1.Modified Maimendong Decoction Inhibits Lung Cancer Metastasis by Up-Regulating Levels of NK and CD8+ T Cells in Peripheral Blood and Tumor Microenvironment
Zhipeng ZHANG ; Jianhui TIAN ; Zujun QUE ; Ziqi CHEN ; Bin LUO ; Shihui LIU
Cancer Research on Prevention and Treatment 2025;52(6):466-473
Objective To explore the mechanism of modified maimendong decoction (MMD) in inhibiting lung cancer metastasis from the perspective of immune regulation. Methods CTC-TJH-01 and LLC cells were intervened with different concentrations of modified maimendong decoction. The cell proliferation was detected with a CCK-8 kit, apoptosis was detected with an Annexin V-FITC/PI kit, and cell migration was detected through Transwell assays. A lung metastasis model was established through the tail vein injection of LLC cells into C57BL/6 mice, and body weight change and lung tumor metastasis in the mice were evaluated after continuous gavage intervention with MMD. HE staining, immunohistochemistry, and immunofluorescence were employed to observe the histomorphology, Ki-67 protein level, and NK and T cell levels of metastatic lesions. The levels of NK and T cells in the peripheral blood of mice were detected throughflow cytometry. Results MMD had no significant inhibitory effect on the proliferation, apoptosis, and migration of CTC-TJH-01 and LLC cells in vitro. In mice, MMD could significantly inhibit the lung metastasis of LLC cells, increase the proportion of NK and CD8+ T cells in peripheral blood and tumor microenvironment (P<0.05), and reduce the expression of Ki-67 protein in metastatic tumor tissues (P<0.05). Conclusion MMD may inhibit the growth of metastatic tumors by upregulating the expression levels of NK and CD8+ T cells in peripheral blood to promote the elimination of circulating tumor cells, and regulating the infiltration of NK and CD8+ T cells in the immune microenvironment of metastatic tumors, then play an antimetastatic role in lung cancer.
2.Research progress on treatment of pleural effusion related to immune checkpoint inhibitors
Tianqi AN ; Jianhui TIAN ; Yiyang ZHOU ; Bin LUO ; Zujun QUE ; Yao LIU ; Pan YU ; Ruihua ZHAO ; Yun YANG
China Oncology 2025;35(3):333-338
Immunotherapy for cancer,as an emerging treatment modality,has made significant strides in recent years and has become a crucial therapeutic approach following surgery,radiotherapy,chemotherapy,and targeted therapy.In particular,the clinical utilization of immune checkpoint inhibitors(ICIs)has not only enhanced the survival rates of patients with refractory or recurrent tumors but has also significantly optimized the overall strategy for cancer treatment.However,as the population undergoing cancer immunotherapy continues to grow,this expansion not only yields clinical benefits but also precipitates a range of specific adverse reactions known as immune-related adverse events(irAEs).Pleural effusion is a common and severe complication in cancer patients,significantly affecting both their quality of life and treatment outcomes.Typically,tumor-related pleural effusion is often due to pleural metastasis,with malignant pleural effusion(MPE)characterized by rapid growth,being difficult to control,and tendency for recurrence.With the approval of new drugs and the expansion of indications for existing medications,the number of cancer patients receiving ICIs treatment is increasing,bringing ICIs-related pleural effusion into focus.While ICIs treatment-related pleural effusion is relatively rare in clinical practice,it is closely linked to treatment choices of patients and prognosis.Unlike MPE,the pathogenesis of ICIs treatment-related pleural effusion is more complex,not only involving non-specific immune activation leading to autoimmune inflammatory reactions but also potentially related to nodular pleural granulomatous reactions,eosinophilic chronic pleurisy,and tumor-infiltrating lymphocytes.In terms of diagnosis,ICIs treatment-related pleural effusion is typically diagnosed through exclusion,requiring the exclusion of other causes such as tumor progression,radiotherapy,and chemotherapy-induced pleural effusion,adding complexity and difficulty to the diagnostic process.Treatment for ICIs treatment-related pleural effusion often involves glucocorticoids,tocilizumab,or infliximab,aiming to alleviate symptoms and improve prognosis by suppressing excessive immune reactions.Preventing the occurrence of ICIs treatment-related pleural effusion is equally crucial,necessitating comprehensive patient assessment before ICIs administration and continuous monitoring during treatment to promptly detect and manage potential adverse reactions.Through this comprehensive management approach,the impact of ICIs treatment-related pleural effusion on patient quality of life and treatment outcomes can be minimized,optimizing overall treatment results.This review aimed to explore the pathogenesis,histological features,clinical manifestations,diagnostic methods and treatment strategies of ICIs treatment-related pleural effusion,and delve into the characteristics of ICIs treatment-related pleural effusion,in order to enhance understanding of this complication and provide a reference for clinical practice.
