and denser coatings than LSM. In addition, MCO coatings prepared by LPPS shows the best electrochemical performance, rising and cooling cycle stability, and Cr diffusion inhibition. The initial area specific resistance (ASR) is 0.0027 Ω·cm2 at 800 °C. After 4 cooling cycle tests, the ASR increases to 0.0032 Ω·cm2 but lower than other samples. Meanwhile, the relative intense of Cr at the interface of SUS430 with MCO coatings fabricated by LPPS is lower than that of MCO fabricated by APS after 4 rising and cooling cycle operations, showing more favorable Cr diffusion inhibition performance.

关键词： interconnector coating     plasma spray     electrochemical performance     Cr diffusion inhibition     solid oxide cells (SOCs)    

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Minimal residual disease in solid tumors: an overview

《医学前沿（英文）》 2023年 第17卷 第4期   页码 649-674 doi: 10.1007/s11684-023-1018-6

摘要： Minimal residual disease (MRD) is termed as the small numbers of remnant tumor cells in a subset of patients with tumors. Liquid biopsy is increasingly used for the detection of MRD, illustrating the potential of MRD detection to provide more accurate management for cancer patients. As new techniques and algorithms have enhanced the performance of MRD detection, the approach is becoming more widely and routinely used to predict the prognosis and monitor the relapse of cancer patients. In fact, MRD detection has been shown to achieve better performance than imaging methods. On this basis, rigorous investigation of MRD detection as an integral method for guiding clinical treatment has made important advances. This review summarizes the development of MRD biomarkers, techniques, and strategies for the detection of cancer, and emphasizes the application of MRD detection in solid tumors, particularly for the guidance of clinical treatment.

关键词： MRD     solid tumor     CTC     ctDNA    

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High-solid anaerobic digestion of sewage sludge: achievements and perspectives

《环境科学与工程前沿（英文）》 2021年 第15卷 第4期 doi: 10.1007/s11783-020-1364-4

摘要：

• High-solid anaerobic digestion (HS-AD) of sewage sludge (SS) is overviewed.

关键词： High-solid effect     Anaerobic fermentation     Methane production     Biodegradability     Sludge treatment    

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Review of SO42-/MxOy solid superacid catalysts

Yanni WU, Shijun LIAO

《化学科学与工程前沿（英文）》 2009年 第3卷 第3期   页码 330-343 doi: 10.1007/s11705-009-0208-3

摘要： Some metal oxides modified with sulfate ions form highly acidic or superacidic catalysts. solid superacid catalysts, play a vital role in more and more fields such as organic synthesis, fine chemicals, pharmaceuticals, and means for strengthening environmental safeguards. This review highlights the recent development of solid superacid catalysts based on , including synthesis method, characterization of acid sites and acid strength, and applications.

关键词： solid superacid catalyst     synthesis method     characterization     applications    

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Repercussions of COVID-19 pandemic on solid waste generation and management strategies

《环境科学与工程前沿（英文）》 2021年 第15卷 第6期 doi: 10.1007/s11783-021-1407-5

摘要：

• Implication of COVID-19 on medical waste and MSW generation is studied.

关键词： COVID-19     Medical waste     Personal protective equipment     Municipal solid waste     Waste management    

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Municipal solid waste management in Dalian: practices and challenges

Xinbei WANG, Yong GENG

《环境科学与工程前沿（英文）》 2012年 第6卷 第4期   页码 540-548 doi: 10.1007/s11783-011-0361-z

摘要： The fast growing of urban areas in developing countries has brought serious problems on municipal solid waste (MSW) management. It will be rational to adopt an integrated approach to deal with such a challenge so that the overall eco-efficiency of MSW management could be improved. To better examine how attributes of integrated MSW management are being interpreted and put into practice, and to explore what changes should be made to improve the application of integrated MSW management, we employ a case study method so that lessons learned could be used to inform initiatives in other cities and the potential solution may offer feasible strategies. The case study city is Dalian, a typical seaport city with fast growing rate in economy. The outcomes of this case study show us that fragmented management structure, ineffective and inefficient enforcement of relevant regulations, backward technologies, limited financial resources and lack of public participation are main barriers for the implementation of integrated MSW management. Consequently, in order to overcome these barriers, we propose an integrated management framework on MSW management, aiming to maximize the overall eco-efficiency of MSW management.

