1.Application of Allograft Endometriosis Rat Model in Pharmaco-dynamic Evaluation of GnRH Agonists
Ruihua ZHONG ; Guoting LI ; Wenjie YANG ; Xiangjie GUO ; Jieyun ZHOU ; Yingyi HU ; Qicheng NI ; Ye YANG ; Min ZHANG ; Yan ZHU
Laboratory Animal and Comparative Medicine 2024;44(2):127-138
Objective To establish an allogeneic rat model of endometriosis and to evaluate the effects of gonadotropin-releasing hormone (GnRH) agonist GenSci006 on experimental rat endometriosis. Methods Endometrium from SPF grade donor female SD rats were transplanted onto the abdominal wall of recipient female rats to construct an allogeneic endometriosis model. The rats undergoing sham surgery were divided into the sham group. Three weeks later, the length, width and height of the ectopic endometrium were measured, and the volume of the endometrium (V1) was calculated before drug administration. The modeling rats were randomly divided into four groups: model group, triptorelin group (0.25 mg/kg), GenSci006-1 group (0.125 mg/kg) and GenSci006-2 group (0.25 mg/kg). Each group had 16 rats and received a single dose of the corresponding drug. The sham group and model group were administered an equal volume of solvent. Three weeks after administration, ectopic endometrium was measured to calculate the volume V2 and inhibition rate. The effect of GenSci006 on rat uterus and ovarian tissues was assessed by comparing organ coefficients and changes in pathological sections. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of serum estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Real-time fluorescent quantitative PCR was used to detect the expression of GnRH receptor (GnRHR) mRNA in the hypothalamus and pituitary. Western blot was used to detect the expression of estradiol receptor alpha (ERα), beta (ERβ) and progesterone receptor (PR) in ectopic endometrium. Results Three weeks after administration, compared with the model group, the body weight of rats in the triptorelin and GenSci006-2 groups significantly increased (P < 0.05), while the volume of ectopic endometrium significantly decreased (P < 0.05). Compared with the sham group, the model group showed no significant changes in uterine and ovarian organ coefficients or endometrial thickness (P > 0.05). Compared with the model group, the uterine organ coefficients and endometrial thickness were significantly reduced in the triptorelin and GenSci006-2 groups (P < 0.05). Compared with the sham group, the serum levels of E2, P4, FSH and LH in the model group showed no significant changes (P > 0.05). Compared with the model group, the ovarian organ coefficient and serum P4 levels of rats in the Triptorelin, GenSci006-1, and GenSci006-2 groups were significantly reduced (P < 0.05), while the serum LH levels of rats in the GenSci006-1 group were significantly increased (P < 0.05). However, there were no significant changes in serum E2 and FSH levels in each group (P > 0.05). Compared with the model group, the expression levels of GnRHR mRNA in the pituitary tissue of rats in the triptorelin and GenSci006-2 groups were significantly downregulated (P < 0.05), with no significantly changes in the hypothalamus (P > 0.05). There were no significant changes in the expression level of GnRHR mRNA in the hypothalamus or the protein levels of ERα, ERβ and PR in the ectopic endometrial tissue in any group (P > 0.05). Conclusion The allogeneic endometriosis rat model is a suitable animal model for screening and evaluating drugs for treating endometriosis. The volume of ectopic endometrium, inhibition rate, uterine and ovarian organ coefficients, and serum E2 levels may serve as indicators for detecting drug efficacy.
2.Prognostic analysis of male patients with breast cancer after mastectomy based on SEER database
Wenjie NI ; Linan SONG ; Hui YANG ; Xiaolei LIU ; Xiaofeng MU
Chinese Journal of Radiation Oncology 2024;33(10):922-927
Objective:To analyze the survival and prognostic factors of male patients with breast cancer after mastectomy.Methods:Male patients with invasive breast ductal cancer who underwent mastectomy from January 1, 2000 to December 31, 2018 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis was performed by Kaplan-Meier method, and compared by log-rank test. Prognostic factors were identified by Cox proportional hazards regression analysis.Results:A total of 1231 cases were included, with an onset age of (67 ± 12) years. The proportion of stage I-II was 81.1%. The 10-year cancer-specific survival (CSS) rates for stage IA, IIA, IIB, IIIA, IIIB, and IIIC patients were 85.4%, 84.9%, 69.0%, 68.1%, 51.9%, and 48.3%, respectively (all P<0.001). For stage IA-IIB patients, the 10-year CSS rate was 79.2% in the postoperative radiotherapy group, compared to 83.0% in the non-radiotherapy group ( P=0.019). For stage IIIA-IIIC patients, the 10-year CSS rate was 61.7% in the postoperative radiotherapy group, compared to 52.9% in the non-radiotherapy group ( P=0.021). For stage IA-IIB patients, the 10-year CSS rate was 83.8% in the postoperative chemotherapy group, compared to 79.8% in the non-chemotherapy group ( P=0.342). For stage IIIA-IIIC patients, the 10-year CSS rate was 59.7% in the postoperative chemotherapy group, compared to 54.1% in the non-chemotherapy group ( P=0.052). Multivariate analysis showed that younger age, married and grade I-II differentiation were favorable prognostic factors. The earlier the tumor staging, the better the prognosis. Conclusions:Postoperative radiotherapy can improve the CSS of stage III male patients with breast cancer. Younger age, married, grade I-II differentiation are favorable prognostic factors. The earlier the tumor staging, the better the prognosis.
