Objective To analyze the expression and significance of adiponectin in serum and placenta tissue in preeclampsia pregnancy women.Methods Serum adiponectin levels were measured by Enzyme-linked immuno sorbent assay (ELISA) in 52 cases of normal pregnant women (control group),58 cases of mild preeclampsia pregnancy women (mild preeclampsia group),and 55 cases of severe preeclampsia pregnancy women (severe preeclampsia group).Insulin resistance was estimated using the homeostatic model assessment-insulin resistance index (HOMA-IR).The expression of adiponectin in placenta tissue was detected by immunohistochemical SP methods in three groups.Results Fasting glucose level in severe preeclampsia group was higher than that in control group and mild preeclampsia group [(5.56 ± 1.37) mmol/L vs.(4.55 ± 0.51),(4.68 ± 0.66) mmol/L],fasting insulin level and HOMA-IR in mild preeclampsia group and severe preeclampsia group were higher than those in control group [(14.19 ±3.42),(14.90 ±6.64) mU/L vs.(9.87 ± 1.75) mU/L,1.04 ±0.37,1.18 ±0.56 vs.0.67 ±0.21],serum adiponectin level in severe preeclampsia group was higher than that in control group and mild preeclampsia group [(15.79 ± 4.86) mg/L vs.(11.47 ±3.50),(11.92 ± 2.96) mg/L],the differences were statistical significance (P ＜ 0.05).There was no difference of adiponectin expression levels in placenta tissue among three groups (P ＞0.05).There was no significant correlations between serum adiponectin level and HOMA-IR,expression levels of adiponectin in placenta tissue(P ＞ 0.05).Conclusions Serum adiponectin levels and HOMA-IR are higher in the severe preeclampsia pregnancy women.Increased serum adiponectin levels may be an appropriate feedback regulation in preeclampsia pregnancy women.

Objectives To investigate the effect of bilateral arcuate artery suture hemostasis of corpus uteri (haemostasia) for postpartum hemorrhage due to uterine inertia during caesarean section,and to explore the change of blood vessels and blood flow of the uterus after surgery.Methods From May 2009 to Dec.2011,the 212 patients in No.202 People's Liberation Army Hospital received bilateral arcuate artery suture hemostasis of corpus uteri for postpartum hemorrhage due to uterine inertia during caesarean section.Among them,127 patients who failed to respond to conservative management and received haemostasia were defined as the ‘ haemostasia' group.23 patients who received the suture after they failed to respond to conservative management and other conventional surgical hemostasis were defined as the ‘ other +haemostasia' group.62 patients who received the suture simultaneously with conservative management were defined as the ‘ drug + haemostasia' group.The suture was done by the following steps:(1) The uterus should be exteriorised,and the fundus of uterus should be towards the head.(2)Transfix the anterior and posterior wall of corpus uteri with big blunt round needle and absorbable suture.The entry point was 2 cm above the uterine incision and 2 cm to lateral border of corpus uteri.The suture spanned the fundus of uterus,and was stretched tightly in front of the fundus,then tied knots were made.Bleeding volume,prompt hemostatic rate,effect rate,total effect rate and operation time were recorded.The resistance index (RI) of uterine artery,systolic/ diastolic blood pressure (S/D),the visualization ratio of uterine artery and the mean value of artery diameter were obtained through color Doppler ultrasonography and enhancement CT 6-12 months after the surgery.Results (1) In the ‘ drug + haemostasia' group,the bleeding volume was (532 ±28) ml.The operation time was (34 ± 3) min,and the prompt hemostatic rate was 97％.While the ‘ haemostasia' group had more bleeding volume,longer operation time and lower prompt hemostatic rate than the ‘ drug + haemostasia' group,with no statistically significant difference (P ＞ 0.05).In ‘ other + haemostasia' group,the bleeding volume was (1379 ± 95) ml.The operation time was (79 ± 15) min,and the prompt hemostatic rate was 78％.The differences were significant when compared to the other groups (P ＜ 0.01).There was no statistically significant difference on total effect rate among the three groups (P ＞ 0.05).(2) There was no statistically significant difference on the RI and S/D of bilateral uterine artery among all the groups 6-12 months after the surgery.(3)The visualization ratio of left uterine artery of the ‘ other + haemostasia' group was lower (87％) than the ‘ haemostasia' group (97％) and the ‘ drug +haemostasia' group (95％,P ＜ 0.05).There was no statistically significant difference between the ‘ haemostasia' group and the ‘ drug + haemostasia' group on the visualization ratio of bilateral uterine artery and the mean value of bilateral uterine artery diameter (P ＞ 0.05).Conclusions The bilateral arcuate artery suture hemostasis of corpus uteri is a simple,rapid,effective and safe method to control postpartum hemorrhage due to uterine inertia during caesarean section.The ovary and uterine blood flow are not affected after the surgery.

Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employ-ing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically reg-ulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

Ataxia telangiectasia mutated (ATM) kinase plays an essential role in the maintenance of genomic stability. ATM-deficient (ATM(-/-)) mice exhibit hematopoietic stem cell (HSC) dysfunction and a high incidence of lymphoma. Gadd45a controls cell cycle arrest, apoptosis and DNA repair, and is involved in the ATM-p53 mediated DNA damage response. However, the role of Gadd45a in regulating the functionality of ATM(-/-) HSCs is unknown. Here we report that Gadd45a deletion did not rescue the defects of T-cells and B-cells development in ATM(-/-) mice. Instead, ATM and Gadd45a double knockout (ATM(-/-) Gadd45a(-/-)) HSCs exhibited an aggravated defect in long-term self-renewal capacity compared to ATM(-/-) HSCs in HSC transplantation experiments. Further experiments revealed that the aggravated defect of ATM(-/-) Gadd45a(-/-) HSCs was due to a reduction of cell proliferation, associated with an accumulation of DNA damage and subsequent activation of DNA damage response including an up-regulation of p53-p21 signaling pathway. Additionally, ATM(-/-) Gadd45a(-/-) mice showed an increased incidence of hematopoietic malignancies, as well as an increased rate of metastasis than ATM(-/-) mice. In conclusion, Gadd45a deletion aggravated the DNA damage accumulation, which subsequently resulted in a further impaired self-renewal capacity and an increased malignant transformation in ATM(-/-) HSCs.
Animals ; Ataxia Telangiectasia Mutated Proteins ; genetics ; B-Lymphocytes ; pathology ; Cell Cycle Proteins ; genetics ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; DNA Damage ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; metabolism ; pathology ; Leukemia ; genetics ; pathology ; Lymphoma ; genetics ; pathology ; Mice, Knockout ; Neoplasm Metastasis ; Nuclear Proteins ; genetics ; T-Lymphocytes ; pathology ; Tumor Suppressor Protein p53 ; metabolism

Objective:To explore the chronic toxicity and its potential mechanism of multi-walled carbon nanotube (MWCNT) in human pleural mesothelial cells.Methods:A sustainable exposure of MeT-5A cells to MWCNT at 10 μg/cm 2 for one year was conducted in 2016. During the exposure, the cell images and cell proliferation was recorded every 4 weeks. The cell apoptosis, cell cycle, cell migration and cell invasion were compared between the control cells and the cells after MWCNT exposure. Finally, the gene expression was screened with Affymetrix clariom D assay, and some of the significantly differential expressed genes was verified by RT-PCR. Results:Compared with the control group, the proliferation ability of the cells in the 1-year exposed group was significantly increased, and the rate of proliferation was about 2-3 times as that in the Control Group ( F=481.32, P<0.05) . MeT-5A cells all showed cell cycle arrest effect, which showed the increase of G1 phase and the decrease of s phase and G2 phase ( F=14.94, P<0.05) . The apoptosis rate of cells in the treated group was significantly higher than that in the control group after 6 months ( F=15.12, P<0.05) , but the early apoptosis rate and the total apoptosis rate of cells in the treated group were not significantly different from those in the control group after 1 year ( F=3.97, P<0.05) . The cell migration and invasion were both promoted by MWCNT. Furthermore, the differentially expressed genes was screened, to find 2, 878 genes with more than 2 folds changes. To further verified, RT-PCR was conducted with PIK3R3、WNT2B、VANGL2、ANXA1, and their expression changes were consistent with above. Conclusion:MWCNT might have a carcinogenic potential to MeT-5A cells after the long term exposure.

