Changes in REVEAL Lite 2 risk status are associated with long-term outcomes in patients with pulmonary arterial hypertension: A post-hoc analysis of the GRIPHON study.

BACKGROUND: Mortality risk assessment informs clinical management of pulmonary arterial hypertension (PAH). The Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 is a simplified risk calculator discriminating 1-year mortality risk. METHODS: This post-hoc analysis of the phase 3 GRIPHON study assessed changes in REVEAL Lite 2 risk score with selexipag versus placebo and whether changes were prognostic or predictive of time to first morbidity/mortality (M/M) event. RESULTS: REVEAL Lite 2 risk category discriminated M/M risk (landmark concordance indices: 0.68-0.76, selexipag; 0.65-0.70, placebo). Across baseline risk categories, hazard ratios supported a lower risk of M/M events with selexipag versus placebo: low, 0.573 (95% confidence interval [CI] 0.361-0.908; p = 0.0178); intermediate, 0.423 (95% CI 0.274-0.655; p = 0.0001); and high, 0.711 (9% CI 0.520-0.972; p = 0.0326). Odds ratios for risk improvement were 2.0 (95% CI 1.50-2.65), 1.8 (95% CI 1.38-2.43), and 2.0 (95% CI 1.43-2.72) for selexipag versus placebo at 16, 26, and 52 weeks, respectively (all p < 0.001). REVEAL Lite 2 risk improvement at week 16 explained 19.1% of the treatment effect in all patients and 47.0% in patients with REVEAL Lite 2 baseline risk score of ≥7. CONCLUSIONS: REVEAL Lite 2 can monitor PAH M/M risk and facilitate treatment optimization. Baseline REVEAL Lite 2 risk score was prognostic of M/M risk in patients with PAH and mediates treatment effect up to 47% for those at higher risk. Lower M/M risk with selexipag versus placebo occurred irrespective of baseline risk category (ClinicalTrials.gov identifier: NCT01106014).

Patient- vs Technologist-Controlled Mammography Compression: A Prospective Comparative Study of Patient Discomfort and Breast Compression Thickness.

OBJECTIVE: We assess whether mammographic patient-assisted compression (PAC) has an impact on breast compression thickness and patient discomfort compared with technologist-assisted compression (TAC). METHODS: A total of 382 female patients between ages 40 and 90 years undergoing screening mammography from February 2020 to June 2021 were recruited via informational pamphlet to participate in this IRB-approved study. Patients without prior baseline mammograms were excluded. The participating patients were randomly assigned to the PAC or TAC study group. Pre- and postmammogram surveys assessed expected pain and experienced pain, respectively, using a 100-mm visual analogue scale and the State-Trait Anxiety Inventory. Breast compression thickness values from the most recent mammogram were compared with the patient's recent prior mammogram. RESULTS: Between the 2 groups, there was no significant difference between the expected level of pain prior to the mammogram (P = .97). While both study groups reported a lower level of experienced pain than was expected, the difference was greater for the PAC group (P <.0001). Additionally, the PAC group reported significantly lower experienced pain during mammography compared with the TAC group (P = .014). The correlation of trait/state anxiety scores with pre- and postmammogram pain scores was weak among the groups. Lastly, the mean breast compression thickness values for standard screening mammographic views showed no significant difference in the PAC group when compared with the patient's prior mammogram. CONCLUSION: Involving patients in compression reduces their pain independent of the patient's state anxiety during mammography while having no effect on breast compression thickness. Implementing PAC could improve the mammography experience.

Assessment of Fetal Ventricular Size and Shape in Women With Intrahepatic Cholestasis of Pregnancy Using Speckle Tracking.

