ObjectiveTo observe the effects ofYushen Zhuyun Prescription on ovarian morphology and sex hormone of rats with decreased ovarian reservation (DOR) induced by tripterygium glycosides; To explore its mechanism of action.Methods Tripterygium glycosides solution was used to establish DOR model rats by gastric gavage. 48 female SD rats were randomly divided into blank group, model group, positive medicine group andYushen Zhuyun Prescription low-, medium- and high-dose groups.Yushen ZhuyunPrescription groups were given the low, medium, high dosagesYushen Zhuyun Prescription liquid; positive medicine group were given estradiol valerate liquid; model group and blank control group were given normal saline with the same amount, by gavage 2 times per day for 14 consecutive days. The general condition of the rats was observed; ovarian was weighed and the viscera index was calculated; ovarian morphology was observed by HE staining; the levels of serum estradiol (E2), follicle stimulating hormone (FSH) and testosterone (T) were detected by radioimmunoassay; the levels of inhibin B (INHB) and anti Mullerian hormone (AMH) were detected by ELISA.Results Compared with the blank group, ovarian tissue atrophied; the number of follicles was reduced; ovarian index and the level of E2, INHB and AMH decreased; the levels of FSH and LH increased in the model group (P<0.01). Compared with the model group, ovarian tissue morphology improved significantly; the number of follicle and corpus luteum increased; follicular atresia was reduced; ovarian index and the levels of E2, INHB, and AMH increased; the levels of FSH and LH decreased in Yushen Zhuyun Prescription high-dose group (P<0.01). INHB and AMH had significant correlation (P<0.01). ConclusionYushen Zhuyun Prescription can regulate hormone levels, promote the growth and secretion of follicle, and inhibit follicular atresia, thereby improve ovarian reserve function.

Objective To investigate the clinical efficacy of neoadjuvant chemotherapy combined with radical gastrectomy for advanced gastric cancer.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 73 patients who underwent neoadjuvant chemotherapy combined with radical gastrectomy for advanced gastric cancer at the First Affiliated Hospital of Zhejiang University between June 2004 and December 2009 were collected.Neoadjuvant chemotherapy regimens included XELOX and FOLFOX.Patients received radical gastrectomy within 2 weeks after the completion of the last cycle of neoadjuvant chemotherapy and then continued to undergo postoperative neoadjuvant chemotherapy.Observation indicators:(1) adverse event of neoadjuvant chemotherapy;(2) surgical and postoperative situations;(3) follow-up situations.Follow-up using outpatient examination and telephone interview was performed to detect survival of patients up to December 2014.Measurement data with skewed distribution were described as M (range).Overall survival time was from the beginning of treatment to death or end of follow-up (patients with loss to follow-up).Progression-free survival time was from the beginning of treatment to tumor progression,recurrence and metastasis or death.The survival curve was drawn by the Kaplan-Meier method.Results (1) Adverse event of neoadjuvant chemotherapy:of 73 patients,38 received XELOX regimens and 35 received FOLFOX regimens,with a median cycle of 3 (range,1-7 cycles).There were 55 adverse events during neoadjuvant chemotherapy,including 47 with grade 1-2 and 8 with grade 3-4.(2) Surgical and postoperative situations:all the 73 patients underwent successful D2 radical gastrectomy for gastric cancer,including 40 receiving total gastrectomy,31 receiving distal gastrectomy,1 receiving total gastrectomy with transverse colon resection and 1 receiving distal gastrectomy with cholecystectomy.Of 73 patients,10 with postoperative complications were improved by conservative treatment,including 3 with pleural effusion,2 with peritoneal effusion,2 with anastomotic bleeding,2 with cholecystitis and 1 with lympha fistula.No patient received reoperations or died within 30 days postoperatively.Pathological TNM staging:22 patients were detected in stage Ⅰ-Ⅱ,45 in stage Ⅲ,4 in stage Ⅳ and 2 in stage T0N1M0.Three patients (in stage T0N0M0) had complete remission.Forty-three patients underwent postoperative chemotherapy.(3) Followup:all the 73 patients were followed up for 8-125 months,with a median time of 51 months.The median survival time,5-year overall survival rate and 5-year disease-free survival rate of 73 patients were 52 months,41.1％ and 34.2％,respectively.Conclusion XELOX and FOLFOX regimens of neoadjuvant chemotherapy combined with radical gastrectomy for advanced gastric cancer are safe and effective.

