Nonlinear association of fibrinogen levels with functional prognosis in patients with acute ischemic stroke: a prospective cohort study.

OBJECTIVE: Fibrinogen, essential in primary hemostasis, platelet aggregation, and leukocyte-endothelial interactions, is also associated with a heightened risk of acute ischemic stroke (AIS). However, its influence on AIS patient outcomes is unclear. This study examines the correlation between fibrinogen levels and the risk of unfavorable outcomes three months post-AIS. METHODS: This is a secondary analysis of a prospective cohort study conducted in Korea. The sample consisted of 1851 AIS patients who received treatment at a Korean hospital between January 2010 and December 2016. Statistical models were established to understand the relationship between fibrinogen levels(mg/dL) and unfavorable outcomes(mRs ≥ 3), including logistic regression models, Generalized Additive Models (GAM), and smooth curve fitting (penalized splines). The log-likelihood ratio test has been utilized to evaluate the best fit. To ensure the robustness of the results, sensitivity analyses were conducted by reanalyzing the relationship after excluding participants with TG > 200 mg/dl and BMI > 25 kg/m2. Subgroup analyses were also performed to assess whether influencing factors modify the association between fibrinogen levels and unfavorable outcomes. RESULTS: After adjusting for multiple covariates including age, BMI, sex, LDL-c, TG, HGB, HDL-c, BUN, FPG, ALB, PLT, AF, hypertension, smoking, DM, mRs score at admission, the binary logistic regression model demonstrated revealed a significant positive association between fibrinogen levels and the risk of unfavorable outcomes in AIS patients (OR = 1.215, 95% CI: 1.032-1.429, p = 0.019). Sensitivity analyses supported these findings, with similar ORs observed in subsets of patients with TG < 200 mg/dL (OR = 1.221, 95% CI: 1.036-1.440) and BMI < 25 kg/m2 (OR = 1.259, 95% CI: 1.051-1.509). Additionally, the relationship between fibrinogen levels and outcomes was nonlinear, with a critical threshold of 2.74 g/L. Below the inflection point, the OR for unfavorable outcomes was 0.666 ((95% CI: 0.360, 1.233, p = 0.196), whereas above it, the OR increased to 1.374 (95% CI: 1.138, 1.659). CONCLUSIONS: This study has provided evidence of a positive and nonlinear correlation between fibrinogen levels and 3-month poor functional outcomes in patients with AIS. When fibrinogen levels exceeded 2.74 g/L, a significant and positive association was observed with the risk of poor outcomes. This study provides a further reference for optimizing rehabilitation exercises and facilitating clinical counseling in patients with acute ischemic stroke.

Case Report: foetal gastroschisis with ideal pregnancy outcomes under multidisciplinary treatment management.

Background: Gastroschisis has increased in recent years, however, complicated gastroschisis is associated with higher mortality, as well as higher health care costs and disease burdens from short- and long-term complications. Case introduction: A woman aged 25 years old at 37 + 1 weeks gestation (gravida 2; para 0) was admitted to the hospital because of foetal gastroschisis. Targeted quaternary ultrasound performed at our hospital showed that 34 mm of the abdominal wall was interrupted continuously, an intestinal echo with a range of approximately 88 × 50 mm was seen bulging outwards the local area close to the intestinal wall showed a 34 × 23 m anecho, and the foetus was measuring 2 weeks smaller than expected. After MDT including the maternal-foetal medicine, ultrasound, paediatric surgery, neonatal intensive care unit (NICU), and anaesthesiology departments, caesarean section was performed at 37 + 2 weeks. A baby boy was delivered, the small intestine, large intestine and stomach were seen outside of the abdomen, the abdominal cavity was excluded from the defect on the right side of the umbilical cord, the mesentery was shortened, and the intestinal tube had obvious oedema After paediatric surgical discussion, silo bag placement and delayed closure was performed, the placement process was smooth. One week following silo placement, the abdominal contents had been fully reduced below the fascia following daily partial reductions of the viscera,and the second stage of the operation was performed under general anaesthesia. The newborn was successfully discharged from the hospital 20 days after the operation and was followed up, with good growth, normal milk intake and smooth bowel movements. Conclusions: The diagnosis and treatment of complicated gastroschisis needs to be carried out under multidisciplinary team treatment. Delivery by cesarean section after 37 weeks is feasible.Immediate postpartum surgery is possible, and the choice of surgical modality is determined by the child's condition, emphasizing that it should be performed without adequate sedation under anaesthesia. A standardized postoperative care pathway appropriate to risk should be developed to optimize nutritional support and antibiotic use, and standardized enteral feeding practices should be sought with long-term follow-up.

