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| 1 | 原因不明复发性流产患者外周血PD-1、Th1/Th2型细胞因子水平测定及其相关性研究显示文摘目的探讨外周血程序性细胞死亡分子1(PD-1)及血清中Th1/Th2型细胞因子变化在原因不明复发性流产(URSA)发病中的作用。方法采用流式细胞术测定140例URSA患者接受淋巴细胞免疫治疗前后外周血PD-1水平;采用ELISA法测定患者治疗前后血清Th1(IL-2、IFN-γ)/Th2(IL-4、IL-10)型细胞因子水平,同时以102例正常已生育妇女作为对照组。结果 (1)淋巴细胞免疫治疗前与对照组相比,PD-1和Th2型细胞因子(IL-4和IL-10)显著下降(P均<0.05)。(2)淋巴细胞免疫治疗后与治疗前相比,Th1型细胞因子(IL-2和IFN-γ)含量明显下调(P均<0.05)。(3)淋巴细胞免疫治疗后与对照组相比,PD-1、Th1/Th2型细胞因子水平无显著性差别(P均>0.05)。(4)URSA患者外周血PD-1含量和血清中Th2型细胞因子水平呈正相关(r=0.67,r=0.81,P均<0.05);与Th1型细胞因子呈负相关(r=-0.55,r=-0.73,P均<0.05)。(5)淋巴细胞免疫治疗后,妊娠成功的妇女PD-1表达水平显著高于妊娠失败者(P<0.05)。结论 PD-1可能通过下调Th1/Th2型细胞因子的水平抑制URSA的发生发展。 | 伍金华 谢志威 车小群 李秀娟 黎淑贞 | 2014 | 中华临床医师杂志(电子版)2014，8，9： | 15 |
| 2 | Immune checkpoint inhibitor-induced colitis:A comprehensive review显示文摘Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1.ICIs have revolutionized the treatment of a variety of malignancies. However,many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis(IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease,however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis. | Aniruddh Som Rohan Mandaliya Dana Alsaadi Maham Farshidpour Aline Charabaty Nidhi Malhotra Mark C Mattar | 2019 | World Journal of Clinical Cases2019，7，4： | 14 |
| 3 | Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma显示文摘AIM To investigate the expression and prognostic role of programmed death ligand-1(PD-L1) in locally advanced esophageal squamous cell carcinoma(ESCC).METHODS A total of 200 patients with ESCC who underwent radical esophagectomy with standard lymphadenectomy as the initial definitive treatment in Seoul National University Hospital from December 2000 to April 2013 were eligible for this analysis. Tissue microarrays were constructed by collecting tissue cores from surgical specimens, and immunostained with antibodies directed against PD-L1, p16, and c-Met. Medical records were reviewed retrospectively to assess clinical outcomes. Patients were divided into two groups by PD-L1 status, and significant differences in clinicopathologic characteristics between the two groups were assessed. RESULTS Tumor tissues from 67 ESCC patients(33.5%) were PDL1-positive. Positive p16 expression was observed in 21 specimens(10.5%). The H-score for c-Met expression was ≥ 50 in 42 specimens(21.0%). Although PDL1-positivity was not significantly correlated with any clinical characteristics including age, sex, smoking/alcoholic history, stage, or differentiation, H-scores for c-Met expression were significantly associated with PDL1-positivity(OR = 2.34, 95%CI: 1.16-4.72, P = 0.017). PD-L1 expression was not significantly associated with a change in overall survival(P = 0.656). In contrast, the locoregional relapse rate tended to increase(P = 0.134), and the distant metastasis rate was significantly increased(HR = 1.72, 95%CI: 1.01-2.79, P = 0.028) in patients with PD-L1-positive ESCC compared to those with PD-L1-negative ESCC.CONCLUSION PD-L1 expression is positively correlated with c-Met expression in ESCC. PD-L1 may play a critical role in distant failure and progression of ESCC. | Ryul Kim Bhumsuk Keam Dohee Kwon Chan-Young Ock Miso Kim Tae Min Kim Hak Jae Kim Yoon Kyung Jeon In Kyu Park Chang Hyun Kang Dong-Wan Kim Young Tae Kim Dae Seog Heo | 2016 | World Journal of Gastroenterology2016，22，37： | 14 |
