Objective To establish a smoke-induced chronic bronchitis rat model and evaluate the patho-logical change semi-quantitatively, and study the characteristics of the inflammatory cells in the bronchoalveolar lav-age flu...Objective To establish a smoke-induced chronic bronchitis rat model and evaluate the patho-logical change semi-quantitatively, and study the characteristics of the inflammatory cells in the bronchoalveolar lav-age fluid (BALF) in various stages. Methods Chronic bronchitis sequential rat model was established by passively inhaling smoke mixture. Experiments were performed in 30 young male Sprague-Dawley rats, which comprised 5 groups in random, i.e.,4 chronic bronchitis model groups and 1 control group. After stained with hematoxylin and eosin, the specimens were studied by semi-quantitative method to evaluate the morphologic changes in various stages. Meanwhile, the inflammatory cells of the BALF and the activity of myeloperoxidase (MPO) of lung tissue were analysed. Results During the process of the chronic bronchitis, the pathologic score was increasing as time went on, and the typical morphologic changes of chronic bronchitis emerged in the group 7 weeks. The total number of inflammatory cells in BALF was increasing as time went on, correlated with the pathologic scores (P <0.01). And the percentage of lymphocyte increased as well as positively correlated with pathologic scores (P < 0. 05) , whereas that of macrophage decreased and negatively correlated with pathologic scores (P <0. 05). The MPO lever of lung tissue was correlated with the pathologic scores (P < 0. 01). But the percentage of the neutrophil in the BALF was just in a high level during the first week, then it maintained relatively lower. Conclusion Smoke-induced chronic bronchitis is a slowly progressive inflammation process. The model we established is convenient and simple for the longitudinal study on the inflammatory process of chronic bronchitis and the therapy in the early stage. The semi-quantitative evaluation for the pathological change is with much more value. During the inflammatory sequential process of early stage of chronic bronchitis, the cellular characteristics are similar to that of the common chronic inflammation.展开更多
Background and Objective:Immune checkpoint inhibitor(ICI)-based therapy has achieved impressive success in various cancer types.Several ICIs have been unprecedentedly approved as the treatment regimens for advanced he...Background and Objective:Immune checkpoint inhibitor(ICI)-based therapy has achieved impressive success in various cancer types.Several ICIs have been unprecedentedly approved as the treatment regimens for advanced hepatocellular carcinoma(HCC)in recent decade.Meanwhile,numerous clinical trials are being performed to exploit more ICIs into initially unresectable HCC and postoperative HCC to expectantly induce adequate tumor downstaging for further resection or implement adjuvant treatment for relapse-free survival,respectively.In this review,we aim to summarize some pragmatic histomorphologic,immunohistochemical,and molecular pathologic parameters which promisingly indicate the response of neoadjuvant/conversion ICI-related therapy and predict the efficacy of adjuvant/therapeutic ICI-related therapy for HCC.Methods:We searched PubMed using the terms hepatocellular carcinoma,immunotherapy,immune checkpoint inhibitor,immune checkpoint blockade,conversion therapy,neoadjuvant therapy,adjuvant therapy,biomarker,pathologic evaluation,pathologic assessment till February 2023.Key Content and Findings:Although there is no consensus regarding the pathologic evaluation of relevant HCC specimens,it is encouraging that a few of studies have concentrated on this field,and moreover,the methods and parameters noted on other cancer types are also worthy of reference.For the pathologic assessment of HCC specimens underwent immunotherapy,a suitable sampling scheme,identifying immunotherapy-related pathologic response,and quantification of pathologic response rate should be emphasized.For the patients of HCC who are scheduled to receive immunotherapy,tumor-infiltrating lymphocyte,intratumoral tertiary lymphoid structure,programmed cell death ligand 1,Wnt/β-catenin,microsatellite instability and mismatch repair,tumor mutational burden and tumor neoantigen,as well as some other signaling pathways are the potential predictive biomarkers of treatment response of ICI.Conclusions:The management of HCC in the era of immunotherapy arises a brand-new pathological challenge that is to provide an immunotherapy-related diagnostic report.Albeit many related researches are preclinical or insufficient,they may tremendously alter the immunotherapy strategy of HCC in future.展开更多
