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Objective To evaluate adverse events(AEs)of hematological toxicities in cyclin-dependent kinase 4/6(CDK4/6)inhibitors based on the FDA adverse event reporting system(FAERS)database,and to provide a reference for rational drug use in the clinic.Methods A total of 29 quarterly AEs were extracted from the FAERS database from January 2015 to March 2022.Reported odds ratio(ROR)and proportional reported ratio(PRR)were used for data mining of CDK4/6 inhibitor AEs.Results A total of 7 872 AEs related to CDK4/6 inhibitors were reported,and the proportion of hematological AEs of each inhibitor was palbociclib(80.31%),ribociclib(15.36%),and abemaciclib(4.33%).Neutropenia and anemia were common in hematological toxicities.Palbociclib(2 982/6 322,47.17%)and ribociclib(613/1 209,50.70%)caused more neutropenia than abemaciclib(117/341,34.31%).Hematological toxicities mainly occurred 60 days after drug initiation(1 630,61.86%).Palbociclib had the longest median onset time,and 32.9%of patients still had hematological toxicities after 90 days of treatment.The clinical features and intensity were different among CDK4/6 inhibitors.Conclusions Palbociclib,abemaciclib,and ribociclib all cause significant hematological toxicities,among which abemaciclib has fewest reports of hematological toxicities.Still,the risk of death after anemia caused by abemaciclib should be noted.Complete blood cell count should be closely monitored within the first two months after treatment to monitor the patient's neutrophils and hemoglobin.The occurrence of hematological AEs associated with CDK4/6 inhibitors should be noted in the clinic.
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【Objective】 To explore the efficacy of transurethral columnar balloon dilation of prostate (TUCBDP) and transurethral bipolar plasmakinetic resection of prostate (TUPKP) for patients with small volume (≤30 mL) benign prostatic hyperplasia (BPH) and the effects on urinary control and sexual function. 【Methods】 Clinical data of BPH patients who underwent surgical treatment during Jun.2021 and Jan.2022 were reviewed. A total of 95 patients with prostate volume ≤30 mL and regular sexual life were selected as subjects, including 45 patients who received TUCBDP as the TUCBDP group and 50 patients who received TUPKP as the TUPKP group. The patients were followed up for 12 months, and the perioperative data and follow-up results were analyzed. 【Results】 The TUCBDP group had shorter operation time, less intraoperative blood loss, less postoperative hemoglobin loss and sodium concentration loss, shorter bladder irrigation time, lower pain score, shorter urinary tube indwelling time and shorter hospital stay than the TUPKP group (P0.05). The TUPKP group had worse ejaculation function score and ejaculation disturbance score after surgery (P0.05), and the two indexes were superior in the TUCBDP group than in the TUPKP group. The TUCBDP group had significantly lower complication rate than the TUPKP group (P<0.05). 【Conclusion】 TUCBDP is safe and effective in the treatment of small volume (≤30 mL) BPH, less trauma, less biochemical interference, less pain, fewer complications, and shorter course of disease. It has little effect on the ejaculation function and erectile function, and is more suitable for patients requiring retention of sexual function. It has a good application prospect in the treatment of small volume BPH.
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Objective To investigate the distribution frequency of allele genetic polymorphism of drug-metabolizing enzyme CYP2C19?2 (rs4244285) in tumor patients of Han population from Hubei province,to provide guidance for clinical rational drug use related to the genetic polymorphism. Methods CYP2C19?2 genotyping was performed by Fluorescence Dye Terminator Cycle Sequencing System in 285 cancer patients. Genotype frequency and allele frequency were calculated and the genotype distribution in different genders was compared. Compared with the previous studies, we clarified the frequencies of CYP2C19?2 gene polymorphisms in different nationalities. Results All the 285 patients in this study were Han population. The genotype frequency of CYP2C19?2 was 113 (39.6%),138 (48.4%) and 34 (11.9%) for wild-type homozygote (GG), heterozygote (GA) and variant homozygote (AA),respectively.The CYP2C19?2 mutant allele frequency was 36.1%.Genotype distribution of male and female patients did not reach significant difference. Conclusion There is no difference in CYP2C19?2 genotypes distribution among different ethnic groups.
