1.Toremifene, an Alternative Adjuvant Endocrine Therapy, Is Better Than Tamoxifen in Breast Cancer Patients with CYP2D6*10 Mutant Genotypes
Xin LI ; Zehao LI ; Lin LI ; Tong LIU ; Cheng QIAN ; Yanlv REN ; Zhigao LI ; Kejin CHEN ; Dongchen JI ; Ming ZHANG ; Jinsong WANG
Cancer Research and Treatment 2024;56(1):134-142
Purpose:
Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes.
Materials and Methods:
CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group.
Results:
A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003).
Conclusion
Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.
2.Inhibitory effect of 6-paradol on the proliferation, migration, and invasion of intrahepatic cholangiocarcinoma cells and its mechanism
Zehao CHEN ; Wenjie ZHU ; Bingbing SHEN ; Jianxin JIANG
Journal of Clinical Hepatology 2022;38(4):857-864
Objective To investigate the effect of 6-paradol on the proliferation, migration, and invasion of human intrahepatic cholangiocarcinoma cells and its mechanism. Methods Human intrahepatic cholangiocarcinoma cell lines HCCC 9810 and HUCCT1 were treated with different concentrations of 6-paradol or an equal volume of DMSO (control group), and then CCK-8 assay, plate colony formation assay, wound healing assay, and Transwell assay were used to measure cell proliferation, migration, and invasion. The bioinformatics software Swiss Target Prediction was used to predict the protein targets of 6-paradol, and Western blot was used to measure the protein expression levels of STAT3, p-STAT3, SRC, p-mTOR, p21, Bcl-2, and p53; Drug Affinity Responsive Target Stability (DARTS) assay was used to investigate the interaction between 6-paradol and STAT3. After cholangiocarcinoma HCCC 9810 and HUCCT1 cells were transfected with STAT3 overexpression plasmid or sh-p21 plasmid, quantitative real-time PCR was used to measure the mRNA expression levels of STAT3 and p21, and Western blot was used to measure the protein expression levels of STAT3 and p21; CCK-8 assay, wound healing assay, and Transwell assay were used to measure cell proliferation, migration, and invasion. The t -test was used for comparison of data between two groups; an analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the control group, the 6-paradol treatment groups had significant reductions in cell proliferation, migration, and invasion ( P < 0.05). Compared with the control group, the 6-paradol treatment groups had significant reductions in the expression levels of STAT3 and p-STAT3 (all P < 0.05) and a significant increase in the expression level of p21 (all P < 0.05), while there were no significant changes in the expression levels of Bcl-2, SRC, and p-mTOR (all P > 0.05). In the 6-paradol treatment groups, the proportion of STAT3 hydrolyzed by protease was reduced by 48.66% and 45.33%, respectively ( t =16.64 and 8.76, both P < 0.05); after transfection with STAT3 overexpression plasmid or p21-silencing plasmid in cholangiocarcinoma cells, there was a significant increase in the mRNA expression level of STAT3 ( t HCCC 9810 =2.82, t HUCCT1 =5.60, both P < 0.05) and a significant reduction in the mRNA expression level of p21 ( t HCCC 9810 =6.84, t HUCCT1 =3.91, both P < 0.05). CCK-8 assay showed that for HCCC 9810 and HUCCT1 cells treated with 6-paradol for 48 and 72 hours, the STAT3 overexpression group had a significantly higher proliferation rate than the single administration group, and the p21 silencing group also had a significantly higher proliferation rate than the single administration group ( P < 0.05). The wound healing assay showed that the HCCC 9810 and HUCCT1 cells with STAT3 overexpression or p21 silencing had a significantly higher wound healing rate than the single administration group (all P < 0.05). Transwell assay showed that the HCCC 9810 and HUCCT1 cells with STAT3 overexpression or p21 silencing had significant increases in migration rate and invasion rate compared with the single administration group (all P < 0.05). Conclusion 6-Paradol inhibits the proliferation, migration, and invasion of cholangiocarcinoma cells by targeting the STAT3-p21 pathway.
