Mesenchymal Stem Cells Ameliorate DSS-Induced Experimental Colitis by Modulating the Gut Microbiota and MUC-1 Pathway.

Purpose: Mesenchymal stem cells (MSCs) have become novel therapeutic agents for the treatment of inflammatory bowel diseases (IBDs). However, the precise cellular and molecular mechanisms by which MSCs restore intestinal tissue homeostasis and repair the epithelial barrier have not been well elucidated. This study aimed to investigate the therapeutic effects and possible mechanisms of human MSCs in the treatment of experimental colitis. Methods: We performed an integrative transcriptomic, proteomic, untargeted metabolomics, and gut microbiota analyses in a dextran sulfate sodium (DSS)-induced IBD mouse model. The cell viability of IEC-6 cells was determined by Cell Counting Kit-8 (CCK-8) assay. The expression of MUC-1 and ferroptosis-related genes were determined by immunohistochemical staining, Western blot, and real-time quantitative polymerase chain reaction (RT-qPCR). Results: Mice treated with MSCs showed notable amelioration in the severity of DSS-induced colitis, which was associated with reduced levels of proinflammatory cytokines and restoration of the lymphocyte subpopulation balance. Treatment with MSC restored the gut microbiota and altered their metabolites in DSS-induced IBD mice. The 16s rDNA sequencing showed that treatment with MSC modulated the composition of probiotics, including the upregulation of the contents of Firmicutes, Lactobacillus, Blautia, Clostridia, and Helicobacter bacteria in mouse colons. Protein proteomics and transcriptome analyses revealed that pathways related to cell immune responses, including inflammatory cytokines, were suppressed in the MSC group. The ferroptosis-related gene, MUC-1, was significantly upregulated in the MSC-treated group. MUC-1-inhibition experiments indicated that MUC-1 was essential for epithelial cell growth. Through overexpression of MUC-1, it showed that upregulation of SLC7A11 and GPX4, and downregulation of ACSL4 in erastin and RSL3-treated IEC-6 cells, respectively. Conclusion: This study described a mechanism by which treatment with MSCs ameliorated the severity of DSS-induced colitis by modulating the gut microbiota, immune response, and the MUC-1 pathway.

Effects of Modes and Timings of Delivery on Feto-Maternal Outcomes in Women with Severe Preeclampsia: A Multi-Center Survey in Mainland China.

BACKGROUND: Pregnancy termination is the only effective treatment for preeclampsia. However, there are controversies on the selection of modes of delivery. The objective was to evaluate whether mode of delivery in labor differentially affected the rate of adverse maternal outcomes related to severe preeclampsia. OBJECTIVE: This study aimed to evaluate whether the modes and timings of delivery affects adverse maternal outcomes in pre-eclampsia. METHODS: Clinical data from 2516 singleton pregnant women with severe preeclampsia were collected in a multicenter, large-sample, cross-sectional study in mainland China. The patients were divided into cesarean-delivery (CD) and vaginal-delivery (VD) categories and then into Group 1 (≤27+ 6 weeks), Group 2 (28-33+ 6 weeks), Group 3 (34-36+ 6 weeks), and Group 4 (≥37 weeks) according to the mode of delivery and gestational weeks. All data were exported into the SPSS software and analyzed by the Student's t-tests or Mann-Whitney U-tests and the chi-squared test. RESULTS: A total of 2516 singleton pregnant women with severe preeclampsia were collected and the overall cesarean section rate was 84.9%. The vaginal delivery rates among the four groups were significantly different with 70%, 19.7%, 6.6%, 15.1% in groups 1, 2, 3, 4, respectively (P<0.05), while perinatal mortality was lower in the CD groups than VD groups (3.3% vs 50.4%, P<0.05). The neonatal asphyxia rate was significantly higher with CD than with VD in Group 2 (36.4% vs 12.9%, P<0.05). The perinatal mortality with CD, 3, and 4 was significantly lower than with VD (10.0% vs 68.5% in Groups 2, 2.3% vs 28.3% in Groups 3, 0.8% vs 5.6% in Groups 4, all P<0.05). CONCLUSION: Most pregnant women with severe preeclampsia opted for a cesarean section in China. The lower perinatal mortality was associated with cesarean section, but the rate of maternal PPH or mortality was not related with the mode of delivery. So cesarean section is the safer delivery mode for the pregnant women complicated with severe preeclampsia.

