1.Exploratory study of fecal microbiota transplantation combined with immune checkpoint inhibitors in the treatment of end-stage malig-nant tumor patients
Yunqian CHU ; Ya XUE ; Hua JIANG ; Chunjian QI ; Hanjue DAI ; Qingying XIAN ; Wenyu ZHU
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(4):509-516
AIM:To explore the efficacy and safe-ty of fecal microbiota transplantation combined with immune checkpoint inhibitors(ICIs)for malig-nant tumor patients with failed multi line anti-tu-mor treatment and concomitant cachexia,and to explore the changes in blood immunity and intesti-nal microbial environment in patients.METHODS:Five patients with malignant tumors who failed multi line anti-tumor treatment were enrolled and treated with ICIs combined with fecal microbiota transplantation.The efficacy was evaluated every 2-3 cycles,and adverse reactions were observed.Fe-cal 16srRNA gene sequencing and serum immuno-logical indicators were dynamically detected.RE-SULTS:Except for one patient who died 2.5 months after transplantation due to excessive tumor bur-den at enrollment,the overall survival of the re-maining four patients were extended(7.4,8.3,28.5,52.3 months).One patient with multiple intra-cranial metastases of lung adenocarcinoma signifi-cantly reduced the intracranial metastasis after in-testinal microbiota transplantation and almost dis-appeared.The serum IL-2,IL-10,TGF-β and other indicators of patients increased rapidly and then slowly decreased with the increase of transplanta-tion time,and finally were higher than before trans-plantation,with statistical differences.16srRNA gene sequencing analysis revealed significant differ-ences in the overall distribution of gut microbiota in patients after transplantation,gradually ap-proaching healthy transplant donors.All patients did not experience grade 2 or above adverse reac-tions,and the safety was good.CONCLUSION:For patients with malignant tumors,the combination of fecal microbiota transplantation and immuno-therapy may improve their quality of life,serum im-mune environment,and intestinal microbiota com-position,have a positive impact on survival progno-sis,and are safe and controllable,opening up new treatment methods for end-stage patients.
2.Exploratory study of fecal microbiota transplantation combined with immune checkpoint inhibitors in the treatment of end-stage malig-nant tumor patients
Yunqian CHU ; Ya XUE ; Hua JIANG ; Chunjian QI ; Hanjue DAI ; Qingying XIAN ; Wenyu ZHU
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(4):509-516
AIM:To explore the efficacy and safe-ty of fecal microbiota transplantation combined with immune checkpoint inhibitors(ICIs)for malig-nant tumor patients with failed multi line anti-tu-mor treatment and concomitant cachexia,and to explore the changes in blood immunity and intesti-nal microbial environment in patients.METHODS:Five patients with malignant tumors who failed multi line anti-tumor treatment were enrolled and treated with ICIs combined with fecal microbiota transplantation.The efficacy was evaluated every 2-3 cycles,and adverse reactions were observed.Fe-cal 16srRNA gene sequencing and serum immuno-logical indicators were dynamically detected.RE-SULTS:Except for one patient who died 2.5 months after transplantation due to excessive tumor bur-den at enrollment,the overall survival of the re-maining four patients were extended(7.4,8.3,28.5,52.3 months).One patient with multiple intra-cranial metastases of lung adenocarcinoma signifi-cantly reduced the intracranial metastasis after in-testinal microbiota transplantation and almost dis-appeared.The serum IL-2,IL-10,TGF-β and other indicators of patients increased rapidly and then slowly decreased with the increase of transplanta-tion time,and finally were higher than before trans-plantation,with statistical differences.16srRNA gene sequencing analysis revealed significant differ-ences in the overall distribution of gut microbiota in patients after transplantation,gradually ap-proaching healthy transplant donors.All patients did not experience grade 2 or above adverse reac-tions,and the safety was good.CONCLUSION:For patients with malignant tumors,the combination of fecal microbiota transplantation and immuno-therapy may improve their quality of life,serum im-mune environment,and intestinal microbiota com-position,have a positive impact on survival progno-sis,and are safe and controllable,opening up new treatment methods for end-stage patients.
3.Exploring the Effect of Ganmai Dazhao Tang on Intestinal Inflammation in ADHD Model Rats Based on Network Pharmacology
Chenhao XUE ; Yunqian XIAN ; Dan TANG ; Jiacheng WANG ; Yamin HE ; Jingjing YANG ; Shaofang GAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(11):2968-2979
Objective Based on network pharmacology,protein mechanism,and experimental validation,this study aims to explore the role of Ganmai Dazao Tang in treating intestinal inflammation in children with attention deficit hyperactivity disorder(ADHD)model rats.Methods Screening the relevant targets and pathways for the effect of Ganmai Dazhao Tang on intestinal inflammation in ADHD model rats using network pharmacology methods,and verifying the affinity of the main components and targets through molecular docking.Forty spontaneously hypertensive rats(SHR)were randomly divided into model group,methylphenidate group,and low,medium,and high dose groups of Ganmai Dazao Tang,with 8 rats in each group.Additionally,8 Wistar Kyoto rats(WKY)were set as the normal group.Rats in each group were treated daily by gavage for 3 weeks.Observing the pathological condition of the small intestine using HE staining technology,and detecting interleukin-1 using enzyme-linked immunosorbent assay(ELISA)and Western blot methods β(IL-1β),tumor necrosis factor α(TNF-α),Expression of the oncogene Fos(FOS).Results Network pharmacology screened 117 chemical components and predicted 248 effective targets.Molecular docking results showed that Isovitexin β-Ingredients such as beta carotene,kaempferol,luteolin,and naringenin have strong affinity with targets such as AKT1,FOS,VEGFA,and TNF.Animal test results show that Ganmai Dazhao Tang can improve the core symptoms of ADHD,protect normal intestinal function and status,and downregulate related IL-1 β,TNF-α,FOS factor content.Conclusion Ganmai Dazao Tang can alleviate the core symptoms of ADHD in SHR rats by protecting normal intestinal function and downregulating inflammatory factors.
