Correlation between plasma PSGL-1 and FIGO stage, tumor metastasis, and survival in epithelial ovarian cancer.

Plasma circulating P-selectin glycoprotein ligand-1 (PSGL-1) levels and its clinical correlation in patients with epithelial ovarian cancer (EOC) are unknown. The study determined plasma PSGL-1 levels in EOC patients and investigated its relationship with clinicopathological factors and prognosis. Plasma PSGL-1 levels were measured using ELISA in 69 patients with EOC, 34 patients with benign ovarian cystadenoma, and 36 healthy controls. Subsequently, the relationship between PSGL-1 levels and clinicopathological characteristics of patients, as well as the prognosis of EOC patients, was examined. Additionally, the specificity and sensitivity of plasma PSGL-1 were assessed through ROC curve analysis. Plasma PSGL-1 was upregulated in EOC patients compared with healthy subjects and/or patients with benign ovarian cystadenoma (p < 0.01). Elevated levels of PSGL-1 in the plasma were positively associated with advanced FIGO stage (p < 0.001), tumor size (p = 0.001), tumor metastasis (p = 0.036), and tumor recurrence (p = 0.013), while was negatively correlated with residual tumor size (p < 0.001). Kaplan-Meier survival analysis showed that high plasma PSGL-1 levels were associated with progression-free survival (p = 0.0345). In univariate and multivariate Cox regression analyses, PSGL-1 (HR = 1.456, p = 0.009) was an independent prognostic marker. Plasma PSGL-1 levels distinguished EOC patients and healthy individuals (AUC = 0.905), patients at late and early FIGO stages (AUC = 0.886), and metastatic and non-metastatic EOC (AUC = 0.722). The expression of plasma PSGL-1 is significantly increased in patients with EOC, serving as a reliable biomarker to differentiate between healthy individuals and those with EOC. Furthermore, PSGL-1 in patients is correlated with prognostic indicators, such as advanced FIGO stage, tumor lymph node metastasis, and progression-free survival.

Prognostic value of APOBEC3A in patients with cervical squamous cell carcinoma in a major urban center in China: a retrospective study.

Background: APOBEC3A (A3A) has been implicated to have vital prognostic value in several common cancers. This study aimed to investigate the prognostic value of A3A expression in cervical squamous cell carcinoma (CESC). Methods: This retrospective study enrolled 59 patients with CESC or cervical squamous intraepithelial neoplasia from January 2014 to January 2017 in Changhai Hospital, Naval Medical University. Then, A3A histoscores (H-scores) using immunohistochemistry (IHC) were analyzed in formalin-fixed paraffin-embedded archival tissue blocks. Moreover, overall survival was analyzed by the Kaplan-Meier method. Results: The H-score of A3A protein expression was relatively higher in CESC than in squamous intraepithelial neoplasia, and the relative expression level of normal cervical tissues was lower than that of cervical squamous intraepithelial neoplasia (P<0.001). Moreover, the H-score of poorly differentiated cases was 6, which was higher than that of moderately differentiated cases (H-score =3), while the H-score of well-differentiated cases was 2, which was lower than that of moderately differentiated cases. Moreover, patients in the A3A low expression group had higher overall survival rates by prognostic analysis (P=0.027). Conclusions: A3A protein expression was increased during CESC progression. Moreover, A3A expression was tightly related to poor prognosis in CESC. Thus, these results showed that A3A overexpression may provide a marker for poor prognosis in CESC.

APOBEC3A suppresses cervical cancer via apoptosis.

