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Junctional adhesion molecule-C (JAM-C) is an important regulator of many physiological processes, ranging from maintenance of tight junction integrity of epithelia to regulation of cell migration, homing and proliferation. Preeclampsia (PE) is a trophoblast-related syndrome with abnormal placentation and insufficient trophoblast invasion. However, the role of JAM-C in normal pregnancy and PE pathogenesis is unknown.The expression and location of JAM-C in placentas were determined by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry. The expression of differentiation and invasion markers were detected by qRT-PCR or western blot. The effects of JAM-C on migration and invasion of trophoblasts were examined using wound-healing and invasion assays. Additionally, a mouse model was established by injection of JAM-C-positive adenovirus to explore the effects of JAM-C in vivo.In normal pregnancy, JAM-C was preferentially expressed on cytotrophoblast (CTB) progenitors and progressively decreased when acquiring invasion properties with gestation advance. However, in PE patients, the expression of JAM-C was upregulated in extravillous trophoblasts (EVTs) and syncytiotrophoblasts (SynTs) of placentas. It was also demonstrated that JAM-C suppressed the differentiation of CTBs into EVTs in vitro. Consistently, JAM-C inhibited the migration and invasion capacities of EVTs through GSK3β/β-catenin signaling pathway. Importantly, Ad-JAMC-infected mouse model mimicked the phenotype of human PE.JAM-C plays an important role in normal placentation and upregulated JAM-C in placentas contributes to PE development.

Preeclampsia (PE) is a pregnancy-related syndrome characterized by new-onset hypertension and proteinuria after gestational 20 weeks. Oxidative stress, resulting from the imbalance between the production of oxidants and antioxidants in placentas, is recognized as a key pathology of PE. To date, the molecules that regulate antioxidants production remain unclear. CD151, a member of tetraspanins, is an important regulator of many physiological functions. However, the function of CD151 in oxidative stress and its association with pregnancy-related complications are currently unknown. In the present study, we have demonstrated that CD151 was a key regulator of antioxidants in placentas. Compared with the placentas of the controls, the placentas of PE patients exhibited decreased CD151 expression accompanying with decreased antioxidant gene expression (HO-1, NQO-1, GCLC and SOD-1). In vitro, overexpression of CD151 in trophoblast cells could enhance HO-1, NQO-1, GCLC and SOD-1 expression but downregulation of CD151 decreased those antioxidant genes expression, which indicates CD151 is the upstream of antioxidants. Importantly, the phenotype of PE (hypertension and proteinuria) was mimicked in the downregulating CD151 induced mouse model. Moreover, the beneficial effect of CD151 in trophoblast cells was hindered when ERK and Nrf2 signaling were blocked. Overall, our results revealed CD151 might be a new target for PE treatment.

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21–5 p to inhibit miR-21–5 p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC–EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC–EMT and administration of miR-21–5 p could reverse this process and improve endometrial fibrosis. Our findings revealed that the dysfunction of circPTPN12/miR-21–5 p/∆Np63α pathway contributed to the pathogenesis of endometrial fibrosis.

BackgroundOwing to the low prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in lupus nephritis (LN), there is no study about the differences between proteinase 3 (PR3)-ANCA positivity and myeloperoxidase (MPO)-ANCA positivity in LN until now.MethodsHere we perform a retrospective study to determine whether there are differences in clinic-pathological characteristics and renal outcomes between PR3-ANCA-positive LN patients and MPO-ANCA-positive LN patients.ResultsA total of 26 (27.4%) PR3-ANCA-positive LN patients and 69 (72.6%) MPO-ANCA-positive LN patients ( p ConclusionMPO-ANCA-positive LN patients had more severely impaired baseline renal function and less active lupus serology. More severely chronic pathological changes, including interstitial fibrosis and tubular atrophy on renal specimens, occurred in MPO-ANCA-positive LN patients. We found that MPO-ANCA-positive LN patients had worse renal outcomes.

