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Serum carbohydrate antigen (CA) 19-9 as a prognostic factor in cholangiocarcinoma: A meta-analysis

Shang-Long LIU, Zi-Fang SONG, Qing-Gang HU, Shao-Bo HU, Jun LI, Qi-Chang ZHENG, Duo SHAN,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 457-462 doi: 10.1007/s11684-010-0240-1

摘要： This study was performed to determine the prognostic role of preoperative serum carbohydrate antigen (CA) 19-9 levels in the survival of patients with cholangiocarcinoma. Articles published up to June 1, 2010 that evaluated preoperative CA19-9 levels and the prognosis of cholangiocarcinoma were collected for meta-analysis. The required information for calculating individual relative risk (RR) was extracted from the studies, and a combined overall RR was estimated. Nine eligible studies were included. One study dealt with extra-hepatic cholangiocarcinoma, while the other eight studies analyzed intra-hepatic cholangiocarcinoma. The mean methodological quality score was 74.1%, ranging from 65.5% to 82.5%. The overall RR for the nine studies was 1.28 (95% confidence interval= 1.10–1.46), and the Z-score for overall effect was 13.83 (<0.001). The association between serum CA19-9 level and lymph node involvement was also assessed. The combined RR was 1.471 (95% confidence interval= 0.411–5.264) and Z-score for overall effect was 0.59 ( = 0.553). CA19-9 levels were associated significantly with the prognosis of patients with cholangiocarcinoma. This meta-analysis shows that elevation of preoperative CA19-9 levels is correlated with a poor prognosis of patients with cholangiocarcinoma. However, larger scale and randomized studies are needed to draw a more substantive conclusion.

关键词： cholangiocarcinoma     prognostic factors     serum carbohydrate antigen 19-9    

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Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function ofCD19-specific CAR T-cells via TGF-β signaling

《医学前沿（英文）》 doi: 10.1007/s11684-023-1010-1

摘要： Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-β signaling

关键词： exosomes induce activation     impair function CD19     exosomal CD19 antigen    

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tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19chimeric antigen receptor T therapy

《医学前沿（英文）》 2023年 第17卷 第4期   页码 699-713 doi: 10.1007/s11684-022-0972-8

摘要： Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%–50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

关键词： anti-CD19 chimeric antigen receptor T     immunotherapy     diffuse large B cell lymphoma     tumor microenvironment     tumor-associated macrophage     metabolism    

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Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large

《医学前沿（英文）》 2022年 第16卷 第2期   页码 285-294 doi: 10.1007/s11684-021-0843-8

摘要： Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive efficacy in treating B-cell malignancies. A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR, a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule, for the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL). Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell (C-CAR011) treatment. The overall response rate was 20% and 50% at 4 and 12 weeks after the infusion of C-CAR011, respectively, and the disease control rate was 60% at 12 weeks after infusion. Treatment-emergent adverse events occurred in all patients. The incidence of cytokine release syndrome in all grades and grade≥3 was 90% and 0, respectively, which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel. Neurotoxicity or other dose-limiting toxicities was not observed in any dose cohort of C-CAR011 therapy. Antitumor efficacy was apparent across dose cohorts. Therefore, C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL, and further large-scale clinical trials are warranted.

关键词： CAR-T cell therapy     refractory diffuse large B-cell lymphoma     cytokine release syndrome     dose-limiting toxicity    

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may affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen

Lili Zhou, Ping Li, Shiguang Ye, Xiaochen Tang, Junbang Wang, Jie Liu, Aibin Liang

《医学前沿（英文）》 2020年 第14卷 第6期   页码 786-791 doi: 10.1007/s11684-020-0751-3

摘要： Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (CAR-T) cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma (r/r NHL) have not been well characterized. In this study, we found that the different sites of extranodal involvement may affect response, overall survival (OS), and progression-free survival (PFS) in patients with r/r NHL treated with anti-CD19 CAR-T cells. In a cohort of 32 treated patients, 12 (37.5%) and 8 (25%) patients exhibited soft tissue lymphoma and bone marrow (BM) infiltrations, respectively, and 13 (41%) patients exhibited infiltration at other sites. The factors that may affect prognosis were identified through multivariable analysis. As an independent risk factor, soft tissue infiltration was the only factor significantly correlated with adverse prognosis ( <0.05), whereas other factors did not reach statistical significance. Furthermore, the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy. PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone. Thus, anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.

