1.Treatment Strategies for Postoperative Complications of Lung Cancer from Protecting Healthy Qi and Treating Qi
Jiajun SONG ; Yichao WANG ; Xueqi TIAN ; Yi LIU ; Lijing JIAO ; Ling XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):94-105
Pulmonary complications, the most common postoperative complications of lung cancer, not only affect the quality of life of the patients after surgery but also increase the prognostic risks of postoperative recurrence and metastasis, threatening the life safety. At present, a multidisciplinary model of diagnosis and rehabilitation with integrated traditional Chinese medicine (TCM) and Western medicine has been initially formed under the guidance of the concept of rapid rehabilitation post operation for lung cancer. However, the treatment that only aims at shortening hospital stay and reducing the incidence of postoperative complications does not pay enough attention to the postoperative functional rehabilitation of the lung and the impact of follow-up adjuvant therapy, which affects the completeness of rehabilitation. This paper classifies the typical postoperative symptoms and manifestations of lung cancer into five groups: Lung system, emotion, digestive tract, pain, and nerve. On this basis, this paper summarizes the three core pathogeneses of postoperative complications of lung cancer as failure of Qi to ascend and descend leading to insecurity of defensive exterior, vessel block leading to Qi stagnation and fluid retention, and lung Qi deficiency leading to spleen and kidney deficiency. Accordingly, this paper proposes the treatment principle of protecting healthy Qi and treating Qi with the core of descending-tonifying-ascending-dispersing Qi and puts forward three treatment methods. The first is replenishing Qi and consolidating exterior, and expelling phlegm and regulating lung. The second is replenishing Qi and promoting blood flow to resolve stasis and relieving pain. The third is replenishing Qi and tonifying lung, and invigorating spleen and tonifying kidney. Furthermore, this paper elaborates on the pathogenesis and treatment principles of four common postoperative complications: Lung infection, pleural effusion, atelectasis, and bronchopleural fistula. On the basis of Western medical treatment, the TCM treatment characteristics of treating symptoms in the acute phase and eradicating the root cause in the chronic phase should be played. While dispelling the pathogen, measures should be taken to protect the healthy Qi, including tonifying lung Qi, regulating spleen Qi, and replenishing kidney Qi. This study summarizes the pathogenesis and treatment strategy of common postoperative complications of lung cancer according to the principle of protecting healthy Qi and treating Qi, aiming to provide guidance for the future treatment of postoperative complications of lung cancer.
2.Research progress of Pinellia ternata and its active ingredients in car-diovascular diseases
Min SONG ; Tingting DIAO ; Yichao WANG ; Luyi LIU ; Qiqi QI ; Jingjing BI ; Nailiang ZHU ; Xinrong QIAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):251-264
Cardiovascular diseases(CVD)are chronic disease with high morbidity and mortality in the world.Pinellia ternatais a traditional Chi-nese medicinal herb and has the effects on drying dampness,resolving phlegm,lowering symptoms,stopping vomiting and relieving swelling.In recent years,researches showed that Pinellia ternataand its active ingredients(β-sitosterol,baicalin,baica-lein,quercetin)had significant effects in the treat-ment of cardiovascular diseases.This review sum-marized and analyzed the role and mechanism of Pinellia ternata and its active ingredients in cardio-vascular diseases,which provided a theoretical ba-sis for its clinical application.
