1.Predictive value of pre-treatment circulating tumor DNA genomic landscape in patients with relapsed/refractory multiple myeloma undergoing anti-BCMA CAR-T therapy: Insights from tumor cells and T cells
Rongrong CHEN ; Chunxiang JIN ; Kai LIU ; Mengyu ZHAO ; Tingting YANG ; Mingming ZHANG ; Pingnan XIAO ; Jingjing FENG ; Ruimin HONG ; Shan FU ; Jiazhen CUI ; Simao HUANG ; Guoqing WEI ; He HUANG ; Yongxian HU
Chinese Medical Journal 2025;138(19):2481-2490
Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.
2.Predictive value of pre-treatment circulating tumor DNA genomic landscape in patients with relapsed/refractory multiple myeloma undergoing anti-BCMA CAR-T therapy: Insights from tumor cells and T cells.
Rongrong CHEN ; Chunxiang JIN ; Kai LIU ; Mengyu ZHAO ; Tingting YANG ; Mingming ZHANG ; Pingnan XIAO ; Jingjing FENG ; Ruimin HONG ; Shan FU ; Jiazhen CUI ; Simao HUANG ; Guoqing WEI ; He HUANG ; Yongxian HU
Chinese Medical Journal 2024;138(19):2481-2490
BACKGROUND:
B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.
METHODS:
Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.
RESULTS:
In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS.
CONCLUSION:
Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.
REGISTERATION
Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).
3.Integrating transcriptomics, metabolomics, and network pharmacology to investigate multi-target effects of sporoderm-broken spores of Ganoderma lucidum on improving HFD-induced diabetic nephropathy rats.
Lidan HU ; Lili YU ; Zhongkai CAO ; Yue WANG ; Caifeng ZHU ; Yayu LI ; Jiazhen YIN ; Zhichao MA ; Xuelin HE ; Ying ZHANG ; Wunan HUANG ; Yuelin GUAN ; Yue CHEN ; Xue LI ; Xiangjun CHEN
Journal of Pharmaceutical Analysis 2024;14(12):101105-101105
Diabetes mellitus (DM) is a major metabolic disease endangering global health, with diabetic nephropathy (DN) as a primary complication lacking curative therapy. Sporoderm-broken spores of Ganoderma lucidum (GLP), an herbal medicine, has been used for the treatment of metabolic disorders. In this study, DN was induced in Sprague-Dawley rats using streptozotocin (STZ) and a high-fat diet (HFD), and the protective mechanisms of GLP were investigated through transcriptomic, metabolomic, and network pharmacology (NP) analyses. Our results demonstrated that GLP intervention ameliorated renal damage and inflammation levels in DN rats. Integrative metabolomic and transcriptomic analysis revealed that GLP treatment modulated glucose and cellular energy metabolisms by regulating relevant genes. GLP significantly suppressed the inflammations by impacting glucose and energy metabolism-related gene expression (Igfbp1 and Angptl4) and enhanced metabolic biomarkers of 4-Aminocatechol. In addition, NP analysis further indicated that GLP may efficiently alleviate DN via immune-related pathways. In conclusion, this study provides supportive evidence of the anti-inflammatory effects of GLP supplements, highlighting their potential for promising clinical applications in treating DN.
4.Integrating transcriptomics,metabolomics,and network pharmacology to investigate multi-target effects of sporoderm-broken spores of Ganoderma lucidum on improving HFD-induced diabetic nephropathy rats
Lidan HU ; Lili YU ; Zhongkai CAO ; Yue WANG ; Caifeng ZHU ; Yayu LI ; Jiazhen YIN ; Zhichao MA ; Xuelin HE ; Ying ZHANG ; Wunan HUANG ; Yuelin GUAN ; Yue CHEN ; Xue LI ; Xiangjun CHEN
Journal of Pharmaceutical Analysis 2024;14(12):1906-1920
Diabetes mellitus(DM)is a major metabolic disease endangering global health,with diabetic ne-phropathy(DN)as a primary complication lacking curative therapy.Sporoderm-broken spores of Ganoderma lucidum(GLP),an herbal medicine,has been used for the treatment of metabolic disorders.In this study,DN was induced in Sprague-Dawley rats using streptozotocin(STZ)and a high-fat diet(HFD),and the protective mechanisms of GLP were investigated through transcriptomic,metabolomic,and network pharmacology(NP)analyses.0ur results demonstrated that GLP intervention ameliorated renal damage and inflammation levels in DN rats.Integrative metabolomic and transcriptomic analysis revealed that GLP treatment modulated glucose and cellular energy metabolisms by regulating relevant genes.GLP significantly suppressed the inflammations by impacting glucose and energy metabolism-related gene expression(Igfbp1 and Angptl4)and enhanced metabolic biomarkers of 4-Aminocatechol.In addition,NP analysis further indicated that GLP may efficiently alleviate DN via immune-related pathways.In conclusion,this study provides supportive evidence of the anti-inflammatory effects of GLP supplements,highlighting their potential for promising clinical applications in treating DN.