OBJECTIVE: To examine the effect of intrahepatic cholestasis of pregnancy (ICP) on fetal heart morphology. METHODS: This case-control study was conducted with 40 women with ICP and 54 pregnant controls. Fetal heart quantification based on speckle tracking technology was used to assess the morphology of the fetal right and left ventricles. Routine ventricular size parameters, global and 24-segment spherical indices (SIs) were measured and compared between groups. RESULTS: The routine fetal cardiac parameters, global and right-ventricular SIs did not differ between the ICP and control groups. The left-ventricular apical (segments 16-24) SIs were lower in the ICP group than in the control group (P < .05), with no significant difference in the other left-ventricular segments. CONCLUSIONS: Subclinical morphological changes were observed in the left ventricular apical segments of the fetal hearts in women with ICP, which indicates an intrauterine environment with high bile acid concentrations. Twenty-four-segment SIs can be used to effectively evaluate these changes.

Correction: Yi et al. An Innovative Inducer of Platelet Production, Isochlorogenic Acid A, Is Uncovered through the Application of Deep Neural Networks. Biomolecules 2024, 14, 267.

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Biomimetic platelet-like nanoparticles enhance targeted hepatocellular carcinoma therapy.

Curcumin (CUR) is a promising natural product for hepatocellular carcinoma (HCC) therapy. However, its clinical application has been limited by some issues such as rapid clearance and inadequate tumor accumulation. To address these drawbacks, we developed platelet membrane-coated CUR-loaded PLGA nanoparticles (PCPNPs). In this work, due to the bioinspired strategy, the PCPNPs exhibited immune evasion, prolonged circulation, and improved accumulation at tumor sites compared to the traditional CUR formulation. The superior tumor targeting of PCPNPs was likely due to the interactions between platelet P-selectin and tumoral CD44. Furthermore, both in vitro and in vivo assays revealed that the PCPNPs showed outstanding anticancer efficacy without obvious toxicity. Therefore, PCPNPs represent a biosafe and promising anti-tumor strategy, overcoming the limitations associated with CUR. These findings not only contribute to the advancement of natural compound nano-formulation but also open new avenues for targeted cancer treatment.

Genistin: A Novel Estrogen Analogue Targeting ERß to Alleviate Thrombocytopenia.

Thrombocytopenia, a prevalent hematologic challenge, correlates directly with the mortality of numerous ailments. Current therapeutic avenues for thrombocytopenia are not without limitations. Here, we identify genistin, an estrogen analogue, as a promising candidate for thrombocytopenia intervention, discovered through AI-driven compound library screening. While estrogen's involvement in diverse biological processes is recognized, its role in thrombopoiesis remains underexplored. Our findings elucidate genistin's ability to enhance megakaryocyte differentiation, thereby augmenting platelet formation and production. In vivo assessments further underscore genistin's remedial potential against radiation-induced thrombocytopenia. Mechanistically, genistin's efficacy is attributed to its direct interaction with estrogen receptor ß (ERß), with subsequent activation of both ERK1/2 and the Akt signaling pathways membrane ERß. Collectively, our study positions genistin as a prospective therapeutic strategy for thrombocytopenia, shedding light on novel interplays between platelet production and ERß.

Alnustone promotes megakaryocyte differentiation and platelet production via the interleukin-17A/interleukin-17A receptor/Src/RAC1/MEK/ERK signaling pathway.

OBJECTIVES: Thrombocytopenia is a disease in which the number of platelets in the peripheral blood decreases. It can be caused by multiple genetic factors, and numerous challenges are associated with its treatment. In this study, the effects of alnustone on megakaryocytes and platelets were investigated, with the aim of developing a new therapeutic approach for thrombocytopenia. METHODS: Random forest algorithm was used to establish a drug screening model, and alnustone was identified as a natural active compound that could promote megakaryocyte differentiation. The effect of alnustone on megakaryocyte activity was determined using cell counting kit-8. The effect of alnustone on megakaryocyte differentiation was determined using flow cytometry, Giemsa staining, and phalloidin staining. A mouse model of thrombocytopenia was established by exposing mice to X-rays at 4 Gy and was used to test the bioactivity of alnustone in vivo. The effect of alnustone on platelet production was determined using zebrafish. Network pharmacology was used to predict targets and signaling pathways. Western blotting and immunofluorescence staining determined the expression levels of proteins. RESULTS: Alnustone promoted the differentiation and maturation of megakaryocytes in vitro and restored platelet production in thrombocytopenic mice and zebrafish. Network pharmacology and western blotting showed that alnustone promoted the expression of interleukin-17A and enhanced its interaction with its receptor, and thereby regulated downstream MEK/ERK signaling and promoted megakaryocyte differentiation. CONCLUSIONS: Alnustone can promote megakaryocyte differentiation and platelet production via the interleukin-17A/interleukin-17A receptor/Src/RAC1/MEK/ERK signaling pathway and thus provides a new therapeutic strategy for the treatment of thrombocytopenia.

Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia.

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induce the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of Vilazodone (VLZ). The effects of VLZ on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate how VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blot, and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.

Differential analysis of immunoglobulin gene expression pattern in chickens of distinct breeds and developmental periods.

Immunoglobulin is an essential component of the body's defense against pathogens, aiding in the recognition and clearance of foreign antigens. Research concerning immunoglobulin gene and its diversity of expression across different breeds within the same species is relatively scarce. In this study, we employed RACE (Rapid Amplification of cDNA Ends) technology, prepared DNA libraries, performed high-throughput sequencing, and conducted related bioinformatics analysis to analyze the differences in immunoglobulin gene diversity and expression at different periods in Hy-line brown hens, Lueyang black-bone chickens, and Beijing-You chickens. The study found that the composition of chicken immunoglobulin genes is relatively simple, with both the light chain and heavy chain having a functional V gene. Additionally, the mechanisms of immunoglobulin diversity generation tended to be consistent among different breeds and periods of chickens, primarily relying on abundant junctional diversity, somatic hypermutation (SHM), and gene conversion (GCV) to compensate for the limitations of low-level V(D)J recombination. As the age increased, the junctional diversity of IgH and IgL tended to diversify and showed similar expression patterns among different breeds. In the three chicken breeds, the predominant types of mutations observed in IGHV and IGLV SHM were A to G and G to A transitions. Specifically, IGLV exhibited a preference for A to G mutations, whereas IGHV displayed a bias toward G to A mutations. The regions at the junctions between framework regions (FR) and complementarity-determining regions (CDR) and within the CDR regions themselves are typically prone to mutations. The locations of GCV events in IGLV and IGHV do not show significant differences, and replacement segments are concentrated in the central regions of FR1, CDR, and FR2. Importantly, gene conversion events are not random occurrences. Additionally, our investigation revealed that CDRH3 in chickens of diverse breeds and periods the potential for diversification through the incorporation of cysteine. This study demonstrates that the diversity of immunoglobulin expression tends to converge among Hy-line brown hens, Lueyang black-bone chickens, and Beijing-You chickens, indicating that the immunoglobulin gene expression mechanisms in different breeds of chickens do not exhibit significant differences due to selective breeding.

Immunoglobulins play a key role in the organism's defense against pathogens, and their diverse expression allows the body to generate a wide array of antibodies. This diversity serves as a critical safeguard for the immune system against various pathogens. Natural geographical variances and artificial breeding and selection can potentially lead to different immune responses in distinct populations of the same species when confronted with the same pathogen. In this study, we investigated the diversity of immunoglobulin gene expression in the natural state of different chicken breeds (Hy-line brown hens, Lueyang black-bone chickens, and Beijing-You chickens) and at different periods from the perspective of immunoglobulin gene expression mechanism. We analyzed the diversity of immunoglobulin based on the results of high-throughput sequencing by extracting Fabricius bursa RNA, RACE (Rapid Amplification of cDNA Ends) technique, and constructing DNA libraries. Our study reveals that the junctional diversity, somatic hypermutation, CDR3 diversity, and gene conversion expression of immunoglobulins in Hy-line brown hens, Lueyang black-bone chickens, and Beijing-You chickens converge during the same time period. This indicates that the immunoglobulin gene expression mechanisms in different chicken breeds do not exhibit significant variations as a result of selective breeding.

