Objective:To construct a signature for identifying active tuberculosis (TB) based on the relative expression orderings (REOs) of gene expression within a single sample.Methods:Using peripheral whole blood samples from 75 active TB and 69 latently infected individuals from four datasets as the training set, and highly stable REO patterns were extracted from the gene expression profile of the two groups of samples. Then, the gene pairs that reversed the REO pattern between the two groups were selected, and each gene pair was ranked in descending order based on their reversal degree. Finally, the top k gene pairs with the highest classification accuracy were selected as the signature for independent dataset validation. Results:A signature composed of seven gene pairs, denoted as 7-GPS, was constructed from the training set. The accuracy rate for 7-GPS to distinguish active TB from latently infected samples was 88.89%, and the accuracy rate for distinguishing active TB from normal samples was 90.09%. In the mixed validation data from different detection platforms, the AUC value for distinguishing active TB from latently infected samples was 0.914 (95% CI: 0.881-0.948), and the AUC value for distinguishing active TB from normal samples was 0.934 (95% CI: 0.904-0.964). In addition, the four genes ETV7, BATF2, ANKRD22 and CARD17P from this signature tended to be highly expressed in peripheral blood samples of active TB, and their expression values were significantly related to the duration of anti-tuberculosis treatment in clinical. Conclusion:The 7-GPS signature is robust and suitable for individualized analysis of a single peripheral blood sample. It has certain clinical application potential.

Objective:To construct a signature for identifying active tuberculosis (TB) based on the relative expression orderings (REOs) of gene expression within a single sample.Methods:Using peripheral whole blood samples from 75 active TB and 69 latently infected individuals from four datasets as the training set, and highly stable REO patterns were extracted from the gene expression profile of the two groups of samples. Then, the gene pairs that reversed the REO pattern between the two groups were selected, and each gene pair was ranked in descending order based on their reversal degree. Finally, the top k gene pairs with the highest classification accuracy were selected as the signature for independent dataset validation. Results:A signature composed of seven gene pairs, denoted as 7-GPS, was constructed from the training set. The accuracy rate for 7-GPS to distinguish active TB from latently infected samples was 88.89%, and the accuracy rate for distinguishing active TB from normal samples was 90.09%. In the mixed validation data from different detection platforms, the AUC value for distinguishing active TB from latently infected samples was 0.914 (95% CI: 0.881-0.948), and the AUC value for distinguishing active TB from normal samples was 0.934 (95% CI: 0.904-0.964). In addition, the four genes ETV7, BATF2, ANKRD22 and CARD17P from this signature tended to be highly expressed in peripheral blood samples of active TB, and their expression values were significantly related to the duration of anti-tuberculosis treatment in clinical. Conclusion:The 7-GPS signature is robust and suitable for individualized analysis of a single peripheral blood sample. It has certain clinical application potential.

Objective:To investigate the effects of standardized treatment combined with medical nutrition intervention on blood glucose level, body mass management and glucose metabolism at 3 months postpartum in patients with gestational diabetes mellitus (GDM).Methods:A total of 114 patients with GDM who received treatment in Shunyi District Hospital of Beijing from June 2017 to October 2019 were included in this study. They were randomly divided into observation group ( n = 57) and control group ( n = 57). The control group was treated with standardized therapy, and the observation group was treated with standardized therapy combined with medical nutrition intervention. Blood glucose level, body mass management, glucose metabolism outcomes at 3 months postpartum, pregnancy outcome, and neonatal outcome were compared between the two groups. Results:After treatment, hemoglobin A1c (HbA1c), fasting blood glucose, 2-hour plasma glucose (2hPG) after breakfast, and 2hPG after dinner in the observation group were (5.20 ± 0.34)%, (4.69 ± 0.31) mmol/L, (7.32 ± 2.13) mmol/L, and (7.54 ± 2.36) mmol/L, respectively, which were significantly lower than those in the control group [(6.38 ± 0.42)%, (6.34 ± 0.45) mmol/L, (9.01 ± 2.27) mmol/L, (9.35 ± 2.47) mmol/L, t = 16.48, 22.79, 4.09, 4.00, all P < 0.001]. The increases in body mass and body mass index during pregnancy in the observation groups were (12.19 ± 2.35) kg and (4.52 ± 1.13) kg/m 2, respectively, which were significantly lower than those in the control group [(16.21 ± 2.64) kg, (6.11 ± 1.25) kg/m 2, t = 8.58, 7.12, both P < 0.001]. The abnormal rate of glucose metabolism at 3 months postpartum in the observation group was significantly lower than that in the control group [5.3% (3/57) vs. 8.8% (5/57), χ2 = 0.53, P = 0.462]. The incidences of premature rupture of membranes, polyhydramnios, and cesarean section in the observation group were 5.3% (3/57), 14.0% (8/57) and 15.8% (9/57), which were significantly lower than those in the control group [22.8% (13/57), 35.1% (20/57), 40.4% (23/57), χ2 = 7.27, 6.81, 8.51, all P < 0.05]. There were no significant differences in the incidences of pregnancy-induced hypertension and postpartum hemorrhage between the two groups (both P > 0.05). The incidences of premature births, macrosomia, respiratory distress, neonatal hypoglycemia and hyperbilirubinemia in the observation groups were 5.3% (3/57), 3.5% (2/57), 7.0% (4/57), 3.5% (2/57), 5.3% (3/57), respectively, which were significantly lower than those in the control group [22.8% (13/57), 17.5% (10/57), 21.1% (12/57), 15.8% (9/57), 19.3% (11/57), χ2 = 7.27, 5.96, 5.60, 4.93, 5.21, all P < 0.05). Conclusion:Standardized treatment combined with medical nutrition intervention can effectively reduce blood glucose level in patients with GMD, control body mass, and improve glucose metabolism at 3 months after delivery.

