Hypoxia-inducible factor-alpha-1 (Hif-lalpha) is an active-transcription nucleoprotein produced in cellular hypoxia condition, and HIF-1 can bring tissues into adaptation reaction when the tissues are in state of hypoxis. Apart from that, the factor is involved in angiogenesis of ovarian tumor, energy metabolism, invasive metabasis of the tumor and prognosis. Therefore, a new treatment of ovarian tumor may rely on the thorough study of the relationship between HIF-1 and the tumor by investigating its expression and mechanism.

Objective To explore the curative effect of the microsurgical excision and spinous process and vertebral plate complex orthotopic replantation to spinal canal plasty for the treatment of spinal canal schwannoma.Methods The clinical data of 18 patients with spinal schwannomas,admitted to our hospital from September 2011 to June 2014,were analyzed retrospectively.All these 18 patients were treated by microsurgical excision and spinous process and vertebral plate complex orthotopic replantation to spinal canal plasty,and were followed up for 3-18 months (mean:10 months).After the surgery,vertebral canal MRI was adopted to evaluate the tumor,and CT three-dimensional reconstruction or X-ray of the spine was used for assessing the vertebral canal formation,and Frankel grading standard was employed to evaluate the recovery of spinal cord function.Results All tumors in 18 patients were excised with the help of a microscope,and no endorachis and nerve roots were damaged during the surgery.After the surgery,the patients showed significantly improved symptoms and signs without the leakage of cerebrospinal fluid,infection of incisional wound,tumor recurrence,spinal stenosis and spinal instability.At 3 months after the surgery,Frankel grading standard was adopted to assess the recovery of the spinal cord function,and the results showed grade D in 4 patients and grade E in 14 patients.Conclusion Microsurgical excision and spinous process and vertebral plate complex orthotopic replantation to spinal canal plasty is an effective way in treating spinal canal schwannoma as it can completely expose the tumor,maximize the excision extension and decrease the spinal cord injury;meanwhile,the spinal canal is formed well and the spine is stable after the surgery.

Objective:To investigate the value of magnetization transfer imaging (MTI) and fat suppression T 2WI (FS-T 2WI) in predicting the clinical activity of Graves ophthalmopathy (GO). Methods:From October 2020 to July 2021, 64 GO patients were prospectively enrolled in the First Affiliated Hospital of Nanjing Medical University. According to the clinical activity score (CAS), the patients were divided into active group (CAS≥3, 39 patients and 78 eyes) and inactive group (CAS<3, 25 patients and 50 eyes). The coronal MTI and FS-T 2WI were scanned for pre-treatment assessment. Magnetization transfer ratio (MTR) of extraocular muscles, and signal intensity ratio (SIR) between extraocular muscles and temporalis were measured, respectively. The independent-sample t-test was used to compare the MTR and SIR between two groups. The correlations between MRI parameters and CAS were analyzed using Spearman correlation analysis. The receiver operating characteristic (ROC) curve was performed to evaluate the value of each and combined parameters for predicting the clinical activity of GO. The DeLong test was used to compare the area under the curve (AUC). Results:The MTR of active group and inactive group were 0.45±0.04 and 0.51±0.04, respectively, the difference was statistically significant ( t=7.62, P<0.001). The SIR were 3.4±0.6 and 2.6±0.5, respectively, and the difference was also statistically significant ( t=-8.20, P<0.001). MTR was negatively correlated with CAS ( r=-0.46, P<0.001), while SIR was positively correlated with CAS ( r=0.63, P<0.001). The AUC of MTR, SIR and the combination of MTR and SIR for predicting the clinical activity of GO were 0.840, 0.845 and 0.905, respectively. The combination of MTR and SIR showed higher performance than MTR or SIR alone, and the differences were statistically significant ( Z=2.61, P=0.009; Z=2.15, P=0.032). Conclusions:The quantitative parameters of MTI and FS-T 2WI, namely MTR and SIR, can be used to evaluate the clinical activity of GO. Integrating MTI and FS-T 2WI can improve the diagnostic efficiency.

