ObjectiveTo explore the mechanism by which Banxia Xiexin Tang （BXT） regulates the advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia （VD）. MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry（UPLC-Q-Orbitrap-MS/MS）， and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries （2-VO） method. The successfully modeled rats were randomly allocated into the model， low-， medium-， and high-dose （3.748 5， 7.497， 14.994 g·kg^-1） BXT （BXT-L， BXT-M， and BXT-H）， and nimodipine （NMP， 0.002 7 g·kg^-1） groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage， and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze， Y-maze， and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin （HE） staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE， RAGE， and phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65） in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry （IHC）. The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze， Y maze， and novel object recognition tests showed that compared with the sham group， the model group demonstrated prolonged successful latency and decreases in number of platform crossings， alternation rate， number of entries into the new arm， preference index， and discrimination index （P0.01）. Compared with the model group， the BXT-H and BXT-M groups showed shortened successful latency （P0.01） and increases in number of platform crossings （P0.05）， alternation rate （P0.01）， number of entries into the new arm （P0.05）， preference index （P0.01）， and discrimination index （P0.01）. HE results showed that compared with the sham group， the cells of model rats were loosely and disorderly arranged， and the nuclei were condensed. Compared with the model group， the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group， the model group presented up-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 in the hippocampus （P0.01）， and compared with the model group， the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 （P0.01）. Western blot results showed that compared with the sham group， the model group presented up-regulated expression of AGE， RAGE， p-NF-κB p65， and tumor necrosis factor-α （TNF-α） （P0.05）， and compared with the model group， the BXT-H group presented down-regulated expression of AGE， RAGE， p-NF-κB p65， and TNF-α （P0.05）. IHC results showed that compared with the sham group， the model group had increased expression of RAGE （P0.01）， and compared with the model group， the BXT-H and BXT-M groups had reduced expression of RAGE （P0.01）. ELISA results showed that compared with the sham group， the model group exhibited elevated levels of TNF-α and Interleukin-1β （IL-1β） and declined levels of acetylcholine （ACh） and dopamine （DA） in the serum （P0.01）. Compared with the model group， the BXT-L， BXT-M， and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum （P0.05） and elevated levels of ACh and DA （P0.05）. ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway， reducing neuroinflammatory responses， and regulating neurotransmitter levels.

ObjectiveTo explore the effects of Yimei Baijiang formula （YMBJF） on colitis-associated colorectal cancer （CAC） and the nuclear factor kappaB （NF-κB） signaling pathway in mice. MethodsSixty male Balb/c mice of 4-6 weeks old were randomized into 6 groups： Normal， model， capecitabine （0.83 g·kg^-1）， and low-， medium-， and high-dose （4.63， 9.25， 18.50 g·kg^-1， respectively） YMBJF. The mouse model of CAC was established by combining azoxymethane （AOM， 10 mg·kg^-1） and dextran sulfate sodium （DSS， 2%）. At the 5^th week after the start of modeling， the capecitabine group and the YMBJF groups were respectively administrated with the corresponding doses of drugs by gavage once a day for a total of 6 weeks. The body weights and general conditions of mice were measured and observed， and the disease activity index （DAI） was scored. The tumors in the colorectal tissue were counted， and the colorectal length was measured. The histological features of the colorectal tissue in each group of mice were observed by hematoxylin-eosin （HE） staining. The levels of inflammatory cytokines including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. The expression and localization of proliferating cell nuclear antigen-67 （Ki67）， proliferating cell nuclear antigen （PCNA）， and phosphorylated nuclear transcription factor-κB p65 （p-NF-κB p65） proteins were observed by immunohistochemistry （IHC）. The apoptosis of tumor cells was observed by the TUNEL assay. The mRNA levels of IL-6，IL-1β， TNF-α， nuclear transcription factor-κB p65 （NF-κB p65）， NF-κB inhibitor alpha （IκBα）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the colorectal tissue were quantified by Real-time polymerase chain reaction（Real-time PCR）. The protein levels of NF-κB p65， phosphorylated （p）-NF-κB p65， IκBα， p-IκBα， Bcl-2， and Bax in the colorectal tissue were determined by Western blot. ResultsCompared with the model group， each YMBJF group showed decreases in DAI and tumor number （P0.01）， and the medium-dose and high-dose YMBJF groups showed increases in colorectal length （P0.05）. In addition， each YMBJF group showed alleviated colorectal mucosal pathological injury， declined levels of IL-6， IL-1β， and TNF-α in the serum （P0.05）， reduced expression of Ki67 and PCNA （P0.01）， and down-regulated expression of p-NF-κB p65 （P0.05）. The apoptosis in the medium-dose and high-dose YMBJF groups increased （P0.01）. Each YMBJF group and the capecitabine group showed down-regulated mRNA levels of IL-1β， TNF-α， IL-6， NF-κB p65， and Bcl-2 （P0.05） and up-regulated mRNA levels of IκBα and Bax （P0.05）. The mRNA level of IκBα was up-regulated， and that of Bcl-2 was down-regulated （P0.05） in the high-dose YMBJF group. The protein levels of p-IκBα and Bcl-2 were down-regulated （P0.05） in each YMBJF group. The protein levels of IκBα and Bax were up-regulated in the medium-dose and high-dose YMBJF groups （P0.01）， while those of NF-κB p65 and p-NF-κB p65 were down-regulated （P0.05）. ConclusionYMBJF can reduce the number of tumors， reduce the levels of inflammatory factors， promote tumor cell apoptosis， and inhibit tumor cell proliferation by regulating the direct effector molecules of the NF-κB signaling pathway in the mouse model of CRC.

