Reference Module-Based Analysis of Ovarian Cancer Transcriptome Identifies Important Modules and Potential Drugs.

Ovarian cancer (OVC) is often diagnosed at the advanced stage resulting in a poor overall outcome for the patient. The disease mechanisms, prognosis, and treatment require imperative elucidation. A rank-based module-centric framework was proposed to analyze the key modules related to the development, prognosis, and treatment of OVC. The ovarian cancer cell line microarray dataset GSE43765 from the Gene Expression Omnibus database was used to construct the reference modules by weighted gene correlation network analysis. Twenty-three reference modules were tested for stability and functionally annotated. Furthermore, to demonstrate the utility of reference modules, two more OVC datasets were collected, and their gene expression profiles were projected to the reference modules to generate a module-level expression. An epithelial-mesenchymal transition module was activated in OVC compared to the normal epithelium, and a pluripotency module was activated in ovarian cancer stroma compared to ovarian cancer epithelium. Seven differentially expressed modules were identified in OVC compared to the normal ovarian epithelium, with five up-regulated, and two down-regulated. One module was identified to be predictive of patient overall survival. Four modules were enriched with SNP signals. Based on differentially expressed modules and hub genes, five candidate drugs were screened. The hub genes of those modules merit further investigation. We firstly propose the reference module-based analysis of OVC. The utility of the analysis framework can be extended to transcriptome data of other kinds of diseases.

Association of Elevated Cord Blood Oxidative Stress Biomarkers with Neonatal Outcomes in Mothers with Pre-Eclampsia: A Case-Control Study.

OBJECTIVES: The objective of this study was to determine the relationship between the levels of stress biomarkers in cord blood and pre-eclampsia (PE) in a hospital-based population of pregnant patients and evaluate the effects on pregnancy outcomes. DESIGN: This was an observational, case-control study. Participants/Materials, Setting, Methods: This case-control study included 282 patients with severe PE and 534 women with normal pregnancy. The umbilical cord was collected at delivery and tested for malonaldehyde (MDA), reactive oxygen species (ROS), superoxide dismutase, and homocysteine (Hcy) analysis. We performed a univariate general linear regression model analysis to control potential confounders and determined the underlying influencing factors for high MDA and ROS. A receiver operating characteristic curve analysis was conducted to determine the cutoff values for identifying severe PE. Further, the severe PE group was divided into the low- or high-MDA and low- or high-ROS subgroups according to the cutoff values. Finally, we created logistic regression models to estimate the adjusted odds ratio for each perinatal outcome in the high-MDA and high-ROS subgroup. RESULTS: The levels of MDA and ROS levels were higher in women with severe PE than in normotensive pregnant patients. However, when adjusted for cord blood Hcy levels, the difference was insignificant. Additionally, both MDA (r = 0.359, p < 0.001) and ROS (r = 0.473, p < 0.001) were positively correlated with the cord blood Hcy level. The areas under the curve of MDA and ROS levels were 0.65 (95% confidence interval [CI]: 0.60-0.69) and 0.88 (95% CI: 0.86-0.90), respectively. Higher MDA and ROS levels were associated with increased risks of a low Apgar score, admission to the NICU, and assisted ventilation for the newborn. LIMITATIONS: The study design led to the exclusion of several participants. CONCLUSIONS: Increased levels of oxidative stress markers in the cord blood might be significantly associated with negative effects on newborns. High levels of Hcy in the cord blood might be associated with elevated MDA and ROS concentrations in women with severe PE.

Network analysis reveals important genes in human placenta.

AIM: To determine which genes are important in placenta by network analysis. METHODS: Placenta expressing genes were screened from RNA-Seq data. Protein-protein interaction data were downloaded from STRING (v11.0) database. Google PageRank (PR) algorithm was used to identify important placental genes from protein interaction network. Six placental disease-related datasets were downloaded from NCBI GEO database, and the differential expression of the 99 genes was identified. RESULTS: We calculated PR for each placenta expressing gene and defined the top 99 genes with high PR as important genes. GAPDH has the highest PR. The 99 genes had different expression pattern in placental cell types. FN1 is up-regulated in 8 w EVT compared to 8 w CTB and 24 w EVT compared to 8 w EVT. HSPA4 is down-regulated in 8 w EVT compared to 8 w CTB and 24 w EVT compared to 8 w EVT. MIB2, TLR4, and UBB are consistently changed in preeclampsia (PE). UBB and ACTG1 were identified to be down-regulated in fetal growth restriction (FGR). SOD1 is down-regulated in preterm birth placenta. CONCLUSION: Our findings confirmed that the importance of these genes in placenta-related diseases, and provide new candidates (MIB2, UBB, ACTG1, and SOD1) for placenta-related disease diagnosis and treatment.

