1.Liver and Kidney Safety Assessment of Chinese Herbal Compound in Treatment of Gastric Cancer Based on Real-World Data
Yumiao SHEN ; Xiaohong ZHU ; Yi WANG ; Ya'nan ZHANG ; Ruohan ZHAO ; Fangqi MA ; Yan XU ; Lin ZENG ; Mingjie CHEN ; Aiguang ZHAO
China Cancer 2025;34(5):408-415
[Purpose]To evaluate the liver and kidney safety of traditional Chinese medicine(TCM)compounds in the treatment of gastric cancer.[Methods]The clinical data of gastric cancer patients who attended in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2012 to February 2022 were collected.The results of liver and renal func-tion tests were rated according to National Cancer Institute-Common Terminology Criteria for Ad-verse Events(NCI-CTCAE)V5.0.The patients were divided into 4 groups:TCM group,TCM+chemotherapy/targeted/antivascular therapy group,TCM+TCM preparation group and TCM+chemotherapy/targeted/antivascular therapy+TCM preparation group,and the effects of TCM on liver and renal functions were analyzed.[Results]A total of 7 943 patients were included in the analysis,of which 2 941 cases receiving TCM ≥12 months,1 468 months ≥36 months,and 687 months≥60 months.The highest incidence rate of liver function abnormality was 13.71%,the highest in-cidence rate of grade 3/4 abnormality was 2.58%;the highest incidence of creatinine abnormality was 2.32%,the highest incidence rate of grade 3/4 abnormality was 0.37%in patients with differ-ent duration of taking TCM.Most of liver and renal function abnormalities occurred in the early stage of drug taking.The incidence of liver and renal function abnormalities in the TCM group was lower than that of the other three groups.The incidence of grade 3/4 abnormality for direct biliru-bin(DBIL)in the TCM group was 0.14%,for aspartate transaminase(AST)was 0.11%,for alka-line phosphatase(ALP)was 0.16%,for alanine aminotransferase(ALT)was 0.06%and for total bilirubin(TBIL)was 0.07%,and there was no grade 3/4 creatinine abnormality observed.The ab-normal liver and renal function indexes were not increased with the increase of the length of herbal medicine taking.[Conclusion]The study shows that long term taking TCM drugs and stan-dardized prescriptions for gastric cancer patients are safe.
2.Comparison of the prognostic value of 15 nutritional/inflammatory indicators in postoperative cancer patients
Xiaoqian LIU ; Kai SUN ; Xiaolin WANG ; Qianqian ZHAO ; Xiaoxiao WU ; Fangqi SHEN ; Xi CHEN ; Chenxu TIAN ; Di WU ; Chunhua SONG ; HongXia XU ; Minghua CONG ; Hanping SHI ; Pingping JIA
Journal of Capital Medical University 2025;46(3):410-419
Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P<0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI<104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.
3.Liver and Kidney Safety Assessment of Chinese Herbal Compound in Treatment of Gastric Cancer Based on Real-World Data
Yumiao SHEN ; Xiaohong ZHU ; Yi WANG ; Ya'nan ZHANG ; Ruohan ZHAO ; Fangqi MA ; Yan XU ; Lin ZENG ; Mingjie CHEN ; Aiguang ZHAO
China Cancer 2025;34(5):408-415
[Purpose]To evaluate the liver and kidney safety of traditional Chinese medicine(TCM)compounds in the treatment of gastric cancer.[Methods]The clinical data of gastric cancer patients who attended in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2012 to February 2022 were collected.The results of liver and renal func-tion tests were rated according to National Cancer Institute-Common Terminology Criteria for Ad-verse Events(NCI-CTCAE)V5.0.The patients were divided into 4 groups:TCM group,TCM+chemotherapy/targeted/antivascular therapy group,TCM+TCM preparation group and TCM+chemotherapy/targeted/antivascular therapy+TCM preparation group,and the effects of TCM on liver and renal functions were analyzed.[Results]A total of 7 943 patients were included in the analysis,of which 2 941 cases receiving TCM ≥12 months,1 468 months ≥36 months,and 687 months≥60 months.The highest incidence rate of liver function abnormality was 13.71%,the highest in-cidence rate of grade 3/4 abnormality was 2.58%;the highest incidence of creatinine abnormality was 2.32%,the highest incidence rate of grade 3/4 abnormality was 0.37%in patients with differ-ent duration of taking TCM.Most of liver and renal function abnormalities occurred in the early stage of drug taking.The incidence of liver and renal function abnormalities in the TCM group was lower than that of the other three groups.The incidence of grade 3/4 abnormality for direct biliru-bin(DBIL)in the TCM group was 0.14%,for aspartate transaminase(AST)was 0.11%,for alka-line phosphatase(ALP)was 0.16%,for alanine aminotransferase(ALT)was 0.06%and for total bilirubin(TBIL)was 0.07%,and there was no grade 3/4 creatinine abnormality observed.The ab-normal liver and renal function indexes were not increased with the increase of the length of herbal medicine taking.[Conclusion]The study shows that long term taking TCM drugs and stan-dardized prescriptions for gastric cancer patients are safe.