Atherosclerosis （AS） is the main pathological basis of cardiovascular diseases and seriously threatens human quality of life. Its prevention and treatment urgently need breakthroughs. The inflammatory response， which runs through the physiological and pathological evolution process of AS， is one of the important mechanisms for AS occurrence. Currently， the treatment methods for AS in Western medicine are relatively mature. However， they have adverse reactions such as abnormal liver and kidney function， drug tolerance， target vessel restenosis， and stent thrombosis， which remain the key bottleneck restricting clinical efficacy. Traditional Chinese medicine （TCM）， characterized by multiple components， multiple targets， and multi-pathway synergy， shows unique clinical application potential and efficacy advantages in the intervention of AS. This article reviewed the research progress of TCM in intervening in AS by regulating inflammatory-related signaling pathways， such as nuclear factor-κB （NF-κB）， Toll-like receptors （TLRs）， mitogen-activated protein kinase （MAPK）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）， in the past five years. It summarized the combined mechanism of action of TCM monomers， TCM pairs， and compound preparations in inhibiting the inflammatory cascade reaction through multiple targets， regulating lipid metabolism disorders， and improving vascular endothelial dysfunction and the imbalance of the microenvironment. It deepened the research on the molecular mechanism of TCM in anti-AS， so as to provide a scientific basis for the clinical transformation application and related theoretical research of TCM in anti-AS.

Chronic obstructive pulmonary disease （COPD）， as one of the three major causes of death， is a complex systemic disease with high prevalence， high mortality， high disability， frequent acute exacerbations， and a variety of pulmonary complications. The pathogenesis is complex. Western medicine has no effective specificity scheme for a complete cure. However， multiple-component and multiple-target characteristics of traditional Chinese medicine （TCM） demonstrate significant advantages in COPD treatment through multi-link， multi-pathway， and multi-mechanism intervention. Therefore， exploring the essence of COPD pathogenesis and discovering effective TCM treatment drugs through the application of TCM principles and prescriptions is a key focus of modern research. Animal models are of paramount importance in medical research. It is the first consideration to select appropriate animals， adopt reasonable modeling methods to replicate stable animal models that closely resemble the clinical manifestations and pathophysiological characteristics of COPD， and use appropriate evaluation methods to determine the success of COPD animal models in experimental research. The core of experimental research lies in observing the intervention effect of TCM on COPD animal models， exploring the specific pathways and regulatory mechanisms of TCM on COPD disease， and finding TCM monomers， single herbs， and TCM formulas with definite curative effects. At present， animal model research on COPD mainly involves model establishment， model evaluation， efficacy observation， mechanism exploration， and other aspects. In recent years， there has been no systematic organization， update， and reflection on the relevant research on TCM intervention in COPD animal models. This study reviewed the selection of animals for the COPD model， methods for establishing COPD animal models， model evaluation methods， and the intervention effects of TCM on COPD animal models. It aims to grasp the current research status and identify existing problems for further improvement， in order to provide evidence and support for scientific research and clinical treatment of COPD.

