Ferroptosis and Preeclampsia: Genetic Analysis of Potential Biomarkers and Therapeutic Targets.

Ferroptosis is the oxidative death of cells attributed to an imbalance in intracellular lipid reactive oxygen species metabolism, a reduction in cell antioxidant capacity, and an accumulation of membrane lipid peroxides. Trophoblast cells are a group of cells susceptible to ferroptosis. The ferroptosis of trophoblast cells has a major effect on the development of preeclampsia (PE), although the impact of ferroptosis-related genes (FRGs) on PE has not been well characterized. This study obtained PE-related information from the Gene Expression Omnibus database and FRGs from the FerrDb ferroptosis database. Seventeen PE-related differentially expressed ferroptosis-related genes (DE-FRGs) that were closely associated with cellular regulation and immune response were obtained. According to the results of a subsequent functional enrichment analysis, it was found that the above marker genes may impact PE by regulating immune response, amino acid metabolism, the cell cycle, and multiple pathways correlated with PE pathogenesis. Subsequently, we used LASSO and support vector machine recursive feature elimination algorithms to help identify GOT1, CFL1, FZD7, VDR, PARP6, TMSB4X, VCP, and ENO3 as marker genes from the 17 obtained genes. According to the results of single-sample gene set enrichment analysis (ssGSEA), the immune microenvironment of PE changed, possibly due to the GOT1 and TMSB4X genes. Furthermore, 23 drugs targeting one marker gene were determined. A constructed ceRNA network revealed a complicated regulatory link based on the eight marker genes. In this study, diagnostic potency was developed, and insight into the mechanism of PE was provided. In-depth research should be conducted before clinical application to evaluate the diagnostic value of DE-FRGs in PE.

CircRNA_0088196 Regulates Trophoblast Proliferation and Apoptosis in Preeclampsia Through the miR-379-5p/HSPA5 Axis.

Existing research has confirmed the dysregulation of circular RNA (circRNA) in a wide variety of human diseases. Thus, in this study, we explored the potential mechanism of circRNA_0088196 in preeclampsia (PE). We performed quantitative real-time PCR to examine circRNA_0088196 expression and verified the function of circRNA_0088196 in vitro using CCK-8, TUNEL, flow cytometry, and Western blotting analyses. Additionally, we studied the mechanism using dual-luciferase reporter gene experiments. The results of our research revealed the up-regulation of circRNA_0088196 in PE patients' placentas and Heat Shock 70 kDa Protein 5 (HSPA5)-stimulated trophoblast (HTR-8/SVneo) cells. An investigation of the mechanism also showed that there was a binding between miR-379-5p and circRNA_0088196. Additionally, circRNA_0088196 inhibited HTR-8/SVneo cell proliferation and promoted cell apoptosis via the miR-337-3p/HSPA5 axis, thereby facilitating PE. In vivo experiments indicated that circRNA_0088196 regulated HTR-8/SVneo cell production through miR-379-5p. Overall, the findings of this study illustrate that circRNA_0088196 interference promotes cell apoptosis and inhibits HTR-8/SVneo proliferation via the miR-379-5p/HSPA5 axis, thereby accelerating the development of PE.

Identification of key biomarkers and related immune cell infiltration in cervical cancer tissue based on bioinformatics analysis.

Cervical cancer (CC) is the most common gynecological malignant tumor. Immunotherapy has become a new model for the treatment of CC, especially advanced and recurrent cancer. At present, many studies are exploring the safety and efficacy of immunotherapy for advanced or recurrent CC. In this study, CIBERSORT was used to analyze the immune cell infiltration in CC patients, to evaluate the proportion of immune cell types in CC samples, to quantify the cell composition of the immune response, and to analyze its prognostic value. The expression profile datasets of CC were downloaded from the GEO. The differentially expressed genes (DEGs) between CC and normal cervical tissues were identified via R software (version 4.1.1), and their functions and pathways were enriched and analyzed. A protein-protein interaction network was constructed to screen the hub gene. Immune cell infiltration in CC was analyzed via scientific reverse convolution algorithm (CIBERSORT), and the hub gene was analyzed via survival analysis to screen the diagnostic biomarkers of CC. A total of 144 DEGs and 12 hub genes were identified. DEGs are mainly involved in molecular functions such as serine-peptidase activity, serine-hydrolase activity, and chemokine activity. The enrichment pathway is closely related to the interaction between viral proteins and cytokines and cytokine receptors, the interleukin 17 signaling pathway, and chemokine signaling pathway. The immune cell infiltration analysis showed that T cells were the main infiltrating immune cells in CC, especially T cells CD8+ and CD4+ . The survival analysis of the hub gene showed that CEP55, MCM2, RFC4, and RRM2 had high diagnostic value. CEP55, MCM2, RFC4, and RRM2 can be used as diagnostic markers for CC. CD8+ and CD4+ T cells are closely related to the occurrence and development of CC.

