Construction and validation of a prognostic model for colon cancer based on inflammatory response-related genes / 肿瘤研究与临床

Objective:To screen the differentially expressed genes (DEG) related to inflammatory response associated with the prognosis of colon cancer based on the bioinformatics approach, and to construct and validate a prognostic model for colon cancer.Methods:RNA sequencing and clinical data of 472 colon cancer patients and normal colon tissues of 41 healthy people were retrieved from the Cancer Genome Atlas (TCGA) database. Gene expression related to prognosis of colon cancer and clinical data were retrieved from the International Cancer Genome Consortium (ICGC) database. The retrieval time was all from the establishment of library to November 2022. A total of 200 genes associated with inflammatory response obtained from the Gene Set Enrichment Analysis (GSEA) database were compared with the RNA sequencing gene dataset of colon cancer and normal colon tissues obtained from the TCGA database, and then DEG associated with inflammatory response were obtained. The prognosis-related DEG in the TCGA database were analyzed by using Cox proportional risk model, and the inflammatory response-related DEG were intersected with the prognosis-related DEG to obtain the prognosis-related inflammatory response-related DEG. The prognostic model of colon cancer was constructed by using LASSO Cox regression. Risk scores were calculated, and colon cancer patients in the TCGA database were divided into two groups of low risk (< the median value) and high risk (≥the median value) according to the median value of risk scores. Principal component analysis (PCA) was performed on patients in both groups, and survival analysis was performed by using Kaplan-Meier method. The efficacy of risk score in predicting the overall survival (OS) of colon cancer patients in the TCGA database was analyzed based on the R software timeROC program package. Clinical data from the ICGC database were applied to externally validate the constructed prognostic model, and patients with colon cancer in the ICGC database were classified into high and low risk groups based on the median risk score of patients with colon cancer in the TCGA database. By using R software, single-sample gene set enrichment analysis (ssGESA), immunophenotyping difference analysis, immune microenvironment correlation analysis, and immune checkpoint gene difference analysis of immune cells and immune function were performed for prognosis-related inflammation response-related DEG in the TCGA database.Results:A total of 60 inflammatory response-related DEG and 12 prognosis-related DEG were obtained; and 6 prognosis-related inflammatory response-related DEG (CCL24, GP1BA, SLC4A4, SRI, SPHK1, TIMP1) were obtained by taking the intersection set. LASSO Cox regression analysis showed that a prognostic model for colon cancer was constructed based on 6 prognosis-related inflammatory response-related DEG, and the risk score was calculated as = -0.113×CCL24+0.568×GP1BA+ (-0.375)×SLC4A4+(-0.051)×SRI+0.287×SPHK1+0.345×TIMP1. PCA results showed that patients with colon cancer could be better classified into 2 clusters. The OS in the high-risk group was worse than that in the low-risk group in the TCGA database ( P < 0.001); the area of the curve (AUC) of the prognostic risk score for predicting the OS rates of 1-year, 3-year, 5-year was 0.701, 0.685, and 0.675, respectively. The OS of the low-risk group was better than that of the high-risk group in the ICGC database; AUC of the prognostic risk score for predicting the OS rates of 1-year, 2-year, 3-year was 0.760, 0.788, and 0.743, respectively. ssGSEA analysis showed that the level of immune cell infiltration in the high-risk group in the TCGA database was high, especially the scores of activated dendritic cells, macrophages, neutrophils, plasmacytoid dendritic cells, T helper cells, and follicular helper T cells in the high-risk group were higher than those in the low-risk group, while the score of helper T cells 2 (Th2) in the high-risk group was lower compared with that in the low-risk group (all P < 0.05); in terms of immune function, the high-risk group had higher scores of antigen-presenting cell (APC) co-inhibition, APC co-stimulation, immune checkpoint, human leukocyte antigen (HLA), promotion of inflammation, parainflammation, T-cell stimulation, type Ⅰ interferon (IFN) response, and type ⅡIFN response scores compared with those in the low-risk group (all P < 0.05). The results of immunophenotyping analysis showed that IFN-γ-dominant type (C2) had the highest inflammatory response score, and the differences were statistically significant when compared with trauma healing type (C1) and inflammatory response type (C3), respectively (all P < 0.05). Immune microenvironment stromal cells and immune cells were all positively correlated with prognostic risk scores ( r values were 0.35 and 0.21, respectively, both P < 0.01). The results of immune checkpoint difference analysis showed there was a statistically significant difference in programmed-death receptor ligand 1 (PD-L1) expression level between high-risk group and low-risk group ( P = 0.002), and PD-L1 expression level was positively correlated with prognostic risk score ( r = 0.23, P < 0.01). Conclusions:Inflammatory response-related genes may play an important role in tumor immunity of colon cancer and can be used in the prognostic analysis and immunotherapy of colon cancer patients.

Downregulation of CDC42 inhibits the proliferation and stemness of human trophoblast stem cell via EZRIN/YAP inactivation.

