1.Study on mechanism of immunogenic cell death induced by ginsenoside octanoate through induction of autophagy in hepatocellular carcinoma cells
Fuxiang SONG ; Zhenzhen DAI ; Jingjing SHENG ; Jiali CHEN ; Hui ZHANG ; Hua FENG ; Yao PAN ; Zeyuan DENG ; Fang CHEN
Chinese Journal of Immunology 2025;41(6):1427-1432
Objective:To investigate the effect of ginsenoside octanoate(Rh2-O)on inducing immunogenic cell death in hepa-tocellular carcinoma cells and its molecular mechanism.Methods:Effects of ginsenoside caprylate(Rh2-O)and autophagy inhibitor 3-MA on the activity of hepatocellular carcinoma cells were detected by CCK-8 assay.The effect of Rh2-O on CRT membrane eversion in Hepa1-6 cells were detected by immunofluorescence assay.Rh2-O treated mouse hepatocellular carcinoma cells were used to pre-pare a tumor vaccine for in vivo vaccination experiments in mice.Extracellular ATP levels were detected in real-time.The expression of autophagy-related genes and proteins were measured by real-time fluorescence PCR and Western blot,and the mitochondrial morphol-ogy and co-localization with autophagy proteins were observed by laser confocal microscopy.Results:Rh2-O showed strong cytotoxicity to Hepa1-6 cells[cell viability:(58.54±3.56)%]at a concentration of 150 μmol/L,and a large amount of CRT was observed on the surface of the cell membrane.The tumor emergence rate was 36.36%in the vaccinated group and 100%in the control group.The tumor vaccine prepared by Rh2-O effectively protected mice from the same type of tumor attack;Rh2-O induced an increase in the level of cellular secreted ATP(P<0.05),the mRNA of autophagy-related genes ATG3,p62,LC3 expression levels and autophagy-associated proteins LC3A and LC3B expression levels were increased(P<0.05),and co-localization of mitochondria with autophagy proteins was significantly increased(P<0.05).In addition,Rh2-O action on 3-MA pretreated hepatocellular carcinoma cells resulted in a signifi-cant decrease in extracellular ATP levels(P<0.001).Conclusion:Rh2-O may induce immunogenic cell death by inducing autophagy in hepatocellular carcinoma cells.
2.Metabolomic analysis of Agrimonia pilosa intervention in proliferation and apoptosis of H1299 cells based on UHPLC-Q-Orbitrap MS technology
Ze-hua TONG ; Wen-jun GUO ; Meng LI ; Ya-juan XU ; Hong-ming ZHANG ; Ze-yu DOU ; Sheng-xu XIE ; Wei-fang WANG
Chinese Pharmacological Bulletin 2025;41(5):970-978
Aim To investigate the effects of Agrimonia pilosa(AP)on the proliferation and apoptosis of non-small cell lung cancer(NSCLC)H1299 cells using non-targeted metabolomics and other methods,and to explore the underlying molecular mechanisms.Meth-ods Taking H1299 cells as the research object,the effect of AP on cell proliferation and apoptosis was de-tected through CCK-8 method,colony formation,LDH,Hoechst 33258 staining,AO/EB staining,flow cytometry detection,RT qPCR and other experiments.The main differential metabolites were detected by the metabolomics method of ultra-high phase liquid chro-matography and mass spectrometry(UHPLC-Q-Orbi-trap MS),and related metabolic pathways were ana-lyzed.Results Compared with the control group,AP treatment was able to significantly inhibit the prolifera-tion and colony formation of H1299 cells,while the re-lease of LDH increased in a dose-dependent manner.Fluorescence microscopy and flow cytometry and RT-qPCR analysis revealed that H1299 cells underwent crumpling and increased nuclear fragmentation after AP administration,blocked in G0/G1 phase,up-regulated apoptotic genes caspase-3 and Bax,and down-regulated apoptosis-inducing effects of Bcl-2.Metabolomics anal-ysis screened 35 differential metabolites,which were PC(O-30∶1),D-Glutamic acid,PE(18∶0/15∶0),etc.The main metabolic pathways involved includ-ed amino acid metabolism,glycerophospholipid metabo-lism and purine metabolism so on.Conclusions AP may exert its pharmacological effects by interfering with multiple metabolic pathways in H1299 cells,inhibiting cell proliferation and promoting apoptosis.