| 4 | The clinicopathological and prognostic significance of PD-L1 expression in pancreatic cancer:A meta-analysis显示文摘Background: Immunotherapy has shown promise against solid tumors. However, the clinical significance of programmed cell death 1(PD-1) and programmed cell death ligand 1(PD-L1) in pancreatic ductal adenocarcinoma(PDAC) remains unclear. This meta-analysis aimed to analyze the prognostic effect of PD-L1 in PDAC.Data sources: Electronic search of the Pub Med, Cochrane Library and Web of Science was performed until December 2016. Through database searches, we identified articles describing the relationship between PD-L1 status and PDAC patient prognosis. Meta-analysis was performed to investigate the relationship between PD-1 and overall survival(OS).Results: Nine studies with 989 PDAC patients were included for PD-L1 expression analysis. And 5 studies with 688 PDAC patients were included in the prognostic analysis. The PD-L1 positive rate measured by immunohistochemistry(IHC) was higher than that measured by polymerase chain reaction(PCR)(P < 0.001). PDAC patients with high expression levels of PD-L1 had significantly reduced OS(HR = 2.34;95% CI: 1.78–3.08). Subgroup analysis showed that the prognostic effect of PD-L1 levels was similar between the IHC and PCR methods. The PD-L1 positive rate was associated with PDAC T stages; the PD-L1 positive rate in the T3–4 group was higher than that in the T1-2 group(OR = 0.37; P = 0.001).Conclusions: High PD-L1 expression levels predicted a poor prognosis in PDAC patients. Thus, PD-L1 status helps determine treatment in PDAC patients. | He-Li Gaoa Liang Liua Zi-Hao Qi Hua-Xiang Xu Wen-Quan Wang Chun-Tao Wu Shi-Rong Zhang Jin-Zhi Xu Quan-Xing Ni Xian-Jun Yua | 2018 | Hepatobiliary & Pancreatic Diseases International2018，17，2： | 13 |
| 5 | 大骨节病与骨关节病软骨组织死亡相关因子表达的比较显示文摘目的观察大骨节病软骨组织中程序化细胞死亡分子5(programmed cell death 5,PDCD5)和早期生长反应蛋白1(early growth response protein-1,EGR-1)表达的变化及其在大骨节病软骨损伤中的作用。方法收集来自大骨节病患者关节软骨(KBD组)10例,同时收集15例骨关节炎病人关节软骨(OA组)作为疾病对照,收集6例正常软骨作为健康对照(正常组)。采用免疫组化染色法检测3组关节软骨组织中死亡受体调节因子PDCD5和EGR-1表达变化,并在显微镜下计数和分析3组关节软骨不同分层间阳性表达率的显著性差异。结果(1)KBD软骨中层PDCD5阳性细胞表达率(41.35±2.97)%显著高于OA组(26.48±2.04)%和正常组(19.02±1.88)%(P=0.001和P=0.000),KBD软骨深层显著高于正常组和OA组(P=0.000和P=0.029),OA组也高于正常组(P=0.038),而3组间的表层软骨细胞PDCD5阳性率无差异(P>0.05);(2)在KBD软骨表层,EGR-1表达显著高于OA软骨和正常软骨表层(P=0.000和P=0.000),3组软骨的阳性表达率分别为(27.94±3.09)%、(3.20±1.49)%和(12.66±1.06)%,KBD软骨中层EGR-1阳性细胞表达率显著低于OA组软骨(P=0.002),而高于正常软骨(P=0.017),KBD软骨和OA软骨深层阳性率均明显高于正常组(P=0.000和P=0.001),而KBD组和OA组的平均阳性率无统计学差异(P=0.187);(3)KBD组与正常组的PDCD5和EGR-1分别在3个软骨细胞层的表达均无相关性,而PDCD5和EGR-1在OA关节软骨表层呈强正相关。结论 KBD软骨深层PDCD5显著上调,而软骨表层和深层EGR-1显著高表达,提示这两种重要的细胞死亡相关因子在大骨节病软骨破坏过程中发挥重要作用。 | 武世勋 郭雄 张峰 郑晶晶 张增铁 | 2014 | 南方医科大学学报2014，34，12： | 12 |
| 6 | Expression and clinical value of programmed cell death-ligand 1(PD-L1)in diffuse large B cell lymphoma:a retrospective study显示文摘Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses.Diffuse large B-cell lymphoma(DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis.Methods: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical(IHC) assay. The expression of anaplastic lymphoma kinase(ALK), CD5,CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus(EBV)-encoded RNAs(EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.Results: Of the 204 patients, 100(49.0%) were PD-L1-positive in tumor cells and 44(21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like(GCB) subtype than in the GCB subtype(P = 0.02 and P= 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment(P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression(r =-0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival(OS)rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells(P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS(P < 0.01).Conclusions: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended. | Li-Yang Hu Xiao-Lu Xu Hui-Lan Rao Jie Chen Ren-Chun Lai Hui-Qiang Huang Wen-Qi Jiang Tong-Yu Lin Zhong-Jun Xia Qing-Qing Cai | 2017 | Chinese Journal of Cancer2017，36，12： | 12 |