Reduced attention on restricted organochlorine pesticides, whereas still noteworthy of the impact on the deep soil and groundwater: a historical site study in southern China.

The use of hexachlorocyclohexanes (HCHs) in pesticides has been prohibited for decades in China. Since then, there have been urbanization and transformation of the functional areas of many sites, which were formerly involved in the HCH industry. However, it is possible that, unless properly managed, these sites may still contain HCH residues in the soil and thus pose a threat to the surrounding environment and the quality of groundwater. This study aimed to characterize soil residues in a typical site that was historically involved in HCH production in southern China, by analyzing the α-HCH, ß-HCH, and γ-HCH contents of the soil. The results suggested that HCHs persist in the environment and can have long-term effects. It was found that α-HCH and ß-HCH were present in many samples in concentrations that were comparable or higher than those specified by China's Class 1 screening values. The distribution of residues was significantly correlated with the historical HCH production activities in the areas. The characteristic ratios of α-HCH/γ-HCH and ß-HCH/(α + γ)-HCH at different soil depths were 1.4-3.7 and 0.21-1.04, respectively, which indicated the presence of significant localized residues of HCHs. The presence of HCHs in the soil suggested a downward migration, with concentrations rapidly decreasing in the upper layer soil (0-5 m), but a gradual increase in the deeper soil (5-14 m). HCHs were detected at depths exceeding 24 m, indicating heavy penetration. The proportions of γ-HCH and ß-HCH changed with increasing soil depth, which was related to their relatively volatile and stable molecular structures, respectively. The results strongly suggested that there is widespread contamination of both soil and groundwater by HCHs even after decades. The likelihood of residual HCHs in the soil should therefore be taken into full consideration during urban planning to limit risks to human and environmental health.

Uterine torsion complicated by severe placental abruption in the second trimester: a case report and literature review.

BACKGROUND: Uterine torsion is a rare obstetric event that can occur during pregnancy and is difficult to diagnose. Its occurrence may lead to serious adverse pregnancy outcomes. CASE INTRODUCTION: The patient was a 33-year-old woman at 30+ 5 weeks' gestation with a singleton pregnancy. The pregnancy course, including fetal growth, and prenatal examinations were regular. Except for a small amount of vaginal bleeding in early pregnancy and treatment with progesterone, there were no prenatal abnormalities, and the patient denied any trauma or sexual history. The patient was admitted to the emergency department with persistent severe pain in the lower abdomen and slight vaginal bleeding during night sleep. Abdominal pain started two hours prior to admission and was accompanied by nausea, vomiting, and dizziness. Examination revealed positive abdominal tenderness, high uterine tone, and no significant intermittent period of uterine contractions, and measurement of the fetal heart rate by means of the nonstress test revealed a rate of 60 beats per minute. Therefore, placental abruption was highly suspected. Subsequently, an emergency cesarean section was performed under general anesthesia. The newborn boy, with Apgar scores of 0-3-4 after birth and weighing 1880 g, was transferred to the neonatal intensive care unit (NICU) and died two days later due to ineffective rescue. After the uterine incision was sutured, the examination revealed that the uterine incision was located on the posterior wall of the uterus, and the uterus was twisted 180° to the right. The diagnosis after cesarean section was 180° uterine torsion to the right, severe placental abruption, and severe neonatal asphyxia. On the fifth day after surgery, the patient recovered and was discharged from the hospital. CONCLUSIONS: Posterior uterine incision cesarean section may be performed in unexpected circumstances and is also feasible as a safe option for resetting if torsion is not complete. Abdominal pain during pregnancy is less likely to be diagnosed as uterine torsion, which often leads to premature birth, fetal asphyxia, placental abruption, and even perinatal death. Therefore, for abdominal pain during pregnancy, obstetricians should consider the possibility of uterine torsion.