Claudin14 promotes colorectal cancer progression via the PI3K/AKT/mTOR pathway.

Colorectal cancer is the third leading cancer in the world in terms of incidence and mortality. The role of differentially expressed Claudin-14 (CLDN14) in CRC has not been reported. We observed that CLDN14 was associated with the progression of CRC. Our functional studies have shown that CLDN14 promoted the proliferation of CRC cells. In addition, CLDN14 also increased the migration and invasion of CRC cells. In vivo experiments also showed that CLDN14 promoted the growth of colorectal cancer via the PI3K/AKT/mTOR. In summary, our research suggests that CLDN14 promotes the progression of colorectal cancer. Our findings may provide new strategies for clinical management and patient prognosis of CRC.

A Comparison Study of Age and Colorectal Cancer-Related Gut Bacteria.

Intestinal microbiota is gaining increasing interest from researchers, and a series of studies proved that gut bacteria plays a significant role in various malignancies, especially in colorectal cancer (CRC). In this study, a cohort of 34 CRC patients (average age=65 years old), 26 young volunteers (below 30 years old), and 26 old volunteers (over 60 years old) was enrolled. 16S ribosomal RNA gene sequencing was used to explore fecal bacteria diversity. The operational taxonomic unit (OTU) clustering analysis and NMDS (non-metric multidimensional scaling) analysis were used to separate different groups. Cluster of ortholog genes (COG) functional annotation and Kyoto encyclopedia of genes and genomes (KEGG) were used to detect enriched pathways among three groups. Community separations were observed among the three groups of this cohort. Clostridia, Actinobacteria, Bifidobacterium, and Fusobacteria were the most enriched bacteria in the young group, old group, and CRC group respectively. Also, in the young, old, and CRC group, the ratio of Firmicutes/Bacteroidetes was increased sequentially despite no statistical differences. Further, COG showed that transcription, cell wall/membrane/envelope biogenesis, inorganic ion transport and metabolism, and signal transduction mechanisms were differentially expressed among three groups. KEGG pathways associated with ABC transporters, amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, and aminoacyl-tRNA biosynthesis also showed statistical differences among the three groups. These results indicated that the intestinal bacterial community varied as age changed and was related to CRC, and we discussed that specific bacteria enriched in the young and old group may exert a protective function, while bacteria enriched in the CRC group may promote tumorigenesis.

Cesarean section does not affect neonatal outcomes of pregnancies complicated with preterm premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes (PPROM) is associated with high neonatal morbidity and mortality. However, the influences of cesarean section (CS) on neonatal outcomes in preterm pregnancies complicated with PPROM are not well elucidated. The aim of this study was to investigate the influence of delivery modes on neonatal outcomes among pregnant women with PPROM. METHODS: A retrospective cross-sectional study was conducted in 39 public hospitals in 14 cities in the mainland of China from January 1st, 2011 to December 31st, 2011. A total of 2756 singleton pregnancies complicated with PPROM were included. Adverse neonatal outcomes including early neonatal death, birth asphyxia, respiratory distress syndrome (RDS), pneumonia, infection, birth trauma, and 5-min/10-min Apgar scores were obtained from the hospital records. Binary variables and ordinal variables were respectively calculated by binary logistic regressions and ordinal regression. Numerical variables were compared by multiple linear regressions. RESULTS: In total, 2756 newborns were involved in the analysis. Among them, 1166 newborns (42.31%) were delivered by CS and 1590 newborns belonged to vaginal delivery (VD) group. The CS proportion of PPROM obviously increased with the increase of gestational age (χ = 5.014, P = 0.025). Compared with CS group, VD was associated with a higher risk of total newborns mortality (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.102-5.118; P = 0.027), and a lower level of pneumonia (OR, 0.32; 95% CI, 0.126-0.811; P = 0.016). However, after multivariable adjustment and stratification for gestational age, only pneumonia was significantly related with CS in 28 to 34 weeks group (OR, 0.34; 95% CI, 0.120-0.940; P = 0.038). There were no differences regarding to other adverse outcomes in the two groups, including neonatal mortality, birth asphyxia, Apgar scores, RDS, pneumonia, and sepsis. CONCLUSIONS: The proportion of CS of pregnant women with PPROM was very high in China. The mode of delivery does not affect neonatal outcomes of pregnancies complicated with PPROM.