The causal role of intestinal microbiome in development of pre-eclampsia.

The correlation of pre-eclampsia (PE) and intestinal microbiome has been widely demonstrated in existing research, whereas their causal relationship has been rarely explored. The causal relationship between intestinal microbiome and PE risk was examined using large-scale genome-wide association studies (GWAS) summary statistics. To be specific, the causal microbial taxa for PE were identified using the two-sample Mendelian randomization (MR) method. The results were verified to be robust through comprehensive sensitive analyses, and the independence of causal relationship was ensured through novel multivariable MR analyses. The possibility of reverse relationships was ruled out through reverse-direction MR analyses. Lastly, the biofunction was explored through enrichment analysis, and a series of validations of PE results in a second GWAS were performed to confirm the results. After correction, four microbial taxa, including Streptococcus genus for PE (FDR q = 0.085), Olsenella genus for PE (FDR q = 0.085), Enterobacteriales order for PE (FDR q = 0.0134), and Akkermansia genus for PE (FDR q = 0.015), had a causal relationship to diverse joint PE (FDR q < 0.15). Moreover, when three different methods were employed on basis of the nominal significance (P < 0.05), five suggestive microbial taxa took on significance. The effect of heterogeneity and horizontal pleiotropy was excluded through sensitive analysis, and the possibility of horizontal pleiotropy of BMI was ruled out through multivariable MR analysis. The protective mechanism of the identified taxa against PE was illustrated through GO enrichment analysis and KEGG pathways. A number of microbial taxa had a causal relationship to PE. The result of this study provides more insights into intestinal microbiome in the pathology of PE.

Bioresorbable PPDO sliding-lock stents with optimized FDM parameters for congenital heart disease treatment.

Stent implantation has been a promising therapy for congenital heart disease (CHD) due to better efficacy. Compared to permanent metal stents, bioresorbable polymer stents have shown a great advantage in accommodating the vascular growth of pediatric patients, but the application is still limited due to inferior radial strength. Here, bioresorbable poly(p-dioxanone) (PPDO) sliding-lock stents for CHD treatment were fabricated by fused deposition modeling (FDM). The effects of FDM processing parameters, including nozzle temperature, bed temperature, layer thickness, and printing speed, on the mechanical properties of PPDO parts were investigated to optimize the processing condition to enhance the radial strength of stents. Finite element analysis (FEA) was also used to evaluate the mechanical properties of stents. PPDO sliding-lock stents fabricated under optimized FDM parameters showed radial strength of 3.315 ± 0.590 N/mm, superior to benchmark commercial metal stents. Radial strength curve and compression behavior of PPDO sliding-lock stents were investigated. Results of FEA exhibited that strut width, shape of the mesh cell and surface coverage ratio had an impact on the compression force of PPDO sliding-lock stents. PPDO sliding-lock stents fabricated with optimized FDM parameters show favorable mechanical performance and meet the requirement of CHD treatment.

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of "Chuanxiong Rhizoma: Radix Salviae miltiorrhizae" Herb Couples in the Treatment of Preeclampsia.

