Vaginal dinoprostone versus Foley catheter for induction of labor at term with an unfavorable cervix: an open-label randomized controlled trial.

BACKGROUND: Induction of labor with mechanical methods or pharmacological agents is used in about 20-30% of all pregnant women. We specialized in comparing the effectiveness and safety of dinoprostone versus transcervical Foley catheter for induction of labor in term pregnant women with an unfavorable cervix with adequate samples. OBJECTIVE: To compare the effectiveness and safety of dinoprostone versus transcervical Foley catheter for induction of labor in term pregnant women with an unfavorable cervix. STUDY DESIGN: This is a parallel, open-label randomized controlled trial in two maternal centers in Shanghai, China between October 2019 and July 2022. Women with a singleton pregnancy in cephalic presentation at term and an unfavorable cervix (Bishop score < 6) scheduled for induction of labor were eligible. 1,860 women were randomly allocated to cervical ripening with either a dinoprostone vaginal insert (10mg) or a 60cc Foley catheter for up to 24 hours. The primary outcomes were vaginal delivery rate and time to vaginal delivery. Secondary outcomes included time to delivery and maternal and neonatal morbidity. Analysis was done from an intention-to-treat perspective. The trial was registered with the China trial registry (CTR2000038435). RESULTS: The vaginal birth rates were 72.8% (677/930) vs. 69.9% (650/930) in vaginal dinoprostone and Foley catheter, respectively (aRR 1.04, 95% CI 0.98 to 1.10, risk difference: 0.03). Time to vaginal delivery was not significantly different between the two groups (sub-distribution hazard ratio 1.11, 95% CI 0.99-1.24). Vaginal dinoprostone was more likely complicated with hyperstimulation with fetal heart rate changes (5.8% vs. 2.8%, aRR 2.09, 95% CI 1.32-3.31) and placenta abruption (0.9% vs. 0.1%, aRR: 8.04, 95% CI 1.01-64.15), while Foley catheter was more likely complicated with suspected intrapartum infection (5.1% vs. 8.2 %, aRR: 0.62, 95% CI 0.44-0.88) and postpartum infection (1.4% vs. 3.7%, aRR: 0.38, 95% CI 0.20-0.72). The composite of poor neonatal outcomes was not significantly different between the two groups (4.5% vs. 3.8%, aRR 1.21, 95% CI 0.78 to 1.88), while more neonatal asphyxia occurred in the dinoprostone group (1.2% vs. 0.2%, aRR 5.39, 95% CI 1.22 to 23.92). In a subgroup analysis, vaginal dinoprostone decreased vaginal birth rate slightly in multiparous women (90.6% vs. 97.0%, aRR 0.93, 95% CI 0.88 to 0.99). CONCLUSIONS: In term pregnant women with an unfavorable cervix, induction of labor with vaginal dinoprostone or Foley catheter has similar effectiveness. Foley catheter leads to better safety for neonates, while it may result in a higher risk of maternal infection. Furthermore, Foley catheter should be preferred in multiparous women.

