OBJECTIVES: To examine the changes in serum levels of endoplasmic reticulum stress (ERS) proteins GRP78/CHOP in patients with lupus nephritis (LN) and analyze their diagnostic value and association with renal pathological features. METHODS: From a sample bank established based on a multicenter cohort study of systemic lupus erythematosus (SLE), 60 LN patients and 35 SLE patients without renal involvement were randomly selected. ELISA was used to detect serum levels of GRP78 and CHOP in the patients to analyze their correlation with clinical features and their diagnostic ability for LN and active LN. MRL/lpr mice were used as an animal model of LN to examine their serum levels of GRP78 and CHOP expression and renal expressions of endoplasmic reticulum apoptosis-related proteins. RESULTS: Serum GRP78 and CHOP levels were significantly higher in LN patients than in SLE patients without renal involvement (P<0.05), and were also higher in active LN patients than in patients in the stable phase (P<0.05). Correlation analysis indicated that serum GRP78 and CHOP levels were positively correlated with SLEDAI scores and 24-h urinary protein. ROC analysis showed that CHOP had a high diagnostic ability for LN (AUC=0.762) and active LN (AUC=0.933). Consistent with the clinical findings, serum GRP78 and CHOP levels were elevated in LN mice, and the expressions of PERK and IRE1α pathway proteins were also increased in the kidneys of the mice. TUNEL staining showed increased renal cell apoptosis and elevated renal expressions of apoptosis-related proteins in LN mice. CONCLUSIONS Serum levels of GRP78/CHOP are increased in LN patients possibly in association with ERS-induced apoptosis mediated by the PERK/IRE1α dual pathway.
Endoplasmic Reticulum Chaperone BiP ; Lupus Nephritis/blood* ; Transcription Factor CHOP/blood* ; Heat-Shock Proteins/blood* ; Animals ; Apoptosis ; Humans ; Mice ; Mice, Inbred MRL lpr ; Female ; Adult ; Endoribonucleases/metabolism* ; Male ; eIF-2 Kinase/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Young Adult ; Endoplasmic Reticulum Stress ; Kidney/metabolism* ; Middle Aged ; Signal Transduction

Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.