Background: Family members of Apolipoprotein B mRNA-editing enzyme catalytic 3 (APOBEC3) play critical roles in cancer evolution and development. However, the role of APOBEC3A in cervical cancer remains to be clarified. Methods: We used bioinformatics to investigate APOBEC3A expression and outcomes using The Cancer Genome Atlas (TCGA)-cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) dataset, GTEx, and GSE7803. Immunohistochemistry was then used to identify APOBEC3A's expression pattern. We performed Cell Counting Kit-8, wound-healing, Transwell, and flow cytometry assays to measure proliferation, migration, invasion, and apoptosis, respectively, using the SiHa and HeLa cell lines transfected with APOBEC3A. BALB/c nude mice were used to investigate the effects of APOBEC3A in vivo. The phosphorylated gamma-H2AX staining assay was applied to measure DNA damage. RNA sequencing (RNA-Seq) was applied to explore APOBEC3A-related signaling pathways. Results: APOBEC3A was more significantly expressed in cancer tissues than in adjacent normal tissues. Higher expression of APOBEC3A was associated with better outcomes in TCGA-CESC and GTEx. Immunohistochemistry showed that the expression of APOBEC3A was significantly higher in cancer tissues than in normal tissues. Transfection experiments showed that APOBEC3A inhibited proliferation, upregulated S-phase cells, inhibited migration and invasion, induced DNA damage, and promoted apoptosis. Overexpression of APOBEC3A inhibited tumor formation in the mouse model. RNA-seq analysis showed that ectopic expression of APOBEC3A inhibited several cancer-associated signaling pathways. Conclusions: APOBEC3A is significantly upregulated in cervical cancer, and higher expression of APOBEC3A is associated with better outcomes. APOBEC3A is a tumor suppressor whose overexpression induces apoptosis in cervical cancer.

Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation.

OBJECTIVE: Xiaotan Sanjie recipe (XTSJ), a Chinese herbal compound medicine, exerts a significant inhibitory effect on gastric cancer (GC) metastasis. This work investigated the mechanism underlying the XTSJ-mediated inhibition of GC metastasis. METHODS: The effect of XTSJ on GC metastasis and the associated mechanism were investigated in vitro, using GC cell lines, and in vivo, using a GC mouse model, by focusing on the expression of Glc-N-Ac-transferase V (GnT-V; encoded by MGAT5). RESULTS: The migration and invasion ability of GC cells decreased significantly after XTSJ administration, which confirmed the efficacy of XTSJ in treating GC in vitro. XTSJ increased the accumulation of E-cadherin at junctions between GC cells, which was reversed by MGAT5 overexpression. XTSJ administration and MGAT5 knockdown alleviated the structural abnormality of the cell-cell junctions, while MGAT5 overexpression had the opposite effect. MGAT5 knockdown and XTSJ treatment also significantly increased the accumulation of proteins associated with the E-cadherin-mediated adherens junction complex. Furthermore, the expression of MGAT5 was significantly lower in the lungs of BGC-823-MGAT5 + XTSJ mice than in those of BGC-823-MGAT5 + solvent mice, indicating that the ability of gastric tumors to metastasize to the lung was decreased in vivo following XTSJ treatment. CONCLUSION: XTSJ prevented GC metastasis by inhibiting the GnT-V-mediated E-cadherin glycosylation and promoting the E-cadherin accumulation at cell-cell junctions. Please cite this article as: Huang N, He HW, He YY, Gu W, Xu MJ, Liu L. Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation. J Integr Med. 2023; 21(6): 561-574.

Comprehensive molecular expression profiling of SARS-CoV-associated factors in the endometrium across the menstrual cycle and elevated susceptibility in women with recurrent pregnancy loss.

Objective: To evaluate the dynamic expression profiling alterations of SARS-CoV-2-associated molecules within the fertile human endometrium throughout the menstrual cycle. Furthermore, to explore the inherent vulnerability of the endometrium to SARS-CoV-2 infection among women experiencing recurrent pregnancy failure, including both recurrent implantation failures (RIF) and recurrent pregnancy losses (RPL). Method: The present study employed multiple datasets to investigate the expression patterns of SARS-CoV-2-associated genes. Firstly, a single-cell RNA-sequencing dataset comprising endometrial samples from 19 healthy women across the menstrual cycle was utilized. Additionally, two microarray datasets encompassing 24 women with RIF, and 24 women with RPL during the peri-implantation phase were included. To complement these analyses, immunohistochemical (IHC) staining was performed on endometrial samples collected from 30 women with RIF, 30 women with RPL, and 20 fertile controls recruited specifically during the implantation period. Results: The investigation revealed a moderate expression percentage of CTSL (22%), TMPRSS4 (15%), FURIN (16%) and MX1 (9%) in endometrium. Conversely, the expression percentages of ACE2 (1%) and TMPRSS2 (4%) were relatively low. Notably, the expression of BSG exhibited an increment towards the window of implantation, reaching its peak during the middle secretary phase. Furthermore, a significant reduction (p < 0.05) in TMPRSS2 expression was observed in the RIF group compared to the control group. While the expression of BSG was significantly increased (p < 0.05) in the RPL group, findings that were corroborated by the IHC staining results. Conclusion: The findings of this study indicate a noteworthy upregulation of BSG expression in the endometrium of women with RPL. These results suggest an augmented susceptibility of endometrium to SARS-CoV-2 infection, potentially contributing to unfavorable pregnancy outcomes.