3.Dahuang Zhechong pill regulates stress fiber remodeling mediated by mechanistic signaling pathway to alleviate liver cirrhosis
Yi-heng ZHANG ; Su-zhou HUANG ; Xing-xing LU ; Hui-hua FANG ; Hong-lin CHEN ; Fan-sheng MENG ; Gao-hong LYU ; Zhi-peng CHEN ; Li WU
Chinese Pharmacological Bulletin 2025;41(8):1562-1568
Aim To explore the effect of the classical famous prescription Dahuang Zhechong pill(DHZCP)on relieving liver cirrhosis by regulating the stress fiber remodeling mediated by mechanistic signaling pathway and to explore the underlying mechanism.Methods Mice were randomly divided into the control group,model group,DHZCP low-dose group,DHZCP high-dose group,and Colchicine-positive control group.The liver cirrhosis mouse model was constructed by intrap-eritoneal injection of olive oil-solubilized CCl4.HE staining and serologic markers were used to reflect liver injury.Masson staining was used to evaluate collagen deposition in liver tissue.ELISA was applied to detect vasoactive molecules and cancer indicators.Atomic force microscopy was employed to detect liver tissue stiffness.Color Doppler diagnostic instrument was used to assess portal blood flow velocity.Western blot was utilized to detect ROCK2 expression and phosphoryla-tion of YAP,Cofilin,and MLC.Results The liver tis-sues in the model group had obvious inflammatory cell infiltration and collagen deposition,accompanied by significant elevation of serum transaminases and fibrosis indexes.Similarly,vasoactive molecules and cancer in-dicators were elevated,and the mechanoregulatory pro-tein ROCK2 expression and phosphorylation of Cofilin and MLC were elevated,with YAP being strongly de-phosphorylated.Both low and high doses of DHZCP re-versed the pathological changes,serological indices,and inhibited the activation of the stress fiber(SF)re-modeling mechanistic signaling pathway.Conclusion DHZCP effectively ameliorates liver tissue lesions in mice with liver cirrhosis,and its mechanism may be re-lated to the inhibition of SF remodeling mechanistic signaling pathway.
4.International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025).
Sheng-Sheng ZHANG ; Lu-Qing ZHAO ; Xiao-Hua HOU ; Zhao-Xiang BIAN ; Jian-Hua ZHENG ; Hai-He TIAN ; Guan-Hu YANG ; Won-Sook HONG ; Yu-Ying HE ; Li LIU ; Hong SHEN ; Yan-Ping LI ; Sheng XIE ; Jin SHU ; Bin-Fang ZENG ; Jun-Xiang LI ; Zhen LIU ; Zheng-Hua XIAO ; Jing-Dong XIAO ; Pei-Yong ZHENG ; Shao-Gang HUANG ; Sheng-Liang CHEN ; Gui-Jun FEI
Journal of Integrative Medicine 2025;23(5):502-518
Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy*
;
Humans
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Medicine, Chinese Traditional/methods*
;
Practice Guidelines as Topic
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Drugs, Chinese Herbal/therapeutic use*
5.Dahuang Zhechong pill regulates stress fiber remodeling mediated by mechanistic signaling pathway to alleviate liver cirrhosis
Yi-heng ZHANG ; Su-zhou HUANG ; Xing-xing LU ; Hui-hua FANG ; Hong-lin CHEN ; Fan-sheng MENG ; Gao-hong LYU ; Zhi-peng CHEN ; Li WU
Chinese Pharmacological Bulletin 2025;41(8):1562-1568
Aim To explore the effect of the classical famous prescription Dahuang Zhechong pill(DHZCP)on relieving liver cirrhosis by regulating the stress fiber remodeling mediated by mechanistic signaling pathway and to explore the underlying mechanism.Methods Mice were randomly divided into the control group,model group,DHZCP low-dose group,DHZCP high-dose group,and Colchicine-positive control group.The liver cirrhosis mouse model was constructed by intrap-eritoneal injection of olive oil-solubilized CCl4.HE staining and serologic markers were used to reflect liver injury.Masson staining was used to evaluate collagen deposition in liver tissue.ELISA was applied to detect vasoactive molecules and cancer indicators.Atomic force microscopy was employed to detect liver tissue stiffness.Color Doppler diagnostic instrument was used to assess portal blood flow velocity.Western blot was utilized to detect ROCK2 expression and phosphoryla-tion of YAP,Cofilin,and MLC.Results The liver tis-sues in the model group had obvious inflammatory cell infiltration and collagen deposition,accompanied by significant elevation of serum transaminases and fibrosis indexes.Similarly,vasoactive molecules and cancer in-dicators were elevated,and the mechanoregulatory pro-tein ROCK2 expression and phosphorylation of Cofilin and MLC were elevated,with YAP being strongly de-phosphorylated.Both low and high doses of DHZCP re-versed the pathological changes,serological indices,and inhibited the activation of the stress fiber(SF)re-modeling mechanistic signaling pathway.Conclusion DHZCP effectively ameliorates liver tissue lesions in mice with liver cirrhosis,and its mechanism may be re-lated to the inhibition of SF remodeling mechanistic signaling pathway.