Quantitative proteomic analysis of down syndrome biomarkers in maternal serum using isobaric tags for relative and absolute quantification (iTRAQ).

Prenatal diagnosis of Down syndrome (DS) is based on calculated risk involving maternal age, biochemical and ultrasonographic markers, and, more recently, cell-free DNA (cfDNA). The present study was designed to identify Down Syndrome biomarkers in maternal serum. We quantified the changes in maternal serum protein levels between 10 non-pregnant women, 10 pregnant women with healthy fetuses, and 10 pregnant women with DS fetuses using isobaric tags for relative and absolute quantification (iTRAQ). We subsequently conducted a Gene Ontology (GO) analysis. A total of 470 proteins were identified, 11 of which had significantly different serum levels between the DS fetus group and Healthy fetuses group. Our data shows the identified proteins may be relevant to DS and constitute potential DS biomarkers.

Intrapartum interventions that affect maternal and neonatal outcomes for vaginal birth after cesarean section.

OBJECTIVE: To investigate maternal and neonatal outcomes after different intrapartum interventions for vaginal birth after cesarean section (VBAC) in mainland China. METHODS: A retrospective study was performed on 143 VBAC cases from Beijing Obstetrics and Gynecology Hospital between January 2015 and November 2016. These cases were divided into two groups on the basis of different intrapartum interventions. Maternal and neonatal outcomes were compared. RESULTS: The durations of the first stage and total labor after oxytocin were significantly longer than those before oxytocin use. The proportion of operative vaginal delivery with oxytocin was significantly higher than that without oxytocin (43.9% vs. 11.8%). The times of the first stage, second stage, and total labor with analgesia were significantly longer than those without analgesia (548.4±198.1 vs. 341.8±233.0 minutes, 52.0±38.9 vs. 36.0± 29.1 minutes, and 606.3±212.1 vs. 387.3±233.0 minutes, respectively). Postpartum hemorrhage and operative vaginal delivery occurred significantly more frequently in women with epidural analgesia than in those without epidural analgesia (29.7% vs. 12.3 and 35.1% vs. 16.0%, respectively). CONCLUSIONS: Induction can increase the rate of operative vaginal delivery in VBAC. Oxytocin and epidural analgesia may increase the risk of operative vaginal delivery, and may be associated with a prolonged duration of labor.

Identifying appropriate pre-pregnancy body mass index classification to improve pregnancy outcomes in women of childbearing age in Beijing, China: a retrospective cohort study.

