OBJECTIVE To investigate the therapeutic effects of Xianlian Jiedu Decoction(XLJDD)on colitis-associated colorectal cancer(CAC)and to explore its potential underlying mechanisms.METHODS An azoxymethane/dextran sulfate...OBJECTIVE To investigate the therapeutic effects of Xianlian Jiedu Decoction(XLJDD)on colitis-associated colorectal cancer(CAC)and to explore its potential underlying mechanisms.METHODS An azoxymethane/dextran sulfate sodium(AOM/DSS)-induced CAC mouse model was established.UPLC-Q-TOF/MS was employed to identify prototype compounds present in colonic tissue after XLJDD administration.Network pharmacology analysis,molecular docking,transcriptomic sequencing,and valida‑tion of key pathway-related genes were further conducted to systematically elucidate the intervention effects and potential mechanisms of XLJDD against CAC.RESULTS In the AOM/DSS-induced CAC mouse model,XLJDD treatment markedly improved tumor-associated pathological features,as evidenced by reduced tumor burden,restored colon length,and alleviated disease activity index(DAI).UPLC-Q-TOF/MS analysis identified 22 exogenous compounds derived from XLJDD in colonic tissue.In addition,XLJDD sig‑nificantly downregulated the expression of multiple inflammatory cytokines while upregulating tight junction-related genes in the co‑lon.Transcriptomic analysis revealed that XLJDD treatment enhanced overall PPAR signaling pathway activity while suppressing the Wnt signaling pathway.Consistently,the expression levels of PPAR pathway-related genes Pparα,Cpt1a,and Ehhadh were upregulated following XLJDD intervention(P<0.05,P<0.01),whereas the Wnt pathway-related genes Axin2 and Lef1 were significantly downregulated(P<0.05,P<0.01).CONCLUSION XLJDD may intervene in inflammation-associated colorectal carcinogenesis by activating the PPAR signaling pathway and suppressing the Wnt signaling pathway.展开更多
Background Mammalian spermatogenesis is critical for the transmission of male genetic information,and singlecell sequencing technology can reveal its complex process.However,at present,there is no research on the dyna...Background Mammalian spermatogenesis is critical for the transmission of male genetic information,and singlecell sequencing technology can reveal its complex process.However,at present,there is no research on the dynamic transcription of bovine germ cell population.Results In this study,we used Stereo-seq to construct a spatial transcription map of bovine testicular tissue at two ages.Four germ cell groups and five somatic cell groups were determined,and functional enrichment characterized their different biological functions and the differences between calves and adult bulls.At the same time,we also defined the subpopulations of cells and marker genes,then,clarified the communications between germ cells.Conclusion Our study constructed a spatial transcription map of bovine testicular tissue for the first time,and systematically described the dynamic transcription changes during spermatogenesis.These data laid the foundation for the study of spermatogenesis in large mammals and elucidated the transcriptional dynamics underlying male germ cell development.展开更多
Background:Cervicitis is a common gynecological disease,which triggers local inflammation and tissue damage by a complex mechanism,seriously affecting women’s health.Chinese medicine plays a prominent role in the tre...Background:Cervicitis is a common gynecological disease,which triggers local inflammation and tissue damage by a complex mechanism,seriously affecting women’s health.Chinese medicine plays a prominent role in the treatment of gynecological inflammation.Shuangshi Tongling Capsule(SSTL),as a traditional Chinese medicine(TCM)compound,needs to be further elucidated for the treatment of cervicitis.Methods:Cervicitis was induced with 25%phenol gel(except controls),followed by 12-day intragastric treatment.Outcomes included genital inflammation scores,uterine index,and histopathology(HE staining).Serum tumor necrosis factor-α(TNF-α),Interleukin(IL)-6,IL-8,and IL-1βwere measured via ELISA.Integrated metabolomics-transcriptomics and Western blotting identified mechanistic pathways.Results:SSTL alleviated cervicitis in rats by improving uterine histopathology,reducing external genital inflammation scores(P<0.01 vs.model),and reversing uterine hypertrophy(P<0.05).Serum pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-8)were suppressed(P<0.01),with concurrent weight restoration.Multi-omics analysis identified AMPK signaling as pivotal,validated by downregulation of p-NF-κB(P<0.05)and upregulation of p-AMPK/SIRT1(P<0.05)in uterine tissues,indicating SSTL mitigates inflammation through AMPK/NF-κB/SIRT1 modulation.Conclusion:This study found that SSTL ameliorates cervicitis in rats through the expression of AMPK pathway-related proteins.展开更多
Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is...Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is not clear.This study aimed to investigate the therapeutic effects of JPHZW and explore its mechanism of action through colonic transcriptomics and gut microbiota analysis.Methods:An ulcerative colitis(UC)mice model was established to evaluate the therapeutic effect of JPHZW.The expression levels of specific inflammatory factors in colon tissue were determined by ELISA.Colonic transcriptome sequencing was performed to identify candidate targets.The effects of JPHZW on gut microbiota were analyzed using 16S rRNA sequencing.Finally,relevant signaling pathways were verified via Western blotting to elucidate the mechanism of action of JPHZW.Results:JPHZW significantly improved the DAI Score and reduced the expression levels of pro-inflammatory factors,such as MCP-1,IL-17A,and IFN-γ,while increasing the expression levels of anti-inflammatory factors,such as IL-4,EGF,and GM-CSF in UC mice.Colonic transcriptome sequencing revealed that the Peroxisome PPAR-γ/NF-κB signaling pathway was closely associated with JPHZW’s anti-UC effect.Furthermore,WB analysis demonstrated that JPHZW treatment significantly inhibited the upregulation the expression of NF-κB and significantly upregulated the expression of PPAR-γ.In addition,16S rRNA sequencing analysis indicated that the relative abundance of beneficial bacteria was improved.Conclusion:These findings demonstrate that JPHZW alleviates DSS-induced ulcerative colitis in mice by regulating the PPAR-γ/NF-κB signaling pathway to suppress inflammatory factors,while simultaneously improving gut microbiota composition by increasing the relative abundance of beneficial bacteria.展开更多
Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,t...Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.展开更多
目的探讨动态心电图参数联合心肌梗死溶栓疗法(TIMI)危险评分对急性ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)术后发生主要不良心血管事件(MACE)的预测价值。方法选取2021年7月至2024年6月于连云港市第一人民医院就诊的S...目的探讨动态心电图参数联合心肌梗死溶栓疗法(TIMI)危险评分对急性ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)术后发生主要不良心血管事件(MACE)的预测价值。方法选取2021年7月至2024年6月于连云港市第一人民医院就诊的STEMI患者119例,根据术后1年随访期内是否发生MACE分为发生组(24例)和未发生组(95例)。比较两组一般临床资料、动态心电图参数;采用多因素Logistic回归分析STEMI患者PCI术后发生MACE的影响因素;采用ROC曲线分析动态心电图参数[包括24 h QT间期变异性(24 h QTV)、窦性心搏RR间期的标准差(SDNN)等]、TIMI危险评分对STEMI患者PCI术后发生MACE的预测价值。结果发生组年龄、Killip心功能分级≥Ⅱ级、TIMI危险评分高于未发生组(P<0.05)。发生组24 h QTV、SDNN水平低于未发生组(P<0.001)。多因素Logistic回归分析显示,年龄、TIMI危险评分是STEMI患者PCI术后发生MACE的独立危险因素,24 h QTV、SDNN是STEMI患者PCI术后发生MACE的独立保护因素(OR=2.098,95%CI:1.022~4.307,P=0.044;OR=2.869,95%CI:1.267~6.497,P=0.012;OR=0.355,95%CI:0.159~0.795,P=0.012;OR=0.376,95%CI:0.174~0.813,P=0.013)。ROC曲线分析显示,24 h QTV、SDNN、TIMI危险评分预测STEMI患者PCI术后发生MACE的曲线下面积分别为0.762、0.740、0.761,联合检测预测的曲线下面积为0.930,显著优于单独检测(P<0.05)。结论动态心电图参数24 h QTV、SDNN及TIMI危险评分均是STEMI患者PCI术后发生MACE的独立影响因素,联合检测可较好地预测STEMI患者PCI术后MACE的发生。展开更多
文摘OBJECTIVE To investigate the therapeutic effects of Xianlian Jiedu Decoction(XLJDD)on colitis-associated colorectal cancer(CAC)and to explore its potential underlying mechanisms.METHODS An azoxymethane/dextran sulfate sodium(AOM/DSS)-induced CAC mouse model was established.UPLC-Q-TOF/MS was employed to identify prototype compounds present in colonic tissue after XLJDD administration.Network pharmacology analysis,molecular docking,transcriptomic sequencing,and valida‑tion of key pathway-related genes were further conducted to systematically elucidate the intervention effects and potential mechanisms of XLJDD against CAC.RESULTS In the AOM/DSS-induced CAC mouse model,XLJDD treatment markedly improved tumor-associated pathological features,as evidenced by reduced tumor burden,restored colon length,and alleviated disease activity index(DAI).UPLC-Q-TOF/MS analysis identified 22 exogenous compounds derived from XLJDD in colonic tissue.In addition,XLJDD sig‑nificantly downregulated the expression of multiple inflammatory cytokines while upregulating tight junction-related genes in the co‑lon.Transcriptomic analysis revealed that XLJDD treatment enhanced overall PPAR signaling pathway activity while suppressing the Wnt signaling pathway.Consistently,the expression levels of PPAR pathway-related genes Pparα,Cpt1a,and Ehhadh were upregulated following XLJDD intervention(P<0.05,P<0.01),whereas the Wnt pathway-related genes Axin2 and Lef1 were significantly downregulated(P<0.05,P<0.01).CONCLUSION XLJDD may intervene in inflammation-associated colorectal carcinogenesis by activating the PPAR signaling pathway and suppressing the Wnt signaling pathway.