Objective: The aim of the study is to explore the molecular mechanism of activating blood circulation and dispersing stasis herbs in the treatment of pre-eclampsia with Chuanxiong Rhizoma-Radix Salvia miltiorrhiza. Methods: The chemical composition and targets of Chuanxiong Rhizoma-Radix Salvia miltiorrhiza were retrieved from the TCMSP database, and a PPI network was constructed for common genes. Subsequently, a graph of the "active component-target-action pathway" was plotted by Cytoscape 3.7.2 and a KEGG pathway enrichment was performed using the R language cluster profiler package. Molecular docking was conducted between the top five PPI targets of Chuanxiong Rhizoma-Radix Salvia miltiorrhiza. Results: According to network pharmacology, there were 32 target genes, 60 active components, and 59 pathways in Chuanxiong Rhizoma-Radix Salvia miltiorrhiza, and its most evident effects were exerted on G-protein-coupled amine receptors and the neuroactive ligand-receptor interaction signaling pathway. Molecular docking indicated that the target protein had a good binding ability with the drugs. Conclusion: Chuanxiong Rhizoma-Radix Salvia miltiorrhiza have therapeutic effects in pre-eclampsia, as confirmed by the results of molecular biology analysis. Thus, the Chuanxiong Rhizoma-Radix Salvia miltiorrhiza regimen provides a basis for the treatment of pre-eclampsia using traditional Chinese medicine.

Gastrointestinal digestibility insights of different levels of coated complex trace minerals supplementation on growth performance of yellow-feathered broilers.

This study was designed to evaluate the optimum additional level of coated complex trace minerals (TMs) and its impacts on the growth performance of broilers through measurement of digestibility of nutrients and intestinal development. In a 56-day trial, a total of 360 one-day-old male yellow-feathered broilers were randomly divided into six dietary treatment groups. Each treatment contained six replicates, with 10 birds. The control group was supplemented with 1,000 mg/kg of uncoated complex TMs in the basal diet (UCCTM1000). The remaining 5 treatments were degressively supplemented with coated complex TMs from 1,000 to 200 mg/kg in the basal diet, which were considered as (CCTM1000), (CCTM800), (CCTM600), (CCTM400), (CCTM200), respectively. Results: On comparing the UCCTM1000 supplementation, the CCTM1000 supplementation decreased the feed to gain ratio (F/G) (P < 0.05), increased digestibility of crude protein (CP) (P < 0.05), crude fat (CF) (P < 0.05), villus height (VH) of duodenum (P < 0.05), and the mRNA expression level of occludin in jejunal mucosa (P < 0.05). In addition, the F/G was lower in the CCTE600 group than that in the CCTE200 group (P < 0.05). The VH to crypt depth (CD) ratio (V/C) of jejunum and ileum in the CCTM400 and CCTM600 groups was higher (P < 0.05) than that in the CCTM1000 group. The serum endotoxin and D-lactate level and CP digestibility were increased by dietary coated complex TMs addition level. The mRNA expression levels of claudin-1 and ZO-1 in the CCTM600 group were higher (P < 0.05) than that in the CCTM1000 group. In conclusion, adding 600 mg/kg of coated complex TMs showed the minimum F/G and the maximum crude protein digestibility and intestine development of yellow-feathered broilers compared with other treatments. This supplementation level of coated complex TMs could totally replace 1,000 mg/kg of uncoated complex TMs to further decrease the dose of TMs and raise economic benefit.

Four kinds of tocolytic therapy for preterm delivery: Systematic review and network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Premature birth affects more than 15 million infants, as well as mothers and families around the world. With the relaxation of the two-child policy, the problem of premature birth has become relatively prominent in China. According to statistics, China had a birth population of 15.23 million in 2018, with a considerably large number of premature births. This study aims to evaluate the efficacy and safety of tocolysis in the treatment of preterm delivery, provide clinical evidence for medical staff and promote the self-management of patients with premature births. METHODS: Four English databases (PubMed, Embase, Cochrane Library and Web of Science) were retrieved by computer, the retrieval time was from the establishment of each database to November 2021, and the randomized controlled trials for the treatment of preterm delivery were screened according to the pre-set natriuretic exclusion criteria. After literature screening, data selection and risk of bias evaluation were independently conducted by two researchers. R 4.1.1 and Stata 17.0 software were used for statistical analysis. RESULTS AND DISCUSSION: A total of 44 RCTs were included, including 6939 patients. The results of network meta-analysis reveal that in terms of effectiveness, indomethacin was the most effective intervention measure, followed by nifedipine, and the difference was statistically significant; regarding safety, nifedipine was the safest intervention measure, followed by indomethacin, and the difference was statistically significant; and in respect of adverse reactions, ritodrine had the highest probability, and the difference was statistically significant. WHAT IS NEW AND CONCLUSION: Nifedipine may be better for delayed delivery and less likely to produce adverse pregnancy outcomes, followed by indomethacin. Limited by the number and quality of recipient studies, the aforementioned conclusions need to be verified through more high-quality studies. At the same time, the focus should be on patients with twin pregnancy and patients with clinical manifestations of extreme preterm delivery.