BACKGROUND AND OBJECTIVES: This study explored the appropriate classification of pre-pregnancy body mass index (BMI) in women of childbearing age in Beijing, China. METHODS AND STUDY DESIGN: Women with singleton pregnancies at more than 28 gestational weeks were retrospectively reviewed. Based on the pre-pregnancy BMI (kg/m2), these patients were divided into 7 groups: <18.5, >=18.5-22.9, >=23-23.9, >=24-24.9, >=25-27.9, >=28-29.9, and >=30. Pregnancy adverse outcomes, including gestational hypertension with or without preeclampsia, gestational diabetes mellitus, initial cesarean section, postpartum hemorrhage, macrosomia, large-for-gestational age infant and so on were recorded. Binary logistic regression analysis was used to calculate the uncorrected and corrected odds ratios and 95% confidence intervals, with the >=18.5-22.9 group serving as a reference. RESULTS: A total of 11,136 pregnant women were analyzed. Incidences of above mentioned six adverse outcomes were greater in women with higher pre-pregnancy BMI. The risks of the abovementioned six adverse outcomes were increased significantly among the >=23-23.9, >=24-24.9, >=25-27.9 groups and substantially higher in the >=28-29.9, >=30 groups after correction. <18.5 group showed an increased risk of small-for-gestational age infants. CONCLUSIONS: For women of childbearing age in Beijing, China, the optimal pre-pregnancy BMI range was >=18.5-22.9 kg/m2, with the cutoff value for overweight status being >=23.0 kg/m2 and the cutoff value for obesity being >=28.0 kg/m2.

Building a predictive model for successful vaginal delivery in nulliparas with term cephalic singleton pregnancies using decision tree analysis.

AIM: To establish a model predicting successful vaginal delivery (VD) in nulliparas with term cephalic singleton pregnancies. METHODS: We retrospectively identified 6799 term nulliparas with cephalic singletons (6416 VD and 383 cesarean section [CS] due to dystocia) who entered labor (cervical dilation ≥2 cm) between September 2014 and August 2015. Using VD as the dependent variable and age, maternal body height, educational attainment, gravidity, gestational age, pre-pregnancy body mass index (BMI), BMI upon admission for delivery, gestational weight gain, gestational hypertension and gestational diabetes as the independent variables, predictors of VD success were identified using a multivariate binary logistic regression and then ranked with decision-tree analysis. RESULTS: While multiple factors are associated with improved VD success, we found body height, gestational age, and intrapartum BMI to be the best predictors of successful VD. Our predictive model has a classification accuracy, sensitivity and specificity of 76.6%, 96.7% and 16.4%, respectively, and it was subsequently confirmed by both internal and external validation. CONCLUSION: Our predictive model indicates body height, gestational age and intrapartum BMI as the major predictors of successful VD in low-risk patients.

Paeoniflorin attenuates impairment of spatial learning and hippocampal long-term potentiation in mice subjected to chronic unpredictable mild stress.

RATIONALE AND OBJECTIVE: Paeoniflorin has been reported to exhibit antidepressant-like effects in several animal model depression; and it also exerts a neuroprotective effect. In the present study, we investigated the effects of paeoniflorin administration on depression-like behaviors and cognitive abilities in mice subjected to chronic unpredictable mild stress (CUMS), an animal model associated with depressive disorders and cognitive deficits. METHODS: We administered paeoniflorin (20 mg/kg), which is the main active constituent extracted from Paeonia lactiflora Pall. and exerts multiple pharmacological actions, to CUMS mice. Subsequently, animals were subjected to tests of depression-like behavior including the sucrose preference test, the forced swimming test and the tail suspension test. The Morris water maze (MWM) task was applied to evaluate learning and memory capacity. Hippocampal CA1 long-term potentiation (LTP) was recorded. Dendritic spine density and the expression levels of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95) in the hippocampus were also investigated. RESULTS: The administration of paeoniflorin protected against CUMS-induced depression-like behavior. Paeoniflorin also improved the performance of CUMS mice in the MWM. The impairment of hippocampal CA1 LTP caused by CUMS was also reversed. Furthermore, paeoniflorin administration prevented decreases in dendritic spine density and in the expression of BDNF and PSD95 in the hippocampus of CUMS mice. CONCLUSION: Our observations suggest that paeoniflorin is a potential antidepressant that protects against cognitive impairment in depression.

Associations of polymorphisms of CYP2D6 and CYP2C9 with early onset severe pre-eclampsia and response to labetalol therapy.

