Visual identification of three kinds of human decidual tissues from elective termination of pregnancy.

INTRODUCTION: The decidua can be classified into the decidua basalis, decidua capsularis and decidua parietalis. This study aimed to visually identify these three kinds of decidual tissues from fresh samples obtained in early pregnancy based on their macroscopic appearances, which can be discerned visually. METHODS: Decidual samples were collected from 15 pregnant women between 6 and 8 weeks of gestation after elective termination of pregnancy. We identified the three different kinds of fresh decidual tissues in early pregnancy according to their different macroscopic appearances by only the naked eye. H&E staining, in situ immunofluorescence and flow cytometry were performed to confirm the accuracy of this method. RESULTS: We developed a method to discern the three different kinds of decidual tissues according to their individual macroscopic features. We found that the decidua parietalis was a thick tissue with less blood, with one side being intact epidermis and the other side being rough tissue. The decidua basalis had rough surfaces, a dense texture and high blood content. The decidua capsularis was a thin membrane tissue with or without blood clots. CK+/HLA-G+ extravillous trophoblast cells (EVTs) and heme oxygenase-1+ (HMOX1+) decidual macrophages were present in large quantities in the decidua basalis and decidua capsularis but were nearly undetectable in the decidua parietalis. We also found a wide distribution of endovascular extravillous trophoblast cells (enEVTs), which participate in spiral artery remodelling in the decidua basalis. DISCUSSION: We successfully identified three kinds of human decidual tissues from early pregnancy with the naked eye for the first time. This breakthrough method will greatly assist studies related to decidua during early pregnancy.

Inhibition of chemokine receptor CXCR2 attenuates postoperative peritoneal adhesion formation.

BACKGROUND: Postoperative peritoneal adhesions remain a problem after general and gynecological surgery. METHODS: Hematoxylin and eosin and Masson's trichrome staining of ischemic buttons were performed 6, 12, 24 hours, and 7 days after button induction. Scanning electron microscopy, ribonucleic acid sequencing, quantitative real-time polymerase chain reaction, immunohistochemical staining, and flow cytometry were used to elucidate the pathophysiology of postoperative peritoneal adhesions. RESULTS: The results showed that thickening of the peritoneum and abscission of mesothelial cells and collagen fibers increased significantly on the surface of the "button" in the control groups at 24 hours postoperatively. Scanning electron microscopy revealed a large number of granulocytes on the button surface in the control group at 24 hours. Ribonucleic acid sequencing and quantitative real-time polymerase chain reaction also revealed that CXCR2 expression was significantly upregulated. In addition, danirixin, a CXCR2 inhibitor, reduced abdominal adhesion in the injured area by inhibiting the infiltration of inflammatory cells and collagen production. Immunohistochemical staining showed decreased expression of CXCR2 in the adhesion area 7 days after surgery in the treatment group. Flow cytometry showed a significantly decreased neutrophil ratio in the treatment group compared with that in the control group 24 hours after the operation. CONCLUSIONS: Inflammation plays an important role in the early stages of postoperative peritoneal adhesion formation, whereas collagen fibers and angiogenesis play important roles in the late stages. The CXCL2-CXCL3-CXCR2 signaling axis is an important link in the mechanism of postoperative peritoneal adhesion formation, and the application of CXCR2 inhibitors can alleviate the formation of postoperative peritoneal adhesions.

Thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriage.