Effects of polymer terminal group inside micelle core on paclitaxel loading promoting and burst release suppressing.

Background: Paclitaxel (PTX) is widely used in the treatment of advanced esophageal and gastric cancer. Polymeric micelles can improve the drug-loading efficiency of PTX. However, the end groups on the amphiphilic blocks affect the drug-loading efficiency and the release kinetics of polymeric micelles. Therefore, there is an urgent need to disclose the tailoring of the core-/shell-forming terminal groups. Methods: Different from the conventional block copolymer synthesis in the reversible addition-fragmentation chain-transfer polymerization, which has a hydrophilic end group on the core-forming blocks, an alternative monomer addition method was applied to tune and obtain two block copolymers with symmetrical and similar block length PBMAn-b-PNAMm [PNAM, poly(N-acryloylmorpholine); PBMA, poly(n-butyl methacrylate)] but distinct end groups on the hydrophobic core-forming blocks, that is, HOOC-PBMA-PNAM-Phen and HOOC-PNAM-PBMA-Phen. The chemical structure of the resulting copolymers was elucidated by proton nuclear magnetic resonance spectroscopy and differential scanning calorimetry. The spherical morphology revealed by transmission electron microscopy and the uniform particle size revealed by dynamic light scattering analysis clearly confirmed the successful preparation of a PTX-polymeric micelle complex. Results: The particle sizes of HOOC-PBMA-PNAM-Phen and HOOC-PNAM-PBMA-Phen were about 40 and 235 nm respectively. The PTX loading efficiency of HOOC-PBMA-PNAM-Phen was much lower than that of HOOC-PNAM-PBMA-Phen. The PTX release from HOOC-PBMA-PNAM-Phen was much slower than that of HOOC-PNAM-PBMA-Phen. The polymers had glass transition temperature (Tg) values of 70.24 and 74.22 ℃, which was from the HOOC-PBMA-PNAM-Phen and HOOC-PNAM-PBMA-Phen micelles, respectively. The systematic study on the PTX loading and releasing profile disclosed that, compared with the HOOC-PBMA-PNAM-Phen, the micelles with Phen group on the hydrophobic block (HOOC-PNAM-PBMA-Phen) enhanced drug loading and prolonged drug release but with a larger particle size. Conclusions: The results indicated that the hydrophobic end group Phen on the core-forming blocks can promote hydrophobic drug loading and suppress burst release.

Peanut skin extract ameliorates high-fat diet-induced atherosclerosis by regulating lipid metabolism, inflammation reaction and gut microbiota in ApoE-/- mice.