Objective:To investigate the role of cyclo-oxygenase-2 (COX-2) in breast cancer metastasis and its possible mechanism. Methods: A total of 45 cases of primary breast cancer tissues and brain metastatic breast cancer tissues were collected from patients, who underwent mastectomy in Yunnan Cancer Hospital from October 2015 to April 2018, including 30 cases of primary lesions and 15 cases of brain metastasis. qPCR was used to detect the expression of COX-2 in breast cancer tissues and brain metastatic breast cancer tissues. Recombinant viruses with COX-2 over-expression (LV6-COX2) or COX-2 knockdown (LV3-COX2 shRNA1, LV3-COX2 shRNA2) were transfected into human breast cancer MDA-MB-231 cells; After obtaining the stable expression cell lines, the effect of COX-2 expression on the proliferation of MDA-MB-231 cells was detected by CCK-8, and the effects of COX-2 expression on the migration and invasion of MDA-MB-231 cells were detected by scratch test and Transwell assay, respectively. The mRNAand protein expressions of COX-2 in each group were examined by qPCR and WB, respectively. The effect of COX-2 expression on the expression of EMT-related genes in MDA-MB-231 cells was analyzed by qPCR. Results: The expression of COX-2 in tissues of patients with brain metastases was significantly higher than that in patients with primary breast cancer tissues (P<0.01), and it was correlated with tumor TMN stage in breast cancer patients. MDA-MB-231 cell lines with stable COX-2 over-expression/knockout were successfully constructed. Over-expression of COX-2 promoted the migration and invasion of MDA-MB-231 cells (all P<0.01), and significantly increased the expressions of MMP2, MMP1, N-cadherin and vimentin (all P<0.01), but exerted insignificant effect on cell proliferation. The effect of COX-2 silence exerted the opposite effect and promoted cell proliferation (P<0.05). Conclusion: COX-2 is highly expressed in brain metastatic breast cancer tissues, which may promote the migration and invasion of breast cancer MDA-MB-231 cells by regulating EMT processes.

Objective To study the application of contrast-enhanced ultrasonography (CEUS) in the evaluation of the stability of carotid atherosclerotic plaque (CAP).Methods 162 patients with CAP were selected as study group.Meanwhile,34 patients with carotid artery strong echo plaques were selected as control group.The color doppler ultrasound was used to observe the CAP.Results The proportions of lipid type,fiber type,calcification and ulcer plaque in the study group were 21.60%,33.33%,34.57% and 10.37%,which were higher than those of the control group (5.88%,2.94%,2.94% and 2.94%),the differences were statistically significant (χ2=4.537,12.859,13.629 and 3.855,all P<0.05).There were 75 patients of soft plaques,36 patients with mixed plaques,51 patients with hard plaque in 162 patients.The new blood vessels classification in soft plaque group (36.00%,45.33% and 10.33%) were higher than the mixed plaque (30.56%,41.67% and 8.33%) and hard plaque group (31.37%,13.72% and 7.84%).The peak intensity (-86.41±7.81) %,tmax (8.34±1.62)s,mean transit time (24.18±8.67)s in the soft plaque group were significantly lower than the mixed plaque [(-100.73±6.52)%,(9.79±2.14)s and (28.93±9.11)s] and hard plaque patients [(-104.14±6.15)%,(10.23±2.33)s and (30.07±9.48)s],the differences were statistically significant (t=9.518,6.966,2.658,13.592,5.374 and 3.064,all P<0.05),but there were no statistically significant differences between mixed plaque and hard plaque (all P>0.05).The plaque diameter (4.13±0.75)mm diagnosed by CEUS was significantly larger than that of conventional ultrasound [(3.62±1.14)mm],the difference was statistically significant (t=4.757,P=0.000).Conclusion The CEUS can qualitatively detect the atherosclerotic plaque angiogenesis,can quantitatively assess plaque,evaluate the stability of the plaques,and the sensitivity is high.