Association between serum homocysteine level and unexplained infertility in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI): A retrospective, hospital-based, case-control study.

BACKGROUND: Lower serum homocysteine (Hcy) levels are found to correlate with a better chance of clinical pregnancy and better embryo grades in assisted reproductive technology (ART). However, there is little knowledge on the association between Hcy level and unexplained infertility until now. METHODS: A total of 388 infertile women undergoing IVF/ICSI treatments were recruited, including 129 women with unexplained causes (case group) and 259 women with known causes (control group), and the case group was further divided into subgroups A (≤8 µmol/L), B (>8 and <15 µmol/L), and C (≥15 µmol/L) based on the serum Hcy level. The associations between serum Hcy level and IVF/ICSI pregnancy outcomes were examined in infertile women with unknown causes. RESULTS: A significantly higher serum Hcy level was measured in the case group than in the control group (P = .008). Subgroup analysis revealed a significant difference in the total number of oocytes retrieved among subgroups A, B, and C (P = .031), and no significant difference was seen among these three groups in terms of age, BMI, E2 level on the hCG day, number of M-II oocytes, number of fertilized oocytes, or total number of high-quality embryos (P > .05). Spearman correlation analysis revealed a negative correlation between serum Hcy level and total number of oocytes retrieved (r = -.406, P = .019). Univariate and multivariate linear regression analyses revealed that serum Hcy level had no correlations with any IVF/ICSI outcomes. CONCLUSION: Serum Hcy level has no associations with IVF/ICSI pregnancy outcomes.

Preparation, Characterization, and Anti-Lung Cancer Activity of Tetrandrine-Loaded Stealth Liposomes.

Background: Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, is a potential candidate for cancer chemotherapy. However, Tet has poor aqueous solubility and a short half-life, which limits its bioavailability and efficacy. Liposomes have been widely utilized to enhance the bioavailability and efficacy of drugs. Methods: In this study, Tet-loaded stealth liposomes (S-LPs@Tet) were prepared by ethanol injection method. Furthermore, physicochemical characterisation, biopharmaceutical behaviour, therapeutic efficacy, and biocompatibility of S-LPs@Tet were assessed. Results: The prepared S-LPs@Tet had an average particle size of 65.57 ± 1.60 nm, a surface charge of -0.61 ± 0.10 mV, and an encapsulation efficiency of 87.20% ± 1.30%. The S-LPs@Tet released Tet in a sustained manner, and the results demonstrated that the formulation remained stable for one month. More importantly, S-LPs significantly enhanced the inhibitory ability of Tet on the proliferation and migration of lung cancer cells, and enabled Tet to escape phagocytosis by immune cells. Furthermore, in vivo studies confirmed the potential for long-circulation and potent tumor-suppressive effects of S-LPs@Tet. Moreover, ex vivo and in vivo safety experiments demonstrated that the carrier material S-LPs exhibited superior biocompatibility. Conclusion: Our research suggested that S-LPs@Tet has potential applications in lung cancer treatment.

Cell-derived biomimetic nanoparticles for the targeted therapy of ALI/ARDS.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common clinical critical diseases with high morbidity and mortality. Especially since the COVID-19 outbreak, the mortality rates of critically ill patients with ARDS can be as high as 60%. Therefore, this problem has become a matter of concern to respiratory critical care. To date, the main clinical measures for ALI/ARDS are mechanical ventilation and drug therapy. Although ventilation treatment reduces mortality, it increases the risk of hyperxemia, and drug treatment lacks safe and effective delivery methods. Therefore, novel therapeutic strategies for ALI/ARDS are urgently needed. Developments in nanotechnology have allowed the construction of a safe, efficient, precise, and controllable drug delivery system. However, problems still encounter in the treatment of ALI/ARDS, such as the toxicity, poor targeting ability, and immunogenicity of nanomaterials. Cell-derived biomimetic nanodelivery drug systems have the advantages of low toxicity, long circulation, high targeting, and high bioavailability and show great therapeutic promises for ALI/ARDS owing to their acquired cellular biological features and some functions. This paper reviews ALI/ARDS treatments based on cell membrane biomimetic technology and extracellular vesicle biomimetic technology, aiming to achieve a significant breakthrough in ALI/ARDS treatments.