Atherosclerosis (AS) is a serious threat to the health and life of humans worldwide. The mitigating effect of polyphenol compounds from peanut skin extract (PSE) on AS has attracted great research attention. However, the mechanism underlying this mitigating effect remains poorly understood. This study aims to investigate the preventive effect of PSE on high-fat diet-induced AS in mice and explore the underlying mechanisms. PSE treatment significantly reduced atherosclerotic plaques, particularly at high doses. Dietary PSE intervention obviously alleviated the lipid metabolism disorder in ApoE-/- mice by reducing the serum TC and LDL-C contents and increasing the HDL-C content. In addition, PSE intervention significantly decreased the level of pro-inflammatory cytokines TNF-α and IL-6 and increased that of anti-inflammatory IL-10, thus exhibiting a significant anti-inflammatory effect. More interestingly, analysis of the 16S rRNA gene sequence revealed that PSE could significantly alter the community composition of the gut microbiota. Specifically, PSE enhanced the abundance of Roseburia, Rothia, Parabacteroides and Akkermansia, and reduced that of Bilophila and Alistipes. Some of these intestinal bacteria exhibited good anti-inflammatory effects, which are related to the production of short chain fatty acids. Thus, the anti-atherosclerotic effect of PSE may be partly attributed to changes in the composition and function of gut microbiota, which may be closely associated with its anti-inflammatory effect. Moreover, untargeted metabolomics analysis indicated that PSE could regulate the levels of differential metabolites in the liver, serum and fecal samples.

Integrated analysis of prognostic immune-related genes in the tumor microenvironment of ovarian cancer.

Background: Ovarian cancer (OC) is a major cause of most gynecological cancer deaths, and the rates of incidence and mortality are increasing worldwide. However, factors in the tumor microenvironment (TME) related to OC and certain prognostic markers of OC are still unknown. We aimed to identify biomarkers connected to prognostic immunity based on clinical patients' data from The Cancer Genome Atlas (TCGA). Methods: We used the ESTIMATE algorithm to compute the immune and matrix scores of OC patients from TCGA. Next, differentially expressed genes (DEGs) according to the immune and matrix scores were obtained. Subsequently, genes (GZMB, C2orf37, CXCL13, and UBD) connected with prognostic immunity were determined. Moreover, functional enrichment analysis and the protein-protein interaction network showed that these genes were enriched in many biological processes related to immune function. The Tumor Immune Estimation Resource (TIMER) algorithm was also used to analyze the immune prognostic genes according to six immuno-infiltrating cells. Results: According to high/low immune-scores and matrix-score groups, 682 common genes were identified, within 420 upregulated genes and 262 downregulated genes. Gene ontology (GO) analysis of biological process primarily enriched in T cell activation, regulation of lymphocyte activation and lymphocyte differentiation. OS analysis showed 45 genes (6.6%) were relevant in the final results. The Kaplan-Meier plotter database verified the top 10 genes related to prognosis, but only GZMB, C2orf37, CXCL13 and UBD were related to overall survival (OS). Conclusions: GZMB, CXCL13, and UBD may influence prognosis via their effects on the infiltration of immune cells and therefore represent potential targets for OC immunotherapy.

The surgical strategies of vaginoplasty for vaginal agenesis patients with or without functional uterus.

BACKGROUND: Vaginal agenesis is a rare condition worldwide. Most reported cases were accompanied by the absence of uterus or uterine hypoplasia; for patients with functional endometrium, hysterectomy was most likely to be conducted to lower postoperative complications. OBJECTIVE: Based on our successful experience in vaginoplasty with autologous buccal mucosal, the purpose of this article is to discuss the surgical strategies in the reconstruction of neovaginal for vaginal agenesis patients with functional uterus and cervical hypoplasia. METHODS: The uterus was preserved in our procedure, and the cervicoplasty was performed to connect the uterine cavity with the neovagina. After the vaginal cavity was formed, the cervix was confirmed and fixed. With the assistance of laparoscope, the direction and angle of the cervix and the uterine body were observed and confirmed. An incision was made in cervix to connect the uterine cavity, and a Foley's catheter was inserted. The newly formed opening of cervix and neovagina was covered by autologous buccal mucosal. RESULTS: The connection between neovagina and cervix uteri was successfully conducted in patient with functional uterus. Unimpeded and regular menstrual was achieved, and the cyclic abdominal pain was disappeared. No complications were observed. CONCLUSION: For patients without functional uterus, vaginoplasty with autologous buccal mucosal can be conducted. However, fertility-preserving surgery should be the primary choice in patients with functional endometrium. It can be concluded from our experience that the utero-vaginal connection with the assistance of laparoscope and the use of autologous buccal mucosa is a promising way to achieve ideal outcomes.