Integrating serum pharmacochemistry, network pharmacology and untargeted metabolomics strategies to reveal the material basis and mechanism of action of Feining keli in the treatment of chronic bronchitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Feining keli (FNKL) is herbal preparation mainly made from Senecio cannabifolius Less., In recent years, more and more studies have found that FNKL has excellent therapeutic effects on chronic bronchitis (CB). Nevertheless, its pharmacodynamic material basis and mechanism of action are still unknown. AIM OF THE STUDY: This study aimed to explore the pharmacodynamic material basis and mechanism of action of FNKL in treating CB. MATERIALS AND METHODS: The CB rat model was induced using nasal drops of lipopolysaccharide (LPS) in combination with smoking. Various assessments including behavioral and body mass examination, lung index measurement, enzyme linked immunosorbent assay (ELISA), as well as histological analyses using hematoxylin and eosin (H&E) and Masson staining were conducted to validate the reliability of the CB model. The serum components of FNKL in CB rats were identified using ultra-high-performance liquid chromatography Orbitrap Exploris mass spectrometer (UHPLC-OE-MS). Network pharmacology was used to predict the network of action of the active ingredients in FNKL based on these serum components. Signaling pathways were enriched and analyzed, and molecular docking was conducted for key targets. Molecular dynamics simulations were performed using GROMACS software. The mechanism was confirmed through a series of experiments including Western blot (WB), immunofluorescence (IF), and reverse transcription (RT)-PCR. Additionally, untargeted metabolomics was employed to identify biomarkers and relevant metabolic pathways associated with the treatment of CB with FNKL. RESULTS: In CB rats, FNKL improved body mass, lung index, and pathological damage of lung tissues. It also decreased interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), malonaldehyde (MDA) levels, and percentage of lung collagen fiber area. Furthermore, FNKL increased IL-10 and superoxide dismutase (SOD) levels, which helped alleviate bronchial inflammation in the lungs. A total of 70 FNKL chemical components were identified in CB rat serum. Through network pharmacology analysis, 5 targets, such as PI3K, AKT, NF-κB, HIF-1α, and MYD88, were identified as key targets of FNKL in the treatment of CB. Additionally, the key signaling pathways identified were PI3K/AKT pathway、NF-κB/MyD88 pathway、HIF-1α pathway. WB, IF, and RT-PCR experiments were conducted to confirm the findings. Molecular docking studies demonstrated successful docking of 16 potential active components with 5 key targets. Additionally, molecular dynamics simulations indicated the stability of quercetin-3-galactoside and HIF-1α. Metabolomics analysis revealed that FNKL primarily regulated pathways related to alpha-linolenic acid metabolism, primary bile acid biosynthesis, bile secretion, arachidonic acid metabolism, neuroactive ligand-receptor interaction, and folate biosynthesis. Furthermore, the expression levels of traumatic acid, traumatin, alpha linolenic acid, cholic acid, 2-arachidonoylglycerol, deoxycholic acid, 7,8-dihydroneopterin, and other metabolites were found to be regulated. CONCLUSION: FNKL exhibits positive therapeutic effects on CB, with quercetin-3-galactoside identified as a key active component. The mechanism of FNKL's therapeutic action on CB involves reducing inflammatory response, oxidative stress, and regulating metabolism, and its molecular mechanism was better elucidated in a holistic manner. This study serves as a reference for understanding the pharmacodynamic material basis and mechanism of action of FNKL in treating CB, and provides avenues for exploring the effects of compounded herbal medicines on CB.

Cage Obliquity in Oblique Lumbar Interbody Fusion-How Common Is It and What Are the Effects on Fusion Rates, Subsidence, and Sagittal Alignment? A Computed Tomography-Based Analysis.

BACKGROUND: Oblique lumbar interbody fusion (OLIF) through a prepsoas approach was identified as an alternative to alleviate complications associated with direct lateral interbody fusion. Cage placement is known to influence cage subsidence and fusion rates due to suboptimal biomechanics. There are limited studies exploring cage obliquity as a potential factor influencing fusion outcomes. Hence, our objective was to assess the effects of cage obliquity and position on fusion rates, subsidence, and sagittal alignment in patients who underwent OLIF. METHODS: Patients who underwent OLIF for levels L1 to L5 in our center, performed by a single surgeon and with a minimum of 12 months of follow-up, were included in the study. Cage obliquity and sagittal placement were measured, and their correlation with fusion, subsidence, and sagittal alignment correction was assessed. Fusion and subsidence were evaluated using the Bridwell Criteria and Marchi Criteria, respectively. RESULTS: Among the included patients (age, 67.5 ± 7.93 years; 16 men and 37 women), 97 fusion levels were studied. The mean cage obliquity was 4.2° ± 2.8°. Ninety-six levels (99.0%) were considered to have achieved fusion with a Bridwell score of 1 or 2. Eighty-one (83.5%), 14 (14.4%), and 2 (2.06%) operated levels had a Marchi score of 0, 1, and 2, respectively. A Marchi grade of 1 or higher was considered indicative of significant subsidence. There was good improvement in both the segmental lordosis angle (4.2° ± 5.7°; P < 0.0001) and disc height (4.5 ± 3.8 mm; P < 0.0001). Cage placement did not have any statistical correlation with fusion rates, subsidence, or sagittal alignment. CONCLUSIONS: Our results indicate that OLIF facilitates appropriate cage placement with only a minor degree of cage obliquity, typically less than 20°. This minor obliquity does not lead to lower fusion rates, increased subsidence, or sagittal malalignment. Despite subsidence being common, the majority of these cases resulted in complete fusion.