Precise nanodrug delivery systems with cell-specific targeting for ALI/ARDS treatment.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common acute and critical diseases in clinics and have no effective treatment to date. With the concept of "precision medicine", research into the precise drug delivery of therapeutic and diagnostic drugs has become a frontier in nanomedicine research and has entered the era of design of precise nanodrug delivery systems (NDDSs) with cell-specific targeting. Owing to the distinctive characteristics of ALI/ARDS, designing NDDSs for specific focal sites is an important strategy for changing drug distribution in the body and specifically increasing drug concentration at target sites while decreasing drug concentration at non-target sites. This strategy enhances drug efficacy, reduces adverse reactions, and ensures accurate nano-targeted treatment. On the basis of the characteristics of pathological ALI/ARDS microenvironments, this paper reviews NDDSs targeting vascular endothelial cells, neutrophils, alveolar macrophages, and alveolar epithelial cells to provide reference for designing accurate NDDSs for ALI/ARDS and novel insights into targeted treatments for ALI/ARDS.

Recent trends in platelet membrane-cloaked nanoparticles for application of inflammatory diseases.

Platelets are multifunctional effectors of inflammatory responses and inseparable from the occurrence and development of various inflammatory diseases. The platelet membrane (PM) is integrated onto the surface of a nano-drug delivery system to form the PM-cloaked nanoparticles (PM@NPs), which can increase the biocompatibility of the nano-drug delivery system and mitigate adverse drug reactions. Owing to the strong affinity of immune regulation and adhesion-related antigens on the surface of PM to the focal sites of inflammatory diseases, which endows PM@NPs with the potential to actively target lesions and improve the therapeutic efficacy of drugs for inflammatory diseases. Based on latest developments in PM biomimetic technique and nanomedicine for the treatment of inflammatory diseases, this paper mainly elaborates three aspects: advantages of PM@NPs, experimental foundation of PM biomimetic nanotechnology, and applications of PM@NPs to the treatment of inflammatory diseases. The aim is to provide reference for the development and application of PM@NPs and novel insights into the treatment of inflammatory diseases.

Reduced Intellectual Ability in Offspring Born from Preeclamptic Mothers: A Prospective Cohort Study.

BACKGROUND: Severe preeclampsia may affect placental development, and high homocysteine (Hcy) levels are linked to intellectual disability. However, the correlation between perinatal Hcy levels and intellectual ability remains unknown in severe preeclampsia-affected offspring. OBJECTIVE: We aimed to investigate the intellectual ability in offspring born from preeclamptic mothers and examine the role of prenatal Hcy in the prediction of intellectual disability in preschool-aged offspring. METHODS: The IQ scores were compared between 101 children born to mothers with severe preeclampsia and 202 offsprings born to normotensive mothers. Maternal Hcy levels within 7 days prior to delivery and postnatal cord blood Hcy were measured. The associations of Hcy with IQ scores were evaluated, and the optimal cut-off values for predicting intellectual disability in the offspring were estimated. RESULTS: The children born to mothers with severe preeclampsia had a greater postnatal cord blood Hcy than those born from normotensive mothers (P < 0.001), and the mothers with severe preeclampsia presented a higher prenatal Hcy (P < 0.001). The children born to mothers with severe preeclampsia had significantly lower IQ scores than those born from normotensive mothers, and a higher Hcy was associated with a lower IQ in preeclampsia-affected offspring. The prevalence of intellectual disability was 2.86 times higher in severe preeclampsia-affected offspring than in children born from normotensive mothers, and the prevalence of low IQ was greater in children born to mothers with severe preeclampsia than in those from normotensive mothers. ROC curve analysis showed that both maternal and cord blood Hcy were predictors of intellectual disability, and the optimal cut-off for predicting intellectual disability was 17.7 and 9.75 µmol/L for maternal and cord blood Hcy. CONCLUSION: Perinatal exposure to severe preeclampsia has an adverse effect on postnatal intellectual development, and high maternal and cord blood Hcy may contribute to this association.

Does high-flow nasal cannula oxygen improve outcome in acute hypoxemic respiratory failure? A systematic review and meta-analysis.