The Release of Nitric Oxide Is Involved in the ß-Arrestin1-Induced Antihypertensive Effect in the Rostral Ventrolateral Medulla.

ß-Arrestin1 is a multifunctional scaffold protein with the ability to interact with diverse signaling molecules independent of G protein-coupled receptors. We previously reported that overexpression of ß-arrestin1 in the rostral ventrolateral medulla (RVLM) decreased blood pressure (BP) and renal sympathetic nerve activity (RSNA) in spontaneously hypertensive rats (SHRs). Nitric oxide (NO) is widely reported to be involved in central cardiovascular regulation. The goal of this study was to investigate whether NO signaling contributes to the ß-arrestin1-mediated antihypertensive effect in the RVLM. It was found that bilateral injection of adeno-associated virus containing Arrb1 gene (AAV-Arrb1) into the RVLM of SHRs significantly increased NO production and NO synthase (NOS) activity. Microinjection of the non-selective NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME; 10 nmol) into the RVLM prevented the ß-arrestin1-induced cardiovascular inhibitory effect. Furthermore, ß-arrestin1 overexpression in the RVLM significantly upregulated the expression of phosphorylated neuronal NOS (nNOS) by 3.8-fold and extracellular regulated kinase 1/2 (ERK1/2) by 5.6-fold in SHRs. The ß-arrestin1-induced decrease in BP and RSNA was significantly abolished by treatment with ERK1/2 small interfering RNA (ERK1/2 siRNA). Moreover, ERK1/2 siRNA attenuated the ß-arrestin1-induced NO production, NOS activity, and nNOS phosphorylation in the RVLM. Taken together, these data demonstrate that the antihypertensive effect of ß-arrestin1 in the RVLM is mediated by nNOS-derived NO release, which is associated with ERK1/2 activation.

DGAT1 Expression Promotes Ovarian Cancer Progression and Is Associated with Poor Prognosis.

BACKGROUND: Ovarian cancer is the most fatal gynecological malignancy. Owing to its insidious onset, rapid development, and poor prognosis, ovarian cancer is the fifth most common cause of death in women. Although immunotherapy-related drugs, such as Olaparib, can alleviate ovarian cancer progression, there are no remarkable breakthroughs for its effective treatment. It is considered that the transformation of normal cells to cancerous ones involves "recoding" of certain metabolic pathways. Diacylglycerol O-acyltransferase 1 (DGAT1) can synthesize triglycerides by transferring acyl-CoA to diacylglycerol, which plays a key role in lipid synthesis. However, the role of DGAT1 in ovarian cancer is not yet elucidated. MATERIALS AND METHODS: We analyzed the correlation between DGAT1 and ovarian cancer staging, grading, vascular invasion, and prognosis by collating the information of ovarian cancer specimens from The Cancer Genome Atlas (TCGA) database. Furthermore, the effects of DGAT1 expression on proliferation, migration, invasion, and tumor growth were studied using ovarian cancer cell lines. GSEA was used to analyze the KEGG pathways and biological function enriched because of DGAT1 expression in ovarian cancer. RESULTS: The expression of DGAT1 was elevated in advanced (p = 0.0432), poorly differentiated (p = 0.0148), and vascular invaded (p = 0.0002) ovarian cancer specimens. Prognosis among patients with high expression of DGAT1 was poor. After DGAT1 expression was interfered, proliferation, migration, invasion, colony forming, and tumor growth of ovarian cancer cells were inhibited. In addition, GSEA showed that DGAT1 may be involved in the immune process. CONCLUSION: DGAT1 expression is associated with the clinical phenotype of ovarian cancer. We suggest that DGAT1 has potential implications in the treatment of ovarian cancer.

B3GNT3: A prognostic biomarker associated with immune cell infiltration in pancreatic adenocarcinoma.