Biofilm-overproducing Bacillus amyloliquefaciens P29ΔsinR decreases Pb availability and uptake in lettuce in Pb-polluted soil.

In this study, one mutant strain P29ΔsinR with increased biofilm production was constructed from a biofilm-producing Bacillus amyloliquefaciens strain P29. Then, the effect of strain P29 and its biofilm-overproducing mutant strain P29ΔsinR on Pb availability and accumulation in lettuce and the associated mechanisms were characterized in the Pb-contaminated soil. The live strains P29 and P29ΔsinR increased the dry masses of roots and edible tissues by 31-74% compared to the controls. The live strains P29 and P29ΔsinR reduced the Pb uptake in the roots by 36-52% and edible tissues by 24-43%, Pb bioconcentration factor by 36-52%, and rhizosphere soil available Pb content by 12-25%, respectively, compared to the controls. The live strains P29 and P29ΔsinR increased the pH, proportion of biofilm-producing bacteria by 46-154%, contents of polysaccharides by 99-139% and proteins by 32-57%, and gene relative abundances of epsC by 7.1-10.2-fold, tasA by 10.3-10.8-fold, and sipW by 6.5-26.1-fold, which were associated with biofilm formation and Pb adsorption in the rhizosphere soils, respectively, compared to the controls. Furthermore, the mutant strain P29ΔsinR showed higher ability to reduce Pb availability and uptake in lettuce and increase the pH, proportion of biofilm-producing bacteria, polysaccharide and protein contents, and relative abundances of these genes. These results showed that the biofilm-overproducing strain P29ΔsinR induced lower Pb availability and accumulation in the vegetable and more biofilm-producing bacteria, polysaccharide and protein production, and Pb-immobilizing related gene abundances in the Pb-contaminated soil.

Study on Mechanical Characteristics of Segmental Joints of a Large-Diameter Shield Tunnel under Ultrahigh Water Pressure.

At present, there is no clear design standard for segmental joints of large-diameter shield tunnels under high water pressure. In this paper, a theoretical calculation model for the bending stiffness of segmental joints under high water pressure is proposed. The numerical simulation method is used to investigate the failure and crack formation processes of single-layer and double-layer lining segments under large axial forces. The effects of axial force, bolt strength, and concrete strength on the bending stiffness of joints are then studied using a theoretical calculation model of segmental joints. The results show that under extremely high water pressure, the influence of double lining on joint stiffness is limited. It is more rational and safe to compute the bending stiffness of segmental joints using this theoretical model rather than the numerical simulation method. The parameter analysis reveals that increasing the bolt strength has a minor impact on bending stiffness and deformation, whereas increasing the concrete strength has the opposite effect. The influence of ultimate bearing capacity and deformation decreases non-linearly as the axial force increases.

Primary Hyperparathyroidism in Pregnancy Followed by Successful Delivery: a Case Report.

BACKGROUND: Primary hyperparathyroidism (PHPT) in pregnancy has a negative impact. Effective treatment should be timely adopted. METHODS: We report a case of a 24-year-old pregnant woman admitted with PHPT, hypercalcemia crisis, hypokalemia, thyroid nodules, hyperthyroidism, and intrauterine single live fetus in the 2nd trimester of pregnancy. Right parathyroidectomy and partial thyroidectomy were timely performed. Postoperative pathology suggested parathyroid adenoma with capsule invasion and thyroid nodules. RESULTS: Postoperative serum PTH and Ca2+ were effectively reduced. Eventually, a healthy fetus was delivered via cesarean at full term. CONCLUSIONS: Parathyroidectomy within reasonable operative timing can improve maternal and fetal prognosis in PHPT during pregnancy, especially with concomitant hypercalcemia crisis.