BACKGROUND: It has been long known that thyroid hormone regulates placental villi development, which is associated with the occurrence of miscarriage. However, whether abnormal thyroid hormone metabolism and transport in placental villi are involved in miscarriage is still to be verified. METHODS: Placental villi of elective terminations of pregnancies (ETPs) and miscarriage were collected. Proliferative activity and apoptosis of villi trophoblasts and angiogenesis were detected by TUNEL and immunochemistry. The expressions of thyroid hormone receptors (THRs), transthyretin (TTR), monocarboxylate transporter 8 (MCT8), organic anion transporting polypeptides 1A1 (OATP1A1), deiodinase 2 (Dio2) and Dio3 were examined by RT-PCR, Western blot, immunohistochemistry and immunofluorescence. JEG3 cell was treated with iopanoic acid (IOP), an inhibitor of Dio2 activity, the expressions of Dio2, placenta growth factor (PLGF) and sFlt1 were detected by RT-PCR and Western blot. RESULTS: Cell proliferation was suppressed and apoptosis was increased in placental villi cytotrophoblasts of miscarriage. CD34+ vessel number and vascular endothelial growth factor (VEGF) protein abundance were decreased in miscarriage. In miscarriage group, the gene expression of Dio2, Dio3, TTR and THRα, but not THRß, MCT8 and OATP1A1, were downregulated. The protein abundances of TTR and THRα were downregulated in miscarriage group, but not THRß. The protein abundance of Dio2 in miscarriage villi was decreased compared with that in ETP. In JEG3 cells, the gene expression of PLGF was decreased and the expression of sFlt1 was increased in IOP treatment; The protein abundance of Dio2 was downregulated but the gene expression of Dio2 was unaffected in IOP treatment. CONCLUSION: Thyroid hormone transport and metabolism in miscarriage were disturbed and may impaired angiogenesis of placental villi, which was associated with the occurrence of miscarriage.

Pyruvate dehydrogenase kinase 1 regulates the function of human decidual natural killer cells.

PROBLEM: Pyruvate dehydrogenase kinase 1 (PDK1) is an important enzyme for immune cell development. However, PDK1's role in human decidual natural killer (dNK) cells remains largely unknown. METHODS OF STUDY: PDK1 expression in dNK cells from patients with recurrent spontaneous abortions (RSA) and age-matched healthy controls was analyzed by qRT-PCR, western bolt and flow cytometry. Moreover, dNK cells were treated with PDK1 inhibitor or the PDK1 siRNA followed by functional assays. RESULTS: The dNK cells from patients who underwent RSAs had higher mRNA expression and increased protein of PDK1, perforin (PRF1), Granzyme B (GZMB), IFN-γ (IFNG), and CD107a expression compared to dNK cells from age-matched healthy controls. Perforin, Granzyme B, IFN-γ and CD107a expression levels in dNK cells were down-regulated when dNK cells were treated with a PDK1 inhibitor. As measured by the 51 Cr release assay, the killing activity of dNK cells was found to be decreased. We also demonstrated that PDK1 blockade could up-regulate the migration and adhesion of dNK cells. Furthermore, PDK1 inhibition reduced the glycolysis of dNK cells. CONCLUSION: This study suggested that PDK1 plays an important role in regulating dNK cell functions and human RSA.

Altered intestinal microflora and barrier injury in severe acute pancreatitis can be changed by zinc.

To investigate the effect of zinc (Zn) supplementation on intestinal microflora changes and bacterial translocation in rats with severe acute pancreatitis (SAP), the rats were divided into the sham surgery (SS), SAP, SS + Zn, and SAP + Zn groups. Saline (0.1 mL/100g) and 5% sodium taurocholate were injected into the pancreaticobiliary duct of the rats in the SS and SAP + Zn groups, respectively. Intraperitoneal injection of 5 mg/kg Zn was performed immediately after injecting saline or 5% sodium taurocholate into the rats in both groups. Serum amylase and Zn levels, plasma endogenous endotoxin, intestinal permeability, and the positive rate of intestinal bacterial translocation were detected, haematoxylin and eosin (H&E) staining was performed, and the pancreatic tissue scores were calculated for each group. In addition, immunohistochemical (IHC) staining was performed to evaluate the expression of IL-1ß and TNF-α. Real-time fluorescence quantitative PCR was used to quantify the gene copy numbers of Escherichia, Bifidobacterium, and Lactobacillus in the cecum. The levels of amylase and plasma endotoxin in the SAP group were significantly higher than those in the SS and SS + Zn groups. Intestinal mucosal permeability and intestinal bacterial translocation in the liver, pancreas, and mesenteric lymph nodes were increased in the SAP group. However, the levels of amylase and plasma endotoxin were decreased as a result of zinc supplementation in the SAP group. The expression of IL-1ß and TNF-α was also reduced to a greater degree in the SAP + Zn group than in the SAP group. Moreover, alleviated intestinal mucosal permeability and intestinal bacterial translocation in the liver, pancreas, and mesenteric lymph nodes were found in the SAP + Zn group. The results of real-time quantitative PCR showed that the gene copy number of Escherichia increased with time, and the gene copy numbers of Lactobacillus and Bifidobacterium decreased over time. Zn supplementation prevented the release of TNF-α and IL-1ß, alleviated intestinal permeability and endotoxemia, reduced bacterial translocation, and inhibited changes in pathogenic intestinal flora in rats with SAP.