PURPOSE: Early onset preeclampsia (PPE) contributes to life-threatening maternal complications and fetal demise. Pharmacogenomics is a precision medicine, and metabolizing enzymes responsive to antihypertensive remains understudied. The aim of this study was to evaluate the associations of polymorphisms of cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) and cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) with PPE and the relationship among CYP2D6, CYP2C9 polymorphisms and response to labetalol therapy. METHODS: Totally 105 gravidas diagnosed with PPE (case) and 103 healthy gravidas (control) were recruited between August 2013 and July 2016. Labetalol was given to control blood pressures (BP) with PPE. If labetalol administration alone did not exceed the mean dose and effectively controlled the BP, it would be considered to be valid (n = 75). Genotype and allele frequencies of CYP2C9 gene (rs1057910 and rs4918758) and CYP2D6 gene (rs1065852, rs28371725, rs35742686, and rs3892097) were analyzed by TaqMan PCR. Differences in the genotype and allele frequencies were compared between case-control groups, and the responsive and nonresponsive to labetalol in PPE. RESULTS: Out of six variants, only CC and CT genotypes of the CYP2D6 variants (rs28371725) in PPE were significantly higher than those in the control group [18.1% (19/105) vs 14.6% (15/103); 56.2% (59/105) vs 42.7% (44/103); χ2 = 6.707]. However, there were no differences in maternal age, diastolic pressure, BMI, BW, serum triglyceride, and creatinine were observed among women with CC, CT, or TT genotype of CYP2D6 gene rs28371725 in the experimental group (all P > 0.05). Compared with the gravidas with CT or TT genotype of CYP2D6 gene rs28371725, those with CC genotype had longer gestational age [(32.5 ± 2.1) vs (29.5 ± 1.8) and (29.8 ± 2.2) weeks] and higher plasma albumin [(27.2 ± 9.3) vs (20.3 ± 10.4) and (22.5 ± 7.4) g/L], but lower systolic pressure and 24 h urine protein (LSD test, all P < 0.05). The G allele frequency in CYP2D6 gene rs1065852 nonresponsive to labetalol group was higher than that in responsive labetalol group [93.3% (56/60) vs 76.0% (114/150), χ2 = 8.351, P = 0.004]. CONCLUSIONS: The polymorphism of CYP2D6 gene rs28371725 may be associated with PPE, and the allele of G in CYP2D6 gene rs1065852 may be associated with the efficacy of labetalol in treatment of PPE.

Novel SNPs of WNK1 and AKR1C3 are associated with preeclampsia.

Preeclampsia is a hypertensive disorder of pregnancy and is one of the most common causes of poor perinatal outcomes. Preeclampsia increases the risk of hypertension in the future. Variants of WNK1 (lysine deficient protein kinase 1), ADRB2 (ß2 adrenergic receptor), NEDD4L (ubiquitin-protein ligase NEDD4-like), KLK1 (kallikrein 1) contribute to hypertension, and AKR1C3 (aldo-keto reductase family1 member C3), is associated with preeclampsia. The association of single nucleotide polymorphisms (SNPs) in these five candidate preeclampsia susceptibility genes and the related traits in Chinese individuals were investigated. In this study, 13 SNPs of the five genes were genotyped in 276 preeclampsia patients and 229 age- and area-matched normal pregnancies in women of Chinese Northern Han origin. The 95% confidence interval (CI) and odds ratio (OR) were estimated by binary logistic regression. No obvious linkage disequilibrium or haplotypes were observed among these SNPs. Those with GG genotype and allele G of AKR1C3 (rs10508293) had a decreased risk of preeclampsia (adjusted OR = 3.011, 95% CI = 1.758-5.159, and adjusted OR = 1.745, 95% CI = 1.349-2.257, respectively). The AA genotype and allele A of WNK1 (rs1468326) were significantly associated with an increased risk in preeclampsia (adjusted OR = 2.307, 95% CI = 1.206-3.443, and adjusted OR = 1.663, 95% CI = 1.283-2.157, respectively). The findings indicate that the GG genotype of AKR1C3 rs10508293 is associated with decreased risk for preeclampsia and the AA genotype of WNK1 rs1468326 are related with an increased risk for preeclampsia.