Single Crystal CdSe X-ray Detectors with Ultra-High Sensitivity and Low Detection Limit.

CdSe single crystals (SCs), with a relatively high atomic number, large X-ray absorption coefficients, and high carrier mobility, are expected to provide high-performance detection for X-ray. However, the difficulty of growing high-quality CdSe SC has severely limited its application in X-ray detection. In this work, we develop an unconstrained physical gas phase method and in situ annealing process to grow high-quality CdSe SCs under unconstrained conditions. Using this method, CdSe SCs exhibit natural exposure planes, ultrahigh resistivity of 5.43 × 1012 to 1.29 × 1013 Ω cm and high µτ product of 1.3 × 10-2 to 1.5 × 10-2 cm2 V-1. It is also observed that CdSe SC X-ray detectors exhibit a record sensitivity of 2.08 × 105 µC Gyair-1 cm-2 and a low detection limit of 85 nGyair s-1, which are both desired in medical diagnostics. Moreover, those devices with different crystal directions provide anisotropic X-ray detection performance. Our findings pave a new avenue to exploit high-performance CdSe SC X-ray detectors.

Comparison of outcomes of pedicled jejunal and colonic conduit for esophageal reconstruction.

BACKGROUND: At present, the gastric tube is the first choice for esophageal reconstruction after esophagectomy for various benign and malignant diseases. However, when the stomach is not available, a pedicled jejunum or colon is used to reconstruct the esophagus. The present study aimed to compare the postoperative outcomes and quality of life of patients receiving jejunal and colonic conduits. METHODS: In the present retrospective study, the clinical data of 71 patients with esophageal carcinoma, who received jejunal reconstruction (jejunum group, n = 34) and colonic reconstruction (colon group, n = 37) from 2005 to 2015, were compared. RESULTS: Compared with the colon group, the jejunum group had a lower incidence of postoperative anastomotic leakage, lesser duration of postoperative drainage, and faster recovery. Furthermore, the scores were better in the jejunum group than in the colon group, in terms of short-term overall quality of life, physical function and social relationships. Moreover, the jejunal group had a significantly lower frequency of pH < 4 simultaneous reflux time > 5 min (N45) and the longest reflux time (LT) at 24 weeks after surgery. CONCLUSION: In esophageal cancer, when gastric tube construction is not feasible, a pedicled jejunum may be preferred over a colonic conduit due to lower incidence of acid reflux, anastomotic leakage and higher postoperative short-term quality of life, and rapid postoperative recovery.

Association between pentraxin-3 and the risk of preeclampsia: A meta-analysis.

An association between circulating pentraxin-3 (PTX3) and the risk of preeclampsia (PE) remains to be established. We performed a meta-analysis of observational studies to evaluate their relationship.The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and WanFang databases were searched for related observational studies evaluating PTX3 and PE risk. A random-effects or a fixed-effects model was used in the meta-analysis, depending on the heterogeneity among the included studies.Nine case-control studies were included, with 396 PE patients and 438 controls. The results showed that PTX3 was significantly higher in pregnant women with PE as compared to those without PE (standardized mean difference [SMD] = 2.48, P < .001), with significant heterogeneity (I2 = 98%), particularly for those over 30 years old (SMD = 3.75, P < .001). Subsequent analyses showed that patients with severe or early-onset PE had higher PTX3 levels compared to those with mild or late-onset PE (SMD = 0.93, P = .01), suggesting that PTX3 may be a marker of PE severity. The association between PTX3 and PE was not significantly affected by the statistical method used. Sensitivity analyses by omitting one study at a time did not significantly affect the results. However, the funnel plots were asymmetric, suggesting the potential existence of publication bias.PTX3 may be related to the risk and severity of PE in pregnant women. These results should be evaluated and confirmed in cohort studies.

Immunotherapies application in active stage of systemic lupus erythematosus in pregnancy: A case report and review of literature.

