Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

To examine the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the horizontal transmission of blaKPC and blaNDM genes for the prevention and treatment of CRKP. A total of 49 clinically isolated CRKP strains were retrospectively analyzed from January to December 2022 at The First Hospital of Hunan University of Chinese Medicine. Phenotypic screening was performed using modified carbapenem inactivation assay (mCIM) and EDTA-carbapenem inactivation assay (eCIM). Polymerase chain reaction (PCR) was utilized to identify carbapenem resistance genes, β-lactamase resistance genes, and virulence genes, while multi-locus sequence analysis (MLST) was employed to assess the homology of CRKP strains. Conjugation experiments were conducted to infer the horizontal transmission mechanism of blaKPC and blaNDM genes. The results showed that the study included 49 CRKP strains, with 44 carrying blaKPC and 8 carrying blaNDM, Three strains were identified as blaKPC+ blaNDM-CRKP. In this study, 28 out of 49 CRKP strains (57.2%) were found to carry virulence genes. Additionally, one CRKP strain tested positive in the string test and was found to carry both Aerobactin and rmpA virulence genes. MLST results revealed a total of 5 ST types, with ST11 being predominant (41/49, 83.7%). Successful conjugation was observed in all 3 blaKPC-CRKP strains, while only 1 out of 3 blaNDM-CRKP strains showed successful conjugation. The transconjugant exhibited significantly reduced susceptibility to imipenem and cephalosporin antibiotics. In conclusion, the resistance mechanism of CRKP in this study is primarily attributed to the production of KPC enzymes, along with the presence of multiple β-lactamase resistance genes. Additionally, there is a local prevalence of hv-CRKP and blaKPC+ blaNDM-CRKP. blaKPC and blaNDM can be horizontally transmitted through plasmids, with varying efficiency among different strains.

To examine the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the horizontal transmission of blaKPC and blaNDM genes for the prevention and treatment of CRKP. A total of 49 clinically isolated CRKP strains were retrospectively analyzed from January to December 2022 at The First Hospital of Hunan University of Chinese Medicine. Phenotypic screening was performed using modified carbapenem inactivation assay (mCIM) and EDTA-carbapenem inactivation assay (eCIM). Polymerase chain reaction (PCR) was utilized to identify carbapenem resistance genes, β-lactamase resistance genes, and virulence genes, while multi-locus sequence analysis (MLST) was employed to assess the homology of CRKP strains. Conjugation experiments were conducted to infer the horizontal transmission mechanism of blaKPC and blaNDM genes. The results showed that the study included 49 CRKP strains, with 44 carrying blaKPC and 8 carrying blaNDM, Three strains were identified as blaKPC+ blaNDM-CRKP. In this study, 28 out of 49 CRKP strains (57.2%) were found to carry virulence genes. Additionally, one CRKP strain tested positive in the string test and was found to carry both Aerobactin and rmpA virulence genes. MLST results revealed a total of 5 ST types, with ST11 being predominant (41/49, 83.7%). Successful conjugation was observed in all 3 blaKPC-CRKP strains, while only 1 out of 3 blaNDM-CRKP strains showed successful conjugation. The transconjugant exhibited significantly reduced susceptibility to imipenem and cephalosporin antibiotics. In conclusion, the resistance mechanism of CRKP in this study is primarily attributed to the production of KPC enzymes, along with the presence of multiple β-lactamase resistance genes. Additionally, there is a local prevalence of hv-CRKP and blaKPC+ blaNDM-CRKP. blaKPC and blaNDM can be horizontally transmitted through plasmids, with varying efficiency among different strains.

Objective:To explore the adverse outcomes of pregnant women with overt diabetes mellitus(ODM).Methods:A retrospective analysis was performed on 1321 pregnant women delivered in Peking Universi-ty International Hospital.Pregnant women were divided into normal blood glucose group(NGDM),gestational di-abetes mellitus group(GDM)and overt diabetes mellitus group(ODM).Maternal and neonatal adverse out-comes were compared.Results:The age,early pregnancy glycosylated hemoglobin,uric acid,triglycerides and late pregnancy glycosylated hemoglobin levels of women in ODM group were significantly higher than those in NGDM group,and the differences were statistically significant(P＜0.01).The risk of developing gestation hyper-tension(OR 6.32,P＜0.01)and cesarean section(OR 1.87,P＜0.05)in the ODM group was significantly high-er than that in the NGDM group.The rate of preterm birth(OR 2.73,P＜0.05)and macrosomia(OR 3.45,P＜0.01)in the ODM group was significantly higher than that in the NGDM group.Compared with the GDM group,the ODM group did not significantly increase the risk of hypertension,eclampsia or preeclampsia,shoulder dysto-cia,premature rupture of placenta,cesarean section,preterm birth,macrosomia,and low body mass infants(P＞0.05).Conclusion:Pregnant women with ODM increase the risk of gestational hypertension,cesarean section,preterm birth and macrosomia.Active management is needed in pregnant women with ODM.