Background The present study aimed to explore the correlation of long non‐coding RNA highly up‐regulating in liver cancer (lncRNA HULC) with disease risk, inflammatory cytokines, biochemical indexes, disease severity, infective features, and 28‐day mortality of sepsis. Methods Totally 174 sepsis patients and 100 controls were enrolled. Peripheral blood samples were collected from sepsis patients after diagnosis and from controls at enrollment, respectively, and further for separation of peripheral blood mononuclear cell (PBMC) and serum samples. PBMC samples were for lncRNA HULC detection, and serum samples were for inflammatory cytokine detection. Results LncRNA HULC expression was increased in sepsis patients compared with controls. Moreover, lncRNA HULC was positively associated with TNF‐α, IL‐6, IL‐17, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, serum creatinine, white blood cell, and C‐reactive protein in sepsis patients, but not in controls. Furthermore, in sepsis patients, lncRNA HULC expression was positively correlated with acute physiology and chronic health evaluation II score and sequential organ failure assessment score, but not correlated with primary infection sites or primary infection organisms; meanwhile, lncRNA HULC expression was increased in deaths compared with survivors; subsequent receiver operating characteristic curve indicated that lncRNA HULC presented good value in predicting increased 28‐day mortality (AUC: 0.785, 95% CI: 0.713–0.857), and its independent predictive value for mortality was also verified by multivariate analysis. Conclusion LncRNA HULC is correlated with higher disease risk, severity, and inflammation and serves as an independent factor for predicting increased mortality, suggesting its potential in promoting accuracy of prognostic prediction for sepsis management., Totally 174 sepsis patients and 100 controls were enrolled and their peripheral blood samples were collected and separated for lncRNA HULC and inflammatory cytokine detection. Results indicated that lncRNA HULC expression was increased in sepsis patients compared with controls; LncRNA HULC was positively associated with higher inflammation level in sepsis patients, but not in controls; In sepsis patients, lncRNA HULC expression was positively correlated with increased disease severity, and serves as an independent factor for predicting increased mortality.

Asherman's syndrome (AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells (BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.

Introduction We evaluated the current status of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) detection in invasive breast carcinoma (IBC) in various laboratories across China. Materials and Methods The Breast Pathology Study Group of the Chinese Society of Pathologists collected HR and HER2 data from 12,467 IBC cases from 19 representative clinical centers in China. The data from every center were compared with the pooled data from the other centers. Results The assessment of HR status showed that the overall positive estrogen receptor (ER) and progesterone receptor (PR) rates were 71.7% and 63.7% (range, 60.9%-87.9% and 43.9%-84.8%), respectively. The ER results in 3 centers and the PR results in 6 centers were outside the 99.5% confidence interval and were considered to be outliers (P Conclusions As the largest study of HR and HER2 status in Chinese patients with IBC, the data from the present study have indicated that the overall rates of HR and HER2 were comparable to those reported in previous studies. However, the rates varied among the laboratories. Individual centers had not met the target values, and they need to improve the detection.

Intrauterine adhesion (IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked angiogenesis is the main pathological change in the scarred endometrium. The fibroblast growth factor 2 (bFGF), a member of FGF family, is usually applied to promote healing of refractory ulcer and contributes to angiogenesis of tissues. In this study, the sustained-release system of bFGF 100 µg was administrated around scarred endometrium guiding by ultrasound every 4 weeks in 18 patients (2–4 times). Results showed that after treatment, the menstrual blood volume, endometrial thickness and the scarred endometrial area were improved. Histological study showed blood vessel density increased obviously. Three patients (3/18) achieved pregnancy over 20 gestational weeks. Therefore, administrating the bFGF surrounding scarred endometrium may provide a new therapeutic approach for the patients with endometrial fibrosis.