关键词： anti-CD19 chimeric antigen receptor T cell     soft tissue     bone marrow     relapsed or refractory non-Hodgkin lymphoma    

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基于抗原和聚合酶链式反应的组合策略对模拟社区内遏制COVID-19传播效果的定量分析 Article

黄蔷如, 孙艳侠, 贾萌萌, 张婷, 陈方圆, 姜明月, 王晴, 冯录召, 杨维中

《工程（英文）》 2023年 第28卷 第9期   页码 234-242 doi: 10.1016/j.eng.2023.01.004

摘要：

新型冠状病毒肺炎（coronavirus disease 2019, COVID-19）病例数量持续增加，这使得许多国家的医疗系统不堪重负并导致超额死亡对感染人群进行检测仍然是遏制COVID-19疫情、延缓疾病的传播以及拉平疫情流行曲线的关键策略。我们开发了一个随机的、基于agent的、离散时间的易感者—潜隐者—感染者—康复者模型来模拟COVID-19在社区内的传播，评估了三个不同强度级别的检测策略与COVID-19传播之间的关联。

关键词： COVID-19     抗原检测     PCR核酸检测     检测策略    

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Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized

《医学前沿（英文）》 2021年 第15卷 第3期   页码 460-471 doi: 10.1007/s11684-021-0861-6

摘要： Lifestyle interventions, including dietary adjustments and exercise, are important for obesity management. This study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet (LCD) or exercise is more effective in metabolism improvement. Forty-five eligible subjects were randomly divided into an LCD group (n=22) and an exercise group (EX, n=23). The subjects either adopted LCD (carbohydrate intake<50 g/day) or performed moderate-to-vigorous exercise (≥30 min/day) for 3 weeks. After the interventions, LCD led to a larger weight loss than EX (−3.56±0.37 kg vs. −1.24±0.39 kg, P<0.001), as well as a larger reduction in fat mass (−2.10±0.18 kg vs. −1.25±0.24 kg, P=0.007) and waist circumference (−5.25±0.52 cm vs. −3.45±0.38 cm, P=0.008). Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin resistance. Triglycerides decreased in both two groups, whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX group. Various glycemic parameters, including serum glycated albumin, mean sensor glucose, coefficient of variability (CV), and largest amplitude of glycemic excursions, substantially declined in the LCD group. Only CV slightly decreased after exercise. This pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin resistance. Compared with exercise, LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.

关键词： low-carbohydrate diet     obesity     nonalcoholic fatty liver disease     continuous glucose monitoring     mean sensor glucose    

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从药物开发的角度看工程化T细胞疗法 Review

Fang Chen, Joseph A. Fraietta, Carl H. June, 许中伟, J. Joseph Melenhorst, Simon F. Lacey

《工程（英文）》 2019年 第5卷 第1期   页码 140-149 doi: 10.1016/j.eng.2018.11.010

摘要： 例如，经基因修饰后，T 细胞可表达嵌合抗原受体（chimeric antigen receptor，CAR），使其能够识别并杀死肿瘤细胞，并形成一个记忆库，准备回击持续存在的恶性细胞。抗CD19 嵌合抗原受体T 细胞（CAR T cells，CART19）对某些恶性肿瘤具有显著的临床疗效。随着制药行业的主要参与者联手使这种新型“活药物”商业化，以CART19 为例，与传统药物相比，研究其开发过程中的相似性和差异性非常有用。本文综述了基于生物标志物的分析方法在优化CAR结构、临床前研究和临床疗效评价、不良反应（AE）和CART19 细胞动力学方面的应用。我们相信，就像胂凡纳明的发现开创了合成药物时代一样，CART19 的成功能够带来其他工程化T 细胞疗法的发展。

关键词： 工程化T细胞疗法     嵌合抗原受体     药物开发过程     生物标志物     CAR19     CART19    

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Chimeric antigen receptor T-cell therapy: a promising treatment modality for relapsed/refractory mantle

Ping Li, Ningxin Dong, Yu Zeng, Jie Liu, Xiaochen Tang, Junbang Wang, Wenjun Zhang, Shiguang Ye, Lili Zhou, Alex Hongsheng Chang, Aibin Liang