3.Significance of target volume delineation of tumor bed according to metal clips or seroma in determing tumor bed position during radiotherapy after breast-conserving surgery for breast cancer
Zhimin YAO ; Wenjie NI ; Dongliang HOU ; Zihong WANG ; Wenzhang CHEN
Cancer Research and Clinic 2023;35(1):23-28
Objective:To investigate the differences between the mental clips placed intraoperatively and the tumor bed's target volume delineation of seroma based on CT scanning during radiotherapy for breast cancer patients who received breast-conserving surgery in the persuit of a better solution to determine the tumor bed position.Methods:The clinical data of 13 patients with early breast cancer who received postoperative radiotherapy after breast-conserving surgery at Beijing Shijingshan Hospital and Beijing Shijitan Hospital of Capital Medical University from December 2020 to January 2022 were retrospectively analyzed. They all had surgical clips implanted during the surgery. The following methods were used to delineate the target volume of tumor bed, including gross target volume delineation of tumor bed based on the mental clips (GTVtb-Clip), the tumor bed's gross target volume delineation of seroma based on CT scanning (GTVtb-Seroma), and the combination of both (GTVtb-C+S). The volume, diameter on three coordinate axis, neutral point displacement and conformability of these delineation methods were compared.Results:The volume of GTVtb-Clip, GTVtb-Seroma and GTVtb-C+S was (25±10) cm 3, (38±17) cm 3, (49±20) cm 3, and the differences were statistically significant (all P<0.05). The diameter on X axis was (4.7±1.2) cm, (5.3±1.4) cm, (5.7±1.6) cm, respectively in GTVtb-Clip, GTVtb-Seroma and GTVtb-C+S; the diameter on Y axis was (4.6±1.7) cm, (5.0±1.6) cm, (5.7±1.7) cm, respectively in GTVtb-Clip, GTVtb-Seroma and GTVtb-C+S; the diameter on Z axis was (4.4±1.5) cm, (5.2±1.4) cm, (5.6±1.4) cm in GTVtb-Clip, GTVtb-Seroma and GTVtb-C+S. The differences in the diameter of GTVtb-Clip and GTVtb-C+S on X,Y, Z axis were statistically significant (all P<0.05); the differences in the diameter of GTVtb-Seroma and GTVtb-C+S on X, Z axis were statistically significant (all P<0.05); the difference in the diameter of GTVtb-Clip and GTVtb-Seroma on X axis was statistically significant ( P<0.05) .Neutral point displacement was (5.8±1.6) cm, (5.5±1.9) cm, (6.0±1.7) cm, respectively of GTVtb-Clip, GTVtb-Seroma, GTVtb-C+S, and the difference was not statistically significant ( P>0.05). Conformability of GTVtb-Clip and GTVtb-Seroma, GTVtb-Clip and GTVtb-C+S, GTVtb-Seroma and GTVtb-C+S was 0.412±0.112, 0.525±0.095, 0.774±0.112,respectively, and the differences were statistically significant (all P<0.05). Conclusions:During radiotherapy after breast-conserving surgery for breast cancer, compared with the single method, the combination of GTVtb-Clip and GTVtb-Seroma can better cover the real tumor bed, thus reducing the omission of tumor bed and recurrence rate. CT position should better take place at 4 to 8 weeks for patients receiving radiotherapy after breast-conserving surgery, and target volume of tumor bed will be delineated based on the postoperative changes of both mental clips and seroma.