| 7 | Programmed death 1 and programmed death ligand 1 expressions in patients with chronic hepatitis B显示文摘BACKGROUND: The role of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) in persistent HBV infection is controversial. Increasing PD-1 and PD-L1 expression has been found in hepatitis B patients during immune clearance phase, but not in HBV-tolerant patients. We investigated PD-1 and PD-L1 expression and inflammation in chronic hepatitis B. METHODS: Twenty patients with chronic hepatitis B participated in this study. Fifteen patients were in the immune clearance phase, and 5 were in the immune inactive phase. Circulating HBV-specific T cells were analyzed by flow cytometric detection of major histocompatibility complex (MHC) class I peptide complexes, known as pentamers. Intra-hepatic PD-1 and PD-L1 expressions were analyzed by immunostaining. RESULTS: The frequency of pentamers, including core 18-27 (1.88%±0.36%), env 335-343 (1.85%±0.37%), and pol 575-583 (1.56%±0.29%) was 8.30-, 7.71- and 8.48-fold greater during immune clearance phase than those during the immune inactive phase. In addition, more than 70% of circulating pentamers were PD-1 positive. During immune clearance phase, the numbers of intra-hepatic PD-1 and PD-L1 positive cells were 108±23/HPF and 97±20/HPF respectively, in contrast, there was a paucity of PD-1 and PD-L1 positive cells in the immune inactive phase. The numbers of intra-hepatic PD-1 and PD-L1 positive cells were positively correlated with serum alanine aminotransferase and the number of intra-hepatic CD8 + T cells. Immunofluorescence showed that almost all of the intra- hepatic CD8 + T cells were PD-1 and CCR6 positive. These cells aggregated around macrophage inflammatory protein-3 alpha (MIP3α) positive cells and mixed with PD-L1 positive cells.CONCLUSIONS: PD-1 and PD-L1 expressions were significantly correlated with inflammation. CCR6 and PD-1 co-expressed in the same cells; these cells were increased both in circulation and the inflamed liver and aggregated around MIP3α positive cells. The mixture of CCR6 and PD-1, MIP3α and PD-L1 positive cells created immune response compartments which played an important role in specific immune response in HBV immune clearance. | Wen-Jin Zhang Chuan-Hui Peng Shu-Sen Zheng | 2013 | Hepatobiliary & Pancreatic Diseases International2013，12，4： | 11 |
| 8 | Advances in immuno-oncology biomarkers for gastroesophageal cancer:programmed death ligand 1,microsatellite instability,and beyond显示文摘Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability(MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with MSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer. | Emily M Lin Jun Gong Samuel J Klempner Joseph Chao | 2018 | World Journal of Gastroenterology2018，24，25： | 10 |
| 9 | Programmed death-1/programmed death-L1 signaling pathway and its blockade in hepatitis C virus immunotherapy显示文摘Chronic hepatitis C virus(HCV) infection is a public health issue that often progresses to life-threatening complications, including liver cirrhosis, fibrosis, and hepatocellular carcinoma. Impaired immune responses to HCV are key features of chronic HCV infection. Therefore, intervention strategies usually involve enhancing the immune responses against HCV. Cytotoxic CD8+ T lymphocytes(CTLs) play a critical role in the control of HCV infection. However, their cytolytic function can be impaired by the expression of co-inhibitory molecules. Programmed death-1(PD-1) receptor and its ligand PD-L1 function in a T cell