3.Preparation of Trop2-targeted chimeric antigen receptor T cells and study of their exhaustion status in vitro
Xiuying LIU ; Xinzhan LI ; Jingjing ZHU ; Jingjing LIU ; Yichao FENG ; Jianxun WANG
Journal of Army Medical University 2025;47(15):1750-1759
Objective To design and construct chimeric antigen receptor(CAR)T cells targeting Trop2,establish an in vitro cell exhaustion model through continuous antigen stimulation,and investigate their anti-tumor activity and exhaustion characteristics.Methods The second-generation CAR plasmid was constructed based on the single-chain variable fragment(scFv)sequence of Sacituzumab Govitecan targeting Trop2.The viral vector titer was determined by retroviral vector packaging and gradient dilution.Peripheral blood mononuclear cells(PBMCs)from healthy donors were isolated using Ficoll density gradient centrifugation,and CAR virus vectors were transduced into PBMCs activated with OKT-3/IL-2 to generate Trop2-targeted CAR T cells.CAR expression levels were assessed by flow cytometry using MYC tags.In vitro 3 tumor cell models were established,including human ovarian cancer cells(SKOV3),human breast cancer cells(MDA-MB-453),and human lung cancer cells(A549).The expression of the Trop2 antigen in these models was confirmed using flow cytometry.Additionally,luciferase assay was employed to evaluate the cytotoxic efficiency of Trop2-targeted therapy at various effector-to-target ratios.An in vitro CAR-T exhaustion model was developed,and the long-term killing ability of CAR-T cells was dynamically monitored using the Incucyte live-cell imaging system.The PD-1/TIM-3 phenotype of CAR-T cells was analyzed by flow cytometry,and cytokine secretion levels were quantified using the cytometric bead array(CBA).Transcriptomic sequencing and RT-qPCR were employed to validate the differentially expressed genes associated with exhaustion.Results The second-generation CAR T cells targeting Trop2 were successfully constructed.Compared to the P-T group,in vitro experiments demonstrated that these CAR T cells exhibited antigen-specific and dose-dependent cytotoxic effects against tumor cells with high Trop2 expression,such as MDA-MB-453 and SKOV3.A CAR-T cell exhaustion model established through repeated tumor antigen stimulation in vitro revealed that,compared to the initial state,the exhausted Trop2 CAR-T cells exhibited significantly reduced tumor-killing capacity while P-T cells showed almost no killing effect,the expression of inhibitory receptors(PD-1 and TIM-3)was up-regulated on the surface of exhausted CAR-T cells,and the secretion of effector cytokines was diminished.Transcriptomic analysis identified multiple differentially expressed genes in the exhausted CAR-T cells.Pathways related to immune response and T cell receptor signaling were down-regulated,while apoptosis-related pathways were activated.RT-qPCR further confirmed abnormal expression of immunoregulatory genes,including IL3,IL5,and IL13(P<0.05).Conclusion During continuous in vitro tumor antigen stimulation,the second-generation CAR-T cells targeting the Trop2 antigen demonstrate declined anti-tumor activity,weakened effector function and up-regulated expression of exhaustion-related molecules.
4.Mechanisms of Neiyiting Decoction in Preventing Postoperative Recurrence of Endometriosis by Inhibiting Macrophage M1 Polarization Through the TREM1/TLR4/NF-κB Signaling Pathway
Lijuan LU ; Weiwei ZENG ; Jingwen WANG ; Lurong ZHANG ; Ying LIU ; Xueliang SUN ; Wen XU ; Xiaohui FANG ; Yichao YAN ; Qinhua XIA
Journal of Sichuan University (Medical Sciences) 2025;56(2):371-381
Objective The high post-surgery recurrence rate of endometriosis(EMs)has emerged as a challenge in the long-term manaagement of the condition.This study is aimed at investigating the mechanisms of Neiyiting(NYT)decoction in preventing postoperative recurrence of EMs.Methods An animal model of EMs postoperative recurrence and a model of endometrial stromal cells(hEM15A)cocultured with macrophages(RAW 264.7 cell line)were established for both in vivo and in vitro experiments.An autotransplantation method was used to establish a rat model of EMs.The rats were divided into 4 groups(6 rats per group)and received the corresponding treatments:a Model group receiving distilled water,a Gestrinone group receiving gestrinone at 0.325 mg/kg,a low-dose NYT(NYT-L)group receiving NYT decoction at 5.04 g/(kg-d),and a high-dose NYT(NYT-H)group receiving NYT decoction at 10.08 g/(kg-d).The treatment was administered for 3 weeks via intragastric gavage.In addition,6 SD rats were randomly selected for the control group(Control group),and were given distilled water for 3 weeks via intragastric gavage.The sizes and pathological changes of recurrent lesions in EMs rats were observed.Immunohistochemistry and qRT-PCR were performed to assess the expression of M1 macrophage marker CD86 protein and mRNA in vivo.Additionally,immunohistochemistry and qRT-PCR were used to assess the expression of indicator proteins related to the triggering receptor expressed on myeloid cells 1(TREM1)/Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling pathway and mRNA.The proliferation of hEM15A cells in the coculture experiment was observed.Flow cytometry was performed to determine the polarization of RAW264.7 macrophages,and qRT-PCR was used to determine the expression levels of inducible nitric oxide synthase(iNOS)and interleukin 1β(IL-1β)mRNA.Western blot was performed to determine the expression of signaling pathway-related indicator proteins in vitro.ELISA was performed to determine the levels of inflammatory factors in vitro.Results Compared with the Model group,the volume of recurrent lesions in the NYT-H group was reduced(P<0.01).Findings from the macrophage M1 polarization assessment showed that the expression levels of CD86 protein and mRNA in the recurrent lesions of the Model group were higher than those in the control group(P<0.01).The expression levels of CD86 protein and mRNA in the recurrent lesions of the