4.Exploring the Effect of Ganmai Dazhao Tang on Intestinal Inflammation in ADHD Model Rats Based on Network Pharmacology
Chenhao XUE ; Yunqian XIAN ; Dan TANG ; Jiacheng WANG ; Yamin HE ; Jingjing YANG ; Shaofang GAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(11):2968-2979
Objective Based on network pharmacology,protein mechanism,and experimental validation,this study aims to explore the role of Ganmai Dazao Tang in treating intestinal inflammation in children with attention deficit hyperactivity disorder(ADHD)model rats.Methods Screening the relevant targets and pathways for the effect of Ganmai Dazhao Tang on intestinal inflammation in ADHD model rats using network pharmacology methods,and verifying the affinity of the main components and targets through molecular docking.Forty spontaneously hypertensive rats(SHR)were randomly divided into model group,methylphenidate group,and low,medium,and high dose groups of Ganmai Dazao Tang,with 8 rats in each group.Additionally,8 Wistar Kyoto rats(WKY)were set as the normal group.Rats in each group were treated daily by gavage for 3 weeks.Observing the pathological condition of the small intestine using HE staining technology,and detecting interleukin-1 using enzyme-linked immunosorbent assay(ELISA)and Western blot methods β(IL-1β),tumor necrosis factor α(TNF-α),Expression of the oncogene Fos(FOS).Results Network pharmacology screened 117 chemical components and predicted 248 effective targets.Molecular docking results showed that Isovitexin β-Ingredients such as beta carotene,kaempferol,luteolin,and naringenin have strong affinity with targets such as AKT1,FOS,VEGFA,and TNF.Animal test results show that Ganmai Dazhao Tang can improve the core symptoms of ADHD,protect normal intestinal function and status,and downregulate related IL-1 β,TNF-α,FOS factor content.Conclusion Ganmai Dazao Tang can alleviate the core symptoms of ADHD in SHR rats by protecting normal intestinal function and downregulating inflammatory factors.
5.Mechanism of Huoxue Jiedu Huayu Recipe Ameliorates Kidney Vascular Smooth Muscle Cell Pyroptosis in the Contralateral Kidneys of 6-Month UUO Rats via MR/NLRP3 Pathway
Yunqian XIAN ; Yutong HAN ; Panpan QIANG ; Juan HAO ; Fan YANG ; Qingyou XU
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(10):3336-3346
Objective The intervention effect of Huoxue Jiedu Huayu Recipe on the pyroptosis of vascular smooth muscle cells(VSMC)on the contralateral renal vessel of 6-month unilateral ureteral obstruction(UUO)rat model was observed,and part of the treatment mechanism of Huoxue Jiedu Huayu Recipe on chronic kidney disease(CKD)was investigated.Methods Forty male wistar rats were randomly divided into 4 groups:the sham operation(Sham)group,the unilateral ureteral obstruction(UUO)group,the eplerenone treatment(EPL)group and the Huoxue Jiedu Huayu Recipe intervention(HJHR)group,10 rats in each group.The EPL group was given eplerenone and the HJHR group was given traditional Chinese medicine.The right kidney was collected after 6 months.Pathological changes were assessed by HE staining and Masson staining.The expressions of Cysteinyl aspartate specific proteinase1(Caspase-1),Interleukin-1β(IL-1β),Serum and glucocorticoid-induced kinase 1(SGK1)and nuclear factor κappa-B(NF-κB)were detected by immunohistochemistry.The DNA damage in renal VSMC was examined by TUNEL staining.Rat VSMCs were used for in vitro experiments.The cells were divided into 4 groups using the random number method:the control(CON)group,the aldosterone(ALD)group,the aldosterone plus eplerenone treatment(EPL)group and the aldosterone plus Huoxue Jiedu Huayu Recipe treatment(HJHR)group.The ALD group was given aldosterone stimulation for 24 h.The EPL group and the HJHR group were given eplerenone and rat serum containing 10%Huoxue Jiedu Huayu Recipe pretreatment before aldosterone stimulation,respectively.The apoptosis rate was detected by flow cytometry.Perforation of gasdermin D(GSDMD)and nuclear translocation of NR3C2(Encode MR)in cell membranes were examined by immunofluorescence.The protein expression of inflammation and pyroptosis-related signaling molecules were examined by western blotting.The mRNA expression of pyroptosis signaling pathway were detected by qRT-PCR.Results Compared with the Sham group,DNA damage of renal blood vessels and VSMCs was increased in UUO group,and expressions of Caspase-1,IL-1β,SGK1 and NF-κB were increased.Compared with the UUO group,the DNA damage of renal blood vessels and VSMCs in EPL and HJHR groups was reduced,and the expressions of Caspase-1,IL-1β,SGK1 and NF-κB were decreased.Compared with the CON group,the ALD group showed pyroptosis and DNA damage of rat VSMC.The expression of NR3C2,NLRP3,Caspase-1,GSDMD,IL-1β,SGK1 and NF-κB was up-regulated.Compared with the ALD group,the pyroptosis and DNA damage were alleviated,and the expression of NR3C2,NLRP3,Caspase-1,GSDMD,IL-1β,SGK1 and NF-κB was decreased in EPL and HJHR groups.Conclusion Huoxue Jiedu Huayu Recipe reduce the vascular damage of the contralateral kidneys of UUO by inhibiting the activation of the MR/NLRP3 inflammasome pathway and inhibiting the pyroptosis of VSMC.

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