The Association Between Congestive Heart Failure and One-Year Mortality After Surgery in Singaporean Adults: A Secondary Retrospective Cohort Study Using Propensity-Score Matching, Propensity Adjustment, and Propensity-Based Weighting.

Background: Although congestive heart failure (CHF) is considered a risk factor for postoperative mortality, reliable quantification of the relationship between CHF and postoperative mortality risk is limited. We aimed to investigate the association between CHF and 1-year mortality after surgery in a large cohort of the Singaporean population. Methods: In this retrospective cohort study, the study population included 69,032 adult patients who underwent surgery at Singapore General Hospital between 1 January 2012 and 31 October 2016. The target independent and dependent variables were CHF and 1-year mortality after surgery, respectively. Propensity score was estimated using a non-parsimonious multivariable logistic regression model. Multivariable adjustment, propensity score matching, propensity score adjustment, and propensity score-based weighting Cox proportional-hazards regression were performed to investigate the association between CHF and 1-year mortality after surgery. Results: The multivariate-adjusted hazard ratio (HR) in the original cohort was 1.39 (95% confidence interval (CI): 1.20-1.61, P < 0.001). In additional propensity score adjustment, the HR between CHF and 1-year mortality after surgery was 1.34 (95% CI: 1.15-1.56, P < 0.001). In the propensity score-matched cohort, the multivariate-adjusted Cox proportional hazard regression model analysis showed participants with CHF had a 54% increased risk of 1-year mortality after surgery (HR 1.54, 95% CI: 1.19-1.98, P < 0.001). The multivariate-adjusted HR of the inverse probability of treatment-weighted and standardised mortality ratio-weighted cohorts was 1.34 (95% CI: 1.10-1.62, P = 0.004) and 1.24 (95% CI: 1.17-1.32, P < 0.001), respectively. Conclusion: CHF is an independent risk factor for 1-year mortality after surgery in patients undergoing surgery. Depending on the statistical method, patients with CHF had a 24-54% increased risk of 1-year all-cause mortality after surgery. This provides a reference for optimising clinical decision-making, improving preoperative consultation, and promoting clinical communication.

Assessment of inflammatory markers and mitochondrial factors in a rat model of sepsis-induced myocardial dysfunction.

The present study aimed to investigate the expression of inflammatory markers and mitochondrial function-related genes, as well as their temporal relationship with cardiac myocyte injury in a rat model of sepsis. The sepsis model was constructed using cecal ligation and puncture (CLP). Two hours after CLP, the levels of inflammatory cytokines (interleukin [IL]-1ß, IL-6, and TNFα) and myocardial function markers (serum brain natriuretic peptide [BNP], cardiac troponin-I [cTNI], and procalcitonin [PCT]) were increased significantly, falling from around 9 hours postoperatively. The concentration of nitric oxide (NO) in the heart tissue was increased 6 hours after CLP. The heart rate (HR) of rats that underwent CLP decreased 2 hours after surgery and then increased to above-normal values. The left ventricular short axis shortening (FS) and left ventricular ejection fraction (LVEF) were decreased at 2 hours postoperatively and reached a minima at 6 hours. Stroke volume (SV), cardiac output (CO), and changes and heart index (CI) results indicated myocardial dysfunction. Western blot analysis demonstrated the increased expression of mitochondrial function-related proteins and activation of mitochondrial apoptotic pathways. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays revealed that the proportion of proapoptotic cells was significantly higher in rats that underwent CLP than sham surgery at 2 to 24 hours postoperatively. Taken together, our results indicate that-in the rat model-CLP-induced sepsis leads to impaired cardiac function. Furthermore, induction of the expression of mitochondrial function-related genes indicated that myocardial cell mitochondrial function was disrupted, further aggravating cardiomyocyte apoptosis. These results provide a theoretical basis for the treatment of sepsis-induced myocardial dysfunction.