3.Repair of sciatic nerve defect in rats by adipose tissue decellularized matrix hydrogel
Yan LI ; Zhaoyang CHEN ; Youbai CHEN ; Jing REN ; Zehao NIU ; Wenwen PU ; Yan HAN
Chinese Journal of Microsurgery 2021;44(3):292-297
Objective:To observe the effect of adipose tissue decellularized matrix hydrogel (DAT-gel) on the repair of sciatic nerve defect in rats.Methods:From April, 2019 to April, 2020, aseptic granular adipose tissue was collected from healthy adult women who underwent thigh or abdominal liposuction in the Department of Plastic Surgery, the First Medical Centre of the PLA General Hospital. Decellularisation and enzymatic digestion of adipose tissue were performed to prepare DAT-gel. Scanning electron microscope (SEM) was used to observe the ultrastructure of the hydrogel, and rheology was employed to test the gel dynamics and viscoelasticity of the hydrogel. A rat model of sciatic nerve defect was established and randomly divided into 3 groups: simple chitin catheter group (Chitin group), DAT-gel plus chitin catheter group (DAT-gel group) and autologous nerve reverse connection group (Autograft group) with 10 rats in each group. At the 12th week after surgery, the general view, function and morphology of the regenerated nerve were observed to evaluate the repairing status of the injured nerve. One-way analysis of variance (one-way ANOVA) was used for data analysis. If the difference between the groups was statistically significant, the Turkey method was further used for pairwise comparison. P<0.05 was considered as statistically significant. Results:The results of SEM showed that the DAT-gel had a three-dimensional structure in porous fibre network. The results of rheological test results showed that the complex viscosity of the hydrogel at 4 ℃ and 37 ℃ were 148.91 mPa·s and 801.29 mPa·s, respectively. DAT-gel underwent a sol-gel phase transition when the temperature had been increased. The results showed that DAT-gel had a good temperature-sensitive effect, and its critical point of sol-gel phase transition was similar to the internal temperature of rat. The results of animal experiments showed that the morphology and function of the regenerated nerve in the DAT-gel group were superior to Chitin group at 12 weeks after surgery, according to macroscopic view of the regenerated nerve, electrophysiology of the nerve, the morphology of the new axon and the target muscle, etc.. There was statistically significant between groups ( P<0.05). Conclusion:DAT-gel can significantly promote a repair of sciatic nerve defects in rats.
4.Construction and practice of the golden course "doctor-patient communication skills"
Ying HUANG ; Jing WU ; Wangbin NING ; Meihua XU ; Xinhua LI ; Zehao LIU ; Zongfeng DING ; Weiru ZHANG ; Xiaobin CHEN
Chinese Journal of Medical Education Research 2021;20(4):378-382
Diagnostics is one of the most important bridge courses for medical students from basic to clinical. Doctor-patient communication runs through the whole process of patient diagnosis and treatment. How to improve medical students' ability of doctor-patient communication? Our teaching team has carried out continuous reform and explored the scientific effective teaching mode. Recently, through the construction of "doctor-patient communication skills" quality online course, efforts have made to build an online and offline blended learning mode, which has gradually realize the integration with diagnostics teaching, and has achieved remarkable results. It also provides a scientific practical basis for the integration of doctor-patient communication and other clinical courses, which is worthy of promotion.
5.Advances in the detection and clinical application of peripheral circulating tumor cells of hepatocellular carcinoma
Wenjie ZHU ; Zehao CHEN ; Jianxin JIANG
Chinese Journal of Hepatobiliary Surgery 2021;27(4):313-316
Circulating tumor cells are found in patients’ peripheral blood circulation, which are the key to tumor metastasis and recurrence. We can achieve early diagnosis and treatment of the tumor if we could detect circulating tumor cells through peripheral blood vessels. It is of great significance to improve the prognosis of hepatocellular carcinoma patients by studying the relationships between hepatocellular carcinoma and peripheral circulating tumor cells. Hence, this paper reviews the recent progress in the detection and clinical application of circulating tumor cells in hepatocellular carcinoma in order to provide references for clinical and related studies.
6.Effects of MCCC2 knockdown on proliferation, migration and apoptosis of DU145 prostate cancer cells
Xue CHEN ; Zehao HUANG ; Chengjian ZHENG
Journal of Pharmaceutical Practice 2021;39(3):215-220
Objective To investigate the change of biological characteristics after stable knockdown of the coding gene of 3-methylcrotonyl-coenzyme A carboxylase β subunit (MCCC2) expression in DU145 by lentivirus shRNA. Methods Three groups were included in this study. shNC was the control group in which MCCC2 was negatively knocked down in DU145. shMCCC2 was the experimental group in which MCCC2 was knocked down. DU145 was the blank group without any treatment. The expression of MCCC2 was assessed by Western blot and qPCR. The proliferation of DU145 cells was detected by CCK8 assay. The migration ability of DU145 was detected by transwell. The apoptosis of DU145 cells was detected by flow cytometry. Results The expression level of MCCC2 in shMCCC2 group was significantly lower than that in shNC group (0.22 ± 0.02 vs 0.61 ± 0.06, P < 0.001). The proliferation (2.24 ± 0.04 vs 3.13 ± 0.15) and migration (23.96 ± 1.85 vs 49.73 ± 0.63) of DU145 cells in shMCCC2 group was significantly lower than that in shNC group, whereas the apoptosis (12.64 ± 0.30 vs 3.68 ± 0.02) of DU145 cells in shMCCC2 was significantly higher than that in shNC group. Conclusion MCCC2 knockdown significantly inhibited the proliferation and migration, and induced apoptosis of DU145 cells, which indicated that the down-regulation of MCCC2 is correlated with the change of tumor biological characteristics of DU145 cell line and can be a potential target for the treatment of prostate cancer.
7.3D-printed models improve surgical planning for correction of severe postburn ankle contracture with an external fixator.
