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.Evidence-based Optimization of Acupuncture Timing Strategies for Ischemic Stroke
Gezhi ZHANG ; An LI ; Weixuan BAI ; Xue CHEN ; Fangqi LIU ; Mengyu LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):144-152
ObjectiveTo investigate the impacts of three types of acupuncture timing factors, including intervention initiation time, needle retention duration, and treatment intervals, on the treatment efficacy of ischemic stroke (IS) and provide evidence-based support for optimizing acupuncture timing strategies. MethodsA systematic search was conducted in both Chinese and English databases, including CNKI, Wanfang Data, VIP, CBM, PubMed, Web of Science, Cochrane Library, and Embase. The randomized controlled trials involving multiple acupuncture intervention time groups were included to reduce inter-study heterogeneity. A network meta-analysis model was constructed to compare the effects of different intervention initiation time, needle retention duration, and treatment intervals on primary IS outcomes, including total clinical response rate, neurological and limb function scores, quality of life score, and hemorheological parameters. Adverse events were also assessed. ResultsA total of 32 studies were included. The results showed that early acupuncture intervention (1-3 days and 4-7 days after onset) outperformed late intervention (>14 days) in terms of response rate, neurological function improvement, and quality of life (P<0.05, P<0.01). Extending needle retention time to 40-60 min was associated with improved response rates and hemorheological parameters (P<0.01). No significant differences were observed among different treatment intervals. The evidence of key outcomes showed high overall certainty, with low heterogeneity and inconsistency. Sensitivity analyses and publication bias assessments indicated the stability of the main results and a low risk of publication bias. No significant adverse reaction was reported. ConclusionDifferent timing factors significantly influence the efficacy of acupuncture treatment for IS. Early intervention and appropriately extended needle retention time result in better clinical outcomes, while treatment interval has no significant effect on efficacy. The inclusion of studies with multiple acupuncture timing groups helps control methodological heterogeneity and enhances the robustness of the analysis, providing evidence-based guidance for optimizing acupuncture timing strategies in IS management.
3.Preliminary Construction of Comprehensive Evaluation System for TCM Clinical Practice Guidelines Based on Bibliometric Analysis and Core Element Extraction
Xue CHEN ; Gezhi ZHANG ; Danping ZHENG ; Fangqi LIU ; An LI ; Junjie JIANG ; Nannan SHI ; Wei YANG ; Xinghua XIANG ; Mengyu LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):209-219
ObjectiveTo construct a comprehensive evaluation indicator system for clinical practice guidelines of traditional Chinese medicine (TCM) that is scientific, systematic, and reflects the characteristics of TCM. MethodsA systematic search was conducted in Chinese and English databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, and Cochrane Library, to include literature on domestic and international guideline evaluation tools and TCM-related research. Document analysis and CiteSpace were utilized for keyword co-occurrence and clustering analysis. ResultsA total of 65 relevant studies were included, from which seven core thematic domains were identified. Based on the research objectives, a two-step construction strategy was adopted: first, an external evaluation framework was established by referencing international tools to cover methodological rigor and procedural standardization; second, an internal evaluation framework was developed to reflect the distinctive features of TCM clinical practice, including syndrome differentiation and efficacy feedback. Through expert consensus, the indicator system was refined, resulting in a dual-layered structure comprising 8 primary indicators, 22 secondary indicators, and 62 evaluation criteria. ConclusionThe comprehensive evaluation system for TCM clinical practice guidelines, based on bibliometric analysis and core element extraction, integrates both theoretical integrity and practical applicability. This study provides a preliminary research foundation for further optimization, validation, and development of a refined comprehensive evaluation system.
4.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.
5.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.
