OBJECTIVE To investigate the mechanism of Shenling baizhu san （SLBZS） in ameliorating ulcerative colitis （UC）. METHODS Mice were randomly divided into normal group， model group， and low-， medium-， high-dose SLBZS groups （3， 6， 12 g/kg）， with 10 mice in each group. Except for the normal group， mice in other groups were given free access to 3% dextran sulfate sodium solution for 7 days to establish UC models. Simultaneously， mice in each group were intragastrically administered corresponding medicinal liquid or double-distilled water once a day for consecutive 7 days. After the last administration， the histopathological morphology of colon tissues was observed； the serum levels of inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and IL-18 were detected； the total bile acid contents in liver， gallbladder and colon tissues were determined； the expression level of NOD-like receptor family pyrin domain-containing protein 3 （NLRP3） in colon tissues was tested. The expression levels of flora metabolism-related proteins [G protein-coupled receptor 41（GPR41），GPR43，farnesoid X receptor （FXR）， G protein-coupled bile acid receptor 1 （TGR5）， flavin-containing monooxygenase 3 （FMO3）， cytochrome P450 family 27 subfamily A member 1 （CYP27A1）， CYP7A1] in liver or colon tissues， as well as the proteins related to Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB）/NLRP3 inflammatory axis [TLR4， NF-κB， phosphorylated NF-κB （p-NF-κB）， myeloid differentiation factor 88 （MyD88）， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， caspase-1] in colon tissues were measured. RESULTS Compared with the model group， the colon tissue injury and inflammatory cell infiltration were alleviated in medium- and high-dose SLBZS groups. The serum levels of TNF-α， IL-1β and IL-18， total bile acid contents in liver and colon tissues， as well as the protein expression levels of FMO3 and CYP7A1 in liver tissues， TLR4， p-NF-κB， NF-κB， MyD88， NLRP3， ASC and caspase-1 in colon tissues were significantly decreased （P＜0.05）. Meanwhile， the total bile acid content in gallbladder， the protein expression levels of GPR41 and GPR43 in colon tissues， along with CYP27A1， FXR and TGR5 in liver tissues were significantly increased （P＜0.05）. CONCLUSIONS SLBZS may relieve colonic inflammatory injury and ameliorate UC by regulating the expression of flora metabolism-related proteins and inhibiting the abnormal activation of TLR4/NF-κB/NLRP3 inflammatory axis.

Objective To analyze the research status and hotspots in the field of astragalus polysaccharides;To provide references for further research.Methods Research literature about astragalus polysaccharides was retrieved from CNKI,Wanfang Data,VIP,PubMed,and Web of Science databases from 1st,Jan.2013 to 1st,July 2023.NoteExpress 3.7 software was used to manage the literature and ultimately establish a database.Excel 2019,CiteSpace 6.2.2R and VOSviewer 1.6.18 were used to visually analyze the publication volume,authors,institutions,and keywords of the included literature.Results A total of 2 462 articles were included,with 1 284 Chinese articles and 1 178 English articles.The main research institutions were Gansu University of Chinese Medicine,Shandong University of Traditional Chinese Medicine,and Beijing University of Chinese Medicine.The core authors of Chinese literature were Liu Yongqi,Wang Hongxin,Lu Meili,etc.The core authors of English literature included Zhang Wei,Li Ke,Yang Xiaojun,etc.High-frequency keywords of Chinese literature included Astragali Radix,rats,polysaccharides,cell apoptosis,and oxidative stress,etc.High frequency keywords in English literature included expression,in vitro,oxidative stress,apoptosis,etc.Conclusion The research on astragalus polysaccharides focuses on their pharmacological effects and mechanisms.Intestinal flora,immune regulation,autophagy and apoptosis are the hot action mechanisms in this field.The focus of disease research involves tumor and diabetes,and antiviral,anti infection and other pharmacological effects are the research trend.

Deficiencies remain in the early identification and screening method for type 2 diabetes mellitus(T2DM).Relying solely on blood glucose indicators as diagnostic criteria fails to capture the systematic evolution of glucose metabolism destabilization and does not allow for the identification of the critical transition period preceding the onset of T2DM.In the complex system of the human body,structural and state variables correspond to the traditional Chinese medicine concepts of"zang"and"xiang."These variables determine the landscape of the systemic state changes over time.The pathogenesis of T2DM is characterized by a shift from compensatory insulin secretion to β-cell dysfunction,driven by negative-positive feedback dynamics,ultimately resulting in a marked increase in blood glucose levels.A critical transition exists between glycemic homeostasis and the establishment of T2DM disease homeostasis.Using theoretical approaches such as critical slowing and dynamic network markers in dynamical systems theory,various clinical case data-including four-diagnosis information,multiple biological samples,and histological analysis method-can be leveraged to identify the critical transition key stage from pre-disease to disease of T2DM,facilitating early intervention.This paper aims to develop a dynamic model describing the transition from"glucose homeostasis-glycemic state of instability-steady state of T2DM"by analyzing the mechanism of the complex human system and the dynamic characteristics underlying T2DM onset.This framework aims to enhance early identification method.Establishing this holistic approach offers a novel perspective for the prevention and treatment of T2DM.