4.Mechanism of human umbilical cord mesenchymal stem cells alleviating ischemia-reperfusion injury of hepatocytes through mitochondrial transfer
Jiarou SHAN ; Beibei NI ; Cuiping LI ; Ruixuan XU ; Wenjie CHEN
Organ Transplantation 2021;12(3):294-
Objective To explore the mechanism of human umbilical cord mesenchymal stem cell (HUC-MSC) alleviating ischemia-reperfusion injury (IRI) of liver cells through mitochondrial transfer. Methods Normal human liver cell line L02 was divided into the blank control group, oxygen-glucose deprivation (OGD) group, experimental control group, and L02 and HUC-MSC co-culture group (L02+HUC-MSC group). L02+HUC-MSC group was further divided into 10:1 co-culture subgroup (group A), 4:1 co-culture subgroup (group B), 2:1 co-culture subgroup (group C), 1:1co-culture subgroup (group D) and 1:2 co-culture subgroup (group E) according to different co-culture ratio of L02 and HUC-MSC. The apoptosis rate and relative reactive oxygen species (ROS) level of L02 cells were detected by flow cytometry. The MitoTracker positive rate of L02 cells was detected by flow cytometry. The mitochondrial transfer from HUC-MSC to L02 cells was observed by laser confocal microscope. Results The apoptosis rate and relative ROS level of L02 cells in the OGD group were significantly higher than those in the blank control group (both
5.Application evaluation of a rapid fluorescence quantitative PCR method for the detection of SARS-CoV-2
Peihua NIU ; Yaowu ZHU ; Roujian LU ; Jing PENG ; Na ZHU ; Yanjun LU ; Wenling WANG ; Ming NI ; Wenjie TAN
Chinese Journal of Microbiology and Immunology 2021;41(8):588-591
Objective:To establish and evaluate a rapid nucleic acid detection method for SARS-CoV-2 based on COYOTE ? Flash20 real-time fluorescent quantitative PCR instrument. Methods:A rapid reaction system was constructed by using specific primer and probe sets targeting ORF1ab and N gene of SARS-CoV-2, and the sensitivity and specificity of the system were verified. At the same time, 108 clinical samples of COVID-19 were used to evaluate the application of this method.Results:The detection method did not require nucleic acid extraction, and the manual operation time was only one minute. After the sample was sent to the system, the test could be completed in 30 minutes. The detection limit of this method was 4×10 2 copies/ml. It had no cross-reactivity with other human coronaviruses (including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV and MERS-CoV) and other respiratory viruses. The evaluation of clinical sample application showed that the total coincidence rate with the conventional RT-qPCR which required nucleic acid extraction was 98.15%. Conclusions:Through the application evaluation of the rapid fluorescent quantitative PCR method of SARS-CoV-2, it was found that the method was simple, fast, specific and sensitive, and it was suitable for real-time and rapid detection needs in varieties of situations.
6.Value of thyroid radioactive iodine uptake on predicting the residual activity in patients with differentiated thyroid carcinoma after 131I treatment
Chang CHEN ; Yang SHEN ; Yongxia WU ; Huifeng ZOU ; Wenjie NI ; Tong SUN ; Qian WANG ; Yi YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2020;40(10):595-598
Objective:To explore the value of thyroid radioactive iodine uptake (RAIU) on predicting the residual activity in patients with differentiated thyroid carcinoma (DTC) after administration of 131I. Methods:A total of 178 patients (63 males, 115 females, age: (39.8±11.4) years) with DTC who underwent initial treatment of 131I in Suzhou Science & Technology Town Hospital between August 2018 and April 2019 were enrolled in this retrospective study. RAIU test and thyroid imaging were performed before 131I treatment. Patients were divided into 3 groups according to the thyroid remnant showed by thyroid imaging: no remnant group, a little remnant group, and obvious remnant group. Radiation dose equivalent rates at different time points (immediately/24 h/48 h/72 h after injection of 131I) were measured to estimate the residual activity of 131I after administration. RAIU and residual activity at 72 h among different thyroid remnant groups were compared by one-way analysis of variance. Relationship between RAIU/ 131I therapeutic dose and residual activity at 72 h was analyzed by Pearson correlation analysis. The linear regression equation between RAIU and residual activity at 72 h after treatment was established. Results:The 3 h RAIU in no remnant group ( n=45), a little remnant group ( n=101), and obvious remnant group ( n=32) were (4.77±1.46)%, (5.53±1.70)% and (8.92±3.75)%, respectively ( F=39.35, P<0.01), and the 24 h RAIU was also significantly different among those 3 groups ((1.54±0.88)%, (3.41±2.55)%, (13.52±8.59)%; F=91.52, P<0.01). The residual activity at 72 h in no remnant group, a little remnant group, and obvious remnant group were (81.70±25.61), (108.24±51.58) and (283.07±133.72) MBq, respectively ( F=92.84, P<0.01). There was a significant positive correlation between RAIU and the residual activity at 72 h (3 h: r=0.753, 24 h: r=0.817, both P<0.01). The linear regression equations between RAIU at 3 h and 24 h and the residual activity at 72 h were y=28.88 x-38.42 and y=13.87 x+ 67.01, respectively. When RAIU was higher than 24.01% at 3 h or 15.18% at 24 h, the residual activity at 72 h after treatment was likely to exceed 400 MBq. There was little correlation between 131I therapeutic dose and the residual activity at 72 h after treatment ( r=0.119, P>0.05). Conclusion:RAIU can be used to predict the residual activity at 72 h after treatment in DTC patients who underwent initial 131I treatment.