co-inhibitory pathway, which either blocks the function of CTLs or the differentiation of CD8+ T cells. During chronic HCV infection, the immune inhibitory receptor PD-1 is upregulated on dysfunctional HCV-specific CD8+ T cells. As such, blockade of the PD-1/PD-L1 pathway in these CD8+ T cells might restore their functional capabilities. Indeed, clinical trials using therapies to block this pathway have shown promise in the fostering of anti-HCV immunity. Understanding how chronic HCV infection induces upregulation of PD-1 on HCV specific T cells and how the PD-1/PD-L1 interaction develops HCV specific T cell dysfunction will accelerate the development of an efficacious prophylactic and therapeutic vaccination against chronic HCV infections, which will significantly improve HCV treatments and patient survival. In this review, we discuss the relationship between PD-1 expression and clinical responses and the potential use of PD-1 blockade for anti-HCV therapy. | Mohamed L Salem Ahmed El-Badawy | 2015 | World Journal of Hepatology2015，7，23： | 9 |
| 10 | Necroptosis:An emerging type of cell death in liver diseases显示文摘Cell death has been extensively evaluated for decades and it is well recognized that pharmacological interventions directed to inhibit cell death can prevent significant cell loss and can thus improve an organ’s physiological function.For long,only apoptosis was considered as a sole form of programmed cell death.Recently necroptosis,a RIP1/RIP3-dependent programmed cell death,has been identified as an apoptotic backup cell death mechanism with necrotic morphology.The evidences of necroptosis and protective effects achieved by blocking necroptosis have been extensively reported in recent past.However,only a few studies reported the evidence of necroptosis and protective effects achieved by inhibiting necroptosis in liver related disease conditions.Although the number of necroptosis initiators is increasing;however,interestingly,it is still unclear that what actually triggers necroptosis in different liver diseases or if there is always a different necroptosis initiator in each specific disease condition followed by specific downstream signaling molecules.Understanding the precise mechanism of necroptosis as well as counteracting other cell death pathways in liver diseases could provide a useful insight towards achieving extensive therapeutic significance.By targeting necroptosis and/or other parallel death pathways,a significant cell loss and thus a decrement in an organ’s physiological function can be prevented. | Waqar Khalid Saeed Dae Won Jun | 2014 | World Journal of Gastroenterology2014，20，35： | 9 |
| 11 | Prognostic value of programmed death.1, programmed death-ligand 1, programmed death-ligand 2 expression, and CD8(+) T cell density in primary tumors and metastatic lymph nodes from patients with stage T1.4N+M0 gastric adenocarcinoma显示文摘Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra-and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy.This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+)T-cell density in primary tumors and PD-1 expression on CD8(+)T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors(45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+)T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes(both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression,PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stageT1-4 N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies. | Yuan Gao Su Li Dazhi Xu Shangxiang Chen Yuchen Cai Wenqi Jiang Xinke Zhang Jin Sun Kefeng Wang Boyang Chang Fenghua Wang Minghuang Hong | 2017 | Chinese Journal of Cancer2017，36，11： | 8 |