Identification of Multievent Stochastic Fuzzy Discrete Event Systems.

We recently introduced a novel category of fuzzy discrete event systems (FDESs) termed stochastic FDESs (SFDESs), wherein multiple fuzzy automata occur randomly with different probabilities. We also developed two techniques for identifying event transition matrices in single-event SFDES employing the max-product fuzzy inference. One of them, named the equation-systems-based technique, focuses on the single-event SFDES identification, where the fuzzy automaton of each FDES has only one event. Expanding on our research, this article delves into multievent SFDES identification, allowing each FDES to encompass a sequence of events. This is a new research direction that has not been mentioned in the literature before. Upon activation of an FDES, all its events occur sequentially. Our mathematical proof first establishes the associativity of the max-product inference operation, leading to the introduction of a pivotal and novel concept called an equivalent overall event transition matrix for a consecutive event sequence. This concept establishes a theoretical framework for utilizing the equation-systems-based technique in a novel three-step method for identifying multievent SFDESs. The technique is employed in the first two steps to: 1) determine the number of fuzzy automata in an SFDES and 2) calculate their occurrence frequencies. In the third step, multievent transition matrices of the SFDES are learned by using the stochastic-gradient-descent-based algorithms that we previously developed for multievent FDESs, provided the numbers of consecutive events for each fuzzy automaton within the SFDES are known. Theoretical analysis reveals, for the first time, the interconnections between the event transition matrices learned by the algorithms, the equivalent overall event transition matrices derived from these matrices, and the target event transition matrices. To illustrate our findings, we present an informative example.

Giant retroperitoneal hemolymphangioma: A case report and review of literature.

BACKGROUND: Hemolymphangioma is a very rare benign tumor in clinical practice caused by abnormalities of the vasculature. Its clinical features are often atypical, and it is easy to miss and misdiagnose. When the time of nuclear magnetic T1 is significantly reduced, the diagnosis of hemangioma should be considered. Therefore, we report this case in the hope of raising clinicians' awareness of the disease. CASE SUMMARY: A 37-year-old man presented with a giant retroperitoneal hemolymphangioma. Computed tomography and magnetic resonance imaging indicated the possibility of a large perirenal lymphatic cyst. The postoperative pathological diagnosis is retroperitoneal hemolymphangioma. The patient underwent surgical excision after adequate drainage. The postoperative recovery was smooth and there were no complications. There was no recurrence during half a year of follow-up. CONCLUSION: This case reiterates that large retroperitoneal cystic masses with significantly shortened nuclear T1 time should be considered hemolymphangioma. Specific clinical basis and experience for the diagnosis and treatment of these diseases is necessary.

The effect of 30-day adequate transitions of acute stroke care on 90-day readmission or death.