Role of AKR1C3 in renal injury and glibenclamide is anti-inflammatory in preeclamptic rats.

Proteinuria is a common adverse effect of renal injury in preeclampsia. To explore the effects of AKR1C3 in renal injury due to preeclampsia and to determine an optimal method to prevent proteinuria, glibenclamide treatment was used in unrestrained Wistar rats exposed to N-nitro-L-arginine methyl ester hydrochloride (L-NAME). Successful rat models for preeclampsia were confirmed based on mean arterial pressure, a 24-h protein urine test, and by observing the structure of the kidney by transmission electron microscopy (TEM). Forty Wistar rats were randomly divided into L-NAME-induced preeclampsia (pregnant and L-NAME), treatment (pregnant, L-NAME, and glybenclamide), non-pregnant (L-NAME), and control (pregnant and 0.9% saline) groups. Rats that were 19 days into their pregnancies were then euthanized and their kidneys were collected. After exposure to L-NAME, the mean arterial pressure increased by ~25 mmHg, which was largely prevented by the co-administration of glibenclamide. At 24 h, protein levels in the urine of the L-NAME-induced preeclampsia group were higher than those of the control and treatment groups. AKR1C3 was downregulated in the kidney and podocytes, whereas glibenclamide increased the expression of AKR1C3. The generation of reactive oxygen species (ROS) detected by ELISA was decreased by the glibenclamide co-administration. Compared with that in the L-NAME-induced preeclampsia group, the expression levels of AKR1C3 protein and mRNA significantly increased in the treatment group ([0.48 ±â€¯0.09] vs.[1.05 ±â€¯0.20];[0.05 ±â€¯0.02] vs.[0.22 ±â€¯0.06]; both P < 0.05]). Therefore, AKR1C3 expression was decreased in the kidneys of L-NAME-induced preeclampsia rats, and glibenclamide may be useful for the treatment of preeclampsia by regulating the generation of ROS and preventing proteinuria.

Labor Onset, Oxytocin Use, and Epidural Anesthesia for Vaginal Birth after Cesarean Section and Associated Effects on Maternal and Neonatal Outcomes in a Tertiary Hospital in China: A Retrospective Study.

BACKGROUND: In the mainland of China, the trial of labor after cesarean section is still a relatively new technique. In this study, we aimed to investigate the effects of labor onset, oxytocin use, and epidural anesthesia on maternal and neonatal outcomes for vaginal birth after cesarean section (VBAC) in a tertiary hospital in China. METHODS: This was a retrospective study carried out on 212 VBAC cases between January 2015 and June 2017 in Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Relevant data were acquired on a form, including maternal age, gravidity and parity, body mass index before pregnancy, weight gain during pregnancy, type of labor onset, gestational age, the use of oxytocin and epidural anesthesia, birth mode, the duration of labor, and neonatal weight. The factors affecting maternal and neonatal outcomes for cases involving VBAC, especially with regards to postpartum hemorrhage (PPH) and fetal distress, were evaluated by univariate analysis and multivariable logistic regression. RESULTS: Data showed that 36 women (17.0%) had postpartum hemorrhage (PPH) and 51 cases (24.1%) featured fetal distress. Normal delivery took place for 163 infants (76.9%) while 49 infants (23.1%) underwent operative vaginal deliveries with forceps. There were 178 cases (84.0%) of spontaneous labor and 34 cases (16.0%) required induction. Oxytocin was used in 54 cases (25.5%) to strengthen uterine contraction, and 65 cases (30.7%) received epidural anesthesia. The rate of normal delivery in cases involving PPH was significantly lower than those without PPH (61.1% vs. 80.1%; χ2 = 6.07, P = 0.01). Multivariate logistic analysis showed that the intrapartum administration of oxytocin (odds ratio [OR] = 2.47; 95% confidence interval [CI] = 1.07-5.74; P = 0.04) and birth mode (OR = 0.40; 95% CI = 0.18-0.87; P = 0.02) was significantly associated with PPH in VBAC cases. Operative vaginal delivery occurred more frequently in the group with fetal distress than the group without (49.0% vs. 14.9%, χ2 = 25.36, P = 0.00). Multivariate logistic analysis also revealed that the duration of total labor (OR = 1.01; 95% CI = 1.00-1.03; P = 0.04) and the gestational week of delivery (OR = 1.08; 95% CI = 1.05-1.11; P = 0.00) were significantly associated with fetal distress in VBAC. CONCLUSIONS: The administration of oxytocin during labor and birth was identified as a protective factor for PPH in VBAC while birth mode was identified as a risk factor. Finally, the duration of total labor and the gestational week of delivery were identified as risk factors for fetal distress in cases of VBAC. This information might help obstetricians provide appropriate interventions during labor and birth for VBAC.