| 12 | Landscape of PD-1/PD-L1 Regulation and Targeted Immunotherapy显示文摘Programmed cell death protein 1(PD-1)/programmed death ligand 1(PD-L1)is a significant immune checkpoint,and the dysfunction of this axis contributes to tumor metastasis and immune escape.PI3K/Akt/mTOR and MAPK signal network induces PD-1/PD-L1 expression and facilitates tumor progression.Transcriptional factors such as hypoxia induced factors,PTEN,p53,CDK5,BRD4,STAT modulate PD-1/PDL1 expression.PD-1/PD-L1 level is also regulated via epigenetic and post-translational manner.The underlying mechanisms mentioned above may provide potential targets for tumor treatment.At present,the combination therapy of PD-1/PD-L1 monoclonal antibodies plus small molecular inhibitors has achieved good outcomes in tumor treatment. | Jieming Ni Anping Ni | 2018 | Chinese Medical Sciences Journal2018，33，3： | 8 |
| 13 | Use of programmed cell death protein ligand 1 assay to predict the outcomes of non-small cell lung cancer patients treated with immune checkpoint inhibitors显示文摘The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the management of non-small cell lung cancer(NSCLC) and this new class of drugs has achieved a rapid development in the treatment of this disease. However, considering the costs of these drugs and the fact that only a subset of patients experience long-term disease control, the identification of predictive biomarkers for the selection of candidates suitable for treatment has become a priority. The research focused mainly on the expression of the PD-L1 receptor on both tumor cells and/or immune infiltrates determined by immunohistochemistry(IHC). However, different checkpoint inhibitors were tested, different IHC assays were used, different targets were considered(tumor cells, immune infiltrates or both) and different expression thresholds were employed in clinical trials. In some trials the assay was used prospectively to select the patients, while in other trials it was evaluated retrospectively. Some confusion emerges, which makes it difficult to easily compare the literature data and to translate them in practice management. This mini-review shows the possibilities and pitfalls of the PD-L1 expression to predict the activity and efficacy of anti PD1/PD-L1 monoclonal antibodies in the treatment of NSCLC. | Carmelo Tibaldi Alice Lunghi Editta Baldini | 2017 | World Journal of Clinical Oncology2017，8，4： | 8 |
| 14 | Breast cancer immunology and immunotherapy:targeting the programmed cell death protein-1/programmed cell death protein ligand-1显示文摘Historically,breast cancer has been regarded as an immunogenic'cold'tumor.However,the discovery of immune checkpoint inhibitors has made immunotherapy becoming an emerging new treatment modality for breast cancer.This review discusses the immune system,immune features of breast cancer,and the programmed cell death protein-1/programmed cell death protein ligand-1(PD-1/PD-L1)inhibitors used in the treatment of breast cancer.High T lymphocyte infiltration and mutation burden were observed in triple-negative breast cancer and human epidermal growth factor receptor 2 positive breast cancer.Increasing breast cancer immunogenicity and modulating the tumor microenvironment has been reported to improve the therapeutic efficacy of immunotherapy.Recent clinical trials involving PD-1/PD-L1 inhibitors monotherapy in breast cancer has revealed little efficacy,which highlights the need to develop combinations of PD-1/PD-L1 inhibitors with chemotherapy,molecularly targeted therapies,and other immunotherapies to maximize the clinical efficacy.Collectively,the immunotherapy might be a promising therapeutic strategy for breast cancer and several clinical trials are still on-going. | Jing Zhao Jian Huang | 2020 | Chinese Medical Journal2020，，7： | 7 |
