1.Research on correlation between GGCX(rs6738645) polymorphism and warfarin stable dose
Yinqiang LIU ; Baihui YANG ; Jianming XIA ; Xueyu ZHANG ; Guimin ZHANG
Chongqing Medicine 2014;(10):1184-1186
Objective To investigate the gamma glutamine carboxylase (GGCX ,rs6738645) genotype distribution in Chinese Han population and the correlation between GGCX (rs6738645) polymorphism and the warfarin stable dose in the patient after valve replacement .Methods The genotypes of 228 cases were detected by the Snapshot technology in order to explore the genotype and allele frequencies .The correlation between the gene polymorphism in 176 cases after valve replacement and the stable dose of warfa-rin was compared .Results In total of 228 research subjects ,the number of TT ,GT and GG genotype were 84(36 .84% ) ,122 (53 .51% ) and 22(9 .65% ) .The frequencies of T and G allele were 63 .60% and 36 .40% respectively ;in 176 patients after the valve replacement ,the maintenance stable dose of warfarin was lower in GG group than in the TT and GT groups ,the differences between the groups showed statistical significance (P<0 .01) .The PT value and INR value had no statistical difference among 3 genotype groups(P>0 .05) .Conclusion The GGCX(rs6738645) polymorphism in Chinese Han population may be the influencing factor of warfarin individual dose difference in the patients after valve replacement .
2.Recent effect of warfarin anticoagulant therapy for 130 elderly cases after heart biological valve replacement in Yunnan-Guizhou plateau
Yinqiang LIU ; Jie TAO ; Baihui YANG ; Jianmin XIA ; Xueyu ZHANG ; Guimin ZHANG
The Journal of Practical Medicine 2014;(9):1490-1492
Objective To investigate the reasonable anticoagulant therapy for patients over sixty five years old in Yunnan-Guizhou plateau after heart biological valve replacement , and study the standard of reasonable anticoagulant therapy. Methods We collected the recent cases by retrospective way . Low-intensity anticoagulation standard INR (1.5~2.5) was used on 130 patients over sixty five years old. The warfarin dose and anticoagulation INR values in different surgery operation were compared when the patients reached the stable anticoagulation status. The frequency of INR values and warfarin dosage were studied. The differences between the patients with high risk factors and the ordinary patients without the high risk factors in INR values and warfarin dosage were investigated. Results The INR values and warfarin doses showed no significant difference (P > 0.05) in different operation groups when they reached stable anticoagulation status. The INR values was 1.94 ± 0.50 and the daily warfarin dose was (2.45 ± 0.82)mg/d. No significant differences in INR values and warfarin doses were found between the high-risk group and the general group (P>0.05) in steady-state. During follow-up, both the incidence rate of thrombosis and general bleeding were 0.77%. Conclusion The precent study showed that the low-intensity anticoagulation INR values (1.5~2.5) can be the standard of reasonable anticoagulation in Yunnan-Guizhou plateau after heart biological valve replacement with satisfactory anticoagulant effect.
3. Treatment strategies of complex lesions in patients with acute Stanford type A dissection of important branches involvement
Guimin ZHANG ; Jianming XIA ; Yi SUN ; Lihua FAN ; Yuyin DUAN ; Songhua YU ; Bingsong DUAN ; Bin LI ; Song MEI ; Long ZHOU ; Hongbo HUANG ; Jiayu LI ; Qiuzhe GUO ; Junming ZHU
Chinese Journal of Surgery 2017;55(4):251-254
Acute Stanford type A aortic dissection with important branches involved is more complex, could lead to organ malperfusion syndrome even organ failure. The understanding of pathological anatomy, classification, staging, and the pathophysiological change has increasingly mature, but not complete. In addition, the treatment strategy for complex lesions is diversified, some questions may not reach consensus. Fully understanding of the anatomical and pathophysiology is very important for surgeons to choose reasonable treatment strategy. As the rapid development of the basic research, imaging techniques and the concept of surgery procedures, the manage technique of Stanfrod type A dissection and branch vessels at the same time is getting seriously, the related issues also need further discussions.
4.Miriplatin-loaded liposome, as a novel mitophagy inducer, suppresses pancreatic cancer proliferation through blocking POLG and TFAM-mediated mtDNA replication.
Xiaowei WANG ; Mengyan WANG ; Meilian CAI ; Rongguang SHAO ; Guimin XIA ; Wuli ZHAO
Acta Pharmaceutica Sinica B 2023;13(11):4477-4501
Pancreatic cancer is a more aggressive and refractory malignancy. Resistance and toxicity limit drug efficacy. Herein, we report a lower toxic and higher effective miriplatin (MPt)-loaded liposome, LMPt, exhibiting totally different anti-cancer mechanism from previously reported platinum agents. Both in gemcitabine (GEM)-resistant/sensitive (GEM-R/S) pancreatic cancer cells, LMPt exhibits prominent anti-cancer activity, led by faster cellular entry-induced larger accumulation of MPt. The level of caveolin-1 (Cav-1) determines entry rate and switch of entry pathways of LMPt, indicating a novel role of Cav-1 in nanoparticle entry. After endosome-lysosome processing, in unchanged metabolite, MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM, to degrade POLG and TFAM. Then, via PINK1-Parkin axis, mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA (mtDNA) replication blocking. Additionally, POLG and TFAM are identified as novel prognostic markers of pancreatic cancer, and mtDNA replication-induced mitophagy blocking mediates their pro-cancer activity. Our findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA (target of most platinum agents), and totally distinct mechanism of MPt and other formulations of MPt. Self-assembly offers LMPt special efficacy and mechanisms. Prominent action and characteristic mechanism make LMPt a promising cancer candidate.