关键词： municipal solid waste (MSW) management     3R principles     challenges     eco-efficiency     effective and efficient enforcement    

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Lagrangian simulation of deposition of CO gas-solid sudden expansion flow

HUANG Dongping, DING Guoliang, QUACK Hans

《能源前沿（英文）》 2008年 第2卷 第2期   页码 216-221 doi: 10.1007/s11708-008-0032-3

摘要： Freezing and blockage resulting from the deposition of solid CO formed because of sudden expansion of the downstream pipe during the release of CO through safety valves, will endanger the protected equipment. To overcome this problem, the characteristics of the CO gas-solid sudden expansion flow are studied by using the disperse Lagrangian model. A comparison of the calculated deposition of the solid CO with the experimental results shows that they are in reasonable agreement. The simulation results show that the size of the solid CO formed should not be in the range of 0.04–0.07 mm ( number 3.2–9.8). This can be achieved by using an appropriate flow cross section of the safety valve.

关键词： comparison     gas-solid     downstream     blockage     Lagrangian    

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Development and prospects of municipal solid waste (MSW) incineration in China

NIE Yongfeng

《环境科学与工程前沿（英文）》 2008年 第2卷 第1期   页码 1-7 doi: 10.1007/s11783-008-0028-6

摘要： With the lack of space for new landfills, municipal solid waste (MSW) incineration is playing an increasingly important role in municipal solid waste management in China. The literatures on certain aspects of incineration plants in China are reviewed in this paper, including the development and status of the application of MSW incineration technologies, the treatment of leachate from stored MSW, air pollution control technologies, and the status of the fly-ash control method. Energy policy and its promotion of MSW-to-energy conversion are also elucidated.

关键词： development     management     municipal     MSW     incineration    

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标题 作者 时间 类型 操作

Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han

期刊论文

CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies

期刊论文

cyclophosphamide for allogeneic peripheral stem cell transplantation for adult patients with lymphoid malignancies

Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu

期刊论文

Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination

null

期刊论文

Clinical characteristics and prognostic factors of patients with mature T-cell lymphoid malignancies:

null

期刊论文

Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies

期刊论文

Clinical risk score for invasive fungal diseases in patients with hematological malignancies undergoing

Ling Wang, Ying Wang, Jiong Hu, Yuqian Sun, He Huang, Jing Chen, Jianyong Li, Jun Ma, Juan Li, Yingmin Liang, Jianmin Wang, Yan Li, Kang Yu, Jianda Hu, Jie Jin, Chun Wang, Depei Wu, Yang Xiao, Xiaojun Huang

期刊论文

Plasma spray coating on interconnector toward promoted solid oxide fuel cells and solid oxide electrolysis

期刊论文

Minimal residual disease in solid tumors: an overview

期刊论文

High-solid anaerobic digestion of sewage sludge: achievements and perspectives

期刊论文

Review of SO42-/MxOy solid superacid catalysts

Yanni WU, Shijun LIAO

期刊论文

Repercussions of COVID-19 pandemic on solid waste generation and management strategies

期刊论文

Municipal solid waste management in Dalian: practices and challenges

Xinbei WANG, Yong GENG

期刊论文

Lagrangian simulation of deposition of CO gas-solid sudden expansion flow

HUANG Dongping, DING Guoliang, QUACK Hans

期刊论文

Development and prospects of municipal solid waste (MSW) incineration in China

NIE Yongfeng

期刊论文