Pancreatic cancer, one of the most malignant gastrointestinal tumors, is prone to liver metastasis. However, due to the lack of appropriate and comprehensive diagnostic methods, it is difficult to accurately predict the survival outcomes. Therefore, there is a need to identify effective biomarkers, such as UDP-GlcNAc: ßGal ß-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3), that predict the survival outcome of patients with pancreatic cancer. In the present study, based on data from 171 cases of pancreatic cancer obtained from The Cancer Genome Atlas portal, the differential expression of mRNAs was screened by comparing cancerous tissues with adjacent tissues. Univariate Cox regression analysis demonstrated that B3GNT3 had prognostic capability and could be an independent prognostic factor for pancreatic adenocarcinoma (PAAD). Using the Tumor Immune Estimation Resource tool and Tumor-Immune System Interaction Database, a potential relationship between B3GNT3 expression and immune cell infiltration was identified in pancreatic carcinoma. Furthermore, 177 samples of pancreatic carcinoma were collected and the association of CD68 expression with B3GNT3 was assessed by immunohistochemical staining. B3GNT3 expression was associated with clinical outcomes in pancreatic carcinoma and related to infiltrating levels of immune cells, which indicated that B3GNT3 could be used as an immunotherapy target for PAAD.

Effect of Whole-Brain and Intensity-Modulated Radiotherapy on Serum Levels of miR-21 and Prognosis for Lung Cancer Metastatic to the Brain.

BACKGROUND The goal of the present study was to explore the influence of whole-brain radiotherapy (WBRT) and intensity-modulated radiotherapy (IMRT) on serum levels of miR-21 and prognosis for lung cancer that has metastasized to the brain. MATERIAL AND METHODS Two hundred patients with lung cancer metastatic to the brain were randomized, half to the control group and half to the observation group. The observation group received WBRT and reduced-field IMRT (WBRT+RF-IMRT) and the control group received conventional-field IMRT (CF-IMRT). The total effective rate after treatment was determined. Serum levels of miR-21 were measured before and after radiotherapy with reverse transcriptase-polymerase chain reaction. In addition, tumor marker levels were measured with enzyme-linked immunosorbent assay. The relationship between miR-21 levels and tumor marker levels was assessed with a Pearson correlation coefficient test. Five-year survival was estimated with Kaplan-Meier curves. RESULTS The total effective rate was higher in the observation group (86%) than in the control group (69%). Lower levels of miR-21 and tumor markers were seen in the observation group. Moreover, miR-21 levels were positively correlated with levels of tumor necrosis factor-a, neuron-specific enolase, SCC-Ag, and carcinoembryonic antigen. Low levels of miR-21 were associated with longer overall survival in patients with lung cancer metastatic to the brain. CONCLUSIONS WBRT+RF-IMRT is superior to CF-IMRT for lung cancer metastatic to the brain. MiR-21 may be a marker for prediction of the efficacy of radiotherapy in this disease setting.

Combination of honey with metformin enhances glucose metabolism and ameliorates hepatic and nephritic dysfunction in STZ-induced diabetic mice.

Honey is a natural sweetener that contains a large amount of monosaccharides such as glucose and fructose, as well as small amounts of disaccharides and trisaccharides such as sucrose and pine trisaccharides. In addition to carbohydrates, honey also contains vitamins, minerals, enzymes, amino acids, and polyphenols including phenolic acids and flavonoids. The polyphenols in honey have been proved to have great antioxidant activity, besides inhibiting α-glycosidase activity and improving blood-lipid metabolism. However, whether it is safe for diabetic patients to consume honey remains controversial. This study investigated the effects of honey, metformin and their combination on the characteristic pathological changes and glucose metabolism in STZ-induced diabetic mice over five weeks. Our results showed that honey and its combination with metformin could prevent hyperglycemia, stimulate insulin secretion, reduce liver fat accumulation, attenuate liver injury and kidney damage in STZ-induced diabetic mice. Moreover, treatment with honey or combination of honey and metformin significantly enhanced glucokinase (GK) activity (p < 0.05), and meanwhile suppressed the activities of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase (PC) and pyruvate dehydrogenase kinases (PDK) (p < 0.05) in diabetic mice.

[Body weight and gestational outcomes in women with high normotension during pregnancy].