OBJECTIVES: We explore patient-reported behaviors and activities within 30-days post-stroke hospitalization and their role in reducing death or readmissions within 90-days post-stroke. METHODS: We constructed the adequate transitions of care (ATOC) composite score, measuring patient-reported participation in eligible behaviors and activities (diet modification, weekly exercise, follow-up medical appointment attendance, medication adherence, therapy use, and toxic habit cessation) within 30 days post-stroke hospital discharge. We analyzed ATOC scores in ischemic and intracerebral hemorrhage stroke patients discharged from the hospital to home or rehabilitation facilities and enrolled in the NIH-funded Transitions of Care Stroke Disparities Study (TCSD-S). We utilized Cox regression analysis, with the progressive adjustment for sociodemographic variables, social determinants of health, and stroke risk factors, to determine the associations between ATOC score within 30-days and death or readmission within 90-days post-stroke. RESULTS: In our sample of 1239 stroke patients (mean age 64 +/- 14, 58 % male, 22 % Hispanic, 22 % Black, 52 % White, 76 % discharged home), 13 % experienced a readmission or death within 90 days (3 deaths, 160 readmissions, 3 readmissions with subsequent death). Seventy percent of participants accomplished a ≥75 % ATOC score. A 25 % increase in ATOC was associated with a respective 20 % (95 % CI 3-33 %) reduced risk of death or readmission within 90-days. CONCLUSION: ATOC represents modifiable behaviors and activities within 30-days post-stroke that are associated with reduced risk of death or readmission within 90-days post-stroke. The ATOC score should be validated in other populations, but it can serve as a tool for improving transitions of stroke care initiatives and interventions.

Concurrent behavioral modeling and multimodal neuroimaging reveals how feedback affects the performance of decision making in internet gaming disorder.

Internet gaming disorder (IGD) prompts inquiry into how feedback from prior gaming rounds influences subsequent risk-taking behavior and potential neural mechanisms. Forty-two participants, including 15 with IGD and 27 health controls (HCs), underwent a sequential risk-taking task. Hierarchy Bayesian modeling was adopted to measure risky propensity, behavioral consistence, and affection by emotion ratings from last trial. Concurrent electroencephalogram and functional near-infrared spectroscopy (EEG-fNIRS) recordings were performed to demonstrate when, where and how the previous-round feedback affects the decision making to the next round. We discovered that the IGD illustrated heightened risk-taking propensity as compared to the HCs, indicating by the computational modeling (p = 0.028). EEG results also showed significant time window differences in univariate and multivariate pattern analysis between the IGD and HCs after the loss of the game. Further, reduced brain activation in the prefrontal cortex during the task was detected in IGD as compared to that of the control group. The findings underscore the importance of understanding the aberrant decision-making processes in IGD and suggest potential implications for future interventions and treatments aimed at addressing this behavioral addiction.

Deubiquitination of CIB1 by USP14 promotes lenvatinib resistance via the PAK1-ERK1/2 axis in hepatocellular carcinoma.

Background: Lenvatinib is the most common multitarget receptor tyrosine kinase inhibitor for the treatment of advanced hepatocellular carcinoma (HCC). Acquired resistance to lenvatinib is one of the major factors leading to the failure of HCC treatment, but the underlying mechanism has not been fully characterized. Methods: We established lenvatinib-resistant cell lines, cell-derived xenografts (CDXs) and patient-derived xenografts (PDXs) and obtained lenvatinib-resistant HCC tumor tissues for further study. Results: We found that ubiquitin-specific protease 14 (USP14) was significantly increased in lenvatinib-resistant HCC cells and tumors. Silencing USP14 significantly attenuated lenvatinib resistance in vitro and in vivo. Mechanistically, USP14 directly interacts with and stabilizes calcium- and integrin-binding protein 1 (CIB1) by reversing K48-linked proteolytic ubiquitination at K24, thus facilitating the P21-activated kinase 1 (PAK1)-ERK1/2 signaling axis. Moreover, in vivo adeno-associated virus 9 mediated transduction of CIB1 promoted lenvatinib resistance in PDXs, whereas CIB1 knockdown resensitized the response of PDXs to lenvatinib. Conclusions: These findings provide new insights into the role of CIB1/PAK1-ERK1/2 signaling in lenvatinib resistance in HCC. Targeting CIB1 and its pathways may be a novel pharmaceutical intervention for the treatment of lenvatinib-resistant HCC.

Upregulation of Siglec-6 induces mitochondrial dysfunction by promoting GPR20 expression in early-onset preeclampsia.