Objective:To explore the chronic toxicity and its potential mechanism of multi-walled carbon nanotube (MWCNT) in human pleural mesothelial cells.Methods:A sustainable exposure of MeT-5A cells to MWCNT at 10 μg/cm 2 for one year was conducted in 2016. During the exposure, the cell images and cell proliferation was recorded every 4 weeks. The cell apoptosis, cell cycle, cell migration and cell invasion were compared between the control cells and the cells after MWCNT exposure. Finally, the gene expression was screened with Affymetrix clariom D assay, and some of the significantly differential expressed genes was verified by RT-PCR. Results:Compared with the control group, the proliferation ability of the cells in the 1-year exposed group was significantly increased, and the rate of proliferation was about 2-3 times as that in the Control Group ( F=481.32, P<0.05) . MeT-5A cells all showed cell cycle arrest effect, which showed the increase of G1 phase and the decrease of s phase and G2 phase ( F=14.94, P<0.05) . The apoptosis rate of cells in the treated group was significantly higher than that in the control group after 6 months ( F=15.12, P<0.05) , but the early apoptosis rate and the total apoptosis rate of cells in the treated group were not significantly different from those in the control group after 1 year ( F=3.97, P<0.05) . The cell migration and invasion were both promoted by MWCNT. Furthermore, the differentially expressed genes was screened, to find 2, 878 genes with more than 2 folds changes. To further verified, RT-PCR was conducted with PIK3R3、WNT2B、VANGL2、ANXA1, and their expression changes were consistent with above. Conclusion:MWCNT might have a carcinogenic potential to MeT-5A cells after the long term exposure.

Objective To investigate noninvasive hemodynamic system in monitoring the hemodynamic trends caused by oxytocin and key time points during cesarean section.Methods Forty pregnant women who tmderwent an elective caesarean section were included in this study.We administered 10 U oxytocin via intravenous infusion at 5 U/h and 10 U into the Murphy's dropper after fetal delivery.Systolic blood pressure (SBP),diastolic blood pressure (DBP),mean arterial pressure (MAP),and heart rate (HR) were measured immediately,and every 10 seconds in the following 180 seconds.All 40 pregnant women were monitored using the noninvasive hemodynamics system.In 20 of these women,simultaneous measurements of invasive blood pressure (IBP) were performed at the same time.Results SBP,DBP,and MAP declined at 20 seconds after oxytocin was administered and reached their minimum values at 50 to 60 seconds.The values returned to normal at 120 seconds (P＜ 0.05),with statistically significant differences (P ＜ 0.05).HR started to increase at 30 seconds,peaked at 60 seconds,and returned to normal at 100 seconds (P ＜0.05),with statistically significant differences (P ＜ 0.05).However,no statistically significant differences in SBP,DBP,and HR were observed between the invasive and noninvasive hemodynamic systems (P ＞ 0.05).Conclusion Application of 10 U of intravenous oxytocin and 10 U oxytocin infusion led to the most significant hemodynamic change within 60 seconds.SBP,DBP,MAP,and HR returned to normal within a short time (120 seconds),without special treatment.

Purpose: 5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy forpatients with advanced colorectal cancer, but many patients still suffer from treatment failuredue to 5-Fu resistance. Emerging observations revealed the important role of chemokine(C-X-C motif) ligand 13 (CXCL-13) in tumor microenvironment and its relationship with prognosisin patients with colorectal cancer. This study is designed to reveal the important roleof CXCL-13 in causing colorectal cancer resistance to 5-Fu. Materials and Methods: CXCL-13 levels of patient's serum or cell culture supernatants were measured separatelyby enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell CountingKit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expressionin cells while its antibody and siRNA were used to reduce CXCL-13 expression in cells. Results: In this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culturemedium exchange experiments and cytokine arrays of colorectal cancer resistant and nonresistantcells. Clinical studies showed that CXCL-13 is highly expressed in the serum of5-Fu–resistant patients. High levels of serum CXCL-13 also predict a worse clinical outcome.The addition of recombinant CXCL-13 cytokine resulted in 5-Fu resistance, while its antibodyovercame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced5-Fu resistance, which can be saved by added recombination CXCL-13. Conclusion These results not only identify a CXCL-13 mediated 5-Fu resistance mechanism but alsoprovide a novel target for 5-Fu–resistant colorectal cancer in prevention and treatmentstrategies.