OBJECTIVE: To investigate the pre-pregnancy body mass index(BMI), gestational weight gain(GWG)and gestational outcomes in women with high normotension during pregnancy. METHODS: The clinical data of 1500 pregnant women who recieved antenatal care and delivered in Songjiang District Maternal and Child Hospital, Shanghai from 2015 to 2017 were retrospectively analyzed. The women were divided into high normotension group, normotension group and hypertensive disorder of pregnancy (HDP) group with 500 cases in each group. The general information, pre-pregnancy body mass index, gestational weight gain and gestational outcomes were analyzed. RESULTS: There were significant differences in pre-pregnancy BMI and GWG between the high normotension group and the normotension group (all P<0.017), and there was significant difference in pre-pregnancy BMI between the high normotension group and HDP group (P<0.017). In terms of adverse pregnancy outcomes, the incidence of oligohydramnios, placental abruption, postpartum hemorrhage, fetal distress and small for gestational age infant were higher in the high normotension group than those in the normotension group, but the differences were not of statistical significance (all P>0.017); the incidence of oligohydramnios, placental abruption, cesarean section, postpartum hemorrhage, premature delivery and small for gestational age infant in HDP group were higher than those in high normotension group (all P<0.01). In high normotension women with adverse gestational outcomes, the proportion of low GWG or too much GWG was higher and the proportion of normal GWG was lower than those in high normotension women without adverse gestational outcomes (all P<0.01). CONCLUSIONS: Pre-pregnancy BMI and GWG are correlated with pregnancy blood pressure and gestational outcomes. Reasonable intervention to gestational weight gain of pregnant women with high normotension is of significance to improve the gestational outcomes.

Integrated Bioinformatic Analysis of a Competing Endogenous RNA Network Reveals a Prognostic Signature in Endometrial Cancer.

In endometrial carcinoma, the clinical outcome directly correlates with the TNM stage, but the lack of sufficient information prevents accurate prediction. The molecular mechanism underlying the competing endogenous RNA (ceRNA) hypothesis has not been investigated in endometrial cancer. Multi-bioinformatic analyses, including differentially expressed gene analysis, ceRNA network construction, Cox regression analysis, function enrichment analysis, and protein-protein network analysis, were performed on the sequence data acquired from The Cancer Genome Atlas (TCGA) data bank. A ceRNA network comprising 366 mRNAs, 27 microRNAs (miRNAs), and 66 long non-coding RNAs (lncRNAs) was established. Survival analysis performed with the univariate Cox regression analysis revealed nine lncRNAs with prognostic power in endometrial carcinoma. In multivariate Cox regression analysis, a signature comprising LINC00491, LINC00483, ADARB2-AS1, and C8orf49 showed remarkable prognostic power. Risk score and neoplasm status, but not TNM stage, were independent prognostic factors of endometrial carcinoma. A ceRNA network comprising differentially expressed mRNAs, miRNAs, and lncRNAs may reveal the molecular events involved in the progression of endometrial carcinoma. In addition, the signature with prognostic value may discriminate patients with increased risk for poor outcome, which may allow physicians to take accurate decisions.

Integrated Analysis of a Competing Endogenous RNA Network Revealing a Prognostic Signature for Cervical Cancer.

Given the high morbidity and the trend of younger individuals being affected observed in cervical cancer, it is important to identify sensitive and effective biomarkers for predicting the survival outcome of patients. Based on data from 307 cervical cancer cases acquired from The Cancer Genome Atlas portal, 1920 differentially expressed mRNAs, 70 microRNAs(miRNAs), and 493 long non-coding(lncRNAs) were screened by comparing cervical cancer tissues with paracancerous tissues. A competing endogenous (ceRNA) network containing 50 lncRNAs, 16 miRNAs, and 81 mRNAs was constructed. Eighteen RNAs, comprising 13 mRNAs, 2 miRNAs, and 3 lncRNAs, were identified as significant prognostic factors by univariate Cox proportional hazards regression. ETS-related gene and fatty acid synthase signatures were discovered using a multivariate Cox regression model built to identify independent prognostic factors in cervical cancer patients. Receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value for distinguishing the risk level of cervical cancer patients. High-risk patients exhibited a poorer prognosis than low-risk patients did. This study focused on ceRNA networks to provide a novel perspective and insight into cervical cancer and suggested that the identified signature can serve as an independent prognostic biomarker in cervical cancer.

