Recent Advance of Newly Therapy for Chronic Myeloid Leukemia with BCR-ABLT315I Mutation--Review / 中国实验血液学杂志

BCR-ABLT315I mutation is the main mechanism of resistance to the first and second generation tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML). Ponatinib as the third generation TKI has been found that can significantly improve the prognosis of CML patients with T315I mutation. However, the latest report has discovered that the T315I compound mutant is even resistant to ponatinib, which aroused the enthusiasm of research on the mechanism of CML resistance and targeted therapy once again. Previous studies have shown that TKI combined with other targeted drugs is effective to CML patients with drug resistance or relapse due to T315I mutation. The latest research has found that the allosteric inhibitor asciminib combined with TKI therapy is equally effective to CML patients with T315I compound mutant, but the specific mechanism is not yet clarified. This review will focus on the latest research progress of therapy for CML with BCR-ABLT315I mutation, hoping to provide reference for researching new drugs and improve therapy for treating CML with T315I mutation.

OTX1 Contributes to Hepatocellular Carcinoma Progression by Regulation of ERK/MAPK Pathway

Orthodenticlehomeobox 1 (OTX1) overexpression had previously been associated with the progression of several tumors. The present study aimed to determine the expression and role of OTX1 in human hepatocellular carcinoma (HCC). The expression level of OTX1 was examined by quantitative real-time PCR (qRT-PCR) in 10 samples of HCC and paired adjacent non-cancerous tissues, and by immunohistochemistry (IHC) analysis in 128 HCC samples and matched controls. The relationship between OTX1 expression and the clinicopathological features werealso analyzed. Furthermore, the effects of OTX1 knockdown on cell proliferation and migration were determined in HCC cell lines. Axenograft mouse model was also established to investigate the role of OTX1 in HCC tumor growth. TheqRT-PCR and IHC analyses revealed that OTX1 was significantly elevated in HCC tissues compared with the paired non-cancerous controls. Expression of OTX1 was positively correlated with nodal metastasis status (P = 0.009) and TNM staging (P = 0.001) in HCC tissues. In addition, knockdown of OTX1 by shRNA significantly inhibited the proliferation and migration, and induced cell cycle arrest in S phase in vitro. Tumor growth was markedly inhibited by OTX1 silencing in the xenograft. Moreover, OTX1 silencing was causable for the decreased phosphorylation level of ERK/MAPK signaling. In conclusion, OTX1 contributes to HCC progression possibly by regulation of ERK/MAPK pathway. OTX1 may be a novel target for molecular therapy towards HCC.

Effects of Different Doses of Flurbiprofen Axetil on Analgesia Effects of Patients after Laparoscopic Chole-cystectomy / 中国药房

OBJECTIVE:To evaluate the effects of different doses of flurbiprofen axetil on analgesia effects of patients after laparoscopic cholecystectomy. METHODS:120 patients undergoing laparoscopic cholecystectomy were selected and randomly divid-ed into group A,B and C,with 40 cases in each group. Group A,B and C were given the mixture 100 ml of flurbiprofen axetil 100,150 and 200 mg combined with tramadol 600 mg and ondansetron 4 mg respectively and 0.9% Sodium chloride injection for patient controlled intravenous analgesia(PCIA)at the end of operation. Mean arterial pressure(MAP),heart rate(HR)and static and dynamic visual analogue scale(VAS)scores were observed in 3 groups at the end of operation,4,8,24 and 36 h after sur-gery. The incidence of incision pain,neck-shoulder pain and hypochondrium,the occurrence of ADR were recorded 36 h after oper-ation. RESULTS:After operation,There was no statistical significance in comparison of 3 groups with MAP,HR,static and dynam-ic VAS(P>0.05),4,8,24,and 36 h after operation,MAP,HR,static and dynamic VAS score of group B and C decreased sig-nificantly,there was statistical significance,compared with group A(P0.05). After operation,the incidence of incision pain,neck-shoulder pain and hypochon-drium in group A were significantly higher than group B and C,with statistical significance(P0.05). After operation,the incidence of ADR in group A and B were significantly lower than in group C,with statistical significance(P0.05). CONCLUSIONS:Flurbiprofen axetil 150 mg combined with tramadol 600 mg and ondansetron 4 mg can improve he-modynamics and patient controlled intravenous analgesia in patients underwent laparoscopic cholecystectomy with lower incidence of ADR.