NF-κB mediates early blood-brain barrier disruption in a rat model of traumatic shock.

BACKGROUND: Blood-brain barrier (BBB) disruption is associated with a large number of central nervous system and systemic disorders. The aim of the present study was to investigate the dynamic change of BBB changes during traumatic shock and resuscitation as well as the mechanisms involved. METHODS: The experiments were performed on male Sprague-Dawley rats anesthetized with pentobarbital sodium. To produce traumatic shock, the rats were subjected to bilateral femoral traumatic fracture and blood withdrawal from the femoral artery to decrease mean arterial pressure (MAP) to 35 mm Hg. Hypovolemic status (at a MAP of 35 to 40 mm Hg) was sustained for 1 hour followed by fluid resuscitation with shed blood and 20 mL/kg of lactated Ringer's solution. RESULTS: The rats were sacrificed at 1 hour, 2 hours, or 6 hours after fluid resuscitation. Blood-brain barrier permeability studies showed that traumatic shock significantly increased brain water contents and sodium fluorescein leakage, which was aggravated by fluid resuscitation. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses revealed that Na-K-Cl cotransporter-1 and vascular endothelial growth factor (VEGF) expression were upregulated in cortical brain tissue of traumatic shock rats, and this change was accompanied by downregulation of occludin and claudin-5. Traumatic shock also significantly increased the protein levels of NF-κB-p65 subunit. Of note, administration of NF-κB inhibitor PDTC effectively attenuated augmentation of the above changes. CONCLUSION: Our results suggest that traumatic shock is associated with early BBB disruption, and inhibition of NF-κB may be an effective therapeutic strategy in protecting the BBB under traumatic shock conditions.

Laparoscopic Yang-Monti Ureteral Reconstruction in Children.

OBJECTIVE: To investigate the clinical outcome of surgical treatment for long ureteral defect in children, we evaluated our experience of managing 6 children with the long defect utilizing laparoscopic ureteral reconstruction technique using Yang-Monti technique. MATERIALS AND METHODS: Six children with long ureteral defect who underwent laparoscopic Yang-Monti ureteral reconstruction between January 2013 and March 2016 were reviewed. The diagnosis and outcomes of long ureteral defects were reviewed based on clinical and imaging data. We assessed preoperative clinical data and outcomes, and analyzed the experience of laparoscopic Yang-Monti ureteral reconstruction. RESULTS: The mean age of the patients was 8.5 years. The etiology of the ureteral defect was failed pyeloplasty in 4 patients, failed pyeloplasty and ureteral reimplantation in 1, and trauma in 1. The mean defect length was 5.83 cm. All operations were performed successfully with no serious intraoperative complications and no conversion. The average operative time was 314 minutes, the average intraoperative blood loss was 25 mL, the average drain removal was 3.83 days, the average start of oral feeding was 5.17 days, and the average postoperative hospital stay was 7.17 days. Six patients suffered Clavien I and II complications postoperatively and were managed conservatively. Two patients suffered Clavien III complications postoperatively and were managed by replacing stent. A diuretic T1/2 showed the improvement of differential renal function without urinary obstruction in all patients. CONCLUSION: Laparoscopic Yang-Monti ureteral reconstruction is safe and feasible in children with an excellent outcome.

Transumbilical multi-port laparoscopic pyeloplasty versus transumbilical single-site laparoscopic pyeloplasty for ureteropelvic junction obstruction in children: A retrospectively comparative study.