N-glycosylation of SCAP exacerbates hepatocellular inflammation and lipid accumulation via ACSS2-mediated histone H3K27 acetylation.

Sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) is a widely expressed membrane glycoprotein that acts as an important modulator of lipid metabolism and inflammatory stress. N-glycosylation of SCAP has been suggested to modulate cancer development, but its role in nonalcoholic steatohepatitis (NASH) is poorly understood. In this study, the N-glycosylation of SCAP was analyzed by using sequential trypsin proteolysis and glycosidase treatment. The liver cell lines expressing wild-type and N-glycosylation sites mutated SCAP were constructed to investigate the N-glycosylation role of SCAP in regulating inflammation and lipid accumulation as well as the underlying mechanisms. The hepatic SCAP protein levels were significantly increased in C57BL/6J mice fed with Western diet and sugar water (WD + SW) and diabetic db/db mice, which exhibited typical liver steatosis and inflammation accompanied with hyperglycemia. In vitro, the enhanced N-glycosylation by high glucose increased the protein stability of SCAP and hence increased its total protein levels, whereas the ablation of N-glycosylation significantly decreased SCAP protein stability and alleviated lipid accumulation and inflammation in hepatic cell lines. Mechanistically, SCAP N-glycosylation increased not only the SREBP-1-mediated acetyl-CoA synthetase 2 (ACSS2) transcription but also the AMPK-mediated S659 phosphorylation of ACCS2 protein, causing the enhanced ACSS2 levels in nucleus and hence increasing the histone H3K27 acetylation (H3K27ac), which is a key epigenetic modification associated with NASH. Modulating ACSS2 expression or its location in the nuclear abolished the effects of SCAP N-glycosylation on H3K27ac and lipid accumulation and inflammation. In conclusion, SCAP N-glycosylation aggravates inflammation and lipid accumulation through enhancing ACSS2-mediated H3K27ac in hepatocytes.NEW & NOTEWORTHY N-glycosylation of SCAP exacerbates inflammation and lipid accumulation in hepatocytes through ACSS2-mediated H3K27ac. Our data suggest that SCAP N-glycosylation plays a key role in regulating histone H3K27 acetylation and targeting SCAP N-glycosylation may be a new strategy for treating nonalcoholic steatohepatitis (NASH).

Effect of Infusion Set Replacement Intervals on Central Line-Associated Bloodstream Infection in the Intensive Care Unit: Study Protocol of the INSPIRATION Study.

INTRODUCTION: The replacement intervals for infusion sets may differ among healthcare institutions, which may have an impact on the occurrence of central line-associated bloodstream infections (CLABSI). Nevertheless, there exists a limited amount of high-quality evidence available to assist clinicians in determining the most suitable replacement intervals for infusion sets. Therefore, the objective of this trial is to compare the efficacy of 24-h and 96-h replacement intervals for infusion sets on CLABSI among critically ill adults who have central venous access devices. METHODS: This is a multicenter, parallel-group randomized controlled trial that will investigate the effect of infusion set replacement intervals on CLABSI in adult patients admitted to intensive care units (ICUs). The study will enroll 1240 participants who meet the inclusion criteria, which includes being 18 years or older, expected to stay in the ICU for longer than 96 h, and in need of central venous access. Participants will be randomly assigned to either a control group receiving a 96-h replacement interval or a treatment group receiving a 24-h replacement interval. PLANNED OUTCOME: The primary outcome of this trial is the rate of CLABSI within 28 days after randomization. CONCLUSION: This is the first randomized controlled trial to investigate the effects of infusion set replacement at 24-h and 96-h intervals on CLABSI in ICU patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05359601.

An Innovative Inducer of Platelet Production, Isochlorogenic Acid A, Is Uncovered through the Application of Deep Neural Networks.

