1.Aspirin resistance and ischemic stroke
Keting LIU ; Shuyu ZHOU ; Qinqin CAO ; Huan CAI ; Xinfeng LIU
International Journal of Cerebrovascular Diseases 2016;24(5):442-446
Stroke has become the leading cause of death in Chinese residents. As the cornerstone of the primary and secondary prevention of ischemic stroke, aspirin can prevent the occurrence and recurrence of ischemic stroke in a certain extent. However, some patients stil have vascular events after taking aspirin regularly or higher platelet aggregation rate. This phenomenon is caled aspirin resistance or aspirin low reactivity. This article reviews the occurrence, detection methods, and treatment measures of aspirin resistance in patients with ischemic stroke.
2.Relationship between single nucleotide polymorphisms of UGT1A6 and aspirin low responsiveness in patients with ischemic stroke
Keting LIU ; Shuyu ZHOU ; Biyang CAI ; Qinqin CAO ; Xinfeng LIU
Chinese Journal of Neurology 2016;49(10):775-779
Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) of UGT1 A6 and aspirin response in a cohort of Chinese Han population.Methods A total of 323 ischemic stroke patients consecutively registered in Nanjing Stroke Registry Program from September 2011 to October 2014 were enrolled.Three SNPs (rs6759892,rs2070959 and rs1105879) of UGT1A6 were genotyped in these ischemic stroke patients.Association of genotypes and aspirin response was evaluated by generalized linear model.Indicated with the inhibition rate of platelets,aspirin response was assessed by thromboelastograph.Results The mutation allele (G) of rs2070959 was positively related to platelets inhibition (β =0.084,P =0.010,Pcorrected =0.029),especially in male (β =0.098,P =0.006,Pcorrected =O.019).The dominant models of rs6759892,rs1105879 were also modestly related to aspirin response (P=0.015,Pcorrected=0.046 in both SNPs) in male.Thus the polymorphisms of UGT1A6 showed a relationship with aspirin response,especially in males.Conclusions The results indicated that genetic polymorphism of UGT1A6 might have an effect on individuals' aspirin response,especially in males.These findings can help clinicians to optimize the antiplatelet therapy for ischemic stroke patients.
3.Effect of domestic wire-reinforced epidural catheter on occurrence of adverse events during epidural block
Zhichao QI ; Xiaobing ZHU ; Zhiqun LIU ; Lun WU ; Xueqiang PENG ; Weiwei ZOU ; Keting ZHOU ; Wei ZHENG
Chinese Journal of Anesthesiology 2012;(11):1331-1333
Objective To evaluate the effect of domestic wire-reinforced epidural catheter on the occurrence of adverse events during epidural block.Methods Three hundred ASA Ⅰ or Ⅱ patients of both sexes,aged 18-64 yr,weighing 41-78 kg,scheduled for elective operations under combined spinal-epidural anesthesia,were randomly divided into 3 groups (n =100 each):polyvinyl chloride epidural catheter group (group A),imported wire-reinforced epidural catheter group (group B) and domestic wire-reinforced epidural catheter group (group C).Combined spinal-epidural anesthesia was performed routinely.The corresponding epidural catheter was inserted in each group.The catheterization without difficulty,paresthesia during catheterization,the number of patients in whom blood or cerebrospinal fluid was withdrawn from the epidural catheter,intravascular catheter insertion,injection obstruction,easiness during removal of the catheter,bleeding after removal,postoperative paresthesia and epidural hematoma within 1 week after operation were recorded.Results Compared with A group,the incidences of paresthesia during catheterization,the number of patients in whom blood or cerebrospinal fluid was withdrawn from the epidural catheter,injection obstruction and postoperative paresthesia were significantly decreased (P < 0.05),and no significant change was found in the other parameters in B and C groups (P > 0.05).There was no significant difference in all the parameters between B group and C group (P > 0.05).Conclusion Domestic wire-reinforced epidural catheter can decrease the occurrence of catheterization-induced damage to the nerve and blood vessels and the efficacy is comparable with that of imported wire-reinforced epidural catheter.
4.Correlation of serum albumin with short-term functional outcome of acute ischemic stroke
Minhui DAI ; Wenjie ZI ; Biyang CAI ; Lulu XIAO ; Keting LIU ; Yumeng ZHANG ; Shuyu ZHOU ; Ling TIAN ; Gelin XU
Journal of Medical Postgraduates 2015;(11):1152-1155
Objective No consensus has yet been achieved on the relationship of serum albumin with the functional out-come of acute ischemic stroke.The aim of our study was to determine whether the serum albumin level was associated with the short-term functional outcome of acute ischemic stroke in well-nourished patients. Methods Totally, 113 patients with first-ever acute ischemic stroke were recruited from Nanjing Stroke Registration Program between January and June 2015.Baseline data including de-mographic and body parameters, vascular risk factors, and laboratory results were collected.The NIH Stroke Scale ( NIHSS) was used to evaluate the severity of neurological deficits and the modified Rankin Scale ( mRS ) employed to assess the short-term functional outcome.According to the mRS at discharge, the patients were divided into a good outcome group ( mRS<3 ) and a poor out-come group ( mRS≥3 ) .The independent predictors of the short-term functional outcome were evaluated by multivariate logistic regression analysis. Results Of the 113 acute ischemic stroke patients included, 52 (46.0%) were in the good outcome group, and 61 (54.0%) in the poor outcome group.Those in the former group had a significantly higher BMI, lower serum LDL-C, lower WBC count, and lower NIHSS at admission than those in the latter .Multivariate logistic regression analysis showed that low serum albumin, NIHSS at admission, and arteriole occlusion were independent predictors of the poor short-term functional outcome ( OR=0.684, 95% CI:0.490-0.956, P=0.026). Conclusion Low serum albumin is an independent predictor of poor short-term functional outcome in acute ischemic stroke patients in well-nourished status.