3.Research progress on treatment of pleural effusion related to immune checkpoint inhibitors
Tianqi AN ; Jianhui TIAN ; Yiyang ZHOU ; Bin LUO ; Zujun QUE ; Yao LIU ; Pan YU ; Ruihua ZHAO ; Yun YANG
China Oncology 2025;35(3):333-338
Immunotherapy for cancer,as an emerging treatment modality,has made significant strides in recent years and has become a crucial therapeutic approach following surgery,radiotherapy,chemotherapy,and targeted therapy.In particular,the clinical utilization of immune checkpoint inhibitors(ICIs)has not only enhanced the survival rates of patients with refractory or recurrent tumors but has also significantly optimized the overall strategy for cancer treatment.However,as the population undergoing cancer immunotherapy continues to grow,this expansion not only yields clinical benefits but also precipitates a range of specific adverse reactions known as immune-related adverse events(irAEs).Pleural effusion is a common and severe complication in cancer patients,significantly affecting both their quality of life and treatment outcomes.Typically,tumor-related pleural effusion is often due to pleural metastasis,with malignant pleural effusion(MPE)characterized by rapid growth,being difficult to control,and tendency for recurrence.With the approval of new drugs and the expansion of indications for existing medications,the number of cancer patients receiving ICIs treatment is increasing,bringing ICIs-related pleural effusion into focus.While ICIs treatment-related pleural effusion is relatively rare in clinical practice,it is closely linked to treatment choices of patients and prognosis.Unlike MPE,the pathogenesis of ICIs treatment-related pleural effusion is more complex,not only involving non-specific immune activation leading to autoimmune inflammatory reactions but also potentially related to nodular pleural granulomatous reactions,eosinophilic chronic pleurisy,and tumor-infiltrating lymphocytes.In terms of diagnosis,ICIs treatment-related pleural effusion is typically diagnosed through exclusion,requiring the exclusion of other causes such as tumor progression,radiotherapy,and chemotherapy-induced pleural effusion,adding complexity and difficulty to the diagnostic process.Treatment for ICIs treatment-related pleural effusion often involves glucocorticoids,tocilizumab,or infliximab,aiming to alleviate symptoms and improve prognosis by suppressing excessive immune reactions.Preventing the occurrence of ICIs treatment-related pleural effusion is equally crucial,necessitating comprehensive patient assessment before ICIs administration and continuous monitoring during treatment to promptly detect and manage potential adverse reactions.Through this comprehensive management approach,the impact of ICIs treatment-related pleural effusion on patient quality of life and treatment outcomes can be minimized,optimizing overall treatment results.This review aimed to explore the pathogenesis,histological features,clinical manifestations,diagnostic methods and treatment strategies of ICIs treatment-related pleural effusion,and delve into the characteristics of ICIs treatment-related pleural effusion,in order to enhance understanding of this complication and provide a reference for clinical practice.