(1) Background: Radiation-induced thrombocytopenia (RIT) often occurs in cancer patients undergoing radiation therapy, which can result in morbidity and even death. However, a notable deficiency exists in the availability of specific drugs designed for the treatment of RIT. (2) Methods: In our pursuit of new drugs for RIT treatment, we employed three deep learning (DL) algorithms: convolutional neural network (CNN), deep neural network (DNN), and a hybrid neural network that combines the computational characteristics of the two. These algorithms construct computational models that can screen compounds for drug activity by utilizing the distinct physicochemical properties of the molecules. The best model underwent testing using a set of 10 drugs endorsed by the US Food and Drug Administration (FDA) specifically for the treatment of thrombocytopenia. (3) Results: The Hybrid CNN+DNN (HCD) model demonstrated the most effective predictive performance on the test dataset, achieving an accuracy of 98.3% and a precision of 97.0%. Both metrics surpassed the performance of the other models, and the model predicted that seven FDA drugs would exhibit activity. Isochlorogenic acid A, identified through screening the Chinese Pharmacopoeia Natural Product Library, was subsequently subjected to experimental verification. The results indicated a substantial enhancement in the differentiation and maturation of megakaryocytes (MKs), along with a notable increase in platelet production. (4) Conclusions: This underscores the potential therapeutic efficacy of isochlorogenic acid A in addressing RIT.

Recent Advances of DNA-Templated Metal Nanoclusters for Food Safety Detection: From Synthesis, Applications, Challenges, and Beyond.

Food safety concerns have become a significant threat to human health and well-being, catching global attention in recent years. As a result, it is imperative to research conceptually novel biosensing and effective techniques for food matrices detection. Currently, DNA-templated metal nanoclusters (DNA-MNCs) are considered as one of the most promising nanomaterials due to their excellent properties in biosensing. While DNA-MNCs have garnered increasing interest, the reviews of design strategies, applications, and futuristic prospects for biosensing have been hardly found especially in food safety. The synthesis of DNA-MNCs and their use as biosensing materials in food contamination detection, including pathogenic bacteria, toxins, heavy metals, residues of pesticides, and others were comprehensively reviewed. In addition, we summarize the properties of DNA-MNCs briefly and discuss the challenges and future trends. The application of DNA-MNCs powered biosensing has been demonstrated and actively studied, which is a promising paradigm for food safety testing that can supplement or even replace current existing methods. Despite the challenges of difficulty regulating accurately, poor stability, low quantum yield, and difficult commercial transformation, the application prospects of DNA-MNCs biosensors are promising. This review aims to provide insights and directions for the future development of DNA-MNCs based food detection technology.

Effect of Five Different Antioxidants on the Effectiveness of Goat Semen Cryopreservation.

The effective combination of semen cryopreservation and artificial insemination has a positive effect on the conservation of germplasm resources, production and breeding, etc. However, during the process of semen cryopreservation, the sperm cells are very susceptible to different degrees of physical, chemical, and oxidative stress damage. Oxidative damage is the most important factor that reduces semen quality, which is affected by factors such as dilution equilibrium, change of osmotic pressure, cold shock, and enzyme action during the freezing-thawing process, which results in the aggregation of a large amount of reactive oxygen species (ROS) in sperm cells and affects the quality of semen after thawing. Therefore, the method of adding antioxidants to semen cryoprotective diluent is usually used to improve the effect of semen cryopreservation. The aim of this experiment was to investigate the effects of adding five antioxidants (GLP, Mito Q, NAC, SLS, and SDS) to semen cryoprotection diluent on the cryopreservation effect of semen from Saanen dairy goats. The optimal preservation concentrations were screened by detecting sperm viability, plasma membrane integrity, antioxidant capacity, and acrosomal enzyme activities after thawing, and the experimental results were as follows: the optimal concentrations of GLP, Mito Q, NAC, SLS, and SDS added to semen cryopreservation diluent at different concentrations were 0.8 mg/mL, 150 nmol/L, 0.6 mg/mL, 0.15 mg/ mL, 0.6 mg/mL, and 0.15 mg/mL. The optimal concentrations of the five antioxidants were added to the diluent and analyzed after 1 week of cryopreservation, and it was found that sperm viability, plasma membrane integrity, and mitochondrial activity were significantly enhanced after thawing compared with the control group (P < 0.05), and their antioxidant capacity was significantly enhanced (P < 0.05). Therefore, the addition of the above five antioxidants to goat sperm cryodilution solution had a better enhancement of sperm cryopreservation. This study provides a useful reference for exploring the improvement of goat semen cryoprotection effect.