INTRODUCTION: Laparoscopic pyeloplasty has achieved good cosmetic and functional outcomes. Both transumbilical single-site and transumbilical multi-port approaches are currently being used. No comparison of transumbilical single-site laparoscopic pyeloplasty (TSLP) and transumbilical multi-port laparoscopic pyeloplasty (TMLP) has been reported in the literature. OBJECTIVES: We present a retrospective comparison study to evaluate clinical outcomes of TSLP and TMLP for children with ureteropelvic junction obstruction (UPJO). STUDY DESIGN: A retrospective study was carried out comparing TSLP and TMLP performed by a single surgeon between July 2012 and June 2014. The patient data of the two groups (90 in each group) were evaluated. All patients underwent urine analysis, ultrasonography, magnetic resonance urography, and diuretic renogram using 99Tc-diethylene triamine pentaacetic acid scan preoperative and postoperative follow-up. Data were analyzed using the SPSS 20.0 software package. RESULTS: DISCUSSION: To our knowledge, our series is the first report in the literature that compares the outcomes of TSLP and TMLP in children. Our study suggested that there were no significant differences in start of oral feeding, drain removal, hospital stay, postoperative renal pelvic anteroposterior diameter and differential renal function at 6 months, postoperative complications, and success rate between the two groups. It demonstrated that TMLP is as effective and safe as TSLP. Although the cosmetic result of the TSLP group is satisfactory, TMLP requires three 0.5-cm ports around the umbilicus and does not change the shape of the umbilicus. Hence, the cosmetic result of the TMLP group is better than that of the TSLP group. TSLP involves some technical challenges. However, TMLP facilitates the procedure and renders the operation easier. Our findings confirmed that the operative time of TMLP group is shorter than that in TSLP group, and also showed that TMLP is relatively easy to perform compared with TSLP. CONCLUSION: TMLP is a feasible and safe operation for pediatric UPJO. TMLP is shorter in operative time and has a better cosmetic result than TSLP. We propose TMLP as a more viable treatment option for pediatric UPJO.

Transumbilical Single-Site Multiport Laparoscopic Pyeloplasty for Children with Ureteropelvic Junction Obstruction in China: A Multicenter Study.

BACKGROUND: Transumbilical single-site multiport laparoscopic pyeloplasty (TSMLP) for children with ureteropelvic junction obstruction (UPJO) has become feasible and popular recently. The purpose of this study was to evaluate the safety and efficacy of TSMLP for pediatric UPJO in a large multicenter series. MATERIALS AND METHODS: Medical records of consecutive patients who underwent TSMLP for pediatric UPJO in six academic institutions between June 2010 and May 2015 were retrospectively analyzed. The data of ultrasound, magnetic resonance urography, and diuretic renogram using 99Tc-diethylene triamine pentaacetic acid scan were collected during preoperative and postoperative periods. RESULTS: A total of 704 patients (750 kidneys) with UPJO who underwent TSMLP were recruited for this study. Of these patients, there were no significant differences in demographics and clinical presentation of the patients among the six centers. The operative time of all patients decreased significantly with time. The earlier the beginning of the operation, such as cohort A, B, and C, the longer the learning curve has been. Of these 704 patients, there were 60 (8.11%) postoperative minor complications during the postoperative hospitalization period, and all minor postoperative complications were cured by observation or drugs. There were 14 (1.99%) major postoperative complications, and all major complications were cured by minimally invasive surgery. No additional complications were encountered during the follow-up of 2.1 years (mean, ranged 1 year to 4 years). Success rate of TSMLP are more than 95% among six centers. CONCLUSIONS: We reported a multi-institutional series of TSMLP in children with UPJO. Our findings suggest that TSMLP represents a feasible treatment option for UPJO by offering reliable outcomes, low postoperative complications and high success rates.

Comparison of Laparoscopic Approaches for Dismembered Pyeloplasty in Children With Ureteropelvic Junction Obstruction: Critical Analysis of 11-Year Experiences in a Single Surgeon.