6.Advances in Research on Pathological and Molecular Mechanism of Hyperuricemic Nephropathy Based on Animal Models
Fangqi BAO ; Haiye TU ; Mingsun FANG ; Qian ZHANG ; Minli CHEN
Laboratory Animal and Comparative Medicine 2024;44(2):180-191
Uric acid (UA), the final product of human purine metabolism, can cause hyperuricemia (HUA) when excessively accumulated. HUA is closely linked to chronic kidney diseases (CKD) and is considered an independent risk factor. Hyperuricemic nephropathy, a form of CKD induced by HUA, has seen significant advances in understanding through research into the pathogenic roles of uric acid and the development of HUA animal models. Although progress has been made in understanding the pathophysiological mechanisms by which UA induces CKD, much remains to be learned about its pathological molecular mechanisms. New approaches in animal modeling or the selection of model animals may potentially lead to significant breakthroughs in research on hyperuricemia as well as related CKD. This paper reviews the research progress on the molecular mechanisms of hyperuricemic nephropathy, focusing on oxidative stress, inflammation, autophagy, fibrosis, and gut microbiota. Oxidative stress is induced by uric acid intracellularly through xanthine oxidase, NADPH oxidases, and mitochondria, leading to cellular damage. In terms of inflammation, uric acid crystals can activate the NLRP3 inflammasome, triggering an inflammatory cascade. The role of free uric acid as a pro-inflammatory agent, however, remains controversial. Depending on the study conducted, autophagy has been found to either alleviate or exacerbate inflammation induced by uric acid. Fibrosis, particularly through epithelial-mesenchymal transition (EMT), is a major mechanism by which uric acid causes glomerulosclerosis and tubulointerstitial fibrosis. Extensive research has explored various signaling pathways involved in uric acid-induced EMT. Beneficial gut microbiota protect the kidneys by synthesizing short-chain fatty acids, reducing urea’s enterohepatic circulation, and decreasing uric acid production. This paper aims to enhance understanding of the complex relationships between HUA and CKD, serving as a reference for further research and new drug development.
7.Method for constructing a mouse model of bile stasis caused by partial bile duct ligation
Haiye TU ; Fangqi BAO ; Lizong ZHANG ; Chen JIANG ; Sisi WEN ; Ziyu ZHAO ; Mingsun FANG ; Minli CHEN
Acta Laboratorium Animalis Scientia Sinica 2024;32(5):620-629
Objective To observe the effects of different ligation sites and fasting method on a C57BL/6J mouse model of partial bile duct ligation(pBDL)-induced cholestasis,to establish a pBDL modeling method with a high modeling rate,typical symptoms,and good stability.Methods C57BL/6J mice were subjected to selective ligation of the left hepatic bile duct(L-pBDL)and left-to-median bile duct junction ligation(ML-pBDL)for modeling,and the effects of different pBDL ligation method on serum alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase(ALP),total bilirubin,total bile acid,and liver histopathology were observed.The effects of different fasting method on symptoms and liver injury in the ML-pBDL model were also observed after fasting for 12 and 16 h before surgery,and for 4 h after surgery.Results(1)The incidence of jaundice in the ML-pBDL group was 52.94%and the survival rate within 3 weeks after surgery was 64.71%,while the incidence of jaundice in the L-pBDL group was 11.76%and the survival rate within 3 weeks after surgery was 82.35%.Compared with those in the sham surgery group,serum liver function indicators were significantly increased in the L-pBDL and ML-pBDL groups(P<0.01),and ALP activity was significantly higher in the ML-pBDL group than in the L-pBDL group(P<0.05).Compared with mice in the L-pBDL group,mice in the ML-pBDL group had more severe liver fibrosis at 3 weeks post-surgery(P<0.01).(2)In addition,the incidence of jaundice in the 16 h fasting group was 93.33%and the survival rate within 3 weeks after surgery was 73.77%,while the incidence of jaundice in the 12 h fasting group was 42.86%and the survival rate within 3 weeks after surgery was 71.42%.Compared with those in the normal group,ALP activity,alanine aminotransferase/aspartate aminotransferase ratio,total bile acid level,and proportion of collagen fiber area were all significantly increased in the 16 h and 12 h fasting groups(P<0.05).Although the observed indicators were higher in the 16 h fasting group compared with those in the 12 h fasting group,the difference was not significant(P>0.05).Mice in the 12 h and 16 h fasting groups both showed significant bile duct hyperplasia and liver fibrosis(P<0.01),with more severe liver fibrosis in the 16 h fasting group(P<0.01).Conclusions Both L-pBDL and ML-pBDL ligation method can be used to establish a mouse model of cholestasis;however,symptoms in the L-pBDL model only exhibit transient damage characteristics,while the liver lesions in the ML-pBDL model are typical and stable.Prolonging the preoperative fasting time can improve the modeling rate and stability of the ML-pBDL model and produce more-typical pathological symptoms.