| 15 | Structural elucidation of sex pheromone components of the Geometridae Semiothisa cinerearia(Bremer et Grey)in China显示文摘An extract from the female sex gland of Semiothisa cinerearia attracted conspecificmales in field tests.A major active component was isolated from the extract and identified byGC-MS,GC-IR and microchemical reactions as cis-3,4-cpoxy-(Z,Z)-6,9-heptadecadiene,whichshowed strong EAG response.Another minor yet important component was identified as(Z,Z,Z)-3,6,9-heptadecatriene. | LI,Zheng-Ming YAO,En-Yun LIU,Tian-Lin LIU,Zi-Ping WANG,Su-Hua Elemento-Organic Chemistry Institute,Nankai University,Tianjin 300071ZHU,Hai-Qing ZHAO,Gang REN,Zi-Li Department of Biology,Nankai University,Tianjin 300071 | 1993 | Chinese Journal of Chemistry1993，11，3： | 6 |
| 16 | ABA与NO,GA在枣果实发育期的网络关系与拮抗效应探讨显示文摘枣裂果问题严重制约着我国枣业发展,这一重大技术难题已经引起了国内外学者的广泛关注。基于ABA可增强水分胁迫耐性作用和诱导抗氧化防护系统的理论研究基础,针对枣裂果发生时胞内Ca2+富集、渗透物质和可溶性物质增加、水势降低、膜过氧化发生、抗氧化防护系统增强,以及果皮细胞发生程序性衰败等现象,提出了在短日照下,ABA信号刺激促进了细胞的程序性衰亡,是诱发枣裂果发生的内因,并对ABA与NO,H2O2以及ABA与GA在枣果实发育期的网络关系与拮抗效应进行了探讨,旨在为枣抗裂果调控机制的建立提供理论依据。 | 杨卫民 杜京旗 赵君 褚盼盼 刘宝琦 | 2014 | 山西农业科学2014，42，2： | 6 |
| 17 | Formalin fixation on HER-2 and PD-L1 expression in gastric cancer:A pilot analysis using the same surgical specimens with different fixation times显示文摘BACKGROUND The needs for human epidermal growth factor receptor 2(HER-2) and/or programmed death-ligand 1(PD-L1) evaluations in gastric cancer are dramatically increasing. Although the importance of standardization of sample fixation has been widely recognized, most of the evidence regarding the fixation duration or type of fixing solution are based on breast cancer.AIM To investigate the real effects of fixation conditions on HER-2 testing or PD-L1 testing for gastric cancer using gastrectomy specimens.METHODS Thirty-two patients who underwent gastrectomy for gastric cancer were enrolled.Their resected specimens were each divided into four pieces and fixed in four strictly controlled different durations(6 h, 24 h, and 48 h, and 1 wk) by 10%formalin(n = 22) or 10% neutral buffered formalin(NBF)(n = 10).Immunohistochemistry(IHC) of HER-2 and PD-1 was performed, and a pathology examination was conducted. In the HER-2-immunoreactive cases, all four specimens were subjected to dual-color in situ hybridization(DISH). Five cases were assessed as HER-2-positive by IHC and DISH. We used the cut-off values of 1%, 10%, and 50% to assess the IHC findings of PD-L1.RESULTS No significant difference was observed in comparisons between the shorter fixation period groups(6 h, 24 h, and 48 h) and the prolonged fixation period(1 wk) group in the HER-2 and PD-L1 analyses. Although no significant difference was observed between 10% formalin and 10% NBF within 1 wk of fixation, the superiority of 10% NBF was confirmed in a long-term(> 3 mo) fixation in both the HER-2 and PD-L1 analyses.CONCLUSION In this small-numbered pilot study, prolonged fixation within 1 wk showed no inferiority in HER-2 or PD-L1 testing. However, a large-numbered prospective study is needed to obtain conclusive results. | Keita Kai Yukie Yoda Atsushi Kawaguchi Akimichi Minesaki Hironori Iwasaki Shinichi Aishima Hirokazu Noshiro | 2019 | World Journal of Clinical Cases2019，7，4： | 4 |