BACKGROUND: Preeclampsia, especially early-onset preeclampsia (EO-PE), is a pregnancy complication that has serious consequences for the health of both the mother and the fetus. Although abnormal placentation due to mitochondrial dysfunction is speculated to contribute to the development of EO-PE, the underlying mechanisms have yet to be fully elucidated. METHODS: The expression and localization of Siglec-6 in the placenta from normal pregnancies, preterm birth and EO-PE patients were examined by RT-qPCR, Western blot and IHC. Transwell assays were performed to evaluate the effect of Siglec-6 on trophoblast cell migration and invasion. Seahorse experiments were conducted to assess the impact of disrupting Siglec-6 expression on mitochondrial function. Co-IP assay was used to examine the interaction of Siglec-6 with SHP1/SHP2. RNA-seq was employed to investigate the mechanism by which Siglec-6 inhibits mitochondrial function in trophoblast cells. RESULTS: The expression of Siglec-6 in extravillous trophoblasts is increased in placental tissues from EO-PE patients. Siglec-6 inhibits trophoblast cell migration and invasion and impairs mitochondrial function. Mechanismly, Siglec-6 inhibits the activation of NF-κB by recruiting SHP1/SHP2, leading to increased expression of GPR20. Notably, the importance of GPR20 function downstream of Siglec-6 in trophoblasts is supported by the observation that GPR20 downregulation rescues defects caused by Siglec-6 overexpression. Finally, overexpression of Siglec-6 in the placenta induces a preeclampsia-like phenotype in a pregnant mouse model. CONCLUSIONS: This study indicates that the regulatory pathway Siglec-6/GPR20 has a crucial role in regulating trophoblast mitochondrial function, and we suggest that Siglec-6 and GPR20 could serve as potential markers and targets for the clinical diagnosis and therapy of EO-PE.

CXCL9 Overexpression Predicts Better HCC Response to Anti-PD-1 Therapy and Promotes N1 Polarization of Neutrophils.

Background: Anti-programmed death-1 (PD1) antibodies have changed the treatment landscape for hepatocellular carcinoma (HCC) and exhibit promising treatment efficacy. However, the majority of HCCs still do not respond to anti-PD-1 therapy. Methods: We analyzed the expression of CXCL9 in blood samples from patients who received anti-PD-1 therapy and evaluated its correlation with clinicopathological characteristics and treatment outcomes. Based on the results of Cox regression analysis, a nomogram was established for predicting HCC response to anti-PD-1 therapy. qRT‒PCR and multiple immunofluorescence assays were utilized to analyze the proportions of N1-type neutrophils in vitro and in tumor samples, respectively. Results: The nomogram showed good predictive efficacy in the training and validation cohorts and may be useful for guiding clinical treatment of HCC patients. We also found that HCC cell-derived CXCL9 promoted N1 polarization of neutrophils in vitro and that AMG487, a specific CXCR3 inhibitor, significantly blocked this process. Moreover, multiple immunofluorescence (mIF) showed that patients with higher serum CXCL9 levels had greater infiltration of the N1 phenotype of tumor-associated neutrophils (TANs). Conclusion: Our study highlights the critical role of CXCL9 as an effective biomarker of immunotherapy efficacy and in promoting the polarization of N1-type neutrophils; thus, targeting the CXCL9-CXCR3 axis could represent a novel pharmaceutical strategy to enhance immunotherapy for HCC.

Analysis of urinary retention after endoscopic prostate enucleation and its subsequent impact on surgical outcomes.