AIM:To investigate the role and molecular mechanisms of SMARCA4(SWI/SNF-related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 4)in ferroptosis.METHODS:(1)Human fi-brosarcoma HT1080 cells were treated with dimethyl sulfoxide(DMSO)and different concentrations(31.25,62.5 and 125 nmol/L)of Ras-selective lethal small molecule 3(RSL3;ferroptosis inducer).Each treatment had 3 replicate wells of cells.The protein levels of SMARCA4 were detected by Western blot.(2)Two small interfering RNAs(siSMARCA4-1 and siSMARCA4-2)were constructed according to the SMARCA4 gene sequence.After SMARCA4 knockdown,each treat-ment had 3 replicate wells of cells,and the protein levels of SMARCA4 were determined by Western blot.Effects of DMSO,necrostatin 2 racemate(Nec-1s;necroptosis inhibitor),Z-VAD(OMe)-FMK(Z-VAD,pan-caspase inhibitor/apoptosis inhibitor)and ferrostatin-1(Fer-1,ferroptosis inhibitor)on cell viability were assessed using high-content analy-sis.The levels of ferroptosis indicators,including prostaglandin-endoperoxide synthase 2(PTGS2)transcription,lipid peroxidation,reactive oxygen species(ROS),labile iron pool(LIP)and glutathione,were determined by RT-qPCR and flow cytometry.The mRNA expression levels of pivotal iron metabolism genes,ferroptosis-related ROS regulatory genes,and cholesterol synthesis-related genes were measured using RT-qPCR.Impact of cholesterol on the cell viability were as-sessed using high-content analysis.(3)Common differential gene analysis and gene ontology(GO)enrichment analysis were performed on published online data.RESULTS:(1)Treatment with RSL3 significantly reduced the protein level of SMARCA4(P＜0.05).(2)Knockdown of SMARCA4 resulted in ferroptosis.(3)Knockdown of SMARCA4 did not induce ferroptosis by modulating the LIP and the transcription levels of ROS-related genes.(4)Knockdown of SMARCA4 affected the pathways associated with the cell membrane,lipid raft,and cholesterol synthesis.(5)Addition of cholesterol to cell culture medium rescued the ferroptosis induced by SMARCA4 knockdown(P＜0.01).CONCLUSION:Treatment with RSL3 reduces the protein level of SMARCA4 in human fibrosarcoma HT1080 cells,and inhibition of cholesterol synthesis by SMARCA4 knockdown leads to the ferroptosis of HT1080 cells.

Objective:To investigate the inhibitory effect and molecular mechanism of microRNA-30d (miR-30d) in the process of proliferation, migration and invasion of malignant mesothelioma cell line MSTO-211H.Methods:In April 2017, the human MSTO-211H cells was used to establish miR-30d overexpressed MSTO-211H cell model by transfection of miR-30d mimics. The qRT-PCR was performed to detect the expression level of miR-30d in the cells transfected miR-30d mimics. The effects of miR-30d on the proliferation, apoptosis, migration and invasion of MSTO-211H cells were analyzed by CCK-8 experiment, flow cytometry, cell scratch experiment and Transwell method.Results:After transfection of miR-30d, the expression level of miR-30d in the MSTO-211H+miR-30d cells group was significantly higher than MSTO-211H+miR NC cells group ( P<0.01) . The cell activity of MSTO-211H+miR-30d group (105.13%±2.35%) was significantly lower than MSTO-211H+miR NC cells group (115.40%±1.35%) , and the level of apoptosis (3.97%±0.36%) was significantly higher than MSTO-211H+miR NC cells group (1.47%±0.10%) ( P<0.01) . The relative migration areas at 12 and 24 h of MSTO-211H+miR-30d cells group (9.35±3.16 μm 2 and 58.19±1.82 μm 2) were significantly lower than MSTO-211H+miR NC cells group (54.42 ±5.26 μm 2 and 88.32 ±1.96 μm 2) ( P<0.01) . Compared with the MSTO-211H+miR NC cells group, the numbers of cell migration and cell invasion were reduced in the MSTO-211H+miR-30d cells group ( P<0.01) . Conclusion:miR-30d can regulate the progression of malignant pleural mesothelioma by inhibiting the proliferation, apoptosis, migration and invasion of MSTO-211H cells.