4.Comparison of the prognostic value of 15 nutritional/inflammatory indicators in postoperative cancer patients
Xiaoqian LIU ; Kai SUN ; Xiaolin WANG ; Qianqian ZHAO ; Xiaoxiao WU ; Fangqi SHEN ; Xi CHEN ; Chenxu TIAN ; Di WU ; Chunhua SONG ; HongXia XU ; Minghua CONG ; Hanping SHI ; Pingping JIA
Journal of Capital Medical University 2025;46(3):410-419
Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P<0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI<104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.
5.Effect and Mechanism of Total Saponins from Panax Japonicus on White Adipose Tissue Browning/Brown Adipose Tissue Activation in High-fat Diet-induced Mice
Shuwen WANG ; Yaqi HU ; Rui WANG ; Yifan ZHANG ; Mengzhen XUE ; Yaqi WANG ; Fangqi XIA ; Leiqi ZHU ; Chengfu YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):71-78
ObjectiveTo investigate the effect and mechanism of total saponins from Panax japonicus (TSPJ) on white adipose tissue (WAT) browning/brown adipose tissue (BAT) activation in C57BL6/J male mice fed on a high-fat diet (HFD). MethodThirty-two C57BL6/J male mice (8-week-old) were randomly divided into a normal group, a model group, a low-dose TSPJ group, and a high-dose TSPJ group. The mice in the low-dose and high-dose TSPJ groups were given TSPJ for four months by gavage at 25, 75 mg·kg-1·d-1, respectively, and those in the other groups were given 0.5% sodium carboxymethyl cellulose (CMC-Na) accordingly. After four months of feeding, all mice were placed at 4 ℃ for acute cold exposure, and the core body temperature was monitored. Subsequently, all mice were sacrificed, and BAT and inguinal WAT (iWAT) were separated rapidly to detect the corresponding indexes. Hematoxylin-eosin (HE) staining was used to observe the morphological changes in each group. The effect of TSPJ on the mRNA expression of uncoupling protein 1 (UCP1), fatty acid-binding protein 4 (FABP4), cytochrome C (CytC), PR domain-containing protein 16 (PRDM16), elongation of very long chain fatty acids protein 3 (ELOVL3), peroxisome proliferator-activated receptor γ (PPARγ), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in iWAT and BAT was detected by Real-time polymerase chain reaction (Real-time PCR). Western blot was also used to detect the protein expression of UCP1, PRDM16, PPARγ, and PGC-1α in BAT and iWAT of each group. The effect of TSPJ on UCP1 expression in BAT and iWAT was detected by immunohistochemistry. Result① Compared with the model group, TSPJ could decrease the body weight and proportions of iWAT and BAT in the HFD-induced mice (P<0.05, P<0.01). ② The body temperature of mice in the model group decreased compared with that in the normal group in the acute cold exposure tolerance test (P<0.05). The body temperature in the high-dose TSPJ group increased compared with that in the model group (P<0.01). ③ Compared with the normal group, the model group showed increased adipocyte diameter in iWAT and BAT and decreased number of adipocytes per unit area. Compared with the model group, the TSPJ groups showed significantly reduced cell diameter and increased number of cells per unit area, especially in the high-dose TSPJ group. ④ Compared with the normal group, the model group showed decreased mRNA expression of FABP4, UCP1, CytC, PRDM16, ELOVL3, PGC-1α, and PPARγ in adipose tissues of mice (P<0.05, P<0.01). Compared with the model group, after intervention with TSPJ, the mRNA expression was significantly up-regulated (P<0.05, P<0.01). ⑤ Compared with the normal group, the model group showed decreased protein expression of UCP1, PRDM16, PPARγ, and PGC-1α in adipose tissues of mice (P<0.05, P<0.01). Compared with the model group, after intervention with TSPJ, the protein expression increased significantly (P<0.05, P<0.01). ConclusionTSPJ could induce the browning of iWAT/BAT activation and enhance adaptive thermogenesis in obese mice induced by HFD. The underlying mechanism may be attributed to the activation of the PPARγ/PGC-1α signaling pathway.