PURPOSE: Postoperative urinary retention (PUR) is a common complication after prostate enucleation, which leads to an increased length of hospital stay and decreased postoperative satisfaction. This study determined the predictive factors of postoperative urine retention within 1 month after prostate enucleation and investigated whether PUR influences surgical outcomes at the 2-week, 3-month, and 6-month follow-up time points. METHODS: Data were collected from the electronic medical records of 191 patients with benign prostatic obstruction (BPO) during October 2018 to September 2021. Of them, 180 patients who underwent thulium laser or plasma kinetic enucleation of the prostate (ThuLEP, PKEP) were separated into the PUR group (n = 24) and the non-PUR (NPUR) group (n = 156). Uroflowmetry and the International Prostate Symptom Score (IPSS) questionnaire were followed up at 2 weeks, 3 months, and 6 months postoperatively. RESULTS: The PUR group had a significantly higher percentage of patients with type 2 diabetes mellitus (DM) than the NPUR group. Postoperatively, compared with the NPUR group, the PUR group had significantly less improvement in changes in the IPSS Quality of Life scores at 2 weeks, the total IPSS(International Prostate Symptom Score) at all follow-up times, the IPSS-S(IPSS storage subscores) at 2 weeks and 3 months, and the IPSS-V(IPSS voiding subscores) at all follow-up times. Predictive factors for PUR include lower preoperative maximum urinary flow (Qmax), lower preoperative total IPSS, and higher operation time. CONCLUSION: Lower preoperative Qmax, lower IPSS scores, and longer operation time were risk factors for PUR. Furthermore, PUR could be a prognostic factor for prostatic enucleation surgical outcomes.

Novel inflammatory and insulin resistance indices provide a clue in cerebral amyloid angiopathy.

This study investigated the correlation of newly identified inflammatory and insulin resistance indices with cerebral amyloid angiopathy (CAA), and explored their potential to differentiate CAA from hypertensive arteriopathy (HA). We retrospectively analyzed 514 consecutive patients with cerebral small vessel disease (CSVD)-related haemorrhage, comparing the differences in novel inflammatory and insulin resistance indices between patients with CAA and HA. Univariate regression, LASSO and multivariate regression were used to screen variables and construct a classification diagnosis nomogram. Additionally, these biomarkers were explored in patients with mixed haemorrhagic CSVD. Inflammatory indices were higher in CAA patients, whereas insulin resistance indices were higher in HA patients. Further analysis identified neutrophil-to-lymphocyte ratio (NLR, OR 1.17, 95% CI 1.07-1.30, P < 0.001), and triglyceride-glucose index (TyG, OR = 0.56, 95% CI 0.36-0.83, P = 0.005) as independent factors for CAA. Therefore, we constructed a CAA prediction nomogram without haemorrhagic imaging markers. The nomogram yielded an area under the curve (AUC) of 0.811 (95% CI 0.764-0.865) in the training set and 0.830 (95% CI 0.718-0.887) in the test set, indicating an ability to identify high-risk CAA patients. These results show that CSVD patients can be phenotyped using novel inflammatory and insulin resistance indices, potentially allowing identification of high-risk CAA patients without haemorrhagic imaging markers.

Peroxiredoxin I and II as novel therapeutic molecular targets in cervical cancer treatment through regulation of endoplasmic reticulum stress induced by bleomycin.

Cervical cancer, significantly affecting women worldwide, often involves treatment with bleomycin, an anticancer agent targeting breast, ovarian, and cervical cancers by generating reactive oxygen species (ROS) to induce cancer cell death. The Peroxiredoxin (PRDX) family, particularly PRDX1 and 2, plays a vital role in maintaining cellular balance by scavenging ROS, thus mitigating the damaging effects of bleomycin-induced mitochondrial and cellular oxidative stress. This process reduces endoplasmic reticulum (ER) stress and prevents cell apoptosis. However, reducing PRDX1 and 2 levels reverses their protective effect, increasing apoptosis. This research highlights the importance of PRDX1 and 2 in cervical cancer treatments with bleomycin, showing their potential to enhance treatment efficacy by managing ROS and ER stress and suggesting a therapeutic strategy for improving outcomes in cervical cancer treatment.

Abnormal maternal apolipoprotein levels during pregnancy are risk factors for preterm birth in women with dichorionic twin pregnancies: A retrospective study.