Objective:To explore the adverse outcomes of pregnant women with overt diabetes mellitus(ODM).Methods:A retrospective analysis was performed on 1321 pregnant women delivered in Peking Universi-ty International Hospital.Pregnant women were divided into normal blood glucose group(NGDM),gestational di-abetes mellitus group(GDM)and overt diabetes mellitus group(ODM).Maternal and neonatal adverse out-comes were compared.Results:The age,early pregnancy glycosylated hemoglobin,uric acid,triglycerides and late pregnancy glycosylated hemoglobin levels of women in ODM group were significantly higher than those in NGDM group,and the differences were statistically significant(P＜0.01).The risk of developing gestation hyper-tension(OR 6.32,P＜0.01)and cesarean section(OR 1.87,P＜0.05)in the ODM group was significantly high-er than that in the NGDM group.The rate of preterm birth(OR 2.73,P＜0.05)and macrosomia(OR 3.45,P＜0.01)in the ODM group was significantly higher than that in the NGDM group.Compared with the GDM group,the ODM group did not significantly increase the risk of hypertension,eclampsia or preeclampsia,shoulder dysto-cia,premature rupture of placenta,cesarean section,preterm birth,macrosomia,and low body mass infants(P＞0.05).Conclusion:Pregnant women with ODM increase the risk of gestational hypertension,cesarean section,preterm birth and macrosomia.Active management is needed in pregnant women with ODM.

Objective:To explore the adverse outcomes of pregnant women with overt diabetes mellitus(ODM).Methods:A retrospective analysis was performed on 1321 pregnant women delivered in Peking Universi-ty International Hospital.Pregnant women were divided into normal blood glucose group(NGDM),gestational di-abetes mellitus group(GDM)and overt diabetes mellitus group(ODM).Maternal and neonatal adverse out-comes were compared.Results:The age,early pregnancy glycosylated hemoglobin,uric acid,triglycerides and late pregnancy glycosylated hemoglobin levels of women in ODM group were significantly higher than those in NGDM group,and the differences were statistically significant(P＜0.01).The risk of developing gestation hyper-tension(OR 6.32,P＜0.01)and cesarean section(OR 1.87,P＜0.05)in the ODM group was significantly high-er than that in the NGDM group.The rate of preterm birth(OR 2.73,P＜0.05)and macrosomia(OR 3.45,P＜0.01)in the ODM group was significantly higher than that in the NGDM group.Compared with the GDM group,the ODM group did not significantly increase the risk of hypertension,eclampsia or preeclampsia,shoulder dysto-cia,premature rupture of placenta,cesarean section,preterm birth,macrosomia,and low body mass infants(P＞0.05).Conclusion:Pregnant women with ODM increase the risk of gestational hypertension,cesarean section,preterm birth and macrosomia.Active management is needed in pregnant women with ODM.

Objective:To explore the adverse outcomes of pregnant women with overt diabetes mellitus(ODM).Methods:A retrospective analysis was performed on 1321 pregnant women delivered in Peking Universi-ty International Hospital.Pregnant women were divided into normal blood glucose group(NGDM),gestational di-abetes mellitus group(GDM)and overt diabetes mellitus group(ODM).Maternal and neonatal adverse out-comes were compared.Results:The age,early pregnancy glycosylated hemoglobin,uric acid,triglycerides and late pregnancy glycosylated hemoglobin levels of women in ODM group were significantly higher than those in NGDM group,and the differences were statistically significant(P＜0.01).The risk of developing gestation hyper-tension(OR 6.32,P＜0.01)and cesarean section(OR 1.87,P＜0.05)in the ODM group was significantly high-er than that in the NGDM group.The rate of preterm birth(OR 2.73,P＜0.05)and macrosomia(OR 3.45,P＜0.01)in the ODM group was significantly higher than that in the NGDM group.Compared with the GDM group,the ODM group did not significantly increase the risk of hypertension,eclampsia or preeclampsia,shoulder dysto-cia,premature rupture of placenta,cesarean section,preterm birth,macrosomia,and low body mass infants(P＞0.05).Conclusion:Pregnant women with ODM increase the risk of gestational hypertension,cesarean section,preterm birth and macrosomia.Active management is needed in pregnant women with ODM.