To investigate the expressions of multidrug resistance-associated protein 1 (MRP1) gene, serum transforming growth factor beta-1 (TGF-β1) and interleukin-8 (IL-8) in patients with breast cancer during chemotherapy, and to analyze their correlations in chemotherapy.346 breast cancer patients admitted to the Department of Surgery (Breast) of Nanjing Drum Tower Hospital from March 2015 to December 2017 were included as study subjects. All selected patients received chemotherapy in our hospital. Quantitative reverse transcription- polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were adopted to detect the expression levels of MRP1 mRNA, as well as MRP1, TGF-β1 and IL-8 proteins in patients before chemotherapy and at 1, 2, 4 and 8 weeks after chemotherapy. Correlations of MRP1 protein/mRNA with clinical features of patients were analyzed, and Pearson's correlation analysis was performed to examine correlations of MRP1 protein/mRNA with TGF-β1 and IL-8 proteins.The expressions of MRP1 mRNA as well as MRP1, TGF-β1 and IL-8 proteins were increased with the prolongation of chemotherapy time, and there were statistically significant differences between the two time points (psemi;0.05). No correlations of MRP1 with the clinical patient features with breast cancer were found. Pearson's correlation analysis showed that the expression level of MRP1 was positively correlated with the expression levels of TGF-β1 (r=0.732, p=0.012) and IL-8 (r=0.709, p=0.018), and the expression level of TGF-β1 was positively related to that of IL-8 (r=0.714, p=0.015).With the prolongation of chemotherapy time in breast cancer patients, the expression level of MRP1 also increased which may affect the therapeutic effect of chemotherapy in breast cancer patients and lead to drug resistance. TGF-β1 and IL-8 may be closely associated with the mechanism of drug resistance in MRP1-guided breast cancer chemotherapy.

Background Cytomegalovirus (CMV) is a significant cause of fetal abnormalities in developed world. Whether this could be applied in developing world remains unknown. Objectives To investigate CMV infection in severe fetal malformations in China. Study design During 2007–2014, 436 fetuses (237 males) with severe malformations and terminated pregnancy at median gestational age of 26+1 weeks were enrolled. CMV DNA was detected in fetal kidneys and other tissues by real-time PCR, and CMV IgG and IgM were measured by ELISA. Results CMV DNA was positive in kidneys and other tissues of seven (1.60%) fetuses. Hematoxylin-eosin staining showed intranuclear and intracytoplasmic inclusion bodies in kidneys of three fetuses, which was also positive for CMV antigens in immunohistochemistry. CMV DNA was found in 5 (6.1%) of 82 fetuses with central nervous system anomalies, 1 (11.1%) of 9 fetuses with abdominal anomalies, 1 (0.59%) of 168 fetuses with multiple congenital malformations, and none of fetuses with other anomalies (177). Of 293 pregnant women with plasma available, 279 (95.2%) were CMV IgG positive only and 6 (2.1%) were CMV IgG and IgM positive. Of 5 mothers with infected fetuses 1 (20%) was CMV IgG and IgM positive, while 5 (1.7%) of 288 mothers with uninfected fetuses were positive respectively (P = 0.099). Conclusions Congenital CMV infection in fetuses with severe congenital malformations is rare, indicating no close association between CMV infection and severe fetal malformations in China. Maternal screening for CMV may have minimal value in identifying fetal malformations in developing world.