As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

ObjectiveTo explore the mechanism by which Banxia Xiexin Tang （BXT） regulates the advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia （VD）. MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry（UPLC-Q-Orbitrap-MS/MS）， and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries （2-VO） method. The successfully modeled rats were randomly allocated into the model， low-， medium-， and high-dose （3.748 5， 7.497， 14.994 g·kg^-1） BXT （BXT-L， BXT-M， and BXT-H）， and nimodipine （NMP， 0.002 7 g·kg^-1） groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage， and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze， Y-maze， and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin （HE） staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE， RAGE， and phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65） in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry （IHC）. The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze， Y maze， and novel object recognition tests showed that compared with the sham group， the model group demonstrated prolonged successful latency and decreases in number of platform crossings， alternation rate， number of entries into the new arm， preference index， and discrimination index （P<0.01）. Compared with the model group， the BXT-H and BXT-M groups showed shortened successful latency （P<0.01） and increases in number of platform crossings （P<0.05）， alternation rate （P<0.01）， number of entries into the new arm （P<0.05）， preference index （P<0.01）， and discrimination index （P<0.01）. HE results showed that compared with the sham group， the cells of model rats were loosely and disorderly arranged， and the nuclei were condensed. Compared with the model group， the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group， the model group presented up-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 in the hippocampus （P<0.01）， and compared with the model group， the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 （P<0.01）. Western blot results showed that compared with the sham group， the model group presented up-regulated expression of AGE， RAGE， p-NF-κB p65， and tumor necrosis factor-α （TNF-α） （P<0.05）， and compared with the model group， the BXT-H group presented down-regulated expression of AGE， RAGE， p-NF-κB p65， and TNF-α （P<0.05）. IHC results showed that compared with the sham group， the model group had increased expression of RAGE （P<0.01）， and compared with the model group， the BXT-H and BXT-M groups had reduced expression of RAGE （P<0.01）. ELISA results showed that compared with the sham group， the model group exhibited elevated levels of TNF-α and Interleukin-1β （IL-1β） and declined levels of acetylcholine （ACh） and dopamine （DA） in the serum （P<0.01）. Compared with the model group， the BXT-L， BXT-M， and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum （P<0.05） and elevated levels of ACh and DA （P<0.05）. ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway， reducing neuroinflammatory responses， and regulating neurotransmitter levels.

ObjectiveTo explore the effects of Yimei Baijiang formula （YMBJF） on colitis-associated colorectal cancer （CAC） and the nuclear factor kappaB （NF-κB） signaling pathway in mice. MethodsSixty male Balb/c mice of 4-6 weeks old were randomized into 6 groups： Normal， model， capecitabine （0.83 g·kg^-1）， and low-， medium-， and high-dose （4.63， 9.25， 18.50 g·kg^-1， respectively） YMBJF. The mouse model of CAC was established by combining azoxymethane （AOM， 10 mg·kg^-1） and dextran sulfate sodium （DSS， 2%）. At the 5^th week after the start of modeling， the capecitabine group and the YMBJF groups were respectively administrated with the corresponding doses of drugs by gavage once a day for a total of 6 weeks. The body weights and general conditions of mice were measured and observed， and the disease activity index （DAI） was scored. The tumors in the colorectal tissue were counted， and the colorectal length was measured. The histological features of the colorectal tissue in each group of mice were observed by hematoxylin-eosin （HE） staining. The levels of inflammatory cytokines including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. The expression and localization of proliferating cell nuclear antigen-67 （Ki67）， proliferating cell nuclear antigen （PCNA）， and phosphorylated nuclear transcription factor-κB p65 （p-NF-κB p65） proteins were observed by immunohistochemistry （IHC）. The apoptosis of tumor cells was observed by the TUNEL assay. The mRNA levels of IL-6，IL-1β， TNF-α， nuclear transcription factor-κB p65 （NF-κB p65）， NF-κB inhibitor alpha （IκBα）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the colorectal tissue were quantified by Real-time polymerase chain reaction（Real-time PCR）. The protein levels of NF-κB p65， phosphorylated （p）-NF-κB p65， IκBα， p-IκBα， Bcl-2， and Bax in the colorectal tissue were determined by Western blot. ResultsCompared with the model group， each YMBJF group showed decreases in DAI and tumor number （P0.01）， and the medium-dose and high-dose YMBJF groups showed increases in colorectal length （P0.05）. In addition， each YMBJF group showed alleviated colorectal mucosal pathological injury， declined levels of IL-6， IL-1β， and TNF-α in the serum （P0.05）， reduced expression of Ki67 and PCNA （P0.01）， and down-regulated expression of p-NF-κB p65 （P0.05）. The apoptosis in the medium-dose and high-dose YMBJF groups increased （P0.01）. Each YMBJF group and the capecitabine group showed down-regulated mRNA levels of IL-1β， TNF-α， IL-6， NF-κB p65， and Bcl-2 （P0.05） and up-regulated mRNA levels of IκBα and Bax （P0.05）. The mRNA level of IκBα was up-regulated， and that of Bcl-2 was down-regulated （P0.05） in the high-dose YMBJF group. The protein levels of p-IκBα and Bcl-2 were down-regulated （P0.05） in each YMBJF group. The protein levels of IκBα and Bax were up-regulated in the medium-dose and high-dose YMBJF groups （P0.01）， while those of NF-κB p65 and p-NF-κB p65 were down-regulated （P0.05）. ConclusionYMBJF can reduce the number of tumors， reduce the levels of inflammatory factors， promote tumor cell apoptosis， and inhibit tumor cell proliferation by regulating the direct effector molecules of the NF-κB signaling pathway in the mouse model of CRC.