4.Clinical value of peripheral immune function status in the assessment of'Deficiency of Vital Qi'in lung cancer metastasis
Fan XU ; Jianhui TIAN ; Youjun LIU ; Zhenyang CHENG ; Zujun QUE ; Bin LUO ; Yun YANG ; Jialiang YAO ; Wang YAO ; Xinyi LU ; Yao LIU ; Yiyang ZHOU ; Jianchun WU ; Yingbin LUO ; Minghua LI ; Wenfei SHI ; Yajing CUI ; Wenji SHANGGUAN ; Yan LI
Chinese Journal of Cancer Biotherapy 2025;32(10):1065-1070
Objective:To investigate the association between peripheral immune function status and lung cancer metastasis,and to identify peripheral blood immune biomarkers for'Deficiency of Vital Qi'assessment in lung cancer metastasis.Methods:A retrospective analysis was conducted on peripheral blood immune markers collected before treatment from lung cancer patients admitted into Shanghai Municipal Hospital of Traditional Chinese Medicine,affiliated to Shanghai University of Traditional Chinese Medicine,between March 2023 and April 2025.Patients were categorized into the non-metastatic and the metastatic groups based on the presence of distant metastasis,and the differences in the expressions of immune cells and cytokines between groups were compared.Peripheral blood immune markers with P<0.05 in univariate analysis were incorporated into a multivariate binary logistic regression model to identify independent predictors of lung cancer metastasis.Results:A total of 193 lung cancer patients were included(101 in the non-metastatic group and 92 in the metastatic group).There were no statistically significant differences between the two groups in terms of gender,age,smoking history,drinking history,or pathological type(all P>0.05).Univariate analysis revealed significant differences in multiple immune markers between the non-metastatic and metastatic groups(all P<0.05),including:lymphocyte count,CD3+,CD4+,and CD8+T,CD19+B cells,absolute counts of CD3-CD16+CD56+NK cells,percentages of Treg cells,CD8+CD28+Treg cells,G-MDSC,and CD3-CD16+CD56+dim NK cells,and levels of cytokine IL-1β,IL-6,and IL-10.Binary logistic regression analysis of differential indicators suggested that the percentage of Treg cells and CD8+CD28+Treg cells in peripheral blood were independent predictors of distant metastasis in lung cancer(OR=1.193,95%CI[1.047,1.36],P<0.01;OR=0.978,95%CI[0.957,0.999],P<0.05).Conclusion:Peripheral blood immune dysfunction is the biological basis for'qi deficiency'in lung cancer metastasis.This study quantitatively demonstrates the correlation between peripheral immune function status and lung cancer metastasis,providing empirical evidence for the theories of'qi deficiency and hidden toxicity'and'metastatic state of tumors'.
5.Advancements in Single-cell RNA Sequencing Technology in the Study of the Tumor Microenvironment in Lung Cancer
WANG YANHONG ; LUO BIN ; WANG ZHUO ; QUE ZUJUN ; JIANG LEI ; TIAN JIANHUI
Chinese Journal of Lung Cancer 2024;27(6):441-450
The immune microenvironment plays a key role in the development and progression of tumors.In recent years,with the rapid advancement of high-throughput sequencing technologies,researchers have gained a deeper under-standing of the composition and function of immune cells in the tumor microenvironment.However,traditional bulk sequenc-ing technologies are limited in resolving heterogeneity at the single-cell level,constraining a comprehensive understanding of the complexity of the tumor microenvironment.The advent of single-cell RNA sequencing technology has brought new opportunities to uncover the heterogeneity of the immune microenvironment in lung cancer.Currently,T-cell-centered im-munotherapy in clinical settings is prone to side effects affecting prognosis,such as immunogenic drug resistance or immune-related pneumonia,with the key factor being changes in the interactions between immune cells and tumor cells in the tumor microenvironment.Single-cell RNA sequencing technology can reveal the origins and functions of different subgroups within the tumor microenvironment from perspectives such as intercellular interactions and pseudotime analysis,thereby discovering new cell subgroups or novel biomarkers,providing new avenues for uncovering resistance to immunotherapy and monitoring therapeutic efficacy.This review comprehensively discusses the newest research techniques and advancements in single-cell RNA sequencing technology for unveiling the heterogeneity of the tumor micro environment after lung cancer immunotherapy,offering insights for enhancing the precision and personalization of immunotherapy.