Studies on specific transient receptor potential melastatin 2 (TRPM2) channel inhibitors can deepen our understanding of the pathological mechanism of related diseases, and allow discovery of novel, effective targets and drugs for therapy. The development of TRPM2 channel inhibitors can be broadly classified into four categories with distinct characteristics: reutilization and structural modification of homologous ion channel modulators to produce a diverse array of TRPM2 channel inhibitors with strong inhibitory effects; TRPM2 channel inhibitors based on channel gating mechanism with high specificity; inhibitors identified through high-throughput screening with novel chemical structures; inhibitors developed from natural antioxidants with higher safety. In recent years, the application of computer-aided drug design has significantly accelerated the development of TRPM2 channel inhibitors. Several promising compounds such as ZA18, A1 and D9 have been discovered, and it is expected that more potent and selective TRPM2 channel inhibitor scaffolds will be discovered in the future. This article reviews the advances on the studies of TRPM2 channel inhibitors, aiming to provide insights for further research and clinical application of TRPM2 channel inhibitors.
TRPM Cation Channels/antagonists & inhibitors* ; Humans ; Drug Design

Deficiencies remain in the early identification and screening method for type 2 diabetes mellitus(T2DM).Relying solely on blood glucose indicators as diagnostic criteria fails to capture the systematic evolution of glucose metabolism destabilization and does not allow for the identification of the critical transition period preceding the onset of T2DM.In the complex system of the human body,structural and state variables correspond to the traditional Chinese medicine concepts of"zang"and"xiang."These variables determine the landscape of the systemic state changes over time.The pathogenesis of T2DM is characterized by a shift from compensatory insulin secretion to β-cell dysfunction,driven by negative-positive feedback dynamics,ultimately resulting in a marked increase in blood glucose levels.A critical transition exists between glycemic homeostasis and the establishment of T2DM disease homeostasis.Using theoretical approaches such as critical slowing and dynamic network markers in dynamical systems theory,various clinical case data-including four-diagnosis information,multiple biological samples,and histological analysis method-can be leveraged to identify the critical transition key stage from pre-disease to disease of T2DM,facilitating early intervention.This paper aims to develop a dynamic model describing the transition from"glucose homeostasis-glycemic state of instability-steady state of T2DM"by analyzing the mechanism of the complex human system and the dynamic characteristics underlying T2DM onset.This framework aims to enhance early identification method.Establishing this holistic approach offers a novel perspective for the prevention and treatment of T2DM.

Objective:To analyze the application of Sengstaken-Blakemore tubes combined with endoscopic intervention on the prognosis of patients with acute esophageal and gastric variceal rupture and bleeding due to portal hypertension in liver cirrhosis, and to explore the impact of Sengstaken-Blakemore tubes combined with endoscopic intervention on the prognosis of patients.Methods:A retrospective study included patients with liver cirrhosis who visited the Zhongshan Hospital, Fudan University from January 2023 to July 2024 due to acute upper gastrointestinal bleeding, had no response to drug treatment and unstable hemodynamics, and received the Sengstaken-Blakemore tubes compression hemostasis. According to whether endoscopic intervention was received or not, the patients were divided into the endoscopic intervention group and the non-endoscopic intervention group. The medication and subsequent treatment of the patients were analyzed, and the survival of the patients 28 days after bleeding was followed up. Kaplan-Meier survival analysis and Cox regression analysis were used to evaluate the effect of endoscopic intervention on the 28-day mortality rate of patients.Results:A total of 31 cases successfully had three-lumen two-cystic tubes indwelled. Among them, 8 cases further received endoscopic examination and intervention, and 23 cases did not receive endoscopic examination. During the 28-day follow-up after bleeding, a total of 20 cases died. The Kaplan-Meier survival analysis showed that the 28-day mortality rate in the endoscopic intervention group was significantly lower than that in the non-endoscopic intervention group (25.0% vs 78.3%, P=0.007). Multivariate Cox regression analysis showed that endoscopic intervention was an independent protective factor for 28-day mortality ( HR: 0.14, 95% CI: 0.03-0.63, P=0.01). In addition, the severity of bleeding and prothrombin time were also important factors affecting the prognosis of patients. Conclusions:The Sengstaken-Blakemore tubes, as an important hemostasis method for acute esophageal and gastric variceal rupture and bleeding, can buy time for subsequent endoscopic treatment, but the risk of complications is relatively high. Creating conditions for early endoscopic intervention as early as possible can significantly reduce the mortality rate of patients and improve the prognosis of patients with liver cirrhosis.