Objective To investigate the effect of microRNA-214-3p(miR-214-3p)expression in cancer-associated fibroblasts(CAFs)on the cisplatin sensitivity of ovarian cancer cells and its mechanism.Methods Sixty-four ovarian cancer patients were selected as study subjects and divided into platinum-partially sensitive group and platinum-sensitive group based on progression-free survival after chemotherapy.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the relative expression of miR-214-3p in ovarian cancer tissues from the two groups,and the 2-year survival rates of patients with different clinical characteristics were compared.CAFs and normal ovarian fibroblasts(NFs)were primarily cultured,and qRT-PCR and immunofluorescence experiments were used to detect the expression of miR-214-3p and p62 protein in CAFs and NFs.The expression lev-els of SQSTM1 gene in different types of ovarian cells were searched through the CSIOVDB data-base.CAFs were transiently transfected with miR-214-3p mimic(mimic group)and miR-214-3p mimic NC(NC group),and untransfected CAFs were selected as control group.Cell culture super-natants from each group were collected,and an indirect co-culture model of ovarian cancer cell line SKOV3 with CAFs from each group was established.The CCK-8 method,DCFH-DA method,qRT-PCR,and immunoblotting were used to detect the proliferation rate,half-maximal inhibitory concen-tration of cisplatin(IC50),reactive oxygen species(ROS)content,and relative expression levels of miR-214-3p,cisplatin resistance gene CCND1,and autophagy protein p62 in SKOV3 cells under different culture conditions.Results The relative expression of miR-214-3p was lower in the plati-num-partially sensitive group than in the platinum-sensitive group(P＜0.01).There were statisti-cally significant differences in the 2-year survival rates among patients with different International Federation of Gynecology and Obstetrics(FIGO)stages,platinum partial sensitivity,and low miR-214-3p expression(P＜0.01).The relative expression of miR-214-3p was lower in ovarian CAFs than in NFs,while the expression level of p62 protein was higher in CAFs than in NFs(P＜0.01).Online analysis of the CSIOVDB database showed that the expression level of SQSTM1 gene in ovari-an CAFs was higher than that in ovarian cancer epithelial cells and NFs(P＜0.01).Compared with SKOV3 cells indirectly co-cultured with CAFs in the control group and CAFs in NC group,SKOV3 cells indirectly co-cultured with mimic CAFs showed reduced proliferation rate,cisplatin IC50,and ROS content,increased relative expression of miR-214-3p,and decreased relative ex-pression of CCND1 mRNA and p62 protein(P＜0.01).Conclusion The expression of miR-214-3p in CAFs is correlated with the sensitivity of ovarian cancer cells to cisplatin.Low expression of miR-214-3p in CAFs can promote the proliferation of ovarian cancer cells and ROS-mediated autophagy,thereby reducing the sensitivity of ovarian cancer cells to cisplatin.

Objective To investigate the effect of microRNA-214-3p(miR-214-3p)expression in cancer-associated fibroblasts(CAFs)on the cisplatin sensitivity of ovarian cancer cells and its mechanism.Methods Sixty-four ovarian cancer patients were selected as study subjects and divided into platinum-partially sensitive group and platinum-sensitive group based on progression-free survival after chemotherapy.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the relative expression of miR-214-3p in ovarian cancer tissues from the two groups,and the 2-year survival rates of patients with different clinical characteristics were compared.CAFs and normal ovarian fibroblasts(NFs)were primarily cultured,and qRT-PCR and immunofluorescence experiments were used to detect the expression of miR-214-3p and p62 protein in CAFs and NFs.The expression lev-els of SQSTM1 gene in different types of ovarian cells were searched through the CSIOVDB data-base.CAFs were transiently transfected with miR-214-3p mimic(mimic group)and miR-214-3p mimic NC(NC group),and untransfected CAFs were selected as control group.Cell culture super-natants from each group were collected,and an indirect co-culture model of ovarian cancer cell line SKOV3 with CAFs from each group was established.The CCK-8 method,DCFH-DA method,qRT-PCR,and immunoblotting were used to detect the proliferation rate,half-maximal inhibitory concen-tration of cisplatin(IC50),reactive oxygen species(ROS)content,and relative expression levels of miR-214-3p,cisplatin resistance gene CCND1,and autophagy protein p62 in SKOV3 cells under different culture conditions.Results The relative expression of miR-214-3p was lower in the plati-num-partially sensitive group than in the platinum-sensitive group(P＜0.01).There were statisti-cally significant differences in the 2-year survival rates among patients with different International Federation of Gynecology and Obstetrics(FIGO)stages,platinum partial sensitivity,and low miR-214-3p expression(P＜0.01).The relative expression of miR-214-3p was lower in ovarian CAFs than in NFs,while the expression level of p62 protein was higher in CAFs than in NFs(P＜0.01).Online analysis of the CSIOVDB database showed that the expression level of SQSTM1 gene in ovari-an CAFs was higher than that in ovarian cancer epithelial cells and NFs(P＜0.01).Compared with SKOV3 cells indirectly co-cultured with CAFs in the control group and CAFs in NC group,SKOV3 cells indirectly co-cultured with mimic CAFs showed reduced proliferation rate,cisplatin IC50,and ROS content,increased relative expression of miR-214-3p,and decreased relative ex-pression of CCND1 mRNA and p62 protein(P＜0.01).Conclusion The expression of miR-214-3p in CAFs is correlated with the sensitivity of ovarian cancer cells to cisplatin.Low expression of miR-214-3p in CAFs can promote the proliferation of ovarian cancer cells and ROS-mediated autophagy,thereby reducing the sensitivity of ovarian cancer cells to cisplatin.

HuR (human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization (FP) based high-throughput screening (HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay (EMSA), simulation docking and surface plasmon resonance (SPR). Further, we showed that eltrombopag inhibited cell proliferation of multiple cancer cell lines and macrophages, and the anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells (HUVECs) mediated by macrophages with cell scratch assay and Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.