NYT-H group were lower than those of the Model group(P<0.01).In addition,the RAW 264.7 cell experiment further verified that NYT decoction could reduce the number of CD86-positive macrophages induced by plasmids overexpressing TREM1 and reduce the expression of IL-1β and iNOS mRNA(P<0.01).The results of the hEM15A cell proliferation assay showed that NYT decoction down-regulated KI-67 protein expression in hEM15A cells induced by macrophage M1 polarization(P<0.01).The results of TREM1/TLR4/NF-κB signaling pathway showed that the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the Model group were higher than those of the control group(P<0.01).Compared with those in the Model group,the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the NYT-H group were lower(P<0.01).In addition,the coculture experiment of RAW264.7 and hEM15A cells further confirmed that NYT decoction reduced the expression of TREM1,TLR4,and P-P65 proteins(P<0.01).Conclusion NYT decoction can inhibit macrophage M1 polarization through the TREM1/TLR4/NF-κB signaling pathway,improve the inflammation level,and inhibit the formation of ectopic endometrial lesions,thereby preventing postoperative recurrence of EMs.
5.Research progress of Pinellia ternata and its active ingredients in car-diovascular diseases
Min SONG ; Tingting DIAO ; Yichao WANG ; Luyi LIU ; Qiqi QI ; Jingjing BI ; Nailiang ZHU ; Xinrong QIAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):251-264
Cardiovascular diseases(CVD)are chronic disease with high morbidity and mortality in the world.Pinellia ternatais a traditional Chi-nese medicinal herb and has the effects on drying dampness,resolving phlegm,lowering symptoms,stopping vomiting and relieving swelling.In recent years,researches showed that Pinellia ternataand its active ingredients(β-sitosterol,baicalin,baica-lein,quercetin)had significant effects in the treat-ment of cardiovascular diseases.This review sum-marized and analyzed the role and mechanism of Pinellia ternata and its active ingredients in cardio-vascular diseases,which provided a theoretical ba-sis for its clinical application.
6.Analysis of predictive value of enhanced CT combined with MRI examination on prognosis of clear cell renal cell carcinoma and its correlation with clinical features
Kunfeng XU ; Xiaohui QIU ; Yichao LIU ; Xiuming DONG
China Medical Equipment 2025;22(1):30-35
Objective:To investigate the predictive value of enhanced computed tomography (CT) combined with magnetic resonance imaging (MRI) examination on prognosis of clear cell renal cell carcinoma (ccRCC) and its correlation with clinical features. Methods:The postoperative follow-up data of enhanced CT and MRI of 80 patients with suspected (ccRCC) who admitted to Bozhou People's Hospital from March 2019 to May 2023 were selected,and they were divided into disease progression group (24 cases) and disease progression-free group (56 cases) according to the condition of disease progression. The disease progression of them were diagnosed through relevant examinations (collection of disease history,physical examination,enhanced CT,MRI,laboratory examination,pathological examination and so on). According to the information of clinical imaging,the age,gender,tumor diameter,with or without tumor thrombus,the location of tumor and surgical method were used to conduct single factor logistic regression analysis,so as to confirm independent predictors. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of enhanced CT combined with MRI to the prognosis of ccRCC. The Pearson linear correlation was adopted to analyze the correlation between the results of enhanced CT combined with MRI and prognosis. Results:Based on the results of the follow-up study,CT value of cortex phase,CT value of medullary phase and apparent dispersion coefficient (ADC) in the disease progression group were significantly smaller than those in the disease progression-free group,and the differences of them between two groups were statistically significant (t=10.610,4.697,2.901,P<0.05),respectively. The diffusion coefficient (K value) of disease progression group was significantly larger than that of disease progression-free group,and there was significant difference between the two groups (t=6.375,P<0.05),while there was no significant in diffusion rate (D) between the two groups (P>0.05). The area under curve (AUC) values of ROC curve of single enhanced CT examination,single MRI examination and the combined examination of them were larger than 0.5 in predicting the prognosis of ccRCC,which indicated that both the two examinations had a certain value in predicting the prognosis of ccRCC,and the AUC value of combined examination was the highest (0.940),which indicated the value of combined examination was the highest in predicting the prognosis of ccRCC. There were not significant differences in gender,surgical method,tumor thrombus and tumor location between the two groups (P>0.05). The age and tumor diameter of the disease progression group were significantly larger than those of the disease progression-free group (t=4.292,3.219,P<0.05),respectively. The results of the logistic regression analysis showed that the age and tumor diameter were respectively independent influencing factor on the prognosis of ccRCC (HR=2.167,0.689,P<0.05). The results of Pearson correlation analysis indicated that there was negative correlation between enhanced CT examination and prognosis (r=-0.65,P<0.05),and there was positive correlation between MRI examination and prognosis (r=0.72,P<0.05). In addition,there was a negative correlation in the results between enhanced CT examination and MRI examination (r=-0.58,P<0.05). Conclusion:The prediction of enhanced CT combined with MRI examination is higher than that of each single examination of them for the prognosis of ccRCC,and there is a certain correlation between that and clinical features,but it is still necessary to conduct comprehensive judgement after combines other influence factors in clinical practice.