Targeting CD38/ ADP-ribosyl cyclase as a novel therapeutic strategy for identification of three potent agonists for leukopenia treatment.

Leukopenia is the most common side effect of chemotherapy and radiotherapy. It potentially deteriorates into a life-threatening complication in cancer patients. Despite several agents being approved for clinical administration, there are still high incidences of pathogen-related disease due to a lack of functional immune cells. ADP-ribosyl cyclase of CD38 displays a regulatory effect on leukopoiesis and the immune system. To explore whether the ADP-ribosyl cyclase was a potential therapeutic target of leukopenia. We established a drug screening model based on an ADP-ribosyl cyclase-based pharmacophore generation algorithm and discovered three novel ADP-ribosyl cyclase agonists: ziyuglycoside II (ZGSII), brevifolincarboxylic acid (BA), and 3,4-dihydroxy-5-methoxybenzoic acid (DMA). Then, in vitro experiments demonstrated that these three natural compounds significantly promoted myeloid differentiation and antibacterial activity in NB4 cells. In vivo, experiments confirmed that the compounds also stimulated the recovery of leukocytes in irradiation-induced mice and zebrafish. The mechanism was investigated by network pharmacology, and the top 12 biological processes and the top 20 signaling pathways were obtained by intersecting target genes among ZGSII, BA, DMA, and leukopenia. The potential signaling molecules involved were further explored through experiments. Finally, the ADP-ribosyl cyclase agonists (ZGSII, BA, and DMA) has been found to regenerate microbicidal myeloid cells to effectively ameliorate leukopenia-associated infection by activating CD38/ADP-ribosyl cyclase-Ca2+-NFAT. In summary, this study constructs a drug screening model to discover active compounds against leukopenia, reveals the critical roles of ADP-ribosyl cyclase in promoting myeloid differentiation and the immune response, and provides a promising strategy for the treatment of radiation-induced leukopenia.

CRISPR/Cas-Powered Amplification-Free Detection of Nucleic Acids: Current State of the Art, Challenges, and Futuristic Perspectives.

CRISPR/Cas system is becoming an increasingly influential technology that has been repositioned in nucleic acid detection. A preamplification step is usually required to improve the sensitivity of CRISPR/Cas-based detection. The striking biological features of CRISPR/Cas, including programmability, high sensitivity and sequence specificity, and single-base resolution. More strikingly, the target-activated trans-cleavage could act as a biocatalytic signal transductor and amplifier, thereby empowering it to potentially perform nucleic acid detection without a preamplification step. The reports of such work are on the rise, which is not only scientifically significant but also promising for futuristic end-user applications. This review started with the introduction of the detection methods of nucleic acids and the CRISPR/Cas-based diagnostics (CRISPR-Dx). Next, we objectively discussed the pros and cons of preamplification steps for CRISPR-Dx. We then illustrated and highlighted the recently developed strategies for CRISPR/Cas-powered amplification-free detection that can be realized through the uses of ultralocalized reactors, cascade reactions, ultrasensitive detection systems, or others. Lastly, the challenges and futuristic perspectives were proposed. It can be expected that this work not only makes the researchers better understand the current strategies for this emerging field, but also provides insight for designing novel CRISPR-Dx without a preamplification step to win practicable use in the near future.

Periostin promotes extensive neovascularization in placenta accreta spectrum disorders via Notch signaling.