基金Supported by the fund from Shanghai Science and Technology Committee (004119060)
文摘Objective To establish a smoke-induced chronic bronchitis rat model and evaluate the patho-logical change semi-quantitatively, and study the characteristics of the inflammatory cells in the bronchoalveolar lav-age fluid (BALF) in various stages. Methods Chronic bronchitis sequential rat model was established by passively inhaling smoke mixture. Experiments were performed in 30 young male Sprague-Dawley rats, which comprised 5 groups in random, i.e.,4 chronic bronchitis model groups and 1 control group. After stained with hematoxylin and eosin, the specimens were studied by semi-quantitative method to evaluate the morphologic changes in various stages. Meanwhile, the inflammatory cells of the BALF and the activity of myeloperoxidase (MPO) of lung tissue were analysed. Results During the process of the chronic bronchitis, the pathologic score was increasing as time went on, and the typical morphologic changes of chronic bronchitis emerged in the group 7 weeks. The total number of inflammatory cells in BALF was increasing as time went on, correlated with the pathologic scores (P <0.01). And the percentage of lymphocyte increased as well as positively correlated with pathologic scores (P < 0. 05) , whereas that of macrophage decreased and negatively correlated with pathologic scores (P <0. 05). The MPO lever of lung tissue was correlated with the pathologic scores (P < 0. 01). But the percentage of the neutrophil in the BALF was just in a high level during the first week, then it maintained relatively lower. Conclusion Smoke-induced chronic bronchitis is a slowly progressive inflammation process. The model we established is convenient and simple for the longitudinal study on the inflammatory process of chronic bronchitis and the therapy in the early stage. The semi-quantitative evaluation for the pathological change is with much more value. During the inflammatory sequential process of early stage of chronic bronchitis, the cellular characteristics are similar to that of the common chronic inflammation.
基金Mengchao Youth Talent Development Program,Shanghai Science and Technology Innovation Action Plan-Medical Innovation Research Project(No.22Y11908700,No.22Y11909100).
文摘Background and Objective:Immune checkpoint inhibitor(ICI)-based therapy has achieved impressive success in various cancer types.Several ICIs have been unprecedentedly approved as the treatment regimens for advanced hepatocellular carcinoma(HCC)in recent decade.Meanwhile,numerous clinical trials are being performed to exploit more ICIs into initially unresectable HCC and postoperative HCC to expectantly induce adequate tumor downstaging for further resection or implement adjuvant treatment for relapse-free survival,respectively.In this review,we aim to summarize some pragmatic histomorphologic,immunohistochemical,and molecular pathologic parameters which promisingly indicate the response of neoadjuvant/conversion ICI-related therapy and predict the efficacy of adjuvant/therapeutic ICI-related therapy for HCC.Methods:We searched PubMed using the terms hepatocellular carcinoma,immunotherapy,immune checkpoint inhibitor,immune checkpoint blockade,conversion therapy,neoadjuvant therapy,adjuvant therapy,biomarker,pathologic evaluation,pathologic assessment till February 2023.Key Content and Findings:Although there is no consensus regarding the pathologic evaluation of relevant HCC specimens,it is encouraging that a few of studies have concentrated on this field,and moreover,the methods and parameters noted on other cancer types are also worthy of reference.For the pathologic assessment of HCC specimens underwent immunotherapy,a suitable sampling scheme,identifying immunotherapy-related pathologic response,and quantification of pathologic response rate should be emphasized.For the patients of HCC who are scheduled to receive immunotherapy,tumor-infiltrating lymphocyte,intratumoral tertiary lymphoid structure,programmed cell death ligand 1,Wnt/β-catenin,microsatellite instability and mismatch repair,tumor mutational burden and tumor neoantigen,as well as some other signaling pathways are the potential predictive biomarkers of treatment response of ICI.Conclusions:The management of HCC in the era of immunotherapy arises a brand-new pathological challenge that is to provide an immunotherapy-related diagnostic report.Albeit many related researches are preclinical or insufficient,they may tremendously alter the immunotherapy strategy of HCC in future.