OBJECTIVE: To explore the reversal effect of mifepristone(MIF) on adriamycin(ADM) resistance in human breast cell line MCF-7/ADM in vitro and in vivo. METHODS: The transplantable models of MCF-7 cells resisting against adriamycin were established in nude mice by subcutaneous implantation to observe the reversal effect of MIF in vivo. The mice were randomly divided into 4 groups: a control group(treated with saline water 0.2 mL intraperitoneally and edible oil 0.5 mL orally), an MIF group (treated with mifepristone 30 mg/kg orally and saline water 0.2 mL intraperitoneally), an ADM group (treated with adriamycin 5 mg/kg intraperitoneally and edible oil 0.5 mL orally) and an ADM+MIF group (treated with ADM 5mg/kg intraperitoneally and mifepristone 30 mg/kg orally every 3 days). Tumor changes were investigated after different drug treatments. The reversal effect of 5 micromol/L MIF in vitro on the ADM resistance cell line MCF-7/ADM and non ADM resistance cell line MCF-7 was determined by 4,5-dimethylthiazol-2-yl (MTT) assay. RESULTS: (1) The inhibitory rate of 5 micromol/L of MIF for both cell lines MCF-7 and MCF-7/ADM was less than 5%, and it had no statistical difference compared with the group that was not treated with MIF(P > 0.05). (2) ADM could inhibit the growth of both MCF-7 and MCF-7/ADM,but the inhibition concentration 50 (IC(50)) of MCF-7 (0.42 mg/L) was obviously less than that of MCF-7/ADM(17.21 mg/L) (P < 0.05). (3) IC(50) of MCF-7/ADM of MIF+ADM group was 1.96 mg/L in vitro, which was significantly less than that in ADM alone group(17.21 mg/L) (P < 0.05), and 5 micromol/L of MIF reversed ADM resistance with fold-reversal of 8.78. (4) MIF had some effect on the inhibition of MCF-7/ADM cell growth in vivo, the xenograft volume in the MIF+ADM group [(232.5149 +/- 309.2377) mm(3)] was significantly smaller than that in the control group[(962.2309 +/- 261.1313) mm(3) ] after the 4 week treatment(P<0.05), and also smaller than that in the MIF group [(778.2846 +/- 42.6919) mm(3)] and in the ADM group [(508.9648 +/- 16.2609) mm(3)](P < 0.05). There was significant inhibition on xenograft weight after MIF combined with ADM treatment in vivo, and the inhibitory rate was 78.0%. CONCLUSION MIF can effectively reverse ADM resistance in human breast cancer cell line MCF-7/ADM both in vitro and in vivo.
Animals ; Breast Neoplasms ; pathology ; Cell Line, Tumor ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; drug effects ; Female ; Humans ; Mice ; Mice, Nude ; Mifepristone ; pharmacology ; Neoplasm Transplantation ; Random Allocation

