In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Objective To analyze the research status of in situ simulation in the medical field and explore its hotspots and trends. Methods Relevant literature was searched in China National Knowledge Infrastructure and Web of Science core collection from the inception to February 2024.CiteSpace 6.3.R1 was used to analyze the authors,institutions,and keywords and draw visual knowledge maps. Results A total of 25 Chinese articles and 438 English articles were included.Only 14 English articles were from China.In Chinese articles,the authors with the largest number of articles were Dai Hengmao and Liu Shangkun,and the institution with the largest number of articles was Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology.There was little cooperation between the authors and institutions.In English articles,the author and institution with the largest number of articles was Auerbach Marc and Yale University,respectively,and the cooperation between authors and institutions was close.Emergency medicine,emergency event handling,and on-the-job training were the keywords with high frequency in Chinese articles.Patient safety,medical education,and cardiac arrest were the keywords with high frequency in English articles.A total of 4 clusters were generated for Chinese keywords and 13 clusters for English keywords. Conclusions The application of in situ simulation in the medical field is still in the initial stage,and the development is not balanced at home and abroad.The number of articles published and the cooperation between authors and institutions in China obviously lags behind those abroad.Treatment and care of emergency critical patients,emergency event handling and skill training,identification of latent safety threats,improvement of readiness,and promotion of medical quality improvement are the future research hotspots and research trends in this field.
Bibliometrics ; Humans ; China ; Simulation Training ; Education, Medical ; Emergency Medicine/education*

Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease caused by excessive lipid accumulation in the liver.Its incidence rate is increasing year by year and has become an increasingly serious public healthy problem.The pathogenesis of NAFLD is complex and has not been fully clarified at present.It is mainly related to multiple factors such as genetics,metabolism,intestinal flora and immune response.In order to explore the medication rules and mechanism of action of traditional Chinese medicine(TCM)in the treatment of NAFLD,and to provide references for the treatment of NAFLD with TCM and the research and development of new drugs,this article summarizes the TCM pathogenesis of NAFLD(such as"phlegm and blood stasis interlacing","liver depression and spleen deficiency",etc.)and modern etiology and pathogenesis(such as insulin resistance,lipid disorder,mitochondrial dysfunction,oxidative stress,etc.).The clinical research and experimental data at home and abroad in recent years were integrated to analyze the pathological process of NAFLD intervention by TCM through multiple targets,including improving insulin resistance and lipid metabolism disorders,inhibiting oxidative stress and mitochondrial dysfunction,etc.TCM has shown unique advantages in the prevention and treatment of NAFLD.However,the depth of its mechanism analysis and the level of clinical research still need to be improved.In the future,it is necessary to deepen the mechanism research by combining multi-omics technology to accelerate the modernization development of TCM.

Objective:To explore the impacts of remimazolam(REM)on the proliferation,migration,and invasion of hepatocellular carcinoma cells by regulating sphingosine kinase 1/sphingosine 1-phosphate/sphingosine 1-phosphate receptor 3(SPHK1/S1P/S1PR3)signaling pathway.Methods:Human hepatocellular carcinoma cell line HepG2 was treated with REM at concentrations of 0,20,40,80,160,and 320 μmol/L respectively.Cell survival rate was measured,and drug concentrations were screened.Based on the results of cell survival rate,the logarithmic phase cells were di-vided into five groups:Control group,low,medium,and high concentrations of remifentanil groups(REM-L,REM-M,REM-H groups;20,40 and 80 μmol/L),and high concentrations of remifentanil+SPHK1 activator group(REM-H+K6PC-5 group).MTT assay was used to detect the survival rate of HepG2 cells.Plate cloning experiment was performed to de-tect cell proliferation ability.Scratch experiment was performed to detect cell migration ability.Transwell chamber method was performed to detect cell invasion ability.Flow cytometry was used to detect cell apoptosis.Western blot was used to detect the SPHK1,S1P,S1PR3,Bax,and Bcl-2 proteins in cells.Results:For the Control group,the REM-L,REM-M,and REM-H groups showed that the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins gradually decreased with increasing REM concentration,while the apoptosis rate and Bax,E-cadherin proteins showed an opposite trend(P<0.05).For the REM-H group,the REM-H+K6PC-5 group showed a clear increase in the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins,and a clear decrease in the apoptosis rate and Bax,E-cadherin proteins(P<0.05).Conclusion:REM may inhibit the proliferation,migration,and invasion of hepatocellular carcinoma cells and promote cell apoptosis by suppressing SPHK1/S1P/S1PR3 signaling pathway.

Aim To explore the role and mechanism of epimedokoreanin B(EKB)in HepaRG cell pyroptosis through endoplasmic reticulum stress and NLRP1-me-diated pyroptosis pathway.Methods The effect of EKB on the viability of HepaRG cells at different con-centrations was determined by MTT assay,and the cell growth status was recorded by Incucyte.Four groups of HepaRG cells were set up.The control group was cul-tured with complete medium for 24 h;the drug admin-istration group was cultured with three concentration gradients of 6.25,12.5 and 25 μmol·L-1 of EKB for 24 h.Western blot was used to detect the expression levels of endoplasmic reticulum stress-related proteins and pyroptosis-related proteins in the cells of each group.Results HepaRG cells showed cytotoxicity at a concentration of 6.25 μmol·L-1 for 24 h,and the half maximal inhibitory concentration(IC50)was 12.41 μmol·L-1.Incucyte recordings of the cell growth status showed that the cells in the control group were in good growth status,and the vesicular pyropto-sis cells appeared in the different concentrations of EKB and the cells swelled and ruptured after 24 h.Western blot showed that the protein expression levels of endoplasmic reticulum stress-related proteins pERK,eIF-2α,ATF-4,GRP78,and CHOP significantly in-creased in HepaRG cells at 25 μmol·L-1 of EKB compared with the control group.The proteins of the classical pathway of cellular pyroptosis mediated by NLRP1,caspase-1,cleaved caspase-1,GSDMD,GS-DMD-N significantly increased in HepaRG cells.Con-clusion EKB administration induces HepaRG cell py-roptosis,and EKB activates HepaRG cells to undergo endoplasmic reticulum stress and activates the NLRP1/caspase-1/GSDMD-mediated pyroptosis pathway.

Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease caused by excessive lipid accumulation in the liver.Its incidence rate is increasing year by year and has become an increasingly serious public healthy problem.The pathogenesis of NAFLD is complex and has not been fully clarified at present.It is mainly related to multiple factors such as genetics,metabolism,intestinal flora and immune response.In order to explore the medication rules and mechanism of action of traditional Chinese medicine(TCM)in the treatment of NAFLD,and to provide references for the treatment of NAFLD with TCM and the research and development of new drugs,this article summarizes the TCM pathogenesis of NAFLD(such as"phlegm and blood stasis interlacing","liver depression and spleen deficiency",etc.)and modern etiology and pathogenesis(such as insulin resistance,lipid disorder,mitochondrial dysfunction,oxidative stress,etc.).The clinical research and experimental data at home and abroad in recent years were integrated to analyze the pathological process of NAFLD intervention by TCM through multiple targets,including improving insulin resistance and lipid metabolism disorders,inhibiting oxidative stress and mitochondrial dysfunction,etc.TCM has shown unique advantages in the prevention and treatment of NAFLD.However,the depth of its mechanism analysis and the level of clinical research still need to be improved.In the future,it is necessary to deepen the mechanism research by combining multi-omics technology to accelerate the modernization development of TCM.

Objective:To explore the impacts of remimazolam(REM)on the proliferation,migration,and invasion of hepatocellular carcinoma cells by regulating sphingosine kinase 1/sphingosine 1-phosphate/sphingosine 1-phosphate receptor 3(SPHK1/S1P/S1PR3)signaling pathway.Methods:Human hepatocellular carcinoma cell line HepG2 was treated with REM at concentrations of 0,20,40,80,160,and 320 μmol/L respectively.Cell survival rate was measured,and drug concentrations were screened.Based on the results of cell survival rate,the logarithmic phase cells were di-vided into five groups:Control group,low,medium,and high concentrations of remifentanil groups(REM-L,REM-M,REM-H groups;20,40 and 80 μmol/L),and high concentrations of remifentanil+SPHK1 activator group(REM-H+K6PC-5 group).MTT assay was used to detect the survival rate of HepG2 cells.Plate cloning experiment was performed to de-tect cell proliferation ability.Scratch experiment was performed to detect cell migration ability.Transwell chamber method was performed to detect cell invasion ability.Flow cytometry was used to detect cell apoptosis.Western blot was used to detect the SPHK1,S1P,S1PR3,Bax,and Bcl-2 proteins in cells.Results:For the Control group,the REM-L,REM-M,and REM-H groups showed that the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins gradually decreased with increasing REM concentration,while the apoptosis rate and Bax,E-cadherin proteins showed an opposite trend(P<0.05).For the REM-H group,the REM-H+K6PC-5 group showed a clear increase in the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins,and a clear decrease in the apoptosis rate and Bax,E-cadherin proteins(P<0.05).Conclusion:REM may inhibit the proliferation,migration,and invasion of hepatocellular carcinoma cells and promote cell apoptosis by suppressing SPHK1/S1P/S1PR3 signaling pathway.

Aim To explore the role and mechanism of epimedokoreanin B(EKB)in HepaRG cell pyroptosis through endoplasmic reticulum stress and NLRP1-me-diated pyroptosis pathway.Methods The effect of EKB on the viability of HepaRG cells at different con-centrations was determined by MTT assay,and the cell growth status was recorded by Incucyte.Four groups of HepaRG cells were set up.The control group was cul-tured with complete medium for 24 h;the drug admin-istration group was cultured with three concentration gradients of 6.25,12.5 and 25 μmol·L-1 of EKB for 24 h.Western blot was used to detect the expression levels of endoplasmic reticulum stress-related proteins and pyroptosis-related proteins in the cells of each group.Results HepaRG cells showed cytotoxicity at a concentration of 6.25 μmol·L-1 for 24 h,and the half maximal inhibitory concentration(IC50)was 12.41 μmol·L-1.Incucyte recordings of the cell growth status showed that the cells in the control group were in good growth status,and the vesicular pyropto-sis cells appeared in the different concentrations of EKB and the cells swelled and ruptured after 24 h.Western blot showed that the protein expression levels of endoplasmic reticulum stress-related proteins pERK,eIF-2α,ATF-4,GRP78,and CHOP significantly in-creased in HepaRG cells at 25 μmol·L-1 of EKB compared with the control group.The proteins of the classical pathway of cellular pyroptosis mediated by NLRP1,caspase-1,cleaved caspase-1,GSDMD,GS-DMD-N significantly increased in HepaRG cells.Con-clusion EKB administration induces HepaRG cell py-roptosis,and EKB activates HepaRG cells to undergo endoplasmic reticulum stress and activates the NLRP1/caspase-1/GSDMD-mediated pyroptosis pathway.