Objective To investigate the incidence of adverse drug reaction (ADR)in patients in a hospital,and evaluate ADR-related factors,so as to provide references for the prevention of ADR and reducing of risk factors in drug use. Methods 223 clinically reported ADR cases were collected from January 1,2011 to December 31,2011, patients'age,types and administration routes of drugs relating to ADR,and ADR-involved organs and systems were analyzed.Results Of 223 patients with ADR,211(94.62% )received intravenous drip,3 received intravenous injec-tion,2 received intramuscular inj ection,and 7 received oral administration. ADR mainly occurred within 1-30 mi-nutes after taking the medicines,39(17.49% )occurred within 1-4 minutes,45(20.18% )within 5-9 minutes,80 (35.87% )within 15-29 minutes. Of organ or system involved by ADR,skin and its appendage damages were com-mon (93 cases),followed by gastrointestinal tract (62 cases)and systemic damage (45 cases);single organ and sys-temic damage were most common (184 cases,82.51% ). 123 cases (55.16% )of ADR were caused by antimicrobial use,60 cases (26.91% )were induced by Chinese medicine injection;Of top 10 ADR-inducing medicines,7 were an-timicrobial agents and 3 were traditional Chinese medicine injections,levofloxacin lactate and sodium chloride injec-tion ranked first(23 cases,10.31% ).Conclusion The occurrence of ADR is related to multiple factors,reporting and surveillance of ADR should be strengthened,the use of antimicrobial agents and traditional Chinese medicine should be rational,thereby reduce the occurrence of ADR.

Objective The aim of this study was to investigate the expression of miR-455-5p in epithelial ovarian cancer and its effect on the development of epithelial ovarian cancer. Methods The miRNA expression data of normal ovarian epithelial tis-sues and epithelial ovarian cancer tissues GSE83693 were downloaded from the GEO database. Differential expression analysis was used to obtain differential expression data of miRNAs in epithelial ovarian cancer. The expression of miR-455 -5p was analyzed whether there is difference expression between normal ovarian epithelium and epithelial ovary cancer tissues; qRT-PCR was used to verify the differential expression prediction results; bio-informatics software was used to analyze the KEGG pathway enrichment and GO gene function annotation of miR-455-5p target genes,and to explore the disorders of dyregulated miR-455-5p in the devel-opment of epithelial ovarian cancer. Results A total of 101 cases of differentially expressed miRNAs were screened,34 cases were up-regulated and 67 cases were down-regulated. Among them,miR-455-5p was down-regulated significantly(P<0. 01),and the different fulds were -2. 9019. The results of qRT-PCR showed that the expression of miR-455-5p in epithelial ovarian cancer cells(SKOV-3,OVCAR-3 and A2780)was significantly lower than that in normal ovarian epithelial cells(IOSE-80),and the dif-ferential expression was statistically significant(P<0. 05). The results of KEGG pathway enrichment analysis showed that miR-455-5p regulated target genes mainly involved in five pathways,including TGF-β signaling pathway,Hippo signaling pathway,ECM-receptor interaction,transcriptional dysregulation pathway in cancer,and chronic granule cellular leukemia,which were associated with tumors. GO functional annotation analysis showed that the target genes regulated by miR-455-5p in the above pathway was mainly involved in protein phosphorylation,promoted cell proliferation and migration,inhibited apoptosis,promoted epithelial-mesenchymal transition,regulated transcription and regulated cell cycle,etc. ,which associated with tumorigenesis. Conclusion The expression of miR-455-5p is down-regulated in epithelial ovarian cancer. The miR-455-5p target genes are involved in the pathogenesis and function of epithelial ovarian cancer,and are associated with the development of epithelial ovarian cancer.