Idiopathic polyhydramnios at term and pregnancy outcomes: a multicenter observational study.

AIM: To assess pregnancy outcomes in pregnancies with idiopathic polyhydramnios at term. METHODS: We conducted a retrospective cohort study of 106 225 term pregnancies from 37 hospitals in China. Maternal and fetal outcomes in pregnancies with idiopathic polyhydramnios were compared with pregnancies with normal amniotic fluid. The primary outcome was intra-uterine fetal death (IUFD). RESULTS: In all, 307 out of 106 225 (0.3%) had idiopathic polyhydramnios at term, 276 of which were mild and 31 of which were moderate-severe. Compared to term pregnancies with normal amniotic fluid, pregnancies idiopathic polyhydramnios was associated with over 24-fold higher risk for IUFD (adjusted odds ratio [aOR] 24.4, 95% confidence interval (CI) 7.3-82.0), macrosomia (aOR 2.8, 95%CI 2.0-3.8), malpresentation (aOR 2.5, 95%CI 1.7-3.7), cesarean delivery (aOR 2.5, 95%CI 1.7-3.7) and low APGAR scores at 5 min (aOR 4.3, 95%CI 2.4-7.8), which increased with severity of idiopathic polyhydramnios. CONCLUSION: Term pregnancies with idiopathic polyhydramnios, especially moderate-severe ones are at a significantly increased rate for adverse pregnancy outcome. Increased antepartum surveillance of fetal well-being and timed delivery are warranted.

Gamma-H2AX upregulation caused by Wip1 deficiency increases depression-related cellular senescence in hippocampus.

The PP2C family member Wild-type p53-induced phosphatase 1 (Wip1) critically regulates DNA damage response (DDR) under stressful situations. In the present study, we investigated whether Wip1 expression was involved in the regulation of DDR-induced and depression-related cellular senescence in mouse hippocampus. We found that Wip1 gene knockout (KO) mice showed aberrant elevation of hippocampal cellular senescence and of γ-H2AX activity, which is known as a biomarker of DDR and cellular senescence, indicating that the lack of Wip1-mediated γ-H2AX dephosphorylation facilitates cellular senescence in hippocampus. Administration of the antidepressant fluoxetine had no significant effects on the increased depression-like behaviors, enriched cellular senescence, and aberrantly upregulated hippocampal γ-H2AX activity in Wip1 KO mice. After wildtype C57BL/6 mice were exposed to the procedure of chronic unpredictable mild stress (CUMS), cellular senescence and γ-H2AX activity in hippocampus were also elevated, accompanied by the suppression of Wip1 expression in hippocampus when compared to the control group without CUMS experience. These CUMS-induced symptoms were effectively prevented following fluoxetine administration in wildtype C57BL/6 mice, with the normalization of depression-like behaviors. Our data demonstrate that Wip1-mediated γ-H2AX dephosphorylation may play an important role in the occurrence of depression-related cellular senescence.

The Synthesis and Evaluation of Arctigenin Amino Acid Ester Derivatives.