《医学前沿（英文）》 2020年 第14卷 第6期   页码 811-815 doi: 10.1007/s11684-020-0740-6

摘要： Mantle cell lymphoma (MCL) is a distinct histological type of B-cell lymphoma with a poor prognosis. Several agents, such as proteasome inhibitors, immunomodulatory drugs, and inhibitors of B cell lymphoma-2 and Bruton’s tyrosine kinase have shown efficacy for relapsed or refractory (r/r) MCL but often have short-term responses. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a novel treatment modality for r/r non-Hodgkin’s lymphoma. However, long-term safety and tolerability associated with CAR T-cell therapy are not defined well, especially in MCL. In this report, we described a 70-year-old patient with r/r MCL with 48-month duration of follow-up who achieved long-term remission after CAR T-cell therapy. CAR T-cell-related toxicities were also mild and tolerated well even in this elderly patient. This report suggested that CAR T-cell therapy is a promising treatment modality for patients with MCL, who are generally elderly and have comorbid conditions.

关键词： anti-CD19 chimeric antigen receptor T cells     mantle cell lymphoma     relapsed or refractory     long-term follow-up    

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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。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-19所致的ARDS患者获益。

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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Acetylated HOXB9 at lysine 27 is of differential diagnostic value in patients with pancreatic ductal

Xiaoran Sun, Jiagui Song, Jing Zhang, Jun Zhan, Weigang Fang, Hongquan Zhang

《医学前沿（英文）》 2020年 第14卷 第1期   页码 91-100 doi: 10.1007/s11684-019-0696-6

摘要： Pancreatic ductal adenocarcinoma (PDAC) is the ninth most common human malignancy and the sixth leading cause of cancer-related death in China. AcK27-HOXB9 is a newly identified HOXB9 post-transcriptional modification that can predict the outcome in lung adenocarcinoma and colon cancer well. However, the role of AcK27-HOXB9 in PDAC is unclear. The present study aims to investigate the differential diagnostic role of patients with AcK27-HOXB9 PDAC. Tissue microarrays consisting of 162 pancreatic tumor tissue samples from patients with PDAC and paired normal subjects were used to examine HOXB9 and AcK27-HOXB9 levels and localizations by immunohistochemical analysis and Western blot assay, respectively. HOXB9 was upregulated ( <0.0001), and AcK27-HOXB9 ( =0.0023) was downregulated in patients with PDAC. HOXB9 promoted ( =0.0115), while AcK27-HOXB9 ( =0.0279) inhibited PDAC progression. AcK27-HOXB9 predicted favorable outcome in patients with PDAC ( =0.0412). AcK27-HOXB9 also suppressed PDAC cell migration in a cell migration assay. The results of this study showed that HOXB9 promoted and AcK27-HOXB9 suppressed PDAC progression. The determination of ratio between HOXB9 and AcK27-HOXB9 exhibited potential diagnostic value in patients with PDAC.

关键词： HOXB9     AcK27-HOXB9     PDAC    

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Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide

null

《医学前沿（英文）》 2017年 第11卷 第4期   页码 502-508 doi: 10.1007/s11684-017-0590-z

摘要：

Although the efficacy of nucleos(t)ide analogue (NA) has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse. In this review, the RNA virion-like particles of hepatitis B virus (HBV) are integrated into the life cycle of HBV replication, and the potential significance of serum HBV RNA is systematically described. The production of HBV RNA virion-like particles should not be blocked by NA; in this regard, serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA (cccDNA), particularly among patients receiving NA therapy. Therefore, the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen (HBsAg) that can originate from either the cccDNA or the integrated HBV DNA fragment, serum HBV RNA, with pregenomic RNA origination, can only be transcribed from cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation. The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a “para-functional cure,” a status nearly close to the functional cure of chronic hepatitis B, to distinguish the “functional cure” characterized as serum HBsAg loss with or without anti-HBs seroconversion.