Objective:To investigate the expression of B7 homolog 4 (B7-H4) and its clinical significance in endometrial cancer.Methods:A total of 833 patients with endometrial cancer admitted to Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from 2009 to 2019, were enrolled. The expression of B7-H4, mismatch repair (MMR), p53, programmed cell death ligand 1 (PD-L1) protein, and CD 8+ T lymphocyte density in endometrial cancer tissues were detected by the EnVision two-step method of immunohistochemical staining. First-generation sequencing (Sanger method) was used to determine molecular subtyping of endometrial cancer. The χ2 test was used to compare the differences in positive expression rate of B7-H4 protein in endometrial cancer tissues with different clinicopathological features and molecular subtyping, PD-L1 protein expression, and CD 8+ T lymphocyte density. Survival analyses [including recurrence-free survival (RFS) and disease-specific survival (DSS)] were performed for 664 patients with follow-up time≥3 months, with a median follow-up time of 31 months (range: 4-121 months), and the Cox proportional hazards regression model was used to analyze the relevant factors affecting the prognosis of patients with endometrial cancer. Results:(1) The median age of 833 patients was 58 years (range: 25-88 years); pathological type: 595 with endometrioid carcinoma, 238 with non-endometrioid carcinoma; surgical-pathological staging: 542 cases at stage Ⅰ, 38 cases at stage Ⅱ, 173 cases at stage Ⅲ, and 45 cases at stage Ⅳ. Molecular subtyping was performed in 590 patients, including 50 with POLE mutation, 163 with mismatch repair defect (MMR-d) type, 246 with nospecific molecular change (NSMP) type, and 131 with p53 mutation subtype. (2) B7-H4 protein was expressed with brownish-yellow stainind in the cell membrane and cytoplasm of endometrial carcinoma, and the positivity rate of B7-H4 protein was 71.5% (596/833). The positivity rates of B7-H4 protein among patients with different age, surgical-pathological stage, tumor grade, pathological type, depth of muscular invasion, presence or absence of lymphovascular space invasion, and molecular subtype were significantly different (all P<0.05). The positivity rates of B7-H4 protein among patients with different PD-L1 protein expression and CD 8+ T lymphocyte density were not significantly different ( P>0.05). The 5-year RFS (83.9%) and DSS (87.3%) of B7-H4 protein-positive patients had an increasing trend compared with the 5-year RFS (77.2%) and DSS (78.1%) of B7-H4 protein-negative patients, but there were not statistically significant differences ( P=0.053, P=0.083). (3) Univariate analysis showed that the 5-year RFS and DSS of patients with different age, tumor grade, surgical-pathological stage, pathological type, depth of muscular invasion, lymphovascular space invasion, and molecular subtype were significantly different (all P<0.01). There were no significant differences in 5-year RFS ( P=0.184, P=0.113) and DSS ( P=0.549, P=0.247) among patients with different CD 8+ T lymphocyte density and PD-L1 protein expression. Further analysis according to molecular subtype, the results of CD 8+ T lymphocyte density and PD-L1 protein expression showed that the 5-year RFS and DSS of B7-H4 protein-positive patients were higher than those of B7-H4 protein-negative patients with NSMP subtype, low density of CD 8+ T lymphocyte and PD-L1 protein-negative endometrial carcinoma (all P<0.05), however, there was no significant difference in 5-year DSS between B7-H4 protein-positive patients and B7-H4 protein-negative patients with PD-L1 protein-negative endometrial cancer ( P=0.060). Multivariate analysis showed that positive expression of B7-H4 protein was an independent factor for 5-year RFS ( HR=0.27, 95% CI: 0.09-0.78, P=0.016) and DSS ( HR=0.16, 95% CI: 0.05-0.58, P=0.005) in patients with NSMP subtype endometrial carcinoma. In patients with low-density CD 8+ T lymphocytes endometrial cancer, positive expression of B7-H4 protein was an independent factor for 5-year RFS ( HR=0.45, 95% CI: 0.26-0.80, P=0.006), but it was not an independent factor for 5-year DSS. In patients with PD-L1 protein-negative endometrial cancer, B7-H4 protein was not an independent factor for 5-year RFS. Conclusion:B7-H4 protein expressed highly in endometrial carcinoma tissues, and its high expression is closely related to clinicopathological features, molecular subtype of p53 mutant and NSMP, and the favorable prognosis of patients with low density of CD 8+ T lymphocyte immunophenotype endometrial carcinoma.

Objective: The molecular classification system of endometrial carcinoma (EC) in ‘The Cancer Genome Atlas’ is widely acknowledged for its prognostic utility. Subsequently, more simplified classification system that incorporate DNA polymerase epsilon (POLE) exonuclease domain mutations, mismatch repair deficiencies (MMRd), and abnormal p53 (P53abn) has also demonstrated its clinical utility. These classifications helped identifying a ‘POLE ultramutated’ (POLEmut) category of patients, most of whom show excellent prognoses despite having high-grade ECs. We aimed to investigate the clinicopathological and molecular characteristics of high-grade ECs with POLEmut. Methods: We investigated 414 patients with high-grade ECs (including endometrioid carcinomas grade 3, serous carcinomas, clear cell carcinomas, mixed carcinomas, undifferentiated and dedifferentiated carcinomas, and carcinosarcomas) by sequencing and immunohistochemical staining. Results: Forty-three tumors (10.4%) were classified as POLEmut, including 2 with new, possibly pathogenic POLE mutations at P286C and L424V. These patients had very good prognoses except for 1 with stage IV disease and residual tumor. Eleven patients in this group also had P53abn and 4 had MMRd; molecular analysis revealed that patients with synchronous POLE pathogenic mutation and other mutations had a POLEmut or MMRd phenotype; survival analysis found no difference in prognosis between these patient categories. The prognoses of patients in the POLEmut EC group were not significantly influenced by treatment or risk category. Conclusions Patients with high-grade EC exhibiting POLEmut have very good clinical outcomes, and should be identified urgently in daily work owing to their conflicting morphology. Our findings also provide guidance on subclassifying ECs with poor histological appearance.