基金supported by Biological Breeding-Major Projects to Yun Ma(Grant No.2023ZD0404803)Key R&D Program of Ningxia Hui Autonomous Region to Lingkai Zhang(2023BBF01007)and(2023BCF01006)。
文摘Background Mammalian spermatogenesis is critical for the transmission of male genetic information,and singlecell sequencing technology can reveal its complex process.However,at present,there is no research on the dynamic transcription of bovine germ cell population.Results In this study,we used Stereo-seq to construct a spatial transcription map of bovine testicular tissue at two ages.Four germ cell groups and five somatic cell groups were determined,and functional enrichment characterized their different biological functions and the differences between calves and adult bulls.At the same time,we also defined the subpopulations of cells and marker genes,then,clarified the communications between germ cells.Conclusion Our study constructed a spatial transcription map of bovine testicular tissue for the first time,and systematically described the dynamic transcription changes during spermatogenesis.These data laid the foundation for the study of spermatogenesis in large mammals and elucidated the transcriptional dynamics underlying male germ cell development.
基金supported by Science and Technology Innovative Talent Program of Shaanxi University of Chinese Medicine(No.2024-CXTD-03)Key Research&Development Program of Shaanxi Provincial Department of Science and Technology(No.2024CY-JJQ-36,2024CY-JJQ-78)+4 种基金Shaanxi Provincial Administration of Traditional Chinese Medicine Research and Innovation Team Project(No.TZKN-CXTD-03)Youth Innovation Team of Aromatic Chinese Medicine Industrialization Key Technology(No.2022-95)Scientific Research Project of Shaanxi Administration of Traditional Chinese Medicine(ZYJXG-L23002)the Science and Technology Innovative Team Project of Shaanxi Administration of Traditional Chinese Medicine(No.2025-CXTD-02)The cartoon elements in the mechanism diagram are from https://www.figdraw.com.Shaanxi Provincial Science and Technology Department’s“two chains”integrated enterprise(institute)joint project(2023-LL-QY-39).
文摘Background:Cervicitis is a common gynecological disease,which triggers local inflammation and tissue damage by a complex mechanism,seriously affecting women’s health.Chinese medicine plays a prominent role in the treatment of gynecological inflammation.Shuangshi Tongling Capsule(SSTL),as a traditional Chinese medicine(TCM)compound,needs to be further elucidated for the treatment of cervicitis.Methods:Cervicitis was induced with 25%phenol gel(except controls),followed by 12-day intragastric treatment.Outcomes included genital inflammation scores,uterine index,and histopathology(HE staining).Serum tumor necrosis factor-α(TNF-α),Interleukin(IL)-6,IL-8,and IL-1βwere measured via ELISA.Integrated metabolomics-transcriptomics and Western blotting identified mechanistic pathways.Results:SSTL alleviated cervicitis in rats by improving uterine histopathology,reducing external genital inflammation scores(P<0.01 vs.model),and reversing uterine hypertrophy(P<0.05).Serum pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-8)were suppressed(P<0.01),with concurrent weight restoration.Multi-omics analysis identified AMPK signaling as pivotal,validated by downregulation of p-NF-κB(P<0.05)and upregulation of p-AMPK/SIRT1(P<0.05)in uterine tissues,indicating SSTL mitigates inflammation through AMPK/NF-κB/SIRT1 modulation.Conclusion:This study found that SSTL ameliorates cervicitis in rats through the expression of AMPK pathway-related proteins.