Objective:To explore the adverse outcomes of pregnant women with overt diabetes mellitus(ODM).Methods:A retrospective analysis was performed on 1321 pregnant women delivered in Peking Universi-ty International Hospital.Pregnant women were divided into normal blood glucose group(NGDM),gestational di-abetes mellitus group(GDM)and overt diabetes mellitus group(ODM).Maternal and neonatal adverse out-comes were compared.Results:The age,early pregnancy glycosylated hemoglobin,uric acid,triglycerides and late pregnancy glycosylated hemoglobin levels of women in ODM group were significantly higher than those in NGDM group,and the differences were statistically significant(P＜0.01).The risk of developing gestation hyper-tension(OR 6.32,P＜0.01)and cesarean section(OR 1.87,P＜0.05)in the ODM group was significantly high-er than that in the NGDM group.The rate of preterm birth(OR 2.73,P＜0.05)and macrosomia(OR 3.45,P＜0.01)in the ODM group was significantly higher than that in the NGDM group.Compared with the GDM group,the ODM group did not significantly increase the risk of hypertension,eclampsia or preeclampsia,shoulder dysto-cia,premature rupture of placenta,cesarean section,preterm birth,macrosomia,and low body mass infants(P＞0.05).Conclusion:Pregnant women with ODM increase the risk of gestational hypertension,cesarean section,preterm birth and macrosomia.Active management is needed in pregnant women with ODM.

Objective:To explore the adverse outcomes of pregnant women with overt diabetes mellitus(ODM).Methods:A retrospective analysis was performed on 1321 pregnant women delivered in Peking Universi-ty International Hospital.Pregnant women were divided into normal blood glucose group(NGDM),gestational di-abetes mellitus group(GDM)and overt diabetes mellitus group(ODM).Maternal and neonatal adverse out-comes were compared.Results:The age,early pregnancy glycosylated hemoglobin,uric acid,triglycerides and late pregnancy glycosylated hemoglobin levels of women in ODM group were significantly higher than those in NGDM group,and the differences were statistically significant(P＜0.01).The risk of developing gestation hyper-tension(OR 6.32,P＜0.01)and cesarean section(OR 1.87,P＜0.05)in the ODM group was significantly high-er than that in the NGDM group.The rate of preterm birth(OR 2.73,P＜0.05)and macrosomia(OR 3.45,P＜0.01)in the ODM group was significantly higher than that in the NGDM group.Compared with the GDM group,the ODM group did not significantly increase the risk of hypertension,eclampsia or preeclampsia,shoulder dysto-cia,premature rupture of placenta,cesarean section,preterm birth,macrosomia,and low body mass infants(P＞0.05).Conclusion:Pregnant women with ODM increase the risk of gestational hypertension,cesarean section,preterm birth and macrosomia.Active management is needed in pregnant women with ODM.

Objective:To explore the adverse outcomes of pregnant women with overt diabetes mellitus(ODM).Methods:A retrospective analysis was performed on 1321 pregnant women delivered in Peking Universi-ty International Hospital.Pregnant women were divided into normal blood glucose group(NGDM),gestational di-abetes mellitus group(GDM)and overt diabetes mellitus group(ODM).Maternal and neonatal adverse out-comes were compared.Results:The age,early pregnancy glycosylated hemoglobin,uric acid,triglycerides and late pregnancy glycosylated hemoglobin levels of women in ODM group were significantly higher than those in NGDM group,and the differences were statistically significant(P＜0.01).The risk of developing gestation hyper-tension(OR 6.32,P＜0.01)and cesarean section(OR 1.87,P＜0.05)in the ODM group was significantly high-er than that in the NGDM group.The rate of preterm birth(OR 2.73,P＜0.05)and macrosomia(OR 3.45,P＜0.01)in the ODM group was significantly higher than that in the NGDM group.Compared with the GDM group,the ODM group did not significantly increase the risk of hypertension,eclampsia or preeclampsia,shoulder dysto-cia,premature rupture of placenta,cesarean section,preterm birth,macrosomia,and low body mass infants(P＞0.05).Conclusion:Pregnant women with ODM increase the risk of gestational hypertension,cesarean section,preterm birth and macrosomia.Active management is needed in pregnant women with ODM.