| 18 | 程序升温汽化大体积进样气相色谱法同时测定空气中的甲醛及其他10种羰基污染物(英文)显示文摘Long-term indoor-air limit for formaldehyde stipulated by the European Commission is 1 μg/m3,while the World Health Organization has set a threshold of 100 μg/m3 that should not be exceeded for more than 30 min. To date,however,only a few analytical techniques have been developed that can be used to detect formaldehyde at these very restrictive limits. Thus,there is a need to develop for comprehensive methods for analyzing airborne formaldehyde and other carbonyl pollutants in the ambient environment. The aim of this study is to develop a highly sensitive online automated preconcentration gas chromatographic method using large-volume injection with a programmed temperature vaporization injector for the analysis of airborne formaldehyde and ten other carbonyl compounds. The influence of several parameters,such as the maximum volume injected,programmed temperature vaporization transfer time and temperature,carrier gas flow rate,and type of packing material was investigated. After optimization,highly satisfactory results in terms of the absolute and methodological detection limits were achieved,i. e. as low as the μg/m3 level for all the carbonyl pollutants studied. A commercially available sampler,originally designed for active sampling,was evaluated as a passive sampling device;this optimized technique was applied to monitor the concentrations of carbonyl pollutants in the indoor air of ten public buildings in Florence. The strength of this methodology lies both in the low detection limits reached in the simultaneous analysis of a wide group of 2,4-dinitrophenylhydrazine derivatives,and the potential adaptability of this method to other gas chromatographic applications to achieve lower sensitivity. | Stefano DUGHERI Nicola MUCCI Ilenia POMPILIO Giovanni CAPPELLI Costanza BOSSI AlessANDro BONARI Giulio ARCANGELI | 2018 | 色谱2018，36，12： | 3 |
| 19 | 恶性淋巴瘤治疗进展:第57届美国血液学会年会报道显示文摘由于近几年恶性淋巴瘤在治疗方面取得了明显进步,新药和新的治疗策略不断出现,如嵌合抗原受体T细胞(CAR-T)免疫疗法,因此关于恶性淋巴瘤的议题备受关注。文章就第57届美国血液学会(ASH)年会关于恶性淋巴瘤的最新进展进行简要介绍。 | 赵东陆 马军 | 2016 | 白血病.淋巴瘤2016，25，2： | 3 |
| 20 | A VPE-like protease NtTPE8 exclusively expresses in the integumentary tapetum and is involved in seed development显示文摘Programmed cell death(PCD)is an essential process for development,and shows conserved cytological features in both plants and animals.Caspases are well-known critical components of the PCD machinery in animals.However,currently few typical counterparts have been identified in plants and only several caspase-like proteases are known to be involved in plant PCD,indicating the existence of great challenge for confirming new caspase-like proteases and elucidating the mechanisms regulating plant PCD.Here,we report a novel cysteine protease,NtTPE8,which was extracted from tobacco seeds and confirmed as a new caspase-like protease.Recombinant NtTPE8 exhibited legumain and caspase-like proteolytic activities,both of which could be inhibited by the pan-caspase inhibitor(Z-VAD-FMK).Notably,NtTPE8 possessed several caspase activities and the capacity to cleave the cathepsin H substrate FVR,indicating a unique character of NtTPE8.NtTPE8 was exclusively expressed in the integumentary tapetum and thus,is the first specific molecular marker reported to date for this cell type.Downregulation of NtTPE8 caused seed abortion,via disturbing early embryogenesis,indicating its critical role in embryogenesis and seed development.In conclusion,we identified a novel caspase-like cysteine protease,NtTPE8,exclusively expressed in the integumentary tapetum that is involved in seed development. | Wei Wang Hanxian Xiong Rongxin Lin Nantian Zhao Peng Zhao Meng-Xiang Sun | 2019 | Journal of Integrative Plant Biology2019，61，5： | 3 |
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