Purpose: This study aimed to investigate the prognostic value of lymph node ratio (LNR) in patients with locally advanced gastric cancer who received neoadjuvant chemotherapy. Materials and Methods: We retrospectively enrolled gastric cancer patients treated with neoadjuvant chemotherapy and curative surgery at the First Affiliated Hospital of Zhejiang University from 2004 to 2015 as the study cohort. Patients with the same inclusion criteria treated in 2016–2017 were enrolled as the validation cohort. Kaplan-Meier curves were assessed using the log-rank test to analyze the differences in overall survival (OS).Multivariate survival analysis was performed using the Cox proportional hazards model.The areas under the receiver operating characteristic curve of ypN and LNR categories for predicting the actual 3-year OS were compared. Results: A total of 265 patients were included in the proposal cohort. The median number of retrieved lymph nodes (rLNs) was 32. The number of positive lymph nodes (pLNs) increased as rLN increased (P=0.037), but the LNR remained relatively constant (P=0.462). The LNR was categorized into 4 groups according to the prognosis: ypNr0, node-negative with rLN>25; ypNr1, node-negative with rLN≤25 or 00.3. In the validation cohort of 43 enrolled patients, there was a clear distinction in OS that significantly (P<0.001) varied depending on the LNR values and LNR was the only independent prognostic factor in multivariate analysis (P<0.001). Conclusions LNR was an independent prognostic factor for survival of patients with gastric cancer after preoperative chemotherapy and might be an alternative predictor for ypN stage.

Objective:To investigate the effect of circ-PRKDC on lung cancer cell proliferation, apoptosis and radiosensitivity and its molecular mechanism.Methods:Normal lung epithelial cells BEAS-2B and lung cancer cell lines NCI-H1299, NCI-H2170, NCI-H1975 were cultured. NCI-H1299 cells were divided into the si-NC, si-PRKDC, pcDNA-NC, pcDNA-PRKDC, miR-NC, miR-505-3p, anti-miR-NC, anti-miR-505-3p, si-PRKDC+ anti-miR-NC and si-PRKDC+ anti-miR-505-3p groups. RT-qPCR was used to detect the expression levels of circ-PRKDC and miR-505-3p. Western blot was employed to measure the protein expression. MTT was used to detect cell proliferation. Flow cytometry was utilized to detect cell apoptosis. Plate clone formation assay was conducted to detect the cell radiosensitivity. Dual luciferase reporter assay was performed to analyze the targeting relationship between circ-PRKDC and miR-505-3p.Results:Compared with normal lung epithelial cells BEAS-2B, the expression levels of circ-PRKDC in the lung cancer cell lines NCI-H1299, NCI-H2170 and NCI-H1975 were significantly up-regulated (3.65, 3.10, 2.67 vs. 1.00, all P<0.05), whereas those of miR-505-3p were significantly down-regulated (0.42, 0.50, 0.54 vs. 1.02, all P<0.05). After low expression of circ-PRKDC, the expression level of CyclinD1 was significantly down-regulated (0.42 vs. 0.81, P<0.05), whereas those of Cleaved-caspase-3(0.71 vs. 0.33, P<0.05) and γ-H 2AX (0.89 vs. 0.46, P<0.05) were significantly up-regulated, the cell A value was significantly decreased (0.413 vs. 0.839, P<0.05), cell apoptosis rate was significantly increased (20.35 vs. 6.21, P<0.05), cell survival fraction was significantly decreased ( P<0.05), and β-catenin expression was significantly down-regulated (0.35 vs. 0.73, P<0.05). After high expression of miR-505-3p, the expression level of CyclinD1 was significantly down-regulated (0.34 vs. 0.83, P<0.05), those of Cleaved-caspase-3(0.65 vs. 0.32, P<0.05) and γ-H 2AX (0.96 vs. 0.45, P<0.05) were significantly up-regulated, the cell A value was significantly decreased (0.386 vs. 0.851, P<0.05), the apoptosis rate was significantly increased (16.38 vs. 6.20, P<0.05), and the cell survival fraction was significantly decreased ( P<0.05). Compared with miR-NC, the luciferase activity of miR-505-3p group transfected with circ-PRKDC wild-type reporter plasmid was significantly decreased (0.44 vs. 1.00, P<0.05). Down-regulation of miR-505-3p could reverse the effect of low expression of circ-PRKDC on the proliferation, apoptosis, radiosensitivity and β-catenin expression of NCI-H1299 cells. Conclusion:Low expression of circ-PRKDC may inhibit lung cancer cell proliferation, promote cell apoptosis and enhance cell radiosensitivity by up-regulating miR-505-3p, which is probably associated with the Wnt/β-catenin signaling pathway.