5.Surgical treatment strategy for acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries
Jianji WANG ; Runqiao LI ; Jiazhen MEI ; Yongliang ZHONG ; Yu XIA ; Chengnan LI ; Zhiyu QIAO ; Haiou HU ; Yipeng GE ; Junming ZHU
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(11):660-663
Objective:To explore surgical strategies for acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries.Methods:From January 2019 to March 2023, a total of 29 patients with acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries were included in the study. All patients underwent emergency surgery, with simultaneous intraoperative neck incision and replacement of the unilateral or bilateral carotid arteries. Among them, there were 19 males with a mean age of(49.57±2.14)years old. Preoperative brain CT indicated abnormalities in 15 cases, transient neurological dysfunction occurred in 5 cases, and syncope in 1 case.Results:Procedures included ascending aorta replacement in 10 cases, Bentall procedure in 18 cases, and Wheat procedure in 1 case. Arch operations involved partial arch replacement in 3 cases and Sun’s procedure in 26 cases. Simple left carotid artery replacement was performed in 6 cases, simple right carotid artery replacement in 19 cases, and bilateral carotid artery replacement in 4 cases. Cerebral protection measures during circulatory arrest included unilateral cerebral perfusion in 24 cases and bilateral cerebral perfusion in 5 cases. The mean operation time was(7. 6±0. 3) h, with a mean cardiopulmonary bypass time of(196. 3±8. 7) min, aortic cross-clamp time of(113.2±6.4) min, ischemic time 12(5-16.5) min, and lowest temperature of(26.3±0.4)°C. One patient experienced in-hospital mortality. Postoperatively, new neurological dysfunction occurred in 2 cases, including 1 case with coma and permanent neurological deficit.Conclusion:In patients with acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries, simultaneous carotid artery replacement via neck incision during aortic surgery is a safe and reliable surgical approach.
6.Some Thoughts and Practices on Demand-Driven School Dissemination of Ancient TCM Books:A Case Study of Zhejiang Chinese Medical University Libraries
Hongyue ZHENG ; Jiazhen ZHU ; Meijun HU
Journal of Zhejiang Chinese Medical University 2024;48(11):1384-1390
[Objective]To summarize the results,value and advantages of demand-driven school dissemination of ancient books of traditional Chinese medicine.[Methods]By employing methods such as literature research and empirical studies,this paper,on the basis of reviewing the deficiencies in the current dissemination of ancient books,emphasizes the decisive value of the "demand" factor and further introduces practical measures for on-campus dissemination of ancient medical texts based on a demand-driven approach.These measures include the implantation of concepts,resolution of technical difficulties in reading ancient books,proactive integration with teaching and research,and platform construction.[Results]The supply-driven dissemination,which has a problem that there is a heat supply side and cold demand side,is relatively indifferent to the needs of elite groups.And its communication mode is ultimately inefficient.After the implementation of the demand-driven dissemination strategy for three years,the annual borrowing volume of medical literature among college students,the number and quality of research papers published by teachers and students sharp have increased.Therefore,the construction of the library's ancient books and related popular science platforms has reached a new level.[Conclusion]Through the case study of campus dissemination of ancient books in Zhejiang Chinese Medical University,explore the implementation of the demand-driven dissemination strategy,give the dissemination endogenous impetus,embodies its unique advantages,and effectively improves the communication efficiency.