The use of arctigenin (ARG), a traditional medicine with many pharmacological activities, has been restricted due to its poor solubility in water. Five amino acid derivatives of ARG have been synthesized using glycine, o-alanine, valine, leucine, and isoleucine, which have t-butyloxy carbonyl (BOC) as a protective group. In this study, we examined the effects of removing these protective groups. The results showed that the amino acid derivatives have better solubility and nitrite-clearing ability than ARG. Among the compounds tested, the amino acid derivatives without protective group were the best. Based on these results, ARG and its two amino acid derivatives without protective group (ARG8, ARG10) were selected to evaluate their anti-tumor activity in vivo at a dosage of 40 mg/kg. The results indicated that ARG8 and ARG10 both exhibit more anti-tumor activity than ARG in H22 tumor-bearing mice. The tumor inhibition rates of ARG8 and ARG10 were 69.27 and 43.58%, which was much higher than ARG. Furthermore, the mice treated with these compounds exhibited less damage to the liver, kidney and immune organs compared with the positive group. Furthermore, ARG8 and ARG10 improved the serum cytokine levels significantly compared to ARG. In brief, this study provides a method to improve the water solubility of drugs, and we also provide a reference basis for new drug development.

A Population-based Study of Invasive Cervical Cancer Patients in Beijing: 1993-2008.

BACKGROUND: In recent years, the incidence of cervical cancer has been rising, particularly in young adults, as the second most common gynecological cancer in China. The aim of this study was to explore the incidence change and the epidemiological characteristics of cervical cancer in Beijing over the past 16 years. METHODS: All the cases of the study were limited to Beijing residents diagnosed with cervical cancer and registered in Beijing from January 1, 1993, to December 31, 2008. A total of 4100 patients with cervical cancer were obtained from the Statistics Database of Beijing Cancer Registry (BJCaR). According to the registered data, we retrospectively reviewed all original cases which we can acquired in reported hospital. Cervical situ cancer, cervical metastatic cancer, non-Beijing residents and repeatedly registered cases were excluded. Totally, 3641 registered cases were verified correctly. Meanwhile, we also collected the following data: Age, occupation, detected methods, histological type, and staging. The trends of incidence and mortality were analyzed by Joinpoint Regression Program 4.1.1.1 produced by National Cancer Institute (NCI, USA). The annual percent change (APC) was calculated using the Joinpoint regression model. RESULTS: The crude rates of incidence and mortality were 10.4 and 1.0 per 100,000 women, respectively during 1993 to 2008. The average WHO age-standardized incidence rates were 11.5 per 100,000 women. There was a decrease in incidence annually by 8.0% (P = 0.3) during 1993-1996 and a rapid increase annually by 18.9% after 1999 (P < 0.01). The median age was 67 years in 1993, but the median age decreased to 45 years in 2008. The peak of the age-specific incidence curve was at 40 years in the most recent period (2005-2008), which was 25-30 years earlier than that in previous periods (1993-1996). In the 2224 cases, the numbers of patients with stage I, II, III and IV were 910 (40.9%), 601 (27%), 542 (24.4%), 171 (7.7%), respectively. The percentage of patients with stage I was 7.6% (13/171) in 1993-1996, but the percentage increased to 51.6% (643/1247) in 2005-2008 (P < 0.01). Otherwise the percentage of advanced stage (stage III-IV) during the same period was dropped down significantly from 52.0% (89/171) to 22.5% (280/1247) (P < 0.01). Unemployed and housewife ranked first accounting for 27.3% of the total (607/2224). Urban low-income people such as worker ranked the second accounting for 17.0% (377/2224), the third place was farmer accounting for 14.0% (312/2224). Only 381 (17.1%, 381/2224) women in 2224 were first detected cervical cancer by routine screenings. Company staff (36.5%, 139/381), professional and technical personnel (22.6%, 86/381), national official (22.0%, 84/381) occupied the top three (total 81.1%) in the 381 patients detected cervical cancer by screening. CONCLUSIONS: The cervical cancer incidence has showed a continuous rise in Beijing since 1999. Government-led mass screening should target the low socioeconomic population primarily. Meanwhile the government should enhance public health education of cancer screening to increase the rate of screening.