Zinc supplement modulates oxidative stress and antioxidant values in rats with severe acute pancreatitis.

Oxidative stress is a main factor in the pathogenesis of severe acute pancreatitis (SAP). The ability of zinc (Zn) to retard oxidative processes has been recognized for many years. This study aims to examine the levels of free oxygen radicals and antioxidant enzyme in SAP rats and know the effect of Zn supplementation on free oxygen radicals and antioxidant system in rats with SAP. Forty-five male Wistar rats were divided into three groups-the SAP group (n=15), the Zn-treated group (n=15), and the controlled group (n=15). For the SAP group, sodium taurocholate is injected into the pancreatic duct to induce SAP; for the Zn-treated group, Zn (5 mg/kg) is subcutaneously injected immediately after injection of 5% sodium taurocholate. Firstly, the activity of erythrocyte glutathione peroxidase (GSH-Px), erythrocyte superoxide dismutase (SOD), and the content of plasma malondialdehyde (MDA), which are the toxic products of oxidative stress, is measured. Secondly, the levels of free oxygen radicals in the liver and kidney are detected. The result showed that the activity of GSH-Px and SOD was lower in the SAP group than that in the controlled group, although the content of plasma MDA increased. However, the activity of SOD and GSH-Px in the Zn-treated group was not significantly decreased after comparing with the controlled group; in the mean time, the content of MDA was not significantly increased either. Moreover, the content of free radical in liver and kidney was higher in the SAP group compared with the controlled group, but the content of free radical in the Zn-treated group was not higher than that in the controlled group (p>0.05). All of the above indicated that Zn may recover the activity of free radical-scavenging enzymes and decrease the content of free radical for the SAP group rats. In conclusion, the content of free radical increase may be one of the reasons that SAP rats are injured, and it is possible for Zn to be used to treat SAP through scavenging free radical and increasing the activity of SOD and GSH-Px of erythrocyte.

Analysis of the association between adiponectin, adiponectin receptor 1 and diabetic cardiomyopathy.

The aim of this study was to explore the association between adiponectin (APN), APN receptors and insulin resistance (IR) using rats with type 2 diabetes mellitus (T2DM) as a model of diabetic cardiomyopathy (DC). Serum and cardiac APN levels were assessed using a double-antibody sandwich ELISA. In addition, the mRNA and protein expression of the myocardial APN receptor 1 (AdipoR1) was determined using the reverse transcription polymerase chain reaction and immunohistochemical staining. The results showed that the heart weight/body weight ratio, fasting plasma glucose (FPG) and lipid levels, and the homeostasis model assessment-estimated IR (HOMA-IR) index were elevated in the T2DM group compared with the control group. Cardiac function was significantly lower in the T2DM group compared with the control group (P<0.05). Furthermore, serum and cardiac APN levels were significantly reduced in the T2DM group compared with the control group, and mRNA and protein expression of AdipoR1 was lower in the T2DM group compared with the control group (P<0.05). Changes in the morphology of myocardial cells were observed under the light microscope using hematoxylin and eosin staining. Myocardial cell hypertrophy, a disordered cell arrangement and irregular nuclear size were observed in the T2DM group. By contrast, myocardial cells in the control group were arranged in neat rows with uniform cytoplasmic and nuclear staining. According to the correlation analyses, serum APN levels in the T2DM group were negatively correlated with FPG, triglyceride, total cholesterol and fasting insulin (FINS) levels, as well as with the HOMA-IR index. Myocardial AdipoR1 protein expression was positively correlated with myocardial APN levels, and negatively correlated with FINS and HOMA-IR. It may be concluded that myocardial and serum levels of APN are reduced in rats with DC. Metabolic disorders of blood glucose and lipid levels, as well as IR, are associated with low APN levels. Furthermore, low levels of myocardial Adipo1R mRNA and protein expression correlate with reduced insulin sensitivity.