Objective:To explore effects of T helper type 1 cells (Th1) to T helper type 2 cells (Th2) ratio and the related cytokines on the prognosis of patients with colorectal neoplasms.Methods:A total of 98 colorectal neoplasms patients undergoing the surgery admitted in Suqian Hospital Affiliated to Xuzhou Medical University from December 2015 to December 2017 were enrolled, and all patients were selected as the colorectal cancer group. According to Dukes staging criteria, patients were divided into stage A (25 cases), stage B (30 cases) and stage C (43 cases). In addition, 72 healthy subjects who underwent physical examination in Suqian Hospital Affiliated to Xuzhou Medical University during the same period were selected as the healthy control group. Preoperative venous blood on an empty stomach was extracted from the healthy control group and the colorectal cancer group. Flow cytometry was used to analyze the Th1/Th2 ratio in peripheral blood. The levels of cytokines interferon (IFN)-γ, interleukin (IL)-2, IL-4 and IL-10 in serum samples were detected by using enzyme-linked immunosorbent assay (ELISA). After operation, patients were followed up by telephone or outpatient service. The Th1/Th2 ratio and levels of IFN-γ, IL-2, IL-4 and IL-10 of both groups at different stages of both groups were compared. The correlation between Th1/Th2 ratio and the clinicopathological characteristics of colorectal cancer patients was analyzed. Kaplan-Meier method was used to make survival analysis and Cox regression model was used to analyze influencing factors for overall survival (OS).Results:The Thl/Th2 ratio in colorectal cancer patients was lower than that in the healthy control group (5.13±2.04 vs. 11.82±2.76, t = 18.177, P < 0.01). The lymphovascular invasion and Dukes stage C ratio in patients with decreased Th1/Th2 ratio were higher than those in patients with increased Th1/Th2 ratio ( χ2 values were 16.403, 16.248, both P < 0.01). The levels of IFN-γ and IL-2 in serums of colorectal patients were (95±15) ng/L and (78±10) ng/L, respectively, which were lower than those in the healthy control group [(157±17) ng/L and (123±12) ng/L, t values were 25.160, 26.622, all P < 0.01]. The levels of IL-4 and IL-10 in the colorectal cancer group were (87±16) ng/L and (178±18) ng/L, respectively, which were higher than those in the healthy control group [(46±9) ng/L and (124±12) ng/L] ( t values were 19.577, 22.095, all P < 0.01). The follow-up time ranged from 31.0 to 55.0 months, and the median follow-up time was 37.2 months and the median OS time was 21.0 months. Survival analysis showed that the OS of patients with increased Th1/Th2 ratio was better than that of patients with reduced Th1/Th2 ratio ( χ2 = 7.287, P = 0.007). Multivariate Cox regression analysis showed that lymph node metastasis, tumor stage, and Th1/Th2 ratio were independent influencing factors for OS in colorectal cancer patients ( OR values were 8.541, 3.442, 1.275, all P < 0.05). Conclusion:The imbalance of related cytokines secreted by Th1 and Th2 cells and the decrease in the ratio of Th1/Th2 are related to the progression and the poor prognosis of colorectal cancer.

Objective To establish an evaluation index system that can be used for medical quality assessment in clini-cal departments.Methods Based on literature analysis and key informant interview,the Delphi method was used to analyze the-importance and operability of the evaluation index system of medical quality in clinical departments.Results A clinical depart-ment medical quality assessment and evaluation system was established,consisting of 3 primary indicators,14 secondary indica-tors,and 24 tertiary indicators.Conclusion By building a medical quality assessment and evaluation index system in clinical departments,a simple,standardized,and highly operational management model is established for medical institutions to carry out medical quality management.It is conducive to directing clinical departments to focus on medical quality management,improving their medical quality awareness and management level,and promoting the high-quality development of public hospitals.

OBJECTIVE To provide reference for strengthening the standardized management of off-label drug use in cancer hospitals. METHODS The evaluation system for off-label drug use was established to standardize the application， approval， and filing process for off-label drug use in our hospital. The changes in off-label drug application quantity， proportion， disease category and drug category in our hospital were compared before （October 1st， 2021-September 30th， 2022） and after （October 1st， 2022- September 30th， 2023） the establishment of the evaluation system； drug items supported by high-level evidence screened by pharmacy department were analyzed statistically. RESULTS The number of off-label drug use applications in our hospital had gradually increased， from 306 pieces in the fourth quarter of 2021 to 3 828 pieces in the third quarter of 2023. In the year before the construction of the evaluation system， there were a total of 4 482 applications for off-label drug use， and in the year after the construction of the evaluation system， there were 11 840 applications for off-label drug use. After the construction of the evaluation system， the proportion of unregistered off-label drug use significantly decreased， compared to the same period last year （P＜0.05）. Among them， there were no unregistered applications for off-label drug use for digestive system tumors， head and neck tumors， and radioactive drugs； lymphoma， breast tumors，urogenital system tumors， cytotoxic drugs and new anti-tumor drugs all had a decrease of over 70% in unregistered off-label drug applications. Twenty-seven off-label drug use items related to 19 drugs supported by high-level evidence were screened by the pharmacy department of our hospital， among which 25 items were drug use beyond indication. CONCLUSIONS The establishment of off-label drug use evaluation system in cancer hospital is helpful to the rational use and refined management of clinical anti-tumor drugs.