BACKGROUND: Pregnancy in the setting of systemic lupus erythematosus can worsen the condition from the stable to active stage, with quality of life and fertility desire being particular concerns. Pregnancy in the active stage of systemic lupus erythematosus (ASLE), although rare and complicated to manage, can be treated favorably with immunotherapies ifs used properly. Here we report such a success case. CASE SUMMARY: A 31-year-old primigravida patient, diagnosed with SLE seven years ago, was induced ASLE after a cold at 21 + weeks. The patient's vital signs on presentation were normal. Her laboratory exam was remarkable for significant proteinuria, liver and renal dysfunction, and low C3 and C4 levels. Infectious work-up was negative. The patient was diagnosed with ASLE. She was given immunosuppressive agents (methylprednisolone, gamma globulin and azathioprine etc.) and plasma adsorption therapy, monitoring blood pressure every 8 h, fetal heart rate twice a day, and liver and renal function at least twice a week. Successful maternal and fetal outcomes are presented here. CONCLUSION: Child-bearing in ASLE has become more promising, even for this difficult case of ASLE with multiple organ damage. Thorough antepartum counseling, cautious maternal-fetal monitoring, and multi-organ function monitoring by multidisciplinary specialties are keys to favorable pregnancy outcomes.

Protective effect of human umbilical cord mesenchymal stem cell exosomes on preserving the morphology and angiogenesis of placenta in rats with preeclampsia.

AIM: This study aims to investigate the effect of human umbilical cord mesenchymal stem cell exosomes (hucMSC-Ex) on placental tissue and angiogenesis in rats with preeclampsia (PE). METHOD: The expression of MSC surface markers were identified by flow cytometry. Alizarin red staining and oil red O staining were used to examine osteogenic and adipogenic differentiation of hucMSCs. Western blotting was used to determine expressions of CD63 and CD81 in hucMSC-Ex. PE rat models were established using endothelial nitric oxide synthase, eNOS)NG-Nitro-l-arginine Methyl Ester, which were then treated with exosome (Exo) of low dosage (L-Exo), Exo of medium dosage (M-Exo) and Exo of high dosage (H-Exo). The blood pressure at the 15d, 17d and 19d of pregnancy and 24-h urinary protein were measured. TUNEL staining and immunohistochemistry were applied to detect the cell apoptosis and micro-vascular density (MVD) in placental tissues, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to examine serum levels of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase receptor-1 (sFlt1). RESULTS: In vitro cultured hucMSCs showed expression of MSC surface markers (CD29, CD90 and CD105), and no expression of CD34 and CD45. Besides, the isolated exosomes expressed the exosome markers (CD63 and CD81). In response to the treatment of L-Exo, M-Exo and H-Exo, the blood pressure of PE rat models on the 17 d and the 19 d as well as the 24-h urinary protein were substantially decreased. Moreover, at the 21 d, PE rat models treated with L-Exo, M-Exo and H-Exo exhibited an increase in the number and quality of fetuses, placenta quality, MVD and VEGF expression, but substantial decreased cell apoptosis and expression of sFlt1. The influence of Exos was exerted in a dosage dependent manner. CONCLUSION: hucMSC-Ex, in a dose-dependent manner, can improve the morphology of placental tissue in rats with PE, by inhibiting cell apoptosis and promoting angiogenesis in placental tissue.

Ground truth delineation for medical image segmentation based on Local Consistency and Distribution Map analysis.

Computer-aided detection (CAD) systems are being increasingly deployed for medical applications in recent years with the goal to speed up tedious tasks and improve precision. Among others, segmentation is an important component in CAD systems as a preprocessing step to help recognize patterns in medical images. In order to assess the accuracy of a CAD segmentation algorithm, comparison with ground truth data is necessary. To-date, ground truth delineation relies mainly on contours that are either manually defined by clinical experts or automatically generated by software. In this paper, we propose a systematic ground truth delineation method based on a Local Consistency Set Analysis approach, which can be used to establish an accurate ground truth representation, or if ground truth is available, to assess the accuracy of a CAD generated segmentation algorithm. We validate our computational model using medical data. Experimental results demonstrate the robustness of our approach. In contrast to current methods, our model also provides consistency information at distributed boundary pixel level, and thus is invariant to global compensation error.