Atherosclerosis （AS） is the main pathological basis of cardiovascular diseases and seriously threatens human quality of life. Its prevention and treatment urgently need breakthroughs. The inflammatory response， which runs through the physiological and pathological evolution process of AS， is one of the important mechanisms for AS occurrence. Currently， the treatment methods for AS in Western medicine are relatively mature. However， they have adverse reactions such as abnormal liver and kidney function， drug tolerance， target vessel restenosis， and stent thrombosis， which remain the key bottleneck restricting clinical efficacy. Traditional Chinese medicine （TCM）， characterized by multiple components， multiple targets， and multi-pathway synergy， shows unique clinical application potential and efficacy advantages in the intervention of AS. This article reviewed the research progress of TCM in intervening in AS by regulating inflammatory-related signaling pathways， such as nuclear factor-κB （NF-κB）， Toll-like receptors （TLRs）， mitogen-activated protein kinase （MAPK）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）， in the past five years. It summarized the combined mechanism of action of TCM monomers， TCM pairs， and compound preparations in inhibiting the inflammatory cascade reaction through multiple targets， regulating lipid metabolism disorders， and improving vascular endothelial dysfunction and the imbalance of the microenvironment. It deepened the research on the molecular mechanism of TCM in anti-AS， so as to provide a scientific basis for the clinical transformation application and related theoretical research of TCM in anti-AS.

Chronic obstructive pulmonary disease （COPD）， as one of the three major causes of death， is a complex systemic disease with high prevalence， high mortality， high disability， frequent acute exacerbations， and a variety of pulmonary complications. The pathogenesis is complex. Western medicine has no effective specificity scheme for a complete cure. However， multiple-component and multiple-target characteristics of traditional Chinese medicine （TCM） demonstrate significant advantages in COPD treatment through multi-link， multi-pathway， and multi-mechanism intervention. Therefore， exploring the essence of COPD pathogenesis and discovering effective TCM treatment drugs through the application of TCM principles and prescriptions is a key focus of modern research. Animal models are of paramount importance in medical research. It is the first consideration to select appropriate animals， adopt reasonable modeling methods to replicate stable animal models that closely resemble the clinical manifestations and pathophysiological characteristics of COPD， and use appropriate evaluation methods to determine the success of COPD animal models in experimental research. The core of experimental research lies in observing the intervention effect of TCM on COPD animal models， exploring the specific pathways and regulatory mechanisms of TCM on COPD disease， and finding TCM monomers， single herbs， and TCM formulas with definite curative effects. At present， animal model research on COPD mainly involves model establishment， model evaluation， efficacy observation， mechanism exploration， and other aspects. In recent years， there has been no systematic organization， update， and reflection on the relevant research on TCM intervention in COPD animal models. This study reviewed the selection of animals for the COPD model， methods for establishing COPD animal models， model evaluation methods， and the intervention effects of TCM on COPD animal models. It aims to grasp the current research status and identify existing problems for further improvement， in order to provide evidence and support for scientific research and clinical treatment of COPD.

As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.