6.Long non-coding RNA AW112010 improves insulin resistance in adipocytes of aging mice through the miR-204/POU2F2 axis
Rui WANG ; Shuwen WANG ; Yifan ZHANG ; Yaqi HU ; Qi YUAN ; Yuan WEN ; Xiaoling CHEN ; Ting LU ; Ying ZHENG ; Zhiyong LIN ; Mengzhen XUE ; Yaqi WANG ; Fangqi XIA ; Leiqi ZHU ; Chengfu YUAN
Chinese Journal of Endocrinology and Metabolism 2024;40(1):44-52
Objective:To investigate whether long non-coding RNA(lncRNA) AW112010 can improve insulin resistance in aging adipocytes through the miR-204/POU2F2 signaling pathway.Methods:In vivo experiment: C57BL/6 mice were divided into young control group(4 months old) and aging model group(18 months old) based on body weight. The expression levels of AW112010, miR-204-5p, POU2F2, aging related indicators(p16, p21), and insulin signaling pathway genes [insulin receptor(INSR), insulin receptor substrate 1(IRS1), phosphatidylinositol kinase(PI3K), protein kinase B(AKT)] in epididymal adipose tissue were detected using real-time fluorescence quantitative PCR(RT-qPCR) and Western blotting. In vitro experiment: Using adriamycin(ADR) to induce 3T3-L1 aging adipocyte model, β-gal staining was used to observe cellular senescence, and miR-204 inhibitor and miR-204 mimic small interfering RNA were successfully constructed and transfected into 3T3-L1 adipocytes. Results:RT-qPCR and Western blot results showed that compared with the young group, the expression of AW112010 in the adipose tissue of aging mice was increased, while the expression of miR-204-5p was decreased. The expressions of POU2F2, p16, and p21 in the adipose tissue of aging mice were increased, while the expressions of INSR, IRS1, PI3K, GLUT4 mRNA and protein were decreased. The β-gal stainging results showed that the number of 3T3-L1 senescent adipocytes induced by ADR was significantly increased, and the expression levels of AW112010, POU2F2, p16, and p21 in ADR-induced senescent adipocytes were increased compared with the control group, while the expression levels of miR-204-5p, INSR, IRS1, PI3K, GLUT4 were decreased, and remaining glucose in the culture medium was increased. Compared with control, overexpression of miR-204 resulted in decreased expressions of aging indicators p16, p21, and target gene POU2F2 while the expressions of INSR and GLUT4 were increased.Conclusion:Upregulation of lncRNA AW112010 in adipocytes of aging mice may induce insulin resistance by targeting miR-204-5p/POU2F2/IRS1.
7.Regulatory T cells and Kawasaki disease
Jiawen XU ; Yujia WANG ; Fangqi GONG
International Journal of Pediatrics 2022;49(10):663-667
Kawasaki disease is an acute, systemic vasculitis that easily injures coronary arteries and is the leading cause of acquired heart disease in children.Although the cause of Kawasaki disease remains unknown, it is widely believed that the pathogenesis of Kawasaki disease is an inflammatory cascade caused by a combination of infection and genetic predisposition.Regulatory T cells, which express Foxp3 + , CD4 + and CD25 + , are a T-cell subpopulation specialized in immune suppression.There are some correlations between regulatory T cells and Kawasaki disease in pathophysiology, treatment and prognosis.The dysfunction of regulatory T cells may be involved with the pathogenesis of Kawasaki disease, but there are few researches on it.This article reviews the progress of regulatory T cells in Kawasaki disease in recent years and summarizes the mechanism of regulatory T cells in the occurrence and repair of Kawasaki disease, prospecting the research future of targeted regulatory T cells therapy in the prevention of coronary artery lesions in Kawasaki disease.
