BACKGROUND:At present,modern medical treatment has certain limitations on the treatment of knee osteoarthritis.Traditional Chinese medicine alkaloids can effectively prevent and treat knee osteoarthritis through various mechanisms. OBJECTIVE:To review the mechanism of alkaloids in traditional Chinese medicine in the prevention and treatment of knee osteoarthritis,providing a scientific basis for the clinical development of drugs for the treatment of knee osteoarthritis. METHODS:CNKI,WanFang,PubMed,Web of Science and Google Scholar were retrieved for relevant literature published from database inception to May 2024.The key words were"knee osteoarthritis""osteoarthritis""osteoclast""chondrocyte""alkaloids"in Chinese and English.Duplicates and obsolete non-referenced literature were excluded,and a total of 68 eligible papers were included for further review. RESULTS AND CONCLUSION:Although traditional Chinese medicine has a long history of treating knee osteoarthritis,only a small number of natural compounds are in the preclinical stage of research against knee osteoarthritis.Alkaloids have a greater potential for the prevention and treatment of knee osteoarthritis,among which,sophocarpidine,oxymatrine,sinomenine,and betaine have been shown to be effective in the prevention and treatment of knee osteoarthritis by modulating multiple signaling pathways.Alkaloids can delay the progression of knee osteoarthritis by inhibiting inflammatory response,exerting antioxidant response,inhibiting chondrocyte apoptosis,promoting chondrocyte proliferation,and inhibiting osteoclast formation and differentiation.

BACKGROUND:With the variation of disease treatment modes and the in-depth research on senile osteoporosis in recent years,increasing studies have confirmed that traditional Chinese medicine has a significant effect on the prevention and treatment of senile osteoporosis. OBJECTIVE:To investigate the effect of Yishen Gushu Formula on bone metabolic markers in patients with osteoporosis of kidney deficiency and blood stasis type. METHODS:102 patients with senile osteoporosis of kidney deficiency and blood stasis type who were treated at Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2020 to March 2022 were enrolled,including 32 males and 70 females,aged 71-93 years.All patients were randomly divided into two groups,with 51 patients in each group.The control group was treated with calcium carbonate D3 granules and sodium alendronate tablets,while the treatment group was treated with Yishen Gushu Formula beyond the control group.Treatments in each group lasted 3 months.Bone mineral density of the L1-4 lumbar vertebrae and left femoral neck,visual analog scale score,and serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were measured before and 3 months after treatment.Traditional Chinese medicine syndrome score and therapeutic efficiency were also assessed. RESULTS AND CONCLUSION:After 3 months of treatment,the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly increased in both two groups(P<0.05),and the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly higher in the treatment group than the control group(P<0.05).The visual analog scale scores of both groups after 3 months of treatment were lower than those before treatment(P<0.05),and the visual analog scores of the treatment group after 3 months of treatment were lower than those of the control group(P<0.05).After 3 months of treatment,the serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly improved in both two groups,while compared with the control group,the serum levels of osteocalcin and osteopontin were significantly higher(P<0.05)and the serum levels of type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly lower in the treatment group(P<0.05).After 3 months of treatment,the Traditional Chinese medicine syndrome scores were decreased in both two groups,while the Traditional Chinese medicine syndrome scores in the treatment group were lower than those in the control group.After 3 months of treatment,no significant adverse reactions occurred in both groups.The total effective rate was 88.2%and 70.6%in the treatment and control groups respectively,and there was a significant difference between the two groups(P<0.05).To conclude,Yishen Gushu Formula combined with anti-osteoporosis drugs can significantly improve the clinical symptoms of patients with senile osteoporosis of kidney deficiency and blood stasis type and prevent disease progression by regulating bone metabolism,increasing bone mineral density,and relieving pain.

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 evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

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.