Background Intrauterine adhesions (IUA) are the most common cause of uterine infertility and are caused by endometrium fibrotic regeneration following severe damage to the endometrium. Although current stem cell treatment options using different types of autologous stem cells have exhibited some beneficial outcomes in IUA patients, the reported drawbacks include variable therapeutic efficacies, invasiveness and treatment unavailability. Therefore, the development of new therapeutic stem cell treatments is critical to improving clinical outcomes. Methods Twenty-six patients who suffered from infertility caused by recurrent IUA were enrolled in this prospective, non-controlled, phase I clinical trial with a 30-month follow-up. During the procedure, 1 × 107 umbilical cord-derived mesenchymal stromal cells (UC-MSCs), loaded onto a collagen scaffold, were transplanted into the uterine cavity following an adhesion separation procedure. Medical history, physical examination, endometrial thickness, intrauterine adhesion score and the biological molecules related to endometrial proliferation and differentiation were assessed both before and 3 months after cell therapy. Results No treatment-related serious adverse events were found. Three months after the operation, the average maximum endometrial thickness in patients increased, and the intrauterine adhesion score decreased compared to those before the treatment. A histological study showed the upregulation of ERα (estrogen receptor α), vimentin, Ki67 and vWF (von Willebrand factor) expression levels and the downregulation of ΔNP63 expression level, which indicates an improvement in endometrial proliferation, differentiation and neovascularization following treatment. DNA short tandem repeat (STR) analysis showed that the regenerated endometrium contained patient DNA only. By the end of the 30-month follow-up period, ten of the 26 patients had become pregnant, and eight of them had delivered live babies with no obvious birth defects and without placental complications, one patient in the third trimester of pregnancy, and one had a spontaneous abortion at 7 weeks. Conclusions Transplanting clinical-grade UC-MSCs loaded onto a degradable collagen scaffold into the uterine cavity of patients with recurrent IUA following adhesiolysis surgery is a safety and effective therapeutic method. Trial registration Clinicaltrials.gov. NCT02313415, Registered December 6, 2014. Electronic supplementary material The online version of this article (10.1186/s13287-018-0904-3) contains supplementary material, which is available to authorized users.

Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas this process is interrupted in PE. However, it is not known how the malformed placenta triggers maternal endothelial crisis and the associated manifestations. Here, we have focused on the association of CD81 with PE. CD81, a member of the tetraspanin superfamily, plays significant roles in cell growth, adhesion, and motility. The function of CD81 in human placentation and its association with pregnancy complications are currently unknown. In the present study, we have demonstrated that CD81 was preferentially expressed in normal first TM placentas and progressively down-regulated with gestation advance. In patients with early-onset severe PE (sPE), CD81 expression was significantly up-regulated in syncytiotrophoblasts (STBs), CTBs and the cells in the villous core. In addition, high levels of CD81 were observed in the maternal sera of patients with sPE. Overexpressing CD81 in CTBs significantly decreased CTB invasion, and culturing primary human umbilical vein endothelial cells (HUVECs) in the presence of a high dose of exogenous CD81 resulted in interrupted angiogenesis and endothelial cell activation in vitro. Importantly, the phenotype of human PE was mimicked in the CD81-induced rat model.

Visual motor integration (VMI) is a vital ability in childhood development, which is associated with the performance of many functional skills. By using the Beery Developmental Test Package and Executive Function Tasks, the present study explored the VMI development and its factors (visual perception, motor coordination, and executive function) among 151 Chinese preschoolers from 4 to 6 years. Results indicated that the VMI skills of children increased quickly at 4 years and peaked at 5 years and decreased at around 5 to 6 years. Motor coordination and cognitive flexibility were related to the VMI development of children from 4 to 6 years. Visual perception was associated with the VMI development at early 4 years and inhibitory control was also associated with it among 4-year-old and the beginning of 5-year-old children. Working memory had no impact on the VMI. In conclusion, the development of VMI skills among children in preschool was not stable but changed dynamically in this study. Meanwhile the factors of the VMI worked in different age range for preschoolers. These findings may give some guidance to researchers or health professionals on improving children’s VMI skills in their early childhood.