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Objective To investigate the effects and mechanism of different doses of rosuvastatin on expression of tissue factor(TF) in cultured human monocyte-macrophage cells which were induced by oxidized low density lipoprotein (ox-LDL).Methods The human monocyte-macrophage cells were divided into seven groups:control group,ox-LDL group,poly-insine monophosphate group,different doses of rosuvastatin group(0.01 μmol/L,0.1 μmol/L,1 μmol/L,5 μmol/L).The expression of LOX-1 mRNA and TF mRNA was assayed by RT-PCR.The enzyme-linked immunosorbent assay was performed to determine the protein concentration of TF.Results Effects of different doses of rosuvastatin on expressions of LOX-1mRNA,TF mRNA and TF in cultured human monocyte-macrophage cells induced by ox-LDL:comparison among seven groups,the difference was statistically significant (F =91.334,58.833,103.552,P <0.05).Compared with control group,the expressions of LOX-1 mRNA,TF mRNA and TF were increased in the ox-LDL group[(3.25156 ± 0.15772) vs (1 ±0) ;(2.522451 ±0.138967) vs (1 ±0) ;(207.7233± 1.154701)ng/L vs (184.8467 ± 0.871799)ng/L],and they were in a concentration-dependent manner (P < 0.05).Compared with the PolyⅠ group and the different doses of rosuvastatin group,the expressions of LOX-1 mRNA,TF mRNA and TF were in the ox-LDL group,and the different doses of rosuvastatin were decreased by dose-dependent manner.It was in a concentration dependent manner (P < 0.05).Different doses of rosuvastatin were compared between groups (between each group P < 0.05),the difference between each two groups was statistically significant (P < 0.05).Conclusions LOX-1 may be responsible for the expression of TF in Human monocyte-macrophage cells induced by ox-LDL.Rosuvastatin by dose dependent manner and by means of ox-LDL reduced monocyte-macrophage LOX-1 mRNA and TF mRNA expressions,which reduced expression of TF.
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Objective To investigate the inhibition mechanism of sodium selenite on HCT116 cells.Methods In the present study,we explored the cytotoxicity induced by sodium selenite and the underlying mechanism by MTS assay,WesternBlot,and small RNA interference technique.Results It was found that the sodium selenite at 5uM concentration could indeed reduce the viability of colon cancer cell line HCT116 by a large margin through increasing the generation of reactive oxygen species (ROS),and that the increased levels of ROS could activate c-Jun Nh2-terninal kinase 1 (JNK1).Additionally,knockdown expression of JNK1 or p53 by using RNAi attenuated the cytotoxicity induced by sodium selenite,indicating that both of JNK1 and p53 are required in the process of cell death induced by sodium selenite.Conclusion The sodium selenite could induces cell death in HCT116 through oxidative stress by involvement of JNK1 and p53,both of which play a critical role in toxicity of sodium selenite.
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ObjectiveTo investigate the effects and mechanism of rosuvastatin on the expression of tissue factor in cultured human monocyte-macrophages cells which was induced by oxidized low density lipoprotein(ox-LDL).MethodsThe human monocyte-macrophages cells were divided into four groups:control group,ox-LDL group,Poly-inosine monophosphate (Poly Ⅰ) group,rosuvastatin group.The expression of LOX-1mRNA and TF mRNA was assayed by RT-PCR.The ELISA was performed to determine the protein concentration of TF.ResultsCompared with control group,the expression of LOX-1 mRNA and TF mRNA was increased in the ox-LDL group[ (3.25156±0.15772) vs (1±0) ; (2.522451±0.138967) vs (1±0) ],and it was in a concentration-dependent manner (P<0.01).Compared with the expression of LOX-1 mRNA in the Poly-inosine monophosphate group and rosuvastatin group,TF mRNA were decreased in the ox-LDL group[ (2.95139±0.157253) vs(3.25156±0.15772) ; (2.877343±0.156558) vs(3.25156±0.15772) ; (1.811956±0.169699) vs (2.522451±0.138967) ; (1.687701±0.174647) vs (2.522451±0.138967)],and it was in a concentration-dependent manner(P<0.05).Compared with control group,the expression of TF in the ox-LDL group was increased [(207.7233±1.154701) vs (184.8467±0.871799) ],and it was in a concentration-dependent manner (P<0.01).Compared with the Poly-inosine monophosphate group and rosuvastatin group [(197.8733±1.505003) vs (207.7233±1.154701) ;(202.9567±2.722744)vs(207.7233±1.154701) ],the expression of TF in the ox-LDL group were decreased,and it was in a concentration-dependent manner (P<0.05).ConclusionsLOX-1 may be responsible for the expression of TF in human monocyte-macrophages cells induced by ox-LDL.Rosuvastatin is able to down-regulate the expression of LOX-1mRNA in human monocyte-macrophages cells through oxLDL,and TF mRNA and TF expression can be reduced.