Youbai CHEN ; Zehao NIU ; Weiqian JIANG ; Ran TAO ; Yonghong LEI ; Lingli GUO ; Kexue ZHANG ; Wensen XIA ; Baoqiang SONG ; Luyu HUANG ; Qixu ZHANG ; Yan HAN
Journal of Zhejiang University. Science. B 2021;22(10):866-875
Gradual distraction with an external fixator is a widely used treatment for severe postburn ankle contracture (SPAC). However, application of external fixators is complex, and conventional two-dimensional (2D) imaging-based surgical planning is not particularly helpful due to a lack of spatial geometry. The purpose of this study was to evaluate the surgical planning process for this procedure with patient-specific three-dimension-printed models (3DPMs). In this study, patients coming from two centers were divided into two cohorts (3DPM group vs. control group) depending on whether a 3DPM was used for preoperative surgical planning. Operation duration, improvement in metatarsal-tibial angle (MTA), range of motion (ROM), the American Orthopedic Foot and Ankle Society (AOFAS) scores, complications, and patient-reported satisfaction were compared between two groups. The 3DPM group had significantly shorter operation duration than the control group ((2.0±0.3) h vs. (3.2±0.3) h,
8.Maffucci syndrome: a case report and review of the literature
Lin GAO ; Jing WU ; Huiling CHEN ; Lan LIAO ; Minxiang LEI ; Zehao LIU
Chinese Journal of Endocrinology and Metabolism 2020;36(5):429-432
Maffucci syndrome is characterized by multiple enchondromas and multiple hemangiomas. Here we report on a 24-year-old woman who was diagnosed with Maffucci syndrome. Our report reviews the literature and outlines of the treatment and management plans for patients with this rare and potentially dangerous disease.
9.Optimization and purification of extraction of polysaccharides from Anoecto-chilus roxburghii
Songbai ZHANG ; Xun ZHANG ; Wen XU ; Wei XU ; Zehao HUANG ; Yu LIN ; Shuyun CHEN
Journal of Pharmaceutical Practice 2020;38(4):354-358
Objective To optimize the process of ultrasonic extraction of polysaccharide in Anoectochilus roxburghii and to investigate the method of protein removal. Methods The extraction rate of polysaccharide was used as the detection index. On the basis of single factor investigation, Box-Behnken experimental design and response surface method were used to optimize the three factors of material-liquid ratio, ultrasonic time and ultrasonic extraction temperature. The five deproteinization methods including Sevage reagent method, TCA method, salt method (NaOH-CaCl2 and NaOH-NaCl) and hydrochloric acid method were investigated with the retention rate of polysaccharide and protein removal rate. Results The optimal extraction conditions of polysaccharide from Anoectochilus roxburghii were as follows: liquid-to-solid ratio was 10∶1, extraction temperature was 48 ℃ and extraction time was 36 min with extraction 2 times, ultrasonic power was 300 W, the extraction rate was 13.13%. NaOH-CaCl2 deproteinized methods∶ the loss rate of polysaccharide was 18.74%, and the removal rate of protein was 95.62%. Conclusion Ultrasonic extraction is easy to operate, and the optimized extraction method can achieve a high extraction rate. NaOH-CaCl2 deproteinization methods can get high protein removal rate and polysaccharide retention rate. This method is suitable for the research and development of the active components of the polysaccharides from Anoectochilus roxburghii.
10.A model combined machine learning with imaging omics characteristics in differentiating anaplastic glioma from glioblastoma
Ce WANG ; Zenghui QIAN ; Zehao CAI ; Zhuang KANG ; Baoshi CHEN
Chinese Journal of Neuromedicine 2020;19(3):224-228
Objective:To construct and validate a prediction model combined machine learning with imaging omics characteristics in differentiating anaplastic glioma from glioblastoma.Methods:Imaging data of 241 patients with anaplastic glioma or glioblastoma, confirmed by pathology in our hospital from August 2005 to August 2012, were retrospectively collected. These patients were divided into a training group ( n=140) and a verification group ( n=101) according to random number table method. MRIcron software was used to delineate tumor boundaries of patients from the training group on preoperative T1 enhanced MR imaging. The regions of interest (ROIs) were outlined on preoperative T1 enhanced MR imaging, and the radiomic features were extracted from ROIs by Matlab software. Least absolute shrinkage and selection operator (LASSO) regression model was used to screen the features, and then, the selected features were used to construct the prediction model by support vector machine (SVM) classifier. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of the model. Results:In these 241 patients, 101 were with anaplastic glioma and 140 were with glioblastoma confirmed by pathology. In the training group and validation group, there was statistical difference in age between patients with anaplastic glioma and glioblastoma ( P<0.05); there was no significant difference in gender distribution, tumor location, and percentages of tumor necrosis or edema between patients with anaplastic glioma and glioblastoma ( P>0.05). Totally, 431 radiomic features were extracted; 11 radiomic features were screened by LASSO regression model and the prediction model was established. The AUC of ROC curve was 0.942 and 0.875, respectively, in the training group and validation group. Conclusion:The prediction model combined machine learning and imaging omics characteristics can effectively discriminate anaplastic glioma from glioblastoma.

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