Diagnostic efficacy of an ultrasound quantitative method in a rat model of experimental liver fibrosis / 中华肝脏病杂志

To evaluate the efficacy of an ultrasound-based quantitative method to diagnose liver fibrosis using a rat model. Ultrasonography was performed on the livers of 90 Sprague-Dawley rats with or without thioacetamide-induced fibrosis. The liver capsule thickness and 13 texture parameters of gray level co-occurrence matrix were extracted from the standard sonograms. After sacrifice, severity of liver fibrosis (S0-S4 classification) was diagnosed by histopathology. Analysis of variance and correlation statistical tests were used to analyze the differences between groups and determine the relationships between each of the 14 quantitative ultrasound index points and the histological results, respectively. Discriminant analysis models were developed for quantitative diagnosis of liver fibrosis, and the leave-one-case-out method was used to verify the efficiency of models. All 14 indices were significantly correlated with the histological stages of fibrosis (P less than 0.05). The accuracy of the discriminant model for S0, S1, S2, S3 and S4 was 83.3%, 84.2%, 70.0%, 50.0% and 88.2%, respectively. In addition, 73.3% of cross-validated rats were accurately classified. Grouping S0 as no fibrosis, S1 as mild fibrosis, S2 with S3 as moderate to severe fibrosis and S4 as early cirrhosis increased the accuracy of the discriminant model for these four groups (respectively, 91.7%, 84.2%, 69.0% and 88.2%) and allowed for 78.9% of cross-validated rats to be correctly identified. Ultrasonography combined with texture analysis was a novel and accurate method to diagnose liver fibrosis in a rat model; further studies may provide insights into its applicability for quantitating liver fibrosis in other animal models or in clinic.

STAT4 gene polymorphism in Chinese Han systemic lupus erythematosus / 中华风湿病学杂志

Objective To explore the association between the signal transducer and activator of transcription 4 (STAT4) gene polymorphism and Chinese Han systemic lupus erythematosus patients. Methods Pyrosequencing technique was used to genotype the 3 single nucleotide polymorphisms (SNP) in the samples of patients and normal individuals. Results Not only these 3 SNPs, but also the haplotypes composed by them showed significant difference between the SLE patients and normal individuals[rs11889341:P=0.012 02, OR (95%CI)=1.22( 1.044～1.424); rs7574865:P=0.003 454, 0R(95%CI)=1.25(1.076～1.451 ); rs8179673: P=0.004 275, OR (95%CI)=1.274 (1.079～1.505)]. Conclusion rs11889341, rs7574865 and rs8179673 of STAT4 are associated with the pathogenesis of Chinese Han SLE, and the STAT4 gene is a susceptibile gene for SLE in a few racial cohorts.

Clinical observation of IEP followed EP chemotherapy in treatment of extensive-stage small cell lung cancer / 中国癌症杂志

Background and purpose: The overall survival time of extensive-stage small cell lung cancer is not satisfactory. No chemotherapy schemes more effective than etoposide combined with cisplatin, and other optimum combinations should be under evaluation. The aim of this study was to investigate the survival advantage of IEP followed by EP chemotherapy in the treatment of extensive-stage small cell lung cancer compared with EP chemotherapy alone. Methods: From Jan 2004 to Sep 2007, 68 extensive-stage small cell lung cancer patients were enrolled in this project and were randomly divided into research group and control group in the ratio of 1:1. In the research group, 34 patients accepted IEP chemotherapy at least two times followed by EP chemotherapy maintenance therapy. 34 patients as control group accepted EP chemotherapy only. Statistical significance was defined as P<0.05. Results: The median overall survival time of the research group was 15.32 months and the control group was 9.30 months. There were no significant differences between the two groups (P=0.0787). The median time to progression of the research group was 7.83 months and 6.92 months for the control group, respectively. There were no significant differences between the two groups (P=0.0164). It is suggested that IEP followed by EP chemotherapy in treatment of extensive-stage small cell lung cancer could get a better progression free survival, but the overall survival time has not been improved. Conclusion: We conclude that those patients with extensive-stage small cell lung cancer could get better progression free survival by accepting IEP chemotherapy.