8.Role and mechanism of XPOT inhibition by atractylenolide I in gastric cancer cells
Yi ZHANG ; Fangqi MA ; Siyuan WEI ; Xuejun LI
The Journal of Practical Medicine 2024;40(14):1928-1934
Objective This study aimed to investigate the role and mechanism of atractylenolide Ⅰ in inhibiting XPOT proliferation and invasion in gastric cancer cells.Methods This study included exploration of XPOT expression in gastric cancer tissues,analysis of gene expression data from GC patients in TCGA and GEO databases,as well as various cellular assays to detect the ability of cancer cells to proliferate,migrate,and invade.Protein expression levels of XPOT,SKP2,CyclinA,and P27 mRNA were also detected by qPCR and Western Blot.Results Analysis confirmed that XPOT was highly expressed in gastric cancer tissues,indicating a poor prognosis.In vitro studies revealed that AT-1 inhibits the proliferation and invasion ability of GC cells;XPOT down-regulation also inhibits these abilities.Furthermore,AT-1 down-regulates the expression of XPOT which then regulates SKP2,P27,and CyclinA-ultimately inhibiting the proliferation and invasion of gastric cancer cells through the regulation of the XPOT pathway.Conclusion The overexpression of XPOT in gastric cancer tissues can indicate a poor prognosis.Atractylenolide Ⅰ down-regulates the XPOT-regulated ubiquitination-proteasome pathway to inhibit proliferation and invasion of gastric cancer cells.
9.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.
10.Characteristics of Implementability of Emergency Health Systems Guidance Based on AGREE-HS
Fangqi LIU ; Mengyu LIU ; Danping ZHENG ; An LI ; Xue CHEN ; Gezhi ZHANG ; Dongfeng WEI ; Wei YANG ; Weixuan BAI ; Yong LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):250-256
Guidance implementation acts as a bridge between theory and practice,enabling the rapid expansion of their impact and application. This study demonstratively evaluated emergency health systems guidance documents (HSG),represented by the COVID-19 emergency HSG,based on the item implementability of the Appraisal of Guidelines for Research and Evaluation-Health Systems (AGREE-HS),aiming to explore the characteristics of implementability in emergency HSG. The evaluation results indicated that the COVID-19 emergency HSG had a low mean score in implementability,which ranked just above the item participants. Criterion 2 (costs and resource considerations for implementing the recommendations) received the highest mean score of 4.29,while criterion 9 (systematic evaluation of implementation) received the lowest mean score of 1.34. The emergency HSG formulated by the World Health Organization(WHO) and those formulated by various countries showed no difference (P=0.114) in criterion 1 (barriers and facilitators to implementation) but had differences (P<0.05) regarding the average item scores and the scores of the remaining criteria. The WHO standard HSG had high overall scores and had differences (P<0.05) in both the mean item scores and the scores of the nine criteria when compared with the emergency HSG. The global/national HSG showed differences in scores of criterion 1 (barriers and facilitators to implementation) compared with the both clinically relevant HSG and material support HSG (P<0.05). Emergency HSG prioritized considerations of implementation costs,resources,and flexibility in terms of implementability,while de-emphasizing aspects such as stakeholder opinions,dissemination strategies,and evaluation of HSG. This may be attributed to the context in which emergency HSG are formulated,given the inherent flexibility and variability of emergency health events. The developers should comprehensively consider the needs and characteristics related to the implementability of emergency HSG during the formulation process.

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