5. Osthole attenuates diabetes-induced renal injury by regulating NF-κB and p38/MAPK pathway mediated inflammatory responses
Yiyi JIN ; Keting ZHOU ; Chengcheng YANG ; Ping XU ; Suyan ZHU
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(6):622-631
To investigate the therapeutic effects of oral osthole on streptozotocin (STZ)-induced type 1 diabetes mellitus(T1DM) mice and explore its internal mechanism. METHODS: The diabetes model induced by STZ was established. Mice were randomly divided into control group, STZ model group, STZ+osthole group (20 mg/kg). Body weight, blood glucose, urine protein, blood urea nitrogen and creatinine were observed to detect renal function. The degree of renal tissue damage was detected by H&E staining and PAS staining, and the degree of renal fibrosis was detected by Sirius Red staining. CD68 and F4/80 immunofluorescence staining was used to observe the infiltration of macrophages in kidney tissue. The mRNA expressive levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in renal tissue were detected by RT-qPCR. The protein expressive levels of phospho-NF-κB p65, NF-κB p65, IκBα, phospho-IκBα, phospho-p38 and p38 were detected by Western blot in renal tissue. RESULTS: Compared with the STZ model group, the levels of urinary protein, blood urea nitrogen, creatinine were significantly decreased after osthole treatment (P<0.05 or P<0.01). The renal structure disorder, mesangial matrix area, collagen fiber accumulation, and macrophage infiltration were significantly improved (P<0.05 or P<0.01). The expression of mRNA of pro-inflammatory cytokines TNF-α and IL-6 were significantly decreased (P<0.05 or P<0.001). The expression of phospho-NF-κB p65, phospho-IκBα and phospho-p38 were significantly down-regulated (P<0.05 or P<0.01), while the protein expression level of NF-κB p65, IκBα was up-regulated (P<0.05). CONCLUSION: Osthole has a protective effect on kidney injury caused by diabetes and inhibits NF-κB and p38/MAPK signaling pathway.
6.Betulinic acid enhances gefitinib-sensitivity of pancreatic cancer cells via inhibition of STAT3 activation
WU Haixia ; MAIMAITI Aikebaier ; WANG Shuai ; ZHOU Keting ; SHI Senlin
Chinese Journal of Cancer Biotherapy 2019;26(9):948-954
Objective: To investigate the effects and the underlying mechanisms of betulinic acid (BEA) on sensitizing pancreatic cancer cell lines Panc-1 and Miapaca-2 to gefitinib. Methods: After the cell culture was completed, Panc-1 and Miapaca-2 cells were randomly divided into 4 groups: control group (without treatment), BEAgroup, gefitinib group and BEAcombined with gefitinib group, respectively.The sensitization effect of BEAon gefitinib-insensitive pancreatic cancer cells was detected by MTS assay. The treatment effects of combined treatment of gefitinib and BEA against Panc-1 and Miapaca-2 cells were evaluated by colony formation assay. Flow cytometry was used to examine the effect of BEAon apoptosis of Panc-1 cells while WB was applied to determine the effect of BEAonapoptosis-related proteins. Surface plasmon resonance (SPR) experiment was used to detect the direct combination between signal transducer and activator of transcription 3(STAT3) and BEA; Molecular docking and molecular dynamics simulation experiments were adopted topredict the combining mode between STAT3 and BEA. Results: BEA synergistically enhanced the gefitinib-sensitivity of pancreatic cancer Panc-1 and Miapaca-2 cells (P<0.05), and IC50 of gefitinib on two cells were reduced by over 50%. Compared with single treatment, the combined treatment of BEA and gefitinib promoted the apoptosis and up-regulated the expressions of apoptosis-relatedproteins (cleaved-PARP and Bax), but reduced the apoptosis-inhibitory protein Bcl-2 (all P<0.05 or P<0.01). Moreover, the inhibitory effect of BEA on STAT3 activation in Panc-1 cells was in a dose-dependent mannar (P<0.01). BEA stabilizes its binding to STAT3 by forming hydrogen bonds with Lys-591 and Ser-613 of STAT3; in the meanwhile, BEA stabilized inthebinding site of STAT3, there by blocking STAT3 dimerization to enhance the drug sensitivity. Conclusion: Combined use of BEA and gefitinib could significantly inhibit the proliferation and induce apoptosis of Panc-1 and Miapaca-2 cells, which might be mediated by the inhibition of BEA on STST3.
7.Intermittent fever, dyspnea.
Xiaoxia HU ; Lili XU ; Keting CHEN ; Yi HUANG ; Daoyin ZHOU ; Yi SUN ; Jianmin WANG ; Jianmin YANG
Chinese Journal of Hematology 2015;36(5):441-444
8.Weakness of limbs and lymphadenopathy.
Xinxin XIA ; Lili XU ; Keting CHEN ; Yi SUN ; Daoyin ZHOU ; Huaimin ZHU ; Bihe MIN ; Jianmin WANG ; Xiaoxia HU ; Jianmin YANG
Chinese Journal of Hematology 2015;36(8):704-706