6.Initial Construction of the Tumor Metastatic State Doctrine under the Perspective of Integration of Chinese and Western Medicine
Jianhui TIAN ; Bin LUO ; Zujun QUE ; Yun YANG ; Jialiang YAO ; Yan LI
Journal of Traditional Chinese Medicine 2024;65(20):2065-2069
Based on the concepts of "people-oriented" in traditional Chinese medicine and "tumor-suppression" in modern medicine, we have combed the studies on the spatial and temporal evolution of tumor metastasis and its biological characteristics in different perspectives, and initially proposed the theory of tumor metastasis from the perspective of the dynamic game between the tumor cells and the body's immune system under the theory of the integration of Chinese and Western medicine, that is, the formation of metastasis is the result of the dynamic evolution of the cancer cells and their surrounding environmental factors in the body over time and space. It is believed that the symptomatic manifestation of metastasis is systematic, the triggering factors of metastasis are constant, and the clinical outcome of metastasis is staged. Accordingly, it is proposed to understand the mechanism of metastasis from the perspective of spatial and temporal dynamics, to establish a clinical and pathological model for identifying metastasis, and to reveal the critical point of metastasis, so as to facilitate the change of the research on tumor metastasis from static to dynamic, and provide ideas for the formulation of metastasis prevention and treatment strategies, and the construction of a new system of metastasis prevention and treatment in the clinical tumor field.
7.Feiji Formula inhibits the migration and invasion of lung cancer cells and lung metastasis in animal models by regulating complement-related proteins CFHR5/MBL2/C9
Bin LUO ; Yanhong WANG ; Jiajun LIU ; Shihui LIU ; Xinyi LU ; Jiaxuan LI ; Zujun QUE ; Jianhui TIAN
Chinese Journal of Cancer Biotherapy 2024;31(12):1194-1203
Objective:To investigate the effects of Feiji Formula on the migration and invasion of lung cancer cells,as well as lung metastasis in animal models and explore its possible mechanisms.Methods:TNMplot,TCGA,and DAVID databases were used to analyze the expression of complement-related proteins(CFHR5[complement factor H-related protein 5],MBL2[mannose-binding lectin 2],C9[complement component 9])in lung metastatic tissues and their relationship with immune cell infiltration,as well as related biological processes and signaling pathways.A subcutaneous xenograft mice model was established using 2LL cells.Mice were administered 2 g/mL Feiji Formula decoction(0.2 mL per dose)via oral gavage for 21 days.The effects of Feiji Formula on the incidence of lung metastasis,the number of lung metastatic nodules,and the protein expression of CFHR5/MBL2/C9 in the lung tissues of the model mice were observed.Exosome tracing assay was performed to observe the secretion and uptake of exosomes by CTC-TJH-01 and H1299 cells.Different concentrations of Feiji Formula were applied to treat H1299 and CTC-TJH-01 cells,and its effects on cell viability,invasion,migration,and CFHR5/MBL2/C9 protein expression were detected by CCK-8,scratch healing assay,Transwell assay,and WB method.Results:Network pharmacology analysis showed that CFHR5/MBL2/C9 proteins were highly expressed in lung metastatic tissues(all P<0.05)and were closely related to the complement system involved in immune response regulation.Compared with the control group,the Feiji Formula group demonstrated a significant reduction in the number of lung metastatic nodules(P<0.05).Feiji Formula(0-200 μg/mL)had no significant effect on the viability of H1299 and CTC-TJH-01 cells(both P>0.05).Both CTC-TJH-01 and H1299 cells could secrete and uptake each other's exosomes.Compared with the 0 μg/mL control group,Feiji Formula at concentrations of 50-200 μg/mL significantly inhibited the migration and invasion abilities of H1299 and CTC-TJH-01 cells(P<0.05 or P<0.01),and significantly reduced the protein expression levels of CFHR5 and MBL2(P<0.05 or P<0.01).Notably,the expression level of C9 protein in CTC-TJH-01 cells increased only after treatment with 200 μg/mL Feiji Formula(P<0.05).Conclusion:Feiji Formula can inhibit the migration and invasion of lung cancer cells as well as lung metastasis in model mice by regulating complement-associated proteins CFHR5/MBL2/C9.This effect may be related to exosome-mediated intercellular communication.
