1.Research progress on the correlation between angiopoietin-like protein 2 and lower extremity arteriosclerosis obliterans
Yizhou LIU ; Xuezhen CHAI ; Zebin YU ; Yue LIANG
International Journal of Surgery 2025;52(3):199-204
Lower extremity arteriosclerosis obliterans(LEASO) is a disease in which systemic atherosclerosis affects the blood-supplying arteries of the lower extremities, resulting in chronic ischemia of the lower extremities. Angiopoietin-like protein 2(Angptl2) is a newly discovered pro-inflammatory protein that promotes the development of atherosclerosis by inducing vascular inflammatory responses. It is closely associated with certain risk factors for LEASO, such as advanced age, obesity, and type 2 diabetes. In addition, the high expression of Angptl2 in LEASO correlates with the continued progression of LEASO and may reflect the severity of the disease, suggesting that Angptl2 may be an important serologic biomarker for LEASO. In this article, we review the progress of research on the correlation between Angptl2 and LEASO, and analyze the value of Angptl2 as a biomarker for LEASO.
2.Gut microbiota and drug-associated osteonecrosis:a two-sample Mendelian randomization study
Jinlian CHAI ; Shudong LI ; Wei LI ; Haitao DU ; Limin DONG ; Xuezhen LIANG ; Ping WANG
Chinese Journal of Tissue Engineering Research 2024;28(27):4325-4331
BACKGROUND:Osteonecrosis due to drugs is a serious adverse reaction occurring after the application of such drugs.Increasing evidence suggests that the gut microbiota composition is associated with osteonecrosis due to drugs.However,the causal relationship of the gut microbiota to osteonecrosis due to drugs is still unclear. OBJECTIVE:To evaluate the potential causal relationship between the gut microbiota and the risk of osteonecrosis due to drugs using the Mendelian randomization method. METHODS:A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis(n=13 266)conducted by the MiBioGen consortium as well as the summary statistics of osteonecrosis due to drugs obtained from the FinnGen consortium R9 release data(264 cases and 377 013 controls).Inverse variance weighted,MR-Egger,weighted median,weighted model and simple model were used to examine the causal association between gut microbiota and osteonecrosis due to drugs.Sensitivity analysis was used to test whether the results of the Mendelian randomization analysis were reliable.Reverse Mendelian randomization analysis was performed on all the bacteria as an outcome for effect analysis and sensitivity analysis. RESULTS AND CONCLUSION:Inverse variance weighted estimates suggested that Lentisphaerae(phylum),Lentisphaeria(class),Melainabacteria(class),Gastranaerophilales(order),Rhodospirillales(order),Victivallales(order)and Bifidobacterium(genus)had protective causal effects on osteonecrosis due to drugs.Methanobacteria(class),Bacillales(order),Methanobacteriaceae(family),Lachnospiraceae(family),Methanobacteriales(order),Holdemania(genus),Holdemania(UCG010 group)(genus),Odoribacter(genus)and Tyzzerella3(genus)had negative causal effects on osteonecrosis due to drugs.According to the results of reverse Mendelian randomization analysis,Clostridiaceae1(family),Peptostreptococcaceae(family),Streptococcaceae(family),Clostridiumsensustricto1(genus)and Streptococcus(genus)showed negative causal effects on osteonecrosis due to drugs.However,Eisenbergiella(genus)showed protective causal effects on osteonecrosis due to drugs.None of the bidirectional sensitivity analysis revealed heterogeneity or horizontal pleiotropy.When gut microbiota were used as exposure and osteonecrosis due to drugs as the outcome,Mendelian randomization analysis found that seven bacterial traits were positively correlated to osteonecrosis due to drugs,nine bacterial traits were negatively related to osteonecrosis due to drugs.When osteonecrosis due to drugs were used as exposure and gut microbiota as the outcome,reverse Mendelian randomization analysis found a negative correlated relationship with five bacterial traits and a positive causal relationship with one bacterial trait.By changing the diversity and composition of gut microbiota,it is expected to improve the incidence and prognosis of osteonecrosis due to drugs,providing new ideas for the study of orthopedic diseases.
3.Causal association of micronutrients with osteonecrosis:evidence from a bidirectional Mendelian randomization trial
Wei LI ; Jinlian CHAI ; Haifeng JIA ; Hanzheng LI ; Tiefeng SUN ; Xuezhen LIANG
Chinese Journal of Tissue Engineering Research 2024;33(33):5308-5314
BACKGROUND:Osteonecrosis is a common refractory disease in clinical practice,and observational studies have suggested that micronutrients may have a prognostic role in osteonecrosis.However,the specific causal association between micronutrients and osteonecrosis is not known. OBJECTIVE:To explore the causal association between micronutrients and osteonecrosis by Mendelian randomization using summary data from a large population-based genome-wide association study(GWAS)for clinical diagnosis and treatment. METHODS:The required exposure and outcome data(calcium,magnesium,iron,vitamin E,carotenoids,retinol&osteonecrosis)were extracted from the IEU OpenGWAS database,GWAS catalog database,and FinnGen database.Data were analyzed by bidirectional Mendelian randomization with inverse-variance weighted as the primary study method,and weighted median method,simple mode method,weighted mode method,and MR-Egger regression to complement the results.The reliability of the data was then verified through sensitivity analyses. RESULTS AND CONCLUSION:(1)The results found a positive correlation between serum iron concentration and osteonecrosis,while no correlation was found for other micronutrients.There was no reverse causality in all the data.(2)The results of sensitivity analysis showed a robust causality.(3)By Mendelian randomization method,this study provided evidence of causality between serum iron concentration and osteonecrosis,and understanding the causality of micronutrient elements on osteonecrosis can help in the clinical diagnosis and treatment of osteonecrosis,which is of great clinical significance.
4.Correlation between multi-drug resisitance and Her-2 gene in breast cancer
Cancer Research and Clinic 2012;24(4):232-234
Objective To investigate the correlation between the expression of p170、GST-π 、TOPO Ⅱ and the expression of Her-2 in human breast cancer. Methods The expression of Her-2 was detected by fluorescence in situ hybridization.The expression of p170,GST-π,TOPO Ⅱ were tested in 48 breast cancer by immunohistochemical SP method,and their correlations with clinicopathological features and the expression of Her-2 were analyzed.Results The positive rate of p170,GST-π,TOPO Ⅱ were 43.8 %(21/48),39.6 %(19/48),56.3 %(27/48),respectively. The expression of p170, GST-π,TOPO Ⅱ positively correlated with the expression of Her-2(P< 0.05).The levels of p170,GST-π,TOPO Ⅱ expression were not associated with age,primary tumor and lymph node metastasis(P > 0.05).Conclusion There is great possibility of chemotherapy drug resistance in breast cancer with expression of Her-2.Expressions of p170,GST-π,TOPO Ⅱ and Her-2 have an instructive significance for chemotherapy.

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