6.Metabolomic analysis of Agrimonia pilosa intervention in proliferation and apoptosis of H1299 cells based on UHPLC-Q-Orbitrap MS technology
Ze-hua TONG ; Wen-jun GUO ; Meng LI ; Ya-juan XU ; Hong-ming ZHANG ; Ze-yu DOU ; Sheng-xu XIE ; Wei-fang WANG
Chinese Pharmacological Bulletin 2025;41(5):970-978
Aim To investigate the effects of Agrimonia pilosa(AP)on the proliferation and apoptosis of non-small cell lung cancer(NSCLC)H1299 cells using non-targeted metabolomics and other methods,and to explore the underlying molecular mechanisms.Meth-ods Taking H1299 cells as the research object,the effect of AP on cell proliferation and apoptosis was de-tected through CCK-8 method,colony formation,LDH,Hoechst 33258 staining,AO/EB staining,flow cytometry detection,RT qPCR and other experiments.The main differential metabolites were detected by the metabolomics method of ultra-high phase liquid chro-matography and mass spectrometry(UHPLC-Q-Orbi-trap MS),and related metabolic pathways were ana-lyzed.Results Compared with the control group,AP treatment was able to significantly inhibit the prolifera-tion and colony formation of H1299 cells,while the re-lease of LDH increased in a dose-dependent manner.Fluorescence microscopy and flow cytometry and RT-qPCR analysis revealed that H1299 cells underwent crumpling and increased nuclear fragmentation after AP administration,blocked in G0/G1 phase,up-regulated apoptotic genes caspase-3 and Bax,and down-regulated apoptosis-inducing effects of Bcl-2.Metabolomics anal-ysis screened 35 differential metabolites,which were PC(O-30∶1),D-Glutamic acid,PE(18∶0/15∶0),etc.The main metabolic pathways involved includ-ed amino acid metabolism,glycerophospholipid metabo-lism and purine metabolism so on.Conclusions AP may exert its pharmacological effects by interfering with multiple metabolic pathways in H1299 cells,inhibiting cell proliferation and promoting apoptosis.
7.Study on mechanism of immunogenic cell death induced by ginsenoside octanoate through induction of autophagy in hepatocellular carcinoma cells
Fuxiang SONG ; Zhenzhen DAI ; Jingjing SHENG ; Jiali CHEN ; Hui ZHANG ; Hua FENG ; Yao PAN ; Zeyuan DENG ; Fang CHEN
Chinese Journal of Immunology 2025;41(6):1427-1432
Objective:To investigate the effect of ginsenoside octanoate(Rh2-O)on inducing immunogenic cell death in hepa-tocellular carcinoma cells and its molecular mechanism.Methods:Effects of ginsenoside caprylate(Rh2-O)and autophagy inhibitor 3-MA on the activity of hepatocellular carcinoma cells were detected by CCK-8 assay.The effect of Rh2-O on CRT membrane eversion in Hepa1-6 cells were detected by immunofluorescence assay.Rh2-O treated mouse hepatocellular carcinoma cells were used to pre-pare a tumor vaccine for in vivo vaccination experiments in mice.Extracellular ATP levels were detected in real-time.The expression of autophagy-related genes and proteins were measured by real-time fluorescence PCR and Western blot,and the mitochondrial morphol-ogy and co-localization with autophagy proteins were observed by laser confocal microscopy.Results:Rh2-O showed strong cytotoxicity to Hepa1-6 cells[cell viability:(58.54±3.56)%]at a concentration of 150 μmol/L,and a large amount of CRT was observed on the surface of the cell membrane.The tumor emergence rate was 36.36%in the vaccinated group and 100%in the control group.The tumor vaccine prepared by Rh2-O effectively protected mice from the same type of tumor attack;Rh2-O induced an increase in the level of cellular secreted ATP(P<0.05),the mRNA of autophagy-related genes ATG3,p62,LC3 expression levels and autophagy-associated proteins LC3A and LC3B expression levels were increased(P<0.05),and co-localization of mitochondria with autophagy proteins was significantly increased(P<0.05).In addition,Rh2-O action on 3-MA pretreated hepatocellular carcinoma cells resulted in a signifi-cant decrease in extracellular ATP levels(P<0.001).Conclusion:Rh2-O may induce immunogenic cell death by inducing autophagy in hepatocellular carcinoma cells.