7.Analysis of predictive value of enhanced CT combined with MRI examination on prognosis of clear cell renal cell carcinoma and its correlation with clinical features
Kunfeng XU ; Xiaohui QIU ; Yichao LIU ; Xiuming DONG
China Medical Equipment 2025;22(1):30-35
Objective:To investigate the predictive value of enhanced computed tomography (CT) combined with magnetic resonance imaging (MRI) examination on prognosis of clear cell renal cell carcinoma (ccRCC) and its correlation with clinical features. Methods:The postoperative follow-up data of enhanced CT and MRI of 80 patients with suspected (ccRCC) who admitted to Bozhou People's Hospital from March 2019 to May 2023 were selected,and they were divided into disease progression group (24 cases) and disease progression-free group (56 cases) according to the condition of disease progression. The disease progression of them were diagnosed through relevant examinations (collection of disease history,physical examination,enhanced CT,MRI,laboratory examination,pathological examination and so on). According to the information of clinical imaging,the age,gender,tumor diameter,with or without tumor thrombus,the location of tumor and surgical method were used to conduct single factor logistic regression analysis,so as to confirm independent predictors. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of enhanced CT combined with MRI to the prognosis of ccRCC. The Pearson linear correlation was adopted to analyze the correlation between the results of enhanced CT combined with MRI and prognosis. Results:Based on the results of the follow-up study,CT value of cortex phase,CT value of medullary phase and apparent dispersion coefficient (ADC) in the disease progression group were significantly smaller than those in the disease progression-free group,and the differences of them between two groups were statistically significant (t=10.610,4.697,2.901,P<0.05),respectively. The diffusion coefficient (K value) of disease progression group was significantly larger than that of disease progression-free group,and there was significant difference between the two groups (t=6.375,P<0.05),while there was no significant in diffusion rate (D) between the two groups (P>0.05). The area under curve (AUC) values of ROC curve of single enhanced CT examination,single MRI examination and the combined examination of them were larger than 0.5 in predicting the prognosis of ccRCC,which indicated that both the two examinations had a certain value in predicting the prognosis of ccRCC,and the AUC value of combined examination was the highest (0.940),which indicated the value of combined examination was the highest in predicting the prognosis of ccRCC. There were not significant differences in gender,surgical method,tumor thrombus and tumor location between the two groups (P>0.05). The age and tumor diameter of the disease progression group were significantly larger than those of the disease progression-free group (t=4.292,3.219,P<0.05),respectively. The results of the logistic regression analysis showed that the age and tumor diameter were respectively independent influencing factor on the prognosis of ccRCC (HR=2.167,0.689,P<0.05). The results of Pearson correlation analysis indicated that there was negative correlation between enhanced CT examination and prognosis (r=-0.65,P<0.05),and there was positive correlation between MRI examination and prognosis (r=0.72,P<0.05). In addition,there was a negative correlation in the results between enhanced CT examination and MRI examination (r=-0.58,P<0.05). Conclusion:The prediction of enhanced CT combined with MRI examination is higher than that of each single examination of them for the prognosis of ccRCC,and there is a certain correlation between that and clinical features,but it is still necessary to conduct comprehensive judgement after combines other influence factors in clinical practice.