Placental dysplasia increases the risk of recurrent spontaneous abortion (RSA). However, the underlying mechanism regulating placental development remains unclear. In this study, we showed that the expression of CDC42 was decreased in the villous tissue of RSA samples compared to healthy controls. Further examination demonstrated that CDC42 deficiency led to the differentiation of human trophoblast stem cells (hTSCs) and inhibited their proliferation. Genetic manipulation of YAP and EZRIN in hTSCs revealed that CDC42 regulates the stemness and proliferation of hTSCs; this is dependent on EZRIN, which translocates YAP into the nucleus. Moreover, the expression pattern of EZRIN, YAP, and Ki67 was also abnormal in the villous tissue of RSA samples, consistent with in vitro experiments. In summary, these findings suggest that the CDC42/EZRIN/YAP pathway plays an important role in placental development.

Effect of function of mobile phone use on the self-perceived stress and mobile phone addiction of high vocational students / 中国学校卫生

Objective@#To explore the impact of function of mobile phone use on self-perceived stress and mobile phone addiction of high vocational students, and the mediating role of coping styles between different mobile phone functions and mobile phone addiction.@*Methods@#A total of 911 participants in two vocational colleges in Wuhan and Liaocheng were investigated by using convenient sampling method. Smartphone Usage, Simplified Coping Style Questionnaire, and Stress subscale of Depression-Anxiety-Stress Scale(short version) were administered to participants.@*Results@#Female students scored significantly higher on mobile phone social features (4.77±1.06) than males( t =2.05， P =0.04), while males scored significantly higher on MPATS and DASS-S, Negative Coping Style subscales than females( P <0.01). The social function of the mobile phone was positively related to the positive coping styles( r =0.17, P <0.01). The game features of mobile phone were positively related to negative coping styles, stress and mobile addiction( P <0.01). Negative coping style could positively predict stress and mobile phone addiction( β =0.53, 0.50, P <0.01). Negative coping styles and stress had significant chain mediation effects in nonsocial functions and mobile phone addiction(95% CI =0.06-0.24, P <0.01).@*Conclusion@#Students of vocational college who often use cellphone not for social purpose have higher self-perceived stress. The game function of mobile phones had an adverse effect on the physical and mental health of vocational students. Negative coping style is a powerful predictor of stress and mobile phone addiction.

Near-infrared quantum dots through one-pot aqueous synthesization for bio-imaging and photodynamic therapy of gliomas / 实用医学杂志

Objective To synthesize a quantum dot (QD) to recognize glioma cells for imaging and photodynamic therapy. Methods By one-pot aqueous approach, near infrared-emitting CdTe was produced. After detection of its physicochemical characterizations, RGD was conjugated. Emission images were observed with confocal microscopy. To test its toxicity, CdTe-RGD with various concentrations was separately added into U251 and 3T3 cells for incubation in dark circulation. To test its photodynamic effect, U251 and 3T3 cells were then irradiated for 5 ~ 60 min using 632.8 nm laser. Results The QD (Φ = 3.75 nm, PL peak wavelength =700 nm, PLQY=20%) achieved was a spherical crystal with excellent monodispersity. Under confocal microscope , U251 cells were visualized but 3T3 cells not. In dark circulation, the survival rates of both U251 and 3T3 cells were above 85%. After laser irradiation, the survival rate of U251 cells decreased to (37 ± 1.6)%with the increasing of irradiation time and CdTe-RGD concentration. Conclusion With good physicochemical characterization and low toxicity, CdTe-RGD could be applied in biomedical imaging and photodynamic therapy of gliomas.

The lowest dosages of mifepristone and misoprostol to terminate ultra-early pregnancy / 中华妇产科杂志

Objective To explore the lowest effective dosage of mifepristone combined with misoprostol in terminating ultra-early pregnancy.Methods All the cases of ultra-early pregnancy classified by amenorrhea days,β-hCG and vaginal B-ultrasonic were randomly divided into two groups.One hundred cases in G1 group (minimized dosage) were orally administered 25 mg mifepristone once a day for 2 days and combined with 200 μg misoprostol 48 hours later,while 150 mg mifepristone combined with 600 μg misoprostol 48 hours later were given to 100 cases in G2 group (normal dosage).All cases were observed for 6 hours after taking misoprostol and returned for assessment three days later.Results None missing.Expulsion of conceptus:G1 and G2 group were 22 (22.0％,22/100) and 25 (25.0％,25/100;P ＞ 0.05).Failure rate:cases with incomplete abortion were 1 (1.0％,1/100) and 2 (2.0％,2/100) in G1 and G2 group,hospitalization for suspected ectopic pregnancies both was 1 (1.0％).Bleeding:bleeding cases during the administration of mifepristone in G1 and G2 group were 71 (71.0％,71/100) and 78 (78.0％,78/100; P＞0.05); the mcan bleeding time were (5.3 ± 1.4) days and (6.0± 1.5) days (P ＜0.01).Other side effects:in G1 group,majority showed light nausea (7.0％,7/100) and light abdominal pain (20.0％,20/100).Menses recovery:99 (99.0％,99/100) for G1 group and 98 (98.0％,98/100) for G2 group to recovery on scheduled time.Satisfactions:both were 99 (99.0％,99/100).Except mean bleeding days and side-effects,the differences above showed no significance (P ＞ 0.05).Conclusion It is safe and effective treatment with the lowest dosages of mifepristone and misoprostol to terminate ultra-early pregnancies.