ANLN functions as a key candidate gene in cervical cancer as determined by integrated bioinformatic analysis.

BACKGROUND: Cervical cancer, one of the leading causes of female deaths, remains a top cause of mortality in gynecologic oncology and tends to affect younger individuals. However, the pathogenesis of cervical cancer is still far from clear. Given the high incidence and mortality of cervical cancer, uncovering the causes and pathogenesis as well as identifying novel biomarkers are of great significance and are desperately needed. MATERIALS AND METHODS: First, raw data were downloaded from the Gene Expression Omnibus database. The Robuse Multi-Array Average algorithm and combat function of the sva package were subsequently applied to preprocess and remove batch effects. Differentially expressed genes (DEGs) analyzed with the limma package were followed by gene ontology and pathway analysis, and a protein-protein interaction (PPI) network based on the STRING website and the Cytoscape software was constructed. Weighted Correlation Network Analysis (WGCNA) was utilized to build the coexpression network. Subsequently, UALCAN websites were employed to conduct survival analysis. Finally, the oncomine database was used to validate the expression of ANLN in other datasets. RESULTS: GSE29570 and GSE89657, including 49 cervical cancer tissues and 20 normal cervical tissues, were screened as the datasets. Three-hundred-twenty-four DEGs were identified and, among them, 123 were upregulated, while 201 were downregulated. The DEGs PPI network complex, contained 305 nodes and 4,962 edges, and 8 clusters were calculated according to k-core =2. Among them, cluster 1, which had 65 nodes and 1,780 edges, had the highest score in these clusters. In coexpression analysis, there were 86 hubgenes from the Brown modules that were chosen for further analysis. Sixty-one key genes were identified as the intersecting genes of the Brown module of WGCNA and DEGs. In survival analysis, only ANLN was a prognostic factor, and the survival was significantly better in the low-expression ANLN group. CONCLUSION: Our study suggested that ANLN may be a potential tumor oncogene and could serve as a biomarker for predicting the prognosis of cervical cancer patients.

Downregulation of SPINK13 Promotes Metastasis by Regulating uPA in Ovarian Cancer Cells.

BACKGROUND/AIMS: Ovarian cancer (OC) is the fifth leading cause of cancer-related death in women, and it is difficult to diagnose at an early stage. The purpose of this study was to explore the prognostic biological markers of OC. METHODS: Univariate Cox regression analysis was used to identify genes related to OC prognosis from the Cancer Genome Atlas(TCGA) database. Immunohistochemistry was used to analyse the level of SPINK13 in OC and normal tissues. Cell proliferation, apoptosis and invasion were performed using MTT assay, flow cytometric analysis and Transwell assay, respectively. RESULTS: We identified the Kazal-type serine protease inhibitor-13 (SPINK13) gene related to OC prognosis from the Cancer Genome Atlas (TCGA) database by univariate Cox regression analysis. Overexpression of SPINK13 was associated with higher overall survival rate in OC patients. Immunohistochemistry showed that the level of SPINK13 protein was significantly lower in OC tissues than in normal tissues (P < 0.05).In vitro experiments showed that the overexpression of SPINK13 inhibited cellular proliferation and promoted apoptosis. Moreover, SPINK13 inhibited cell migration and epithelial to mesenchymal transition (EMT). SPINK13 was found to inhibit the expression of urokinase-type plasminogen activator (uPA), while recombinant uPA protein could reverse the inhibitory effect of SPINK13 on OC metastasis. CONCLUSION: These results indicate that SPINK13 functions as a tumour suppressor. The role of SPINK13 in cellular proliferation, apoptosis and migration is uPA dependent, and SPINK13 may be used as a potential biomarker for diagnosis and targeted therapy in OC.