8.Xuebijing enhances antitumor efficacy of anti-CD19 CAR-T cells
Jingjing Zhu ; Jing Zhang ; Ping Wang ; Xiuying Liu ; Jingjing Liu ; Yichao Feng ; Mary Yue Jiang ; Zhiqiao Feng ; Xiaoqing Yao ; Jianxun Wang
Journal of Traditional Chinese Medical Sciences 2024;11(4):466-475
Objective:
To investigate the effects and mechanisms of Xuebijing injection (XBJ) on Chimeric antigen receptor-T (CAR-T) cell function and its therapeutic potential against CAR-T therapy-associated cytokine storms (CRS).
Methods:
Anti-CD19 CAR-T cells were established based on FMC63 antibodies. Different doses of XBJ (1 and 10 mg/mL) were added to the culture system. Untreated anti-CD19 CAR-T cells served as negative controls. After 48-h co-culture, the effects of XBJ on CAR-T cell function were assessed. Carboxyfluorescein diacetate succinimidyl ester staining was used to assess the effect of XBJ on CAR-T cell proliferation. Flow cytometry, luciferase reporter gene assays, and real time cellular analysis were employed to evaluate the effects of XBJ on CAR-T cell cytotoxicity in vitro. RNA-sequencing was performed to analyze the effects of XBJ on CAR-T cell gene expression. Network pharmacology predicted potential XBJ therapeutic targets for CRS, which were verified in a THP-1 macrophage inflammation model.
Results:
XBJ enhanced both the proliferation and tumor killing capacities of CAR-T cells. Transcriptome analysis showed that XBJ treatment affects multiple genes and pathways in CAR-T cells, with differential gene enrichment in multiple cell proliferation and growth factor pathways. Potential targets for CRS control by XBJ were predicted using network pharmacology, and the inhibitory effect of XBJ on the expression of relevant genes was verified using a macrophage model.
Conclusion
The results of this study indicate that XBJ can enhance the killing effect of CAR-T cells on tumor cells and that the mechanism is related to the regulation of T cell proliferation and activation. Moreover, XBJ inhibited excessive inflammation associated with CAR-T therapy. However, the current findings remain to be further validated through in vivo experiments.
9.Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma.
Zhikun LIU ; Yichao WU ; Abid Ali KHAN ; L U LUN ; Jianguo WANG ; Jun CHEN ; Ningyang JIA ; Shusen ZHENG ; Xiao XU
Journal of Zhejiang University. Science. B 2024;25(1):83-90
Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).
Humans
;
Aged
;
Sarcopenia/diagnostic imaging*
;
Carcinoma, Hepatocellular/diagnostic imaging*
;
Muscle, Skeletal/diagnostic imaging*
;
Deep Learning
;
Prognosis
;
Radiomics
;
Liver Neoplasms/diagnostic imaging*
;
Retrospective Studies
10.Construction of Raji-Luc CD19 KO Lymphoma Cell Line Using CRISPR/Cas9 Technology
Jingjing LIU ; Xiuying LIU ; Yaru FENG ; Yichao FENG ; Mengyuan YU ; Jianxun WANG
Journal of Modern Laboratory Medicine 2024;39(1):10-15,99
Objective To construct Raji-Luc lymphoma cells with CD19 knockout using CRISPR/Cas9 technology and preliminarily validate their immune escape ability.Methods PB-CRISPR-CD19 small guide RNA(sgRNA)plasmids was constructed,the optimal sgRNA sequence was screened,and Raji-Luc cells with pCAG-PBase,PB-CD19 sgRNA,and PB-CRISPR-Cas9 were co-transfected.Stable knockout monoclonal cell lines were screened by flow sorting and limit dilution method and the knockout effect was verified through gene sequence testing.The expression of luciferase on the surface of the cell line was detected by microplate reader,CD19 CAR-T and CD38 CAR-T previously constructed in the laboratory were used as effector cells,and the immune escape ability of Raji-Luc CD19 KO cell line was verified by universal luciferase chemiluminescence method.Results The transfection efficiency of Raji-Luc CD19 KO cells prepared by electro transfection was high,and the knockout efficiency of the two monoclonal cells was more than 99%.There was no significant difference in luciferase expression compared to the original Raji-Luc cells,and CD19 CAR-T cells could not be activated to the kill them.Conclusion Successfully constructed Raji-Luc CD19 KO lymphoma cell line.


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