Objective:To evaluate the effect of circLPAR3 on the radiosensitivity of esophageal cancer cells and investigate its mechanism.Methods:The cancer tissues and and adjacent tissues of 37 patients with esophageal cancer were collected, and esophageal cancer cell lines Eca-109, EC9706 and KYSE30 and esophageal epithelial cells HET-1A were cultured in vitro. The expression levels of circLPAR3 and miR-1238 in the tissues and cells were measured by RT-qPCR. Eca-109 cells were transfected with circLPAR3 siRNA and miR-1238 mimics or co-transfected with circLPAR3 siRNA and miR-1238 inhibitor. Cell cloning experiment was conducted to evaluate the effects of silencing circLPAR3, overexpressing miR-1238, or silencing both circLPAR3 and miR-1238 on the radiosensitivity of Eca-109 cells. After Eca-109 cells that silenced circLPAR3, overexpressed miR-1238 or silenced both circLPAR3 and miR-1238 were exposed to 4 Gy irradiation, CCK-8 assay (A value), flow cytometry and Western blot were employed to assess the effects of silencing circLPAR3, overexpressing miR-1238, or silencing both circLPAR3 and miR-1238 combined with 4 Gy irradiation on the proliferation and apoptosis of Eca-109 cells and the expression levels of CyclinD1, p21, Bcl-2 and Bax proteins. Dual luciferase reporter gene experiment and RNA pull down experiment were performed to verify the regulatory relationship between circLPAR3 and miR-1238. Results:Compared with adjacent tissues, the expression level of circLPAR3 was up-regulated in the esophageal cancer tissues ( P<0.05), while that of miR-1238 was down-regulated ( P<0.05). Compared with HET-1A cells, the expression levels of circLPAR3 were up-regulated in the esophageal cancer cell lines Eca-109, EC9706 and KYSE30(all P<0.05), whereas those of miR-1238 were down-regulated (all P<0.05). Silencing circLPAR3 or overexpressing miR-1238 reduced the survival fraction of Eca-109 cells (all P<0.05), and the sensitization ratio was 1.21 and 1.75, respectively. Silencing circLPAR3 or overexpressing miR-1238 decreased the A value of Eca-109 cells and the expression levels of CyclinD1 and Bcl-2 proteins (all P<0.05), while increased the apoptosis rate of Eca-109 cells and the expression levels of p21 and Bax proteins (all P<0.05). After silencing circLPAR3 or overexpressing miR-1238 combined with 4 Gy irradiation, the A value of Eca-109 cells and the expression levels of CyclinD1 and Bcl-2 proteins were decreased (all P<0.05), while Eca-109 cell apoptosis rate and the expression levels of p21 and Bax proteins were increased (all P<0.05). circLPAR3 targeted and negatively regulated the expression level of miR-1238 in Eca-109 cells. After silencing miR-1238 and circLPAR3 simultaneously, the survival fraction of Eca-109 cells was higher than that when only silencing circLPAR3, and the sensitization ratio was 0.59. Silencing miR-1238 reversed the effects of silencing circLPAR3 combined with 4 Gy irradiation on the proliferation and apoptosis of Eca-109 cells. Conclusion:circLPAR3 is highly expressed in esophageal cancer tissues and cell lines, and silencing the expression of circLPAR3 can inhibit the proliferation of esophageal cancer Eca-109 cells, promote their apoptosis, and enhance cell radiosensitivity by up-regulating miR-1238.