Shenqi fuzheng, an injection concocted from Chinese medicinal herbs, combined with platinum-based chemotherapy for advanced non-small cell lung cancer: a systematic review.

BACKGROUND: Platinum-based chemotherapy has been a standard therapy for advanced non-small cell lung cancer (NSCLC), but it has high toxicity. In China, Shenqi Fuzheng, a newly developed injection concocted from Chinese medicinal herbs has been reported that may increase efficacy and reduce toxicity when combined with platinum-based chemotherapy, but little is known about it outside of China. The aim of this study was to systematically review the existing clinical evidence on Shenqi Fuzheng Injection(SFI) combined with platinum-based chemotherapy for advanced NSCLC. METHODS: Pubmed, Cochrane Library, EMBASE, CNKI, and CBM search were organized for all documents published, in English and Chinese, until April 2010. The randomized controlled clinical trials were selected based on specific criteria, in which a SFI plus platinum-based chemotherapy treatment group was compared with a platinum-based chemotherapy control group for patients with advanced NSCLC. The quality of studies was assessed by modified Jadad's scale, and Revman 4.2 software was used for data syntheses and analyses. RESULTS: Twenty nine studies were included in this review based on our selection criteria. Of them, ten studies were of high quality and the rest were of low quality, according to the modified Jadad scale. The meta-analysis showed there was a statistically significant higher tumor response (RR, 1.19; 95% CI, 1.07 to 1.32; P = 0.001) and performance status ((RR, 1.57; 95% CI, 1.45 to 1.70; P < 0.00001); but lower severe toxicity for WBC (RR, 0.37; 95% CI, 0.29 to 0.47; P < 0.00001), PLT (RR, 0.33; 95% CI, 0.21 to 0.52; P < 0.00001), HB (RR, 0.44; 95% CI, 0.30 to 0.66; P < 0.0001) and nausea and vomiting (RR, 0.32; 95% CI, 0.22 to 0.47; P < 0.00001), when the SFI plus platinum-based chemotherapy treatment group was compared with the platinum-based chemotherapy control group. Sensitivity analysis was restricted to studies with the high quality, and the result was similar when the studies with low quality were excluded. Asymmetry was observed in a funnel plot analysis, and Egger's test also indicated an evidence of publication bias (P = 0.016). CONCLUSIONS: SFI intervention appears to be useful to increase efficacy and reduce toxicity when combined with platinum-based chemotherapy for advanced NSCLC, although this result needs to be further verified by more high-quality trials.

The association between arsenic and children's intelligence: a meta-analysis.

This present study was undertaken to investigate whether arsenic exposure increases the risk of children's low intelligence quotient (IQ) in China. MEDLINE, SCI, CNKI, and CBM search were organized for all documents published, in English and Chinese, between 1988 and 2008 using the following keywords: arsenic, intelligence, and IQ. As a result, four cross-sectional studies that assessed the development of low IQ in children who had been exposed to arsenic earlier in their life were included in this study. The summary weighted mean difference of IQ was calculated in this meta-analyses, when arsenicosis areas or slight arsenicosis areas were compared with non-arsenicosis areas; it is -6.85 (95% confidence interval [CI] = -8.30 to -5.41; p < 0.01, using a fixed effect model) and -6.54 (95%CI = -8.93 to -4.15; p < 0.01, using a random effect model), which means that children who live in an arsenicosis area or a slight arsenicosis area have lower IQ than those who live in a non-arsenicosis area, and there may be a strong association between arsenic and children's intelligence.