With the objective of being able to assess response to disease or clinical treatment, the densitometry community has long sought the ability to assess short-term change in bone density. The mandible, known to have a high bone turnover, an increased vascularity, and a greater susceptibility to osteoclastic and osteoblastic activities, has long been suggested but has fallen short as a site from which to monitor an early change in the response to a treatment or a disease. The current study developed a method to assess bone density in the superimposed left and right mandibles. Examining a skull in a positioning platform showed that studies between −5.0° and +12.5° from the preferred 0° orientation generated studies that were statistically similar to studies in the preferred orientation. After establishing the distribution of bone density in the mandibles, a software was developed that would execute a search for an area of intermediate content within the body and ramus regions of the mandible; in subsequent studies of the same individual, the analysis software would place the body and ramus regions in the same location without operator dependence. Studies in a population of subjects showed that the density in the body and ramus regions varied independently and that the density in these regions was independent of age. Repeat studies with repositioning showed repeatability of 1.73% and 2.44% for the body and ramus, resulting in computed least significant change limits of 4.84% for the body and 6.83% for the ramus. Examining 45 subjects undergoing treatment for osteoporosis up to over 46 wk showed 22 (49%) subjects with an increase in 1 of the mandible sites, suggesting a benefit from treatment, whereas 12 (27%) subjects showed a decrease in both mandible sites, suggesting a poor response to treatment. We conclude that applying the methodology and allowing the software to locate and define regions of interest allow assessments of change in the bone mineral content at the mandible that will reflect early changes occurring with disease or treatment.

The incidence and mortality of gastric and colorectal cancers are among the highest malignant tumors in China. The aim of this study is to investigate whether variations of the human oxoguanine glycosylase 1 (hOGG1) gene are related to the risk of gastric and colorectal cancers in the Chinese population. There were 622 gastric cancer patients, 383 colorectal cancer patients, and 932 healthy controls recruited to screen for variations in the 5′untranslated region (UTR) and to screen for the missense mutation (p.Ser326Cys) in exon7 of the hOGG1 gene using high-resolution melting curve analysis (HRM) and subsequent sequencing. The promoter luciferase activity assay was applied to assess the potential influence of the detected variants on gene function. Four variations, c.−53G>C, c.−45G>A, c.−23A>G, and c.−18G>T, were detected in the 5′-UTR of the hOGG1 gene. The case–control study indicated that the c.−53G/C heterozygous genotype was markedly associated with gastric cancer (P = 0.008, OR = 2.304, 95% CI, 1.258–4.221), but not with colorectal cancer. The clinicopathological association analysis showed that the variant of c.−53G>C in the hOGG1 gene was prevalent in low-differentiation patients (P = 0.012, OR = 3.174, 95% CI: 1.352–7.448). This variant decreased the gene promoter activity by approximately 17.8% (P = 0.041) and exhibited a synergistic effect with the missense mutation p.Ser326Cys of hOGG1 by enhancing susceptibility to gastric cancers. The variant c.−53G>C in the 5′-UTR of the hOGG1 gene is a risk factor for gastric cancer and is potentially associated with low-differentiation degree, but not with colorectal cancer, in the Chinese population.

8-Hydroxy-2′-deoxyguanine (8-OHdG) is produced by the oxidative stress-induced damage in DNA, which could pair with adenine (A) during DNA replication, leading to G-T transversion mutations. Glycosylase hOGG1 can recognize and excise oxidized guanines from duplex DNA. This work aims to investigate the relationship between the functional variations in 5-untranslated region (5′-UTR) of hOGG1 gene and the risk of breast cancer. Genotypes were analyzed in 518 sporadic breast cancer patients and 777 health controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Risk-stratified subgroup analysis was performed to reveal the associations between the detected variations and the risk of characteristic breast cancer. In addition, immunohistochemistry was carried out to assess the functional effect of these variations on hOGG1gene expression. Five variations in 5′-UTR of hOGG1 gene are found in this study. Three of them, c.-18G>T, c.-23A>G, and c.-53G>C, are known single nucleotide polymorphisms, the other two, c.-45G>A and c.-63G>C, are rare variations. The frequency of c.-18G/T and c.-53G/C was significantly higher in breast cancer patients than those in healthy controls (P = 0.03, OR 2.01, 95% CI 1.04–3.90; and P = 0.01, OR 2.43, 95% CI 1.17–5.04, respectively). Both variations were especially prevalent in premenopausal status, and in the triple (estrogen receptor, progesterone receptor, and human epidermal growth factor Receptor 2) negative subgroups, respectively. Moreover, the variation of c.-18G>T could cause a reduced expression of hOGG1 gene.