OBJECTIVE: The choice of different laparoscopic approaches of laparoscopic pyeloplasty (LP) in children remains controversial. We present a comparison of different approaches of LP in children and a critical analysis of 11-year experiences in a single surgeon. MATERIALS AND METHODS: There were 1750 patients (1889 sides) who underwent LP between 2003 and 2014 reviewed. The diagnosis and outcomes of ureteropelvic junction obstruction (UPJO) were reviewed based on clinical and imaging data. Retroperitoneal laparoscopic pyeloplasty (RPLP) were performed in 451 cases (RPLP group), conventional transperitoneal laparoscopic pyeloplasty (CTLP) were performed in 311 cases (CTLP group), transumbilical single-site laparoscopic pyeloplasty (TSLP) were performed in 322 cases (TSLP group), and transumbilical multiport laparoscopic pyeloplasty (TMLP) were performed in 805 cases (TMLP group). We assessed preoperative clinical data and outcomes, and analyzed the transition experience. Data are expressed as medians for continuous variables. RESULTS: The start of oral feeding, hospital stay, and the operative time of RPLP group were 1.10 ± 0.10 days, 5.22 ± 1.32 days, and 138.2 ± 20.1 minutes, respectively. Compared with the other 3 groups, the start of oral feeding was the soonest, hospital stay was the shortest, and the operative time was the longest in the RPLP group (P < .01 or .05). The cosmetic result of the TMLP group was 7.07 ± 1.20 scores, and there are significant differences in cosmetic results between the TMLP group and the other 3 groups (P < .05). CONCLUSION: Although the 4 laparoscopic approaches for LP in children with UPJO are safe and efficient procedures with equivalent success rates, we recommend RPLP or TMLP as a treatment option for children with UPJO.

A modified technique of paraumbilical three-port laparoscopic dismembered pyeloplasty for infants and children.

BACKGROUND: Common causes of complications of laparoscopic pyeloplasty in children include anastomotic stricture, poor drainage due to high ureteropelvic anastomosis, and torsion of ureter. Herewith, we described our modified technique of paraumbilical three-port laparoscopic dismembered pyeloplasty (PTLDP) to minimize these complications. PATIENTS AND METHODS: Data from 62 patients (age: 1-180 months, median: 12 months) with ureteropelvic junction obstruction (UPJO) who underwent pyeloplasty using our modified technique of PTLDP between February 2014 and September 2014 at our institution were reviewed. The key steps of our modified method involve identifying the lowest point of the renal pelvis and the lateral aspect of the ureter to guarantee a low pelviureteric and correct orientation anastomosis, and using a 4-0 silk for assistant suturing to avoid crushing of the anastomotic tissue. RESULTS: All surgeries were successfully completed without conversion. Three patients required an accessory port for the anastomosis. All the patients achieved complete clinical or radiologic resolution after the operation. The mean operative time was 103.4 min, and mean estimated blood loss was 14.4 mL. Mean postoperative differential function of affected kidney was 43.0 ± 16.3 % (range 24-100 %), increased from 39.7 ± 18.0 % (range 18-100 %), preoperatively (p < 0.001). The success rate was 100 % at a mean follow-up of 18.3 ± 2.9 (range 13-25) months. CONCLUSIONS: Our modified technique of PTLDP is safe and feasible and to allow high success rate for the treatment of pelviureteric junction obstruction in children.

Histone deacetylase 5 promotes Wilms' tumor cell proliferation through the upregulation of c-Met.

The histone deacetylase (HDAC) family is comprised of enzymes, which are involved in modulating the majority of critical cellular processes, including transcriptional regulation, apoptosis, proliferation and cell cycle progression. However, the biological function of HDAC5 in Wilms' tumor remains to be fully elucidated. The present study aimed to investigate the expression and function of HDAC5 in Wilm's tumor. It was demonstrated that the mRNA and protein levels of HDAC5 were upregulated in human Wilms' tumor tissues. Overexpression of HDAC5 in G401 cells was observed to significantly promote cellular proliferation, as demonstrated by the results of an MTT assay and bromodeoxyuridine incorporation assay. By contrast, HDAC5 knockdown using small interfering RNA suppressed the proliferation of the G401 cells. At the molecular level, the present study demonstrated that HDAC5 promoted the expression of c­Met, which has been previously identified as an oncogene. In addition, downregulation of c­Met inhibited the proliferative effects of HDAC5 in human Wilms' tumor cells. Taken together, these results suggested that HDAC5 promotes cellular proliferation through the upregulation of c­Met, and may provide a novel therapeutic target for the treatment of patients with Wilms' tumor.

Alterations in gene expression during sexual differentiation in androgen receptor knockout mice induced by environmental endocrine disruptors.