Objective:To analyze the application of Sengstaken-Blakemore tubes combined with endoscopic intervention on the prognosis of patients with acute esophageal and gastric variceal rupture and bleeding due to portal hypertension in liver cirrhosis, and to explore the impact of Sengstaken-Blakemore tubes combined with endoscopic intervention on the prognosis of patients.Methods:A retrospective study included patients with liver cirrhosis who visited the Zhongshan Hospital, Fudan University from January 2023 to July 2024 due to acute upper gastrointestinal bleeding, had no response to drug treatment and unstable hemodynamics, and received the Sengstaken-Blakemore tubes compression hemostasis. According to whether endoscopic intervention was received or not, the patients were divided into the endoscopic intervention group and the non-endoscopic intervention group. The medication and subsequent treatment of the patients were analyzed, and the survival of the patients 28 days after bleeding was followed up. Kaplan-Meier survival analysis and Cox regression analysis were used to evaluate the effect of endoscopic intervention on the 28-day mortality rate of patients.Results:A total of 31 cases successfully had three-lumen two-cystic tubes indwelled. Among them, 8 cases further received endoscopic examination and intervention, and 23 cases did not receive endoscopic examination. During the 28-day follow-up after bleeding, a total of 20 cases died. The Kaplan-Meier survival analysis showed that the 28-day mortality rate in the endoscopic intervention group was significantly lower than that in the non-endoscopic intervention group (25.0% vs 78.3%, P=0.007). Multivariate Cox regression analysis showed that endoscopic intervention was an independent protective factor for 28-day mortality ( HR: 0.14, 95% CI: 0.03-0.63, P=0.01). In addition, the severity of bleeding and prothrombin time were also important factors affecting the prognosis of patients. Conclusions:The Sengstaken-Blakemore tubes, as an important hemostasis method for acute esophageal and gastric variceal rupture and bleeding, can buy time for subsequent endoscopic treatment, but the risk of complications is relatively high. Creating conditions for early endoscopic intervention as early as possible can significantly reduce the mortality rate of patients and improve the prognosis of patients with liver cirrhosis.

Objective To analyze the research status and hotspots in the field of astragalus polysaccharides;To provide references for further research.Methods Research literature about astragalus polysaccharides was retrieved from CNKI,Wanfang Data,VIP,PubMed,and Web of Science databases from 1st,Jan.2013 to 1st,July 2023.NoteExpress 3.7 software was used to manage the literature and ultimately establish a database.Excel 2019,CiteSpace 6.2.2R and VOSviewer 1.6.18 were used to visually analyze the publication volume,authors,institutions,and keywords of the included literature.Results A total of 2 462 articles were included,with 1 284 Chinese articles and 1 178 English articles.The main research institutions were Gansu University of Chinese Medicine,Shandong University of Traditional Chinese Medicine,and Beijing University of Chinese Medicine.The core authors of Chinese literature were Liu Yongqi,Wang Hongxin,Lu Meili,etc.The core authors of English literature included Zhang Wei,Li Ke,Yang Xiaojun,etc.High-frequency keywords of Chinese literature included Astragali Radix,rats,polysaccharides,cell apoptosis,and oxidative stress,etc.High frequency keywords in English literature included expression,in vitro,oxidative stress,apoptosis,etc.Conclusion The research on astragalus polysaccharides focuses on their pharmacological effects and mechanisms.Intestinal flora,immune regulation,autophagy and apoptosis are the hot action mechanisms in this field.The focus of disease research involves tumor and diabetes,and antiviral,anti infection and other pharmacological effects are the research trend.