Objective To estimate the excess relative risk coefficients of stomach cancer for Chinese population attributable to ionizing radiation.Methods The excess relative risk and excess absolute risk coefficients of stomach cancer were estimated based on Life Span Study by using risk models developed by BEIR Ⅶ committee (Biological Effect of Ionizing Radiation).Guided by transportation methods from Life Span Study to Americans,we determined that transportation method for Chinese population includes both multiplicative and additive models with a weight of 0.7 and 0.3 respectively,on an arithmetic scale.Besides,curve fitting was used to obtain sex-age-specific stomach cancer baseline incidence based on Chinese cancer annual report.Then,Chinese excess relative risk coefficients of stomach cancer were obtained by substituting excess relative risk,excess absolute risk of Life Span Study and Chinese baseline incidence rate into risk transportation model.Results Excess relative risk coefficients of stomach cancer for Chinese population are 0.26/Sv for male and 0.64/Sv for female,whose exposure age is 30 years old and cancer age is 60 years old.Coefficients increase with decreased exposure age and cancer age.Conclusions Excess relative risk coefficients of stomach cancer for Chinese population are by larger higher than that of Life Span Study,and their sex-age tendency are similar.

Objective To estimate the averaged excess relative risk(ERR) in Chinese population based on the radiogenic cancer risk of leukemia in Japanese atomic bomb survivor cohort,and to discuss proper method suitable for risk transfer between populations.Methods Based on BEIR Ⅶ radiogenic cancer model and population transfer model,and the 2009 Chinese leukemia baseline rates given in 2012 Chinese Cancer Registry Annual Report,comparison was made of population incidences in seveal countries to adjust the weighting factors.Results The ERR of three subtypes of leukemia as a whole was obtained,and the weighting factors for risk transfer model was assumed.The additive factor for male was 0.2,and the multiplicative factor was 0.8,while the additive factor for female was 0.15,and the multiplicative factor was 0.85.Conclusions For the risk transfer between populations,weighting factor was adjusted as a whole to obtain the ERR value for estimating the risk to Chinese population.The risk transfer method suitable for Chinese population was obtained by using the incidence rate available for Chinese population to directly transfer radiation-induced leukemia risk to Chinese from Japanese.

Objective To investigate the radiosensitization of artesunate on nude mouse transplanted with HeLa cells,and to explore its possible mechanisms.Methods HeLa cells were inoculated into the nude mice to establish tumor model.Mice were randomly divided into 4 groups as blank control,artesunate group,radiation group and artesunate + radiation group when average volume of tumor were about 5 mm × 5 mm× 5 mm.During the term of treatment,the volume of tumors were measured every 2days.After 14 days treatment,the mice were killed and tumor tissues were harvested for flow cytometry to detect the alteration of cell cycle.Meanwhile,the pathological change of the tumor tissue was observed with HE staining method,and the change of expression of cycle regulatory protein Cyclin B1,Cdc2 and Wee1 were detected by Western blot.Results The growth of tumor was significantly inhibited by artesunate combined with radiation and its inhibition rate was 72.34％.Flow cytometry results showed that the percent of cells in G1 phase increased and G2 phase decreased in the artesunate + radiation group compared with those in irradiation group ( t =4.41,4.12,P ＜ 0.05 ).The expression level of Cyclin B1 was obviously increased while that of Wee1 decreased in the artesunate + radiation compared with irradiation group.There was no difference in the expression of Cdc2 among the four groups.Conclusions Artesunate can dramatically increase the radiosensitivity of transplanted tumor of HeLa cells.The possible mechanism might be related to the decreasing G2 phase by regulating the expression of Cyclin B1 and Wee1.

Objective To observe the changes of cell cycle on cancer cells after dihydroartemisinin and X-ray irradiation. Methods Human HeLa cells of cervical cancer with p53 mutation was used and human SiHa cells of cervical cancer with wild p53 was used as control. Flow cytometry was used to detect the effect of dihydroartemisinin (20 and 100 μmol/L) and irradiation (6 Gy)on cell cycle. Western blot was used to measure the levels of cell cycle protein. Results G2 arrest was observed in irradiated HeLa cells, which the proportion of cells in G2 phase was increased from 14.45% to 73. 58% after 6 Gy X-ray irradiation, but it was abrogated by dihydroartemisinin from 73. 58% to 48.31%in HeLa cells, and it had no change on the SiHa cells. The elevated Weel protein and the lowered Cyclin B1 protein were observed with the G2 arrest severity. The expression of radiation-induced Weel protein was suppressed and the Cyclin B1 protein was increased after dihydroartemisinin treatment, which was in accordance with the abrogation of radiation-induced G2 delay. Conclusions The main effect of irradiation on cell cycle of p53 mutated HeLa cells is G2 arrest. Dihydroartemisinin could abrogate it, which is associated with the changes of Weel protein and Cyclin B1 protein. In Siha cells, the main effect of irradiation on cell cycle is G1 arrest, and dihydroartemisinin has no effect on it.

Rhesus retinal vascular endothelial cell line RF/6A cells were treated with human insulin. Cell proliferation, migration, and lumen formation, as well as the expressions of vascular endothelial growth factor-A ( VEGF-A ), VEGF-A receptors, and phosphorylated receptors were measured. Insulin promoted RF/6A cell proliferation, migration, and lumen formation ( all P＜0. 01 ). Insulin increased the expression of VEGF-A mRNA and improved its protein activity ( all P＜0. 05 ), and promoted the expression of VEGFR2 mRNA and its phosphorylation ( both P＜0. 01 ). There was no significant difference in the expression of VEGFR1 mRNA among the groups ( P＞0. 05 ).