The biological effects of soy isoflavones have attracted considerable interest in recent years, leading to numerous studies on dietary intake and epidemiology. (-)-(S)-equol (3) is a metabolite produced in vivo from the isoflavone daidzein, a kind of soy phytoestrogen, by the action of gut microflora. It has higher biological activity than its precursor. Here, we wish to report the isolation and first X-ray crystal structure of 3 from the feces of rats fed a soy-isoflavone-containing diet.

The present study was designed to explore the cross talk between fatty acid synthase (FASN) and HER2 (ErbB2) in ovarian cancer. A total of 60 ovarian cancer patients and 15 normal ovarian tissues were enrolled. Tissue array was conducted by using a tissue microarray instrument. Immunohistochemistry was performed to quantify the expressions of HER2 and FASN. The FASN was detected to be distributed in the cell cytoplasm and was significantly correlated with cancer grade (p = 0.000) and FIGO staging (p = 0.000). Patients with FASN overexpression in ovarian cancer tend to have a worse overall survival rate (p = 0.000). HER2 was also stained to be distributed in the cell cytoplasm associated with higher expression in high-grade cancer. It was also disclosed that FASN expression level is not correlated with HER2 status in ovarian cancer. These results for the first time indicated that a cross talk in FASN and HER2 expressions might be associated with prognosis in malignant ovarian cancer.

Animation creates a vivid, virtual world and expands the scope of human imagination. In this study, we investigated the time-courses of brain responses related to the evaluation of the attractiveness of cartoon faces using the event-related potential (ERP) technique. The results demonstrated that N170 amplitude was higher for attractive than for unattractive cartoon faces in males, while the opposite was found in females. Facial attractiveness notably modulated the late positive component (LPC), which might reflect the task-related process of aesthetic appraisal of beauty. The mean LPC amplitude in males was significantly higher for attractive cartoon faces than for unattractive faces, while the LPC amplitude in females did not significantly differ between attractive and unattractive cartoon faces. Moreover, the paint mode (computer graphics, gouache, and stick figure) modulated the early encoding of facial structures and the late evaluative process. The early modulation effect by paint mode may be related to the spatial frequency of the pictures. The processing speed and intensity in females were both higher than those in males. In conclusion, our study, for the first time, reported ERP modulation based on the assessment of cartoon facial attractiveness, suggesting the facilitated selection of attractiveness information at the early stage, and that the attentional enhancement of attractive faces at the late stage only exists in males. This suggests that men’s brains are hard-wired to be sensitive to facial beauty, even in cartoons.

Alzheimer's disease is characterized by the accumulation and deposition of Aβ peptides in human brains and Aβ induced free radical-mediated damage is one of the hypotheses. In the present study, we explored the protective effects of hyperbaric oxygen (HBO) and Ginkgo Biloba extract (EGB761) on Aβ25-35-induced brain toxicity. Our results demonstrated that EGB761, HBO, and the combination HBO and EGB761, could significantly improve the cognitive function in AD rats' model, especially the combination group. What's more, the activities of superoxide dismutase (SOD) in rat hippocampal tissue were obviously enhanced followed by evidently reduced malondialdehyde (MDA) levels in the same treatment groups mentioned earlier. There were no differences of nitric oxide (NO) productions in the group of EGB761, HBO, and HBO and EGB761, but they were all lower than that of model group. These findings suggest that both HBO and EGB761 may relieve cell toxicity and oxidative stress in AD and thus play a potential protective role in AD. Furthermore, the combination could have better effects compared with single one.

Serious injuries of uterine which lead to scar formation will finally result in infertility or pregnancy complications. There are few effective methods to treat such damages because of the shortage of native tissues. Vascular endothelial growth factor (VEGF) is important for the formation of new vessels and re-epithelialization of endometrium. Here we produced a collagen-binding VEGF by fusing a collagen-binding domain to the N-terminal of native VEGF. After injection into a rat scarred uterus model (partial of rat uterine horn was excised and left for scar formation) the collagen targeting VEGF promoted remodeling of the scarred uterus including the regeneration of endometrium, muscular cells, and vascularization and improved pregnancy outcomes. Thus, collagen-binding VEGF may be a pragmatic solution for the treatment of severe uterine damages.