8.Recent advance in molecular mechanism of neural stem cell homing after ischemic stroke
Zhaodi YUE ; Yanyan YIN ; Fangqi WANG ; Shaohong YU
Chinese Journal of Neuromedicine 2021;20(5):519-524
The irreversibility of nerve cell injury is the main pathological basis of disability in stroke patients. In recent years, it has been found that neural stem cells (NSCs) with multi-directional differentiation potential and self-renewal capacity can proliferate under stress in the adult central nervous system, migrate to the injured area and differentiate into neural cells, thus participating in the repair of nerve injury. However, due to the limited number of homing stem cells, it is difficult to make up for the vacancy caused by the massive necrosis of neurons. This paper reviews the molecular mechanism of NSCs homing under ischemia and hypoxia, and explains the application prospect of NSCs in ischemic stroke.
9.The prediction and treatment for intravenous immunoglobulin resistant Kawasaki disease
Chinese Pediatric Emergency Medicine 2020;27(9):650-653
Kawasaki disease(KD) is an acute febrile vasculitis and approximate 10% to 20% children with KD are resistant to initial intravenous immunoglobulin(IVIG) treatment at a dose of 2 g/kg, who are named IVIGRKD.Treatments for IVIGRKD include second dose IVIG, second dose IVIG plus glucocorticoid, single intravenous injection of infliximab, intravenous or oral cyclosporine, subcutaneous injection of Anakinra, intravenous cyclophosphamide, and plasma exchange, etc.No evidence suggests which treatment method is better than the others.Therefore, early prediction and timely identification of IVIGRKD are extremely important.Unfortunately, most of current prediction models are based on the statistical analysis of retrospective data, and due to the discrepancy of region and race, their further application are limited.
10.Trend analysis of morbidity and mortality of colorectal cancer in China from 1988 to 2009.
Tian'an GUO ; Li XIE ; Jiang ZHAO ; Wang SONG ; Weixing DAI ; Fangqi LIU ; Ying ZHENG ; Ye XU ;
Chinese Journal of Gastrointestinal Surgery 2018;21(1):33-40
OBJECTIVETo explore the trend change of the morbidity and mortality of colorectal cancer in China in order to provide reference to the prevention and control of colorectal cancer.
METHODSAccording to the 1-3 volumes of "Pathogenesis and death of malignancies in pilot program city and county of China", "Pathogenesis and death of cancer in China"(2003-2007) and "Registration annual report of tumor in China" published in 2011 and 2012, data of pathogenesis and death of colorectal cancer from 10 tumor registration spots, including Beijing urban, Shanghai urban, Wuhan urban, Harbin urban (defined as city urban), and Hebei Ci County, Jiangsu Qidong District, Zhejiang Jiashan District, Guangxi Fusui County, Fujian Changle District, Henan Lin County (defined as rural district), between 1988 and 2009 were collected. The morbidity and mortality were elucidated with world population standardized rate. Ratio of pathogenesis to death was calculated with crude rate of morbidity and mortality. Data of 22 years were enrolled into the linear regression analysis to calculate the annual change rate of morbidity and mortality statistically.
RESULTS(1) Colon cancer: morbidity presented increasing trend; male morbidity in city urban increased faster; mortality presented increasing trend as well; no significant difference of increasing velocity was observed between city urban and rural district; morbidity and mortality in city urban were higher compared to rural district; morbidity and mortality of males were higher compared to females; except stable Fujian Changle District, ratio of pathogenesis to death presented decreased trend in Shanghai urban and Hebei Ci County, and increased trend in other 7 spots (all P<0.05). (2) Rectal cancer: morbidity presented increasing trend, and its increasing velocity of city urban was faster compared to rural district; mortality presented decreased trend, especially in females, and this trend in rural district was worse compared to city urban; morbidity and mortality of males were higher compared to females, while no significant difference was observed between city urban and rural district; morbidity and mortality of males and females in Zhejiang Jiashan District were all decreased (all P<0.05); except stable Harbin city, ratio of pathogenesis to death presented increased trend in other 9 spots (all P<0.05). (3) Ratio analysis of morbidity and mortality showed that percentage of colon cancer increased gradually in all 10 spots between 1988-2009.
CONCLUSIONSIn the past 2 decades, the overall morbidity and mortality of colorectal cancer are higher in city urban and in male as compared with rural district and female. Colon cancer has higher morbidity than rectal cancer and its morbidity and mortality present increased trend, while morbidity of rectal cancer presents increased trend but its mortality presents decreased trend.

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