OBJECTIVE: Extensive neovascularization, closely linked to massive intraoperative blood loss, is a pathological hallmark of placenta accreta spectrum (PAS) cases. This study aims to explore proteins related to neovascularization and elucidate their regulatory roles in PAS, enhancing our understanding of this condition. METHODS: The isobaric tags for relative and absolute quantitation technique were used to identify and quantify the differentially expressed proteins in placentas from PAS and healthy pregnant women. Immunofluorescence staining and western blot analysis were conducted to determine the protein expression and localization. Gain-of-function experiments were used to conduct cell proliferation and migration assays. In addition, the tube formation assay was performed to evaluate angiogenesis in vitro. The Notch inhibitor DAPT was used to determine the involvement of Notch signaling in angiogenesis in PAS. RESULTS: Periostin (POSTN) exhibited higher expression in PAS placentas than in normal placentas. Moreover, the overexpression of POSTN in endothelial cells promoted cell proliferation, mobility, and endothelial angiogenesis via the Notch signaling pathway in vitro. CONCLUSION: Elevated POSTN expression in PAS is associated with increased angiogenesis, indicating its potential as a molecular marker for significant intraoperative blood loss.

Associations of characteristics of previous induced abortion with different grades of current placenta accreta spectrum disorders.

OBJECTIVE: Induced abortion could increase the risk of placenta accreta spectrum (PAS) in the next pregnancy. We aimed to explore the associations between characteristics of previous induced abortion and grades of current PAS. METHODS: A retrospective case-control study was performed in eligible pregnant women with PAS between January 2014 and June 2022. Data collected included demographics, obstetric characteristics, and information on previous induced abortion. RESULTS: The study included 211 pregnant women, with 51 and 160 in the invasive (placenta increta or percreta) and adherence (placenta creta) PAS groups, respectively. The risk of invasive PAS was 14.3-fold higher in patients with abnormal vaginal bleeding after abortion (odds ratio = 14.3, 95% confidence interval 5.6-36.4, p < .01) than those without abnormal vaginal bleeding and approximately 5.8-fold higher in patients with the last induced abortion ≥5 years ago than those within 5 years (odds ratio = 5.8, 95% confidence interval 2.2-15.2, p < .01). The risk of invasive PAS was 13.4-fold higher in patients with placenta attached to uterine cornu than patients with the placenta attached to uterine wall (odds ratio = 17.5, 95% confidence interval 5.5-55.5, p < .01). The number of previous induced abortions, hospital grades, and gestational age at abortion were not different between two groups. CONCLUSION: In pregnant women with a history of induced abortion, abnormal vaginal bleeding after induced abortion and prolonged duration after the last induced abortion increased the risk for invasive PAS in the current pregnancy. The number of previous induced abortions and gestational age at abortion had no relation to the grades of PAS.

Disease burden contributed by dietary exposure to aflatoxins in a mountainous city in Southwest China.

Introduction: Aflatoxins (AFT) identified as a Group 1 human carcinogen naturally contaminate various types of food and could increase the risk of hepatocellular carcinoma (HCC) through dietary intake. Chongqing municipality is located in Southwest China with subtropical monsoon climate which is conducive to AFT contamination in crops. However, the burden of HCC caused by the dietary exposure of the population in Chongqing to AFT has not been quantified. Methods: The burden of HCC was estimated in terms of Disability Adjusted Life Year (DALY) using FDA-iRISK software. Dietary exposure to AFT in three food categories including grain and its products, nuts and seeds, and spices was assessed. Results: The lifetime average daily dose (LADD) of AFT exposure for the population ranged from 2.40 to 8.25 ng/kg bw/day and 9.51 to 15.10 ng/kg bw/day at the mean and heavy (P95) AFT contamination levels, respectively. Among the three food categories, grain and its products contributed most to AFT exposure of the population. The estimated DALYs related to HCC induced by AFT were 162,000-556,000 and 641,000-1,020,000; the DALY rates were 6.47-22.20 and 25.59-40.72 per 100,000 persons per year; and the population attribution fractions (PAF) were 1.68-5.78% and 6.66-10.60%. Discussion: Although the burden of HCC caused by dietary AFT was estimated to be relatively low among the population, the overall health burden might be underestimated owing to the uncertainties of this dataset. Thus, the overall health burden associated with AFT intake should still be of concern in further studies.