7.Some Thoughts and Practices on Demand-Driven School Dissemination of Ancient TCM Books:A Case Study of Zhejiang Chinese Medical University Libraries
Hongyue ZHENG ; Jiazhen ZHU ; Meijun HU
Journal of Zhejiang Chinese Medical University 2024;48(11):1384-1390
[Objective]To summarize the results,value and advantages of demand-driven school dissemination of ancient books of traditional Chinese medicine.[Methods]By employing methods such as literature research and empirical studies,this paper,on the basis of reviewing the deficiencies in the current dissemination of ancient books,emphasizes the decisive value of the "demand" factor and further introduces practical measures for on-campus dissemination of ancient medical texts based on a demand-driven approach.These measures include the implantation of concepts,resolution of technical difficulties in reading ancient books,proactive integration with teaching and research,and platform construction.[Results]The supply-driven dissemination,which has a problem that there is a heat supply side and cold demand side,is relatively indifferent to the needs of elite groups.And its communication mode is ultimately inefficient.After the implementation of the demand-driven dissemination strategy for three years,the annual borrowing volume of medical literature among college students,the number and quality of research papers published by teachers and students sharp have increased.Therefore,the construction of the library's ancient books and related popular science platforms has reached a new level.[Conclusion]Through the case study of campus dissemination of ancient books in Zhejiang Chinese Medical University,explore the implementation of the demand-driven dissemination strategy,give the dissemination endogenous impetus,embodies its unique advantages,and effectively improves the communication efficiency.
8.Research progress in nutritional support for liver cirrhosis patients
Yumei HE ; Liping WU ; Zhiming WANG ; Menghao HAO ; Ling HU ; Jiazhen LI ; Xiaobin SUN
Journal of Clinical Hepatology 2022;38(12):2846-2849
Malnutrition in liver cirrhosis is associated with ascites, hepatic encephalopathy, infection, and other complications even death. To date, the hazard and disease burden of malnutrition in cirrhosis patients have been severely underestimated. This review summarized the most recent advancement in the field and discussed the techniques and methodologies in detection and evaluation of malnutrition in cirrhosis patients, nutritional support therapy, and future research directions and clinical care of the patients.
9.Research progress on pathogenesis and molecular targeted therapy of radiation-induced lung injury
Jiazhen CHEN ; Yu WANG ; Cunliang WANG ; Xudong HU
Chinese Journal of Radiological Health 2021;30(3):377-380
Radiation-induced lung injury is a common complication of radiotherapy for thoracic tumor, usually involves the radiation-induced pneumonitis at early stage and radiation-induced pulmonary fibrosis at late stage, which seriously affects the treatment and prognosis of patients. At present the common treatments for radiation-induced pulmonary fibrosis include anti-inflammatory therapy, glucocorticoid therapy, antioxidant therapy and so on. Recentlywith the further research of radiation-induced pulmonary fibrosis, more and more attention has attracted in molecular targeted therapy. Molecular targeted inhibitors is a new class of drugs for the treatment of radiation-induced lung injury, mainly targeting a variety of cytokines, signaling pathways, tyrosine kinase receptors and other targets. This article systematically reviews the pathogenesis and molecular targeted therapy of radiation-induced lung injury.
10.Effect of modified Sanjia-Fumai decoction on the endocrine and immune function of patients with climacteric syndrome
Fuju WANG ; Yiting JI ; Jiazhen HU
International Journal of Traditional Chinese Medicine 2019;41(3):238-242
Objective To observe the effect of modified SanJia-Fumai decoction with hormone replacement therapy on the endocrine and immune function of patients with climacteric syndrome. Methods A total of 84 patients with climacteric syndrome were divided into two groups according to the random number table, 42 cases in each group. The control group was treated with hormone replacement therapy. While the observation group was treated with modified Sanjia-Fumai decoction on the basis of the control grop. Both groups were treated for 4 weeks. The efficacy by scoring the changes of the patients clinical symptoms and signs was evaluated, and the serum hormones (LH, FSH, E2) levels were detected by radioimmunoassay, and the immune function index (CD3+, CD4+, CD8+) levels by immunofluorescence method, and the IL-2 by ELLSA. Results After treatment, the total efficiency of observation group was 92.8% (39/42), while the control group was 73.8% (31/42), and the difference was statistically significant (Z=-2.736, P=0.003). After treatment, the scores of hot flashes, menstrual disorders, insomnia and dreaminess, hot sweating, restlessness and dry mouth constipation in the observation group were significantly lower than those in the control group (t were 7.745, 10.364, 11.201, 16.765, 18.442, 18.625 respectively, P<0.001); the Serum LH and FSH levels in observation group were significantly lower than those in control group (t were 4.837, 5.016 respectively, P<0.01); the E2 level was significantly higher than that of control group (t=7.309, P<0.01). The levels of CD3+, CD4+, CD4+/CD8+, IL-2 in the observation group were significantly higher than those in the control group (t were 5.139, 6.083, 6.158, 5.932 respectively, P<0.01); The level of CD8+ was significantly lower than that of the control group (t=5.994, P<0.01). Conclusions The modified SanJia-Fumai decoction with hormone replacement therapy can regulate the endocrine function, improve the body's immunity and improve clinical symptoms of climacteric syndrome patients.

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