INTRODUCTION: To evaluate the efficacy of high-flow nasal cannula (HFNC) in the rate of intubation and mortality for patients with acute hypoxemic respiratory failure. METHODS: We searched Pubmed, EMBASE, and the Cochrane Library for relevant studies. Two reviewers extracted data and reviewed the quality of the studies independently. The primary outcome was the rate of intubation; secondary outcome was mortality in the hospital. Study-level data were pooled using a random-effects model when I2 was >50% or a fixed-effects model when I2 was <50%. RESULTS: Eight randomized controlled studies with a total of 1,818patients were considered. Pooled analysis showed that no statistically significant difference was found between groups regarding the rate of intubation (odds ratio [OR] = 0.79; 95% confidence interval [CI]: 0.60-1.04; P = 0.09; I2 = 36%) and no statistically significant difference was found between groups regarding hospital mortality (OR = 0.89; 95% CI: 0.62-127; P = 0.51; I2 = 47%). CONCLUSIONS: The use of HFNC showed a trend toward reduction in the intubation rate, which did not meet statistical significance, in patients with acute respiratory failure compared with conventional oxygen therapy (COT) and noninvasive ventilation (NIV). Moreover no difference in mortality. So, Large, well-designed, randomized, multi-center trials are needed to confirm the effects of HFNC in acute hypoxemic respiratory failure patients.

Diagnostic value of brain natriuretic peptide and ß-endorphin plasma concentration changes in patients with acute left heart failure and atrial fibrillation.

RATIONALE: This study aims to evaluate the diagnostic value of beta-endorphin (ß-EP) and brain natriuretic peptid (BNP) plasma concentrations for the early diagnosis of acute left heart failure and atrial fibrillation. PATIENT CONCERNS: A total of 45 patients were included. These patients comprised 23 male and 22 female patients,and 20 healthy subjects who underwent physical examinations in the Outpatient Department during the same periodwere included and assigned to the control group. DIAGNOSES: The diagnos stand was that of the Chinese guidelines for the diagnosis and treatment of heart failure. INTERVENTIONS: Enzyme-linked immunosorbent assay was performed to detect the plasma concentration of ß-EP and BNP in the treatment and control groups, and electrocardiogram targeting was performed to determine the left ventricular ejection fraction (LVEF). OUTCOMES: BNP, ß-EP, and LVEF levels were higher in the treatment group (688.01 ±â€Š305.78 ng/L, 394.06 ±â€Š180.97 ng/L, and 70.48 ±â€Š16.62%) compared with the control group (33.90 ±â€Š8.50 ng/L, 76.87 ±â€Š57.21 ng/L, and 32.11 ±â€Š5.25%). The P-values were .015, .019, and .026, respectively, which were <.05. The difference was statistically significant. The BNP and ß-EP's 4 correlations (r = 0.895, P <.001), BNP, ß-EP, and the combination of BNP and ß-EP for acute left heart failure diagnosis in maximizing Youden index sensitivity, specific degree, area under the ROC curve (AUC), and 95% confidence interval (CI) were respectively 93.5%, 81.3%, 0.921, 0.841, 0.921; 80.5%, 78.6%, 0.697, 0.505, 0.697; 94.1%, 83.5%, 0.604 to 0.979, and 0.604. Acute left heart failure in patients with LVEF acuity plasma BNP and ß-EP 50% group was obviously lower than that in the LVEF <50% group (P <.01). BNP, ß-EP, and LVEF were negatively correlated (r = -0.741, -0.635, P = .013, .018). LESSONS: ß-EP and BNP have high specificity and sensitivity for detecting early acute left heart failure and atrial fibrillation in patients, which is convenient, easy to perform, and suitable for clinical applications.

Corrigendum to "Effects of Shenfu Injection in the Treatment of Septic Shock Patients: A Multicenter, Controlled, Randomized, Open-Label Trial".

[This corrects the article DOI: 10.1155/2016/2565169.].

Effects of Shenfu Injection in the Treatment of Septic Shock Patients: A Multicenter, Controlled, Randomized, Open-Label Trial.

The effect of Shenfu on biochemical parameters and survival during resuscitation in patients with septic shock was examined. This was a multicenter, controlled, randomized, open-label trial carried out in 210 patients with septic shock from seven medical centers in China. They were randomized to Shenfu or saline. The primary outcome was lactate clearance. The secondary outcomes were shock index normalization, dose of vasopressors, ICU stay, hospital stay, and mortality. A total of 199 patients completed the trial. Blood pressure, heart rate, and other routine lab tests showed no difference between the groups. Lactate levels and lactate clearance were similar between the two groups. Hospital and ICU stay were similar between the two groups. When considering all patients, the 7- and 28-day mortality were similar between the two groups, but when considering only patients with lactate levels ≥4.5 mmol/L, the Shenfu group showed a better 7-day survival than the control group (7 days: 83.3% versus 54.5%, P = 0.034; 28 days: 72.7% versus 47.6%, P = 0.092). Shenfu may improve the 7-day survival in patients with impaired lactate clearance (≥4.5 mmol/L), but the mechanism for this effect is unclear. Additional studies are necessary to characterize the hemodynamic changes after Shenfu infusion. This trial is registered with ChiCTR-TRC-11001369.