7.NUP210 and MicroRNA-22 Modulate Fasto Elicit HeLa Cell Cycle Arrest
Qiao GU ; Wenjie HOU ; Huan LIU ; Lijuan SHI ; Zonghao ZHU ; Wenfeng YE ; Xiaoyuan NI
Yonsei Medical Journal 2020;61(5):371-381
Purpose:
Cervical cancer is one of the most fatal diseases among women in under-developed countries. To improve cervical cancertreatment, discovery of new targets is needed. In this study, we investigated the expression of NUP210, miR-22, and Fas in cervicalcancer tissues and their functions in cell cycle regulation.
Materials and Methods:
We detected and compared the expression levels of NUP210, miR-22, and Fas in cervical cancer tissueswith paired normal tissues using immunohistochemistry, Western blot, and real-time quantitative polymerase chain reaction.NUP210 was knocked down in HeLa cells via lentivirus, followed by cell cycle and proliferation analysis. Using a luciferase reporterassay, we explored the link between miR-22 and NUP210. We overexpressed miR-22 in HeLa cells and analyzed cell cycle and proliferationfunction. We then overexpressed miR-22 in NUP210 knockdown cells to explore the connection between Fas and miR-22-NUP210 signaling.
Results:
We found that NUP210 was overexpressed in cervical cancer patients. Knocking down NUP210 restored cell apoptosisand proliferation. We confirmed miR-22 as a regulator of NUP210 and verified that miR-22 was inhibited in cervical cancer development.We also found that restoring miR-22 expression could induce cell apoptosis. Finally, we found that miR-22-regulated expressionof NUP210 could alter Fas expression and, in turn, elicit cell cycle arrest and proliferation.
Conclusion
miR-22 in cervical cancer is downregulated, resulting in NUP210 overexpression and inhibition of Fas-induced cellapoptosis.
8. Research progress on postoperative adjuvant therapy for esophageal carcinoma
Chinese Journal of Radiation Oncology 2019;28(12):945-948
In China, radical esophagectomy remains the main strategy for resectable esophageal cancer. However, the high locoregional recurrence rate and hematogenous metastasis rate are the main causes of surgical failure. Therefore, whether postoperative adjuvant therapy can become one of the important means for esophageal cancer remains controversial. In this article, the research progress on the postoperative recurrent pattern and adjuvant therapy for esophageal carcinoma was reviewed to provide references for clinicians.
9. The value of the planned neoadjuvant radiotherapy or chemoradiotherapy for the non-radical resection of esophageal squamous cell carcinoma
Wenjie NI ; Wei DENG ; Zefen XIAO ; Zongmei ZHOU ; Xin WANG ; Dongfu CHEN ; Qinfu FENG ; Jun LIANG ; Jima LYU ; Nan BI ; Lei DENG ; Tao ZHANG ; Wenqing WANG ; Qi XUE ; Shugeng GAO ; Juwei MU ; Yousheng MAO ; Dali WANG ; Jun ZHAO ; Yushun GAO ; Jinfeng HUANG ; Fengwei TAN ; Liang ZHAO ; Fang LYU ; Guochao ZHANG
Chinese Journal of Oncology 2019;41(4):295-302
Objective:
The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non-radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors.
Methods:
We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy (33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single-institution database.The survival rates were calculated by Kaplan-Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model.
Results:
The median follow-up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease-free survival (DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3-year OS were 75.5%, 57.4%, 27.3% (
10. Study on safety of adjuvant radiotherapy concurrent with weekly chemotherapy for stage ⅡB-ⅣA esophageal carcinoma after radical resection
Wenjie NI ; Shufei YU ; Jinsong YANG ; Wencheng ZHANG ; Zongmei ZHOU ; Hongxing ZHANG ; Dongfu CHEN ; Qinfu FENG ; Jima LYU ; Jun LIANG ; Xiaozhen WANG ; Xin WANG ; Lei DENG ; Wenqing WANG ; Tao ZHANG ; Nan BI ; Zefen XIAO
Chinese Journal of Oncology 2019;41(6):415-420
Objective:
To evaluate the tolerability and short-term efficacy of chemo-radiotherapy in 125 patients with stage ⅡB-ⅣA esophageal carcinoma after radical resection.
Methods:
We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo-radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model.
Results:
122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo-radiotherapy (41.6%), while 73 patients underwent only 1-4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up (6.4%). The 1-year and 3-year overall survival rate were 91.6% and 57.0%, respectively, with a median survival time of 64.4 months. The 1-year and 3-year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo-radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1-2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (

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