Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective: To investigate the expression of TTK (tyrosine and threonine protein kinase) in the process of colorectal cancer (CRC) development and its relationship to prognosis in CRC patients. Methods: Colitis-associated colon cancer model was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in C57BL/6 mice. Mice at four different stages of colon cancer development were obtained, named AD1 (inflammation of the recovery), AD2 (mild dysplasia), AD3 (adenoma) and AD4 (adenocarcinoma), as well as negative control (no treatment). The expression of TTK was measured by real time fluorescent quantitative PCR (qPCR) and immunohistochemical staining in mouse colon tissues and 24 pairs of CRC specimens. The relationship between TTK and prognosis was analyzed in a set of CRC genome-wide gene expression microarray data that was obtained from Gene Expression Omnibus (GEO) of National Center for Biotechnology Information (NCBI). Results: The genome-wide microarray data from mouse AOM-DSS model indicated that the expression of TTK mRNA was gradually elevated during the development of colon cancer. The subsequent qPCR results showed that TTK mRNA levels in negative control, AD1, AD2, AD3 and AD4 groups were 1.05±0.42, 1.10±0.03, 1.38±0.15, 1.33±0.17 and 2.12±0.22, respectively. And TTK expression in AD2, AD3 and AD4 groups were significantly higher than that in negative control (P<0.05). The protein expression of TTK showed by immunohistochemical staining had similar tendency as the results of TTK mRNA. Besides that, the TTK mRNA levels in tumor tissues (0.71±0.10) from 24 CRC patients were significantly higher than those in paired adjacent normal tissues (0.18±0.04; P<0.001). The positive expression rate of TTK protein in 5 pairs of CRC clinical samples was 80.0%, and it was significantly higher than that in adjacent normal tissues (30.8%, P=0.014). Furthermore, according to a public transcriptomic data (GSE17536), the high levels of TTK were associated with poor prognosis in CRC patients. Conclusions Elevated expression of TTK is related to colonic carcinogenesis in both of mouse model and human CRC samples. TTK is a poor prognostic factor in CRC.

Objective Currently , the targeted therapy is the first-choice treatment of advanced non-small cell lung cancer (NSCLC) in with epidermal growth factor receptor (EGFR) mutations, but few studies have been reported on the relationship between immunohistochemical markers and the EGFR mutation.The aim of this study is to analyze the relationship of the EGFR mutation with the ex-pressions of thymidylate synthetase (TS), excision repair cross-com-plementation group 1 ( ERCC1 ) , β-tubulin-III, and ribonucleofide reductase large subunit-l ( RRM1) in NSCLC. Methods We retro-spectively analyzed 336 cases of NSCLC treated in the Department of Medical Oncology , the Affiliated Hospital of Inner Mongolia Medical University, from June 2014 to December 2015 and examined 29 EGFR mutations.We divided the patients into a mutation and a non-mutation group, performed immunohistochemical staining of the TS, ERCC1,β-tubulin-III and RRM1 proteins and compared their expressions in the NSCLC tissue between the two groups . Results EGFR mutations were found in 138 ( 41.07%) of the 336 NSCLC patients but not in the other 198 ( 58.93%) .The expression of TS was significantly lower in the mutation than in the non-mutation group (9.42%vs 39.39%, P<0.05), and so was that of β-tubulin-III (44.2%vs 60.1%, P<0.05).EGFR mutations were correlated with decreased expressions of TS (r=-0.332, P<0.05) andβ-tubulin-III (r=-0.157, P<0.05).Multivariate regression analysis showed that the risk of EGFR mutations was 2.109 times higher in the fe-male patients than in the males (OR=2.109, 95%CI:1.268-3.509), 24.265 times higher in the adenocarcinoma than in the adeno-squamous carcinoma patients (OR=24.265, 95%CI:3.508-167.845), 15.2 times higher in the squamous carcinoma than in the ade-nocarcinoma patients (OR=15.200, 95%CI:4.480-51.569), 2.364 times higher in the lung biopsy specimens than in the surgically treated patients (OR=2.364, 95%CI:1.266-4.413), and 6.171 times higher in the patients with lowly expressed than in those with highly expressed TS (OR=6.171, 95%CI: 3.145-12.109). Conclusion The decreased expressions of TS and β-tubulin-Ⅲ in NSCLC indicate the mutation of the EGFR gene.

Objective To explore the effects of ZNF330 on erythroid differentiation of K562 cells and underlying mechanism .Methods Realtime PCR was performed to detect the expression of ZNF 330 in K562 cells induced by hemin .After CD34 +cells being infected by the recombination lentivirus ZNF 330-RNAi, Realtime PCR was applied to detect the expression of CD235a and γ-globin.The luciferase report assay was performed to examine if ZNF 330 could act as a trans-acting factor in 293T/17 cells.Co-Immunoprecipitation (Co-IP) was applied in 293T/17 cells to detect the interaction between ZNF 330 and ZNF408 which was involved in mRNA degradation .Results The ex-pression of ZNF330 was up-regulated after hemin treatment .The expression of CD235a andγ-globin decreased after inhibition expression of ZNF 330 had no effect on report gene .Co-Ip in two ways confirmed the direct binding be-tween ZNF330 and ZNF408 .Conclusions ZNF330 can promote erythroid differentiation , and a possible mecha-nism is that ZNF330 inhibits the function of ZNF 408 , a factor that is involved in mRNA degradation , through the interaction between the two proteins .

Objective To study the results comparability of two kinds of different chemiluminescence systems(Antu chemilumi-nescence analyzer ADC CLIA 400 and Siemens centaur xp)in the detection of tumor markers.Methods The tumor markers were detected in 50 specimens by using the Antu chemiluminescence analyzer ADC CLIA 400 and the Siemens centaur xp chemilumines-cence analyzer respectively.Then the results were analyzed and compared.Results The quantitative analysis results on the serum specimens showed that there was no significant difference in the detection results between the two kinds of detection system(P >0.05).The correlation coefficients of 5 test items between the two kinds of detection system were more than 0.836,suggesting a good correlation between the two kinds of method.The accuracy and repeatability of the Siemens centaur xp chemiluminescence ana-lyzer were higher than those of the Antu chemiluminescence analyzer ADC CLIA 400 in detecting the tumor markers.Conclusion The Siemens centaur xp chemiluminescence analyzer is better than the Antu chemiluminescence analyzer ADC CLIA 400 in detec-ting the tumor immune markers.