8.Expert consensus on surgical treatment of oropharyngeal cancer
China Anti-Cancer Association Head and Neck Oncology Committee ; China Anti-Cancer Association Holistic Integrative Oral Cancer on Preventing and Screen-ing Committee ; Min RUAN ; Nannan HAN ; Changming AN ; Chao CHEN ; Chuanjun CHEN ; Minjun DONG ; Wei HAN ; Jinsong HOU ; Jun HOU ; Zhiquan HUANG ; Chao LI ; Siyi LI ; Bing LIU ; Fayu LIU ; Xiaozhi LV ; Zheng-Hua LV ; Guoxin REN ; Xiaofeng SHAN ; Zhengjun SHANG ; Shuyang SUN ; Tong JI ; Chuanzheng SUN ; Guowen SUN ; Hao TIAN ; Yuanyin WANG ; Yueping WANG ; Shuxin WEN ; Wei WU ; Jinhai YE ; Di YU ; Chunye ZHANG ; Kai ZHANG ; Ming ZHANG ; Sheng ZHANG ; Jiawei ZHENG ; Xuan ZHOU ; Yu ZHOU ; Guopei ZHU ; Ling ZHU ; Susheng MIAO ; Yue HE ; Jugao FANG ; Chenping ZHANG ; Zhiyuan ZHANG
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(11):821-833
With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth>3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.
9.Clinical trial of propofol and remazolam in patients of painless fiberoptic bronchoscopic biopsy
Zhi-Hua HUANG ; Yan-Fang WANG ; Chao-Sheng QIN ; Yi-Hong JIANG
The Chinese Journal of Clinical Pharmacology 2024;40(12):1699-1703
Objective To observe clinical outcomes of propofol and remazolam in patients undergoing elective painless fiberoptic bronchoscopic biopsy.Methods Patients who underwent painless fibreoptic bronchoscopic biopsy in our hospital from March 2022 to April 2023 were selected for the study and divided into 2 groups using simple randomisation method.In the control group,anaesthesia was induced with 1 mg·kg-1 propofol,3 μg·kg-1 fentanyl,0.1 mg·kg-1 cis-atracurium,and anaesthesia was maintained with 4-6 mg·kg-1·h-1 propofol.In the treatment group,anaesthesia was induced with 0.2 mg·kg-1 remazolam,3 μg·kg-1 fentanyl,0.1 mg·kg-1 cis-atracurium,and anaesthesia was maintained with 0.2-0.4 mg·kg-1·h-1 remazolam.We compared the awakening time,laryngeal mask removal time,microscopy time,and the proportion of additional anaesthetics in the 2 groups,and detected the levels of S100β,neuron-specific enolase(NSE),interleukin-6(IL-6),tumour necrosis factor-alpha(TNF-α)in the 2 groups preoperatively and at 24 h postoperatively,and statistically counted the occurrences of adverse reactions in the 2 groups.Results The time for pulling out the laryngeal mask in the treatment group was significantly lower than that in the control group,while the time for microscopy,time for awakening,and proportion of additional anaesthesia drugs were not statistically significant when compared with that in the control group(all P>0.05).The overall anaesthesia effect grading of the test group was not statistically significant when compared with the control group(P>0.05).S100β were(0.66±0.17)and(0.78±0.21)μg·L-1;NSE were(8.47±1.78)and(11.47±2.06)μg·L-1;IL-6 were(8.64±1.21)and(12.89±1.47)pg·mL-1;TNF-α were(6.27±1.07)and(9.13±1.41)pg·mL-1,respectively,which were higher than that of preoperative period,and the treatment group was lower than that of the control group at 24 h postoperatively,and the difference was statistically significant(all P<0.05).The incidence of adverse drug reactions in the treatment group and the control group were 13.75%and 22.50%,respectively,and the difference was not statistically significant(P>0.05).Conclusion The use of remazolam in painless fiberoptic bronchoscopic biopsy is less neurologically damaging,stabilizes hemodynamics.
10.Two new isoflavones from Dalbergia rimosa Roxb.
Wei-yu WANG ; Wen-jiao CHEN ; Mei-fang HUANG ; Cheng-sheng LU ; Xu FENG ; Chen-yan LIANG ; Jian-hua WEI
Acta Pharmaceutica Sinica 2024;59(7):2053-2057
Studies on chemical constituents in the rhizome of


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