基金financially supported by the Science and Technology Project of Nantong City(Grant No.JC2021097)the Key Project Fund for Clinical Medicine Special Program of Nantong University(Grant No.2024JZ043)Jiangsu Provincial Administration for Market Regulation Science and Technology Program Project(Grant No.KJ2026104).
文摘Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is not clear.This study aimed to investigate the therapeutic effects of JPHZW and explore its mechanism of action through colonic transcriptomics and gut microbiota analysis.Methods:An ulcerative colitis(UC)mice model was established to evaluate the therapeutic effect of JPHZW.The expression levels of specific inflammatory factors in colon tissue were determined by ELISA.Colonic transcriptome sequencing was performed to identify candidate targets.The effects of JPHZW on gut microbiota were analyzed using 16S rRNA sequencing.Finally,relevant signaling pathways were verified via Western blotting to elucidate the mechanism of action of JPHZW.Results:JPHZW significantly improved the DAI Score and reduced the expression levels of pro-inflammatory factors,such as MCP-1,IL-17A,and IFN-γ,while increasing the expression levels of anti-inflammatory factors,such as IL-4,EGF,and GM-CSF in UC mice.Colonic transcriptome sequencing revealed that the Peroxisome PPAR-γ/NF-κB signaling pathway was closely associated with JPHZW’s anti-UC effect.Furthermore,WB analysis demonstrated that JPHZW treatment significantly inhibited the upregulation the expression of NF-κB and significantly upregulated the expression of PPAR-γ.In addition,16S rRNA sequencing analysis indicated that the relative abundance of beneficial bacteria was improved.Conclusion:These findings demonstrate that JPHZW alleviates DSS-induced ulcerative colitis in mice by regulating the PPAR-γ/NF-κB signaling pathway to suppress inflammatory factors,while simultaneously improving gut microbiota composition by increasing the relative abundance of beneficial bacteria.
基金the National Natural Science Foundation of China(82204935)the construction project of Zhao Feng National Old Pharmacist Inheritance Studio of State Administration of Traditional Chinese Medicine(National Traditional Chinese Medicine Education Letter[2024]255)+1 种基金the open project of the Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine in Shaanxi Province(KF202302)the project of Xi’an Municipal Bureau of Science and Technology(23YXYJ0042)for financial support.
文摘Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.
文摘目的探讨动态心电图参数联合心肌梗死溶栓疗法(TIMI)危险评分对急性ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)术后发生主要不良心血管事件(MACE)的预测价值。方法选取2021年7月至2024年6月于连云港市第一人民医院就诊的STEMI患者119例,根据术后1年随访期内是否发生MACE分为发生组(24例)和未发生组(95例)。比较两组一般临床资料、动态心电图参数;采用多因素Logistic回归分析STEMI患者PCI术后发生MACE的影响因素;采用ROC曲线分析动态心电图参数[包括24 h QT间期变异性(24 h QTV)、窦性心搏RR间期的标准差(SDNN)等]、TIMI危险评分对STEMI患者PCI术后发生MACE的预测价值。结果发生组年龄、Killip心功能分级≥Ⅱ级、TIMI危险评分高于未发生组(P<0.05)。发生组24 h QTV、SDNN水平低于未发生组(P<0.001)。多因素Logistic回归分析显示,年龄、TIMI危险评分是STEMI患者PCI术后发生MACE的独立危险因素,24 h QTV、SDNN是STEMI患者PCI术后发生MACE的独立保护因素(OR=2.098,95%CI:1.022~4.307,P=0.044;OR=2.869,95%CI:1.267~6.497,P=0.012;OR=0.355,95%CI:0.159~0.795,P=0.012;OR=0.376,95%CI:0.174~0.813,P=0.013)。ROC曲线分析显示,24 h QTV、SDNN、TIMI危险评分预测STEMI患者PCI术后发生MACE的曲线下面积分别为0.762、0.740、0.761,联合检测预测的曲线下面积为0.930,显著优于单独检测(P<0.05)。结论动态心电图参数24 h QTV、SDNN及TIMI危险评分均是STEMI患者PCI术后发生MACE的独立影响因素,联合检测可较好地预测STEMI患者PCI术后MACE的发生。