In the present study, we aimed to explore the effect of environmental endocrine disruptors (EEDs) on sexual differentiation in androgen receptor (AR)-/-, AR+/- and AR+/+ male mice. By using a Cre-loxP conditional knockout strategy, we generated AR knockout mice. By mating flox-AR female mice with AR-Cre male mice, the offspring male mice which were produced were examined. Mice not subjected to any type of intervention were used as the controls. Furthermore, male mice of different genotypes were selected and further divided into subgroups as follows: the control group, bisphenol A (BPA) group and the dibutyl phthalate [corrected] (DBP) group. The expression of the Wilms tumor 1 (WT1), lutropin/choriogonadotropin receptor (LHR), 17-ß-hydroxysteroid dehydrogenase type 3 (17ßHSD3) and steroid-5-alpha-reductase, alpha polypeptide 2 (SRD5A2) genes was determined by RT-qPCR and western blot analysis. There was no statistically significant difference in the weight of the mice between the control group and the knockout group (P>0.05). The results revealed that, compared with the control group, in the knockout group, anogenital distance was shortened, and testicular weight and testosterone levels were decreased; estradiol levels were elevated; the differences were statistically significant (P<0.05). In the group of AR+/- male mice exposed to 100 mg/l EEDs, hypospadias was successfully induced, suggesting that EEDs are involved in the embryonic stage of sexual development in male mice. The quantitative detection of WT1, LHR, 17ßHSD3 and SRD5A2 gene expression by RT-qPCR and western blot analysis indicated that these genes were significantly downregulated in the mice in the BPA group. In conclusion, exposure to EEDs induces hypospadias in heterozygous and wild-type male mice offspring during sexual differentiation, but has no effect on homozygous offspring. Therefore, EEDs play an important role during the third stage of sexual differentiation.

Stat3 inhibits WTX expression through up-regulation of microRNA-370 in Wilms tumor.

Wilms tumor (WT) is a genetically heterogeneous childhood kidney tumor. Several genetic mutations have been identified in WT patients, including inactivation of WTX, somatic stabilizing CTNNB1, and p53 mutations. However, the molecular mechanisms in tumorigenesis remain largely unexplored. Stat3 is a transcription factor that can promote oncogenesis. Stat3 activation is commonly viewed as crucial for multiple tumor proliferation and metastasis. We show that Stat3 is highly activated in Wilms tumor tissues compared to those in adjacent tissues. IL-6 treatment or transfection of a constitutively activated Stat3 in G401 cells promotes cell proliferation. At the molecular level, we further elucidate that Stat3 inhibits WTX expression through up-regulation of microRNA-370. Our results suggest that Stat3/miR-370/WTX regulatory axis might be a critical mechanism in Wilms tumor cells.

Protective effect of estrogen on intestinal ischemia-reperfusion injury in pubertal rats.

PURPOSE: This study investigated the role of 17beta-estradiol (E(2)) in intestinal ischemia-reperfusion (I/R) injury and its possible mechanism. METHODS: Rats of pubertal age were ovariectomized and injected subcutaneously with vehicle (vehicle group) or E(2) (100 or 500 mug/kg/every other day, E(2) or 5E(2) group) for 4 weeks. Other rats of the same age underwent sham ovariectomy as a control group. The rats in each group (n = 15) were subjected to superior mesenteric artery occlusion followed by 1 hour (n = 5), 6 hours (n = 5), or 24 hours (n = 5) reperfusion. Intestine specimens then were obtained for the determination of histopathologic score, inducible nitric oxide synthase (iNOS) mRNA expression, and iNOS activity. RESULTS: In vehicle, control, E(2), and 5E(2) groups, the histopathologic scores were 3.31 +/- 0.12, 3.00 +/- 0.09, 2.57 +/- 0.12, and 2.98 +/- 0.08, respectively. The expression levels of iNOS mRNA were 3.85 +/- 0.42, 4.86 +/- 0.76, 5.17 +/- 0.34, and 4.25 +/- 0.41 log copies, respectively. Lower histopathologic score but higher iNOS mRNA expression were found in E(2) group than in the other groups (P < .01). The level of iNOS activity paralleled the expression of iNOS mRNA. CONCLUSIONS: Estrogen may exert a protective effect on intestinal I/R injury in pubertal rats, probably by enhancing iNOS expression.