8.Jinfukang Inhibits Lung Cancer Metastasis by Regulating Immune Senescence
Wang YAO ; Zujun QUE ; Jialiang YAO ; Pan YU ; Bin LUO ; Jianhui TIAN
Cancer Research on Prevention and Treatment 2022;49(11):1134-1138
Objective To explore the effect of immune senescence on lung cancer metastasis and reveal the mechanism of Fuzheng traditional Chinese medicine Jinfukang in the prevention and treatment of the metastasis. Methods A lung metastasis model of Lewis lung cancer cells was established in C57BL/6 mice with different ages (15 months, 6 months, and 2 months). Mice in the 6-month-old group were given Jinfukang intragastrically for 42 days. Pulmonary metastasis was analyzed by
9.Progress on metastasis induced by myeloid-derived suppressor cells to promote circu-lating tumor cell
Bin LUO ; Zujun QUE ; Jianhui TIAN
Chinese Journal of Clinical Oncology 2016;43(11):493-497
Circulating tumor cells (CTCs), as the seeds of tumor metastasis, manage to escape from immune clearance both in microen-vironment and in peripheral blood. CTCs can also facilitate formation of pre-existing environment, which is the crucial step in metasta-sis. Myeloid-derived suppressor cells (MDSC), as a group of immunosuppressive cells derived from bone marrow cells, may play a key role in this process. In this review, the progress in MDSC and its role in the formation, survival, and immune escape of CTCs were exten-sively discussed to explore a new target for tumor immunotherapy.
10.A study of the interference and influence of sample hemolysis on biochemical test results and its the countermeasures
Zujun LUO ; Dexue ZOU ; Qiang WANG ; Zhongren CAI ; Yanfen XUE ; Qirong LIN
Chongqing Medicine 2014;(22):2879-2880,2883
Objective To observe the interference and influence of sample hemolysis on biochemical test results and to make cor-responding countermeasures based on the research results .Methods There were 58 cases of people who underwent physical exami-nation in the hospital .They were selected as study objects .Sample of venous blood was 5 mL in fasting .After natural coagulation and centrifugation ,K+ ,Na+ in blood were measured ,followed by the TP ,CK ,CK-MB ,AST ,ALB ,TG ,HDL ,LDH ,HBDH and other biochemical indexes .Then all indexes mentioned above were detected again after the sample hemolysis of serum ,and analysis results were compared between them .Results Of biochemical indicators detected before and after the determination of hemolysis , there were of statistical significance in the differences in K + ,Na+ ,TP ,CK ,CK-MB ,AST ,LDH and HBDH(P<0 .05);but there were no significant differences in biochemical indicators like ALB ,HDL and TG(P>0 .05) .Through regression analysis ,biochemi-cal indicators such as K + ,Na+ ,TP ,CK ,CK-MB ,AST ,LDH and HBDH were found to be related to hemolysis .Conclusion Sample hemolysis has certain influences on the results of biochemical test in terms of K + ,Na+ ,TP ,CK ,CK-MB ,AST ,LDH and HBDH , which is of certain application value with the proofreading of serum Hb concentration .

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