Objective: 8-Hydroxydeoxyguanosine (8-OHdG) is an oxidized nucleoside that can lead to misincorporation of bases. Human 8-oxoguanine DNA glycosylase (hOGG1) is the key defense enzyme against mutation by the cellular 8-OHdG in duplex DNA. The present study was aimed to explore whether the hOGG1 gene variants play an important role in the carcinogenesis of epithelial ovarian cancer (EOC). Methods: Germ line variants in 5′-untranslated region (c.-18G>T, c.-23A>G, c.-45G>A, and c.-53G>C) and c.977C>G (Ser326Cys) polymorphism in exon7 of the hOGG1 gene in 420 sporadic EOCs and 840 controls were detected. Immunohistochemical and promoter luciferase activity assays were used to explore the effect of c.-18G>T variant on hOGG1 expression. Results: In contrast to type I EOC cases, patients with type II EOC were usually older, already in the advanced stage, and exhibited a common protein 53 (p53) overexpression. The frequencies of genotypes c.-18G/T and c.977G/G in hOGG1 were significantly high in the patients with type II EOC (odds ratio, 2.83; 95% confidence interval, 1.45-5.52; odds ratio, 1.66; 95% confidence interval, 1.26-2.17) but not in the patients with type I EOC. The average level of hOGG1 protein in the normal tissues adjacent to the type II EOC-carried c.-18G/T was lower than that with c.-18G/G (P = 0.01). The luciferase activity in the c.-18T allele was lower than that in the c.-18G allele (P = 0.001). Conclusion: The genotypes of c.-18G/T in 5′-untranslated region and c.977G/G in exon7 of the hOGG1 gene would confer risk to type II EOC.

Severe damages of uterine endometrium which prevent embryos from implantation and placentation finally often result in infertility or pregnant complications. There is lack of effective treatments due to the limitation of native materials available and complexity of the function and internal environment of uterus. In the present study, a collagen targeting basic fibroblast growth factor (bFGF) delivery system was constructed by a collagen membrane loaded with bFGF fused a collagen-binding domain (CBD) to the N-terminal which limits the diffusion of bFGF from collagen. We tested the bFGF delivery system in rats under the severe uterine damage model (partial rat uterine horn excision/reconstruction), and found this delivery system improved regeneration abilities of uterine endometrium and muscular cells, improved vascularization, as well as better pregnancy outcomes in rats. Therefore, this targeting delivery system may be an effective strategy for uterine tissue regeneration.

In this study, 62 preoperative peripheral blood samples from patients with gastrointestinal carcinomas, 12 healthy volunteers, and ten patients with inflammatory gastrointestinal diseases were analyzed for the determination of CEA, CK19, and CK20 mRNA expression in peripheral blood, and its clinical significance was evaluated. Nested reverse transcriptase-polymerase chain reaction (nested RT-PCR) was used to analyze CEA, CK19, and CK20 mRNA expression in peripheral blood. Fresh tumor tissues from patients with colorectal cancer (n=15) were used as a positive control. Among 62 blood samples from patients with gastrointestinal cancer, the expression of CEA, CK19, and CK20 mRNA was 51.6% (32/62), 35.5% (22/62), and 48.4% (30/62), respectively. 74.2% (46/62) were positive for at least one marker. Fifteen tumor tissues were all positive for CEA, CK19, and CK20 mRNA. Only one blood sample from patients with no gastrointestinal carcinoma was positive for CEA mRNA. Our results indicate that the molecular detection of circulating tumor cells in peripheral blood in patients with gastrointestinal carcinoma was significantly correlated with its malignant biological properties, and may be helpful in the selection of clinical treatment and judgment of prognosis.