关键词： chronic hepatitis B     serum HBV RNA     nucleos(t)ide analogs     virological response     para-functional cure    

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662 A/G gene variation in human tumor necrosis factor receptor superfamily, member 9 (TNFRSF9)

QU Yanchun, YANG Ze, SUN Liang, JI Linong

《医学前沿（英文）》 2008年 第2卷 第3期   页码 283-285 doi: 10.1007/s11684-008-0053-7

摘要： The aim of this paper is to report a new coding variance of the gene, a candidate for autoimmune diseases. We found the variation in two families with type 2 diabetes mellitus by D-HPLC mutation screening method and confirmed our results by direct sequencing and PCR-RFLP. Although without changing the amino acid coding, the variance may have an effect on codon usage and play a role in disease development, such as type 2 diabetes mellitus. However, we cannot define the role of this variance because the frequency of the minor allele is low in the Chinese population and no homozygote of the variance was found. More research in multiple populations will be necessary to define the role of this variance.

关键词： D-HPLC mutation     development     autoimmune     PCR-RFLP     candidate    

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The 9th China Engineering Management Forum Guangzhou Consensus

《工程管理前沿（英文）》 2015年 第2卷 第2期   页码 105-107 doi: 10.15302/J-FEM-2015019

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Microorganism-derived biological macromolecules for tissue engineering

《医学前沿（英文）》 2022年 第16卷 第3期   页码 358-377 doi: 10.1007/s11684-021-0903-0

摘要： According to literature, certain microorganism productions mediate biological effects. However, their beneficial characteristics remain unclear. Nowadays, scientists concentrate on obtaining natural materials from live creatures as new sources to produce innovative smart biomaterials for increasing tissue reconstruction in tissue engineering and regenerative medicine. The present review aims to introduce microorganism-derived biological macromolecules, such as pullulan, alginate, dextran, curdlan, and hyaluronic acid, and their available sources for tissue engineering. Growing evidence indicates that these materials can be used as biological material in scaffolds to enhance regeneration in damaged tissues and contribute to cosmetic and dermatological applications. These natural-based materials are attractive in pharmaceutical, regenerative medicine, and biomedical applications. This study provides a detailed overview of natural-based biomaterials, their chemical and physical properties, and new directions for future research and therapeutic applications.

关键词： biological macromolecules     regenerative medicine     tissue engineering     exopolysaccharide     carbohydrate    

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标题 作者 时间 类型 操作

Serum carbohydrate antigen (CA) 19-9 as a prognostic factor in cholangiocarcinoma: A meta-analysis

Shang-Long LIU, Zi-Fang SONG, Qing-Gang HU, Shao-Bo HU, Jun LI, Qi-Chang ZHENG, Duo SHAN,

期刊论文

Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function ofCD19-specific CAR T-cells via TGF-β signaling

期刊论文

tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19chimeric antigen receptor T therapy

期刊论文

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large

期刊论文

may affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen

Lili Zhou, Ping Li, Shiguang Ye, Xiaochen Tang, Junbang Wang, Jie Liu, Aibin Liang

期刊论文

基于抗原和聚合酶链式反应的组合策略对模拟社区内遏制COVID-19传播效果的定量分析

黄蔷如, 孙艳侠, 贾萌萌, 张婷, 陈方圆, 姜明月, 王晴, 冯录召, 杨维中

期刊论文

Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized

期刊论文

从药物开发的角度看工程化T细胞疗法

Fang Chen, Joseph A. Fraietta, Carl H. June, 许中伟, J. Joseph Melenhorst, Simon F. Lacey

期刊论文

Chimeric antigen receptor T-cell therapy: a promising treatment modality for relapsed/refractory mantle

Ping Li, Ningxin Dong, Yu Zeng, Jie Liu, Xiaochen Tang, Junbang Wang, Wenjun Zhang, Shiguang Ye, Lili Zhou, Alex Hongsheng Chang, Aibin Liang

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

Acetylated HOXB9 at lysine 27 is of differential diagnostic value in patients with pancreatic ductal

Xiaoran Sun, Jiagui Song, Jing Zhang, Jun Zhan, Weigang Fang, Hongquan Zhang

期刊论文

Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide

null

期刊论文

662 A/G gene variation in human tumor necrosis factor receptor superfamily, member 9 (TNFRSF9)

QU Yanchun, YANG Ze, SUN Liang, JI Linong

期刊论文

The 9th China Engineering Management Forum Guangzhou Consensus

期刊论文

Microorganism-derived biological macromolecules for tissue engineering

期刊论文