ObjectiveTo explore the mechanism of Buyang Huanwutang in regulating macrophage polarization based on the Toll-like receptor 4 （TLR4） / nuclear factor-κB （NF-κB） / nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） pathway. MethodRAW264.7 macrophages were intervened with lipopolysaccharide （LPS） of different concentrations （0， 1.25， 2.5， 5， 10， 20， 40， and 80 mg·L^-1） for 24 hours. Cell Counting Kit-8 （CCK-8） assay was used to determine the cell viability of RAW264.7 macrophages. The optimal concentration was chosen to establish an in vitro inflammation model induced by LPS. Cells were divided into a blank group （20% blank serum）， a model group （20% blank serum + 10 mg·L^-1 LPS）， a model control group （20% FBS + 10 mg·L^-1 LPS）， low-， medium-， and high-dose （5%， 10%， and 20%） Buyang Huanwutang-containing serum groups， a high-dose （20%） Buyang Huanwutang combined with NLRP3 inhibitor MCC950 （50 μmol·L^-1） group， a high-dose （20%） Buyang Huanwutang combined with reactive oxygen species （ROS） inhibitor NAC （10 μmol·L^-1） group， and a high-dose （20%） Buyang Huanwutang combined with NF-κB inhibitor PDTC （10 μmol·L^-1） group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and tumor necrosis factor-α （TNF-α） in RAW264.7 macrophages. Flow cytometry was employed to measure ROS levels in macrophages. Western blot was used to determine the protein expression of M1-type macrophage-related factors inducible nitric oxide synthase （iNOS） and TNF-α， M2-type macrophage-related factors arginase-1 （Arg-1） and interleukin-10 （IL-10）， as well as the proteins in the TLR4/NF-κB/NLRP3 pathway. ResultCCK-8 results indicated that under 10 mg·L^-1 LPS stimulation， RAW264.7 macrophages exhibited the highest cell viability （P<0.01）. Compared with the blank group， the model group showed significantly increased levels of IL-1β， IL-18， and TNF-α （P<0.05，P<0.01）， increased ROS expression （P<0.05，P<0.01）， increased protein expression of M1-type macrophage factors iNOS and TNF-α （P<0.01）， decreased protein expression of M2-type macrophage factors Arg-1 and IL-10 （P<0.05，P<0.01）， and upregulated expression levels of TLR4， myeloid differentiation factor 88 （MyD88）， phosphorylated inhibitor of NF-κB （p-IκB）/NF-κB inhibitor （IκB）， phosphorylated NF-κB （p-NF-κB） p65/NF-κB p65， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， and pro-Caspase-1 （P<0.05， P<0.01）. Compared with the model group， all Buyang Huanwutang-treated groups and inhibitor groups significantly reduced levels of IL-1β， IL-18， and TNF-α （P<0.01）， suppressed the expression of inflammatory factors in RAW264.7 macrophages， decreased cellular ROS expression levels （P<0.01）， downregulated M1-type macrophages iNOS and TNF-α protein expression （P<0.01）， upregulated M2-type macrophages Arg-1 and IL-10 protein expression （P<0.01）， and lowered protein expression levels of TLR4， MyD88， p-IκB/IκB， p-NF-κB p65/NF-κB p65， NLRP3， ASC， and pro-Caspase-1 （P<0.05， P<0.01）. ConclusionBuyang Huanwutang can improve macrophage inflammation， potentially by reducing macrophage ROS levels， inhibiting RAW264.7 macrophage polarization， and downregulating the protein expression levels of the TLR4/NF-κB/NLRP3 pathway.

Objective:In this study, the liver, spleen, and hepatic portal vein in the portal venous phase images of abdominal enhanced computed tomography (CT) are artificially segmented and annotated, and the radiomics features are extracted from them. A model for predicting portal pressure in patients with hepatitis B virus (HBV) related cirrhosis is constructed by combining radiomics features with clinical indicators.Methods:A total of 171 patients who had abdominal enhancement CT examination and trans-jugular hepatic venous pressure gradient (HVPG) measurement at the same time were enrolled from January 2016 to May 2020 in the Zhongshan Hospital Affiliated to Fudan University. The liver, spleen, and hepatic portal vein in the portal venous phase images of the CT were manually labeled by using ITK-SNAP 3.8 software. The radiomics features of these three sites were extracted using Python programming, and an HVPG prediction model was established.Results:A total of 171 patients was included in the study. The average age was (51.1±10.3)years, of which 134(78.4%) were males, and the average HVPG was 16.87±5.695. A total of 2 553 radiomics features were extracted from three sites of the portal venous phase images of abdominal enhanced CT in each patient. The 2 553 features extracted were screened using LASSO, and by combing with clinical features and radiomics features, the predictive model of HVPG was obtained: m_HVPG=31.622+ 0.028 8T×total bile acids-6.31(portal venous wavelet-LHH_glcm_ClusterShade)=0.253(portal venous wavelet-LHL_glszm_LargeAreaLowGrayLevelEmphasis)-20.9(spleen wavelet-LLH_glcm_Correlation)-0.000 127(liver original_shape_SurfaceArea)+ 2.79(liver wavelet-LLH_glcm_ClusterShade). The coefficient of determination R2 was 0.345. Conclusions:The study suggests that radiomics features of the liver, spleen, and portal venous combined with clinical features may be used as a non-invasive method to assess the portal pressure in patients with HBV-related cirrhosis.