OBJECTIVE: In singleton-pregnant women, abnormal maternal apolipoprotein levels have been confirmed as a risk factor for preterm birth. However, there are currently no studies on the relationship of the related research in twin-pregnant women. METHODS: This single-center retrospective study included 743 dichorionic twin-pregnant women who delivered between January 2019 and December 2020. Twins delivered before 37 weeks gestation were categorized as the preterm group, while those delivered at or after 37 weeks gestation were classified as the term group. Maternal serum apolipoprotein A1 (ApoA1) levels, apolipoprotein B (ApoB) levels, and the ApoB/ApoA1 ratio were measured in the first trimester(6-14 weeks), the second trimester(18-28 weeks) and the third trimester(after 28 weeks). We conducted SPSS analysis to evaluate the correlation between ApoA1 levels, ApoB levels, the ApoB/ApoA1 ratio and preterm birth. RESULTS: Among the 743 included dichorionic twin-pregnant women, 53.57 % (398/743) delivered preterm. Compared with the term group, the ApoA1 levels in the third trimester were lower (p < 0.001), while the Apo B/ApoA1 ratio was higher in the second (p = 0.01) and third trimesters in the preterm group (p = 0.001). When preterm birth was categorized as iatrogenic and spontaneous preterm birth, the results were similar. In the analysis stratified by prepregnancy BMI, a higher risk of preterm birth was associated with low ApoA1 levels and a high Apo B/ApoA1 ratio in the second and third trimesters only among the subgroup of overweight/obese dichorionic twin-pregnant women. CONCLUSIONS: Low ApoA1 levels and a high Apo B/ApoA1 ratio during the second and third trimesters were associated with a high incidence of preterm birth for overweight/obese dichorionic twin-pregnant women.

Peroxiredoxin II exerts neuroprotective effects by inhibiting endoplasmic reticulum stress and oxidative stress-induced neuronal pyroptosis.

BACKGROUND: Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator. However, its exact role and action mechanisms need clearer definition. This research aims to explore Prx II impact on neuronal pyroptosis and elucidate its mechanisms, especially regarding endoplasmic reticulum (ER) stress and oxidative stress-induced neuronal damage modulation. METHODS AND RESULTS: Utilizing MTT assays, Microscopy, Hoechst/PI staining, Western blotting, and immunofluorescence, we found Prx II effectively reduces LPS/ATP-induced pyroptosis and neuroinflammation in HT22 hippocampal neuronal cells. Our results indicate Prx II's neuroprotective actions are mediated through PI3K/AKT activation and ER stress pathway inhibition, diminishing mitochondrial dysfunction and decreasing neuronal pyroptosis through the ROS/MAPK/NF-κB pathway. These findings highlight Prx II potential therapeutic value in improving intracerebral hemorrhage outcomes by lessening secondary brain injury via critical signaling pathway modulation involved in neuronal pyroptosis. CONCLUSIONS: Our study not only underlines Prx II importance in neuroprotection but also opens new therapeutic intervention avenues in intracerebral hemorrhage, stressing the complex interplay between redox regulation, ER stress, and mitochondrial dynamics in neuroinflammation and cell death management.

Nonvolatile Modulation of Bi2O2Se/Pb(Zr,Ti)O3 Heteroepitaxy.

The pursuit of high-performance electronic devices has driven the research focus toward 2D semiconductors with high electron mobility and suitable band gaps. Previous studies have demonstrated that quasi-2D Bi2O2Se (BOSe) has remarkable physical properties and is a promising candidate for further exploration. Building upon this foundation, the present work introduces a novel concept for achieving nonvolatile and reversible control of BOSe's electronic properties. The approach involves the epitaxial integration of a ferroelectric PbZr0.2Ti0.8O3 (PZT) layer to modify BOSe's band alignment. Within the BOSe/PZT heteroepitaxy, through two opposite ferroelectric polarization states of the PZT layer, we can tune the Fermi level in the BOSe layer. Consequently, this controlled modulation of the electronic structure provides a pathway to manipulate the electrical properties of the BOSe layer and the corresponding devices.

Identifying competing endogenous RNA regulatory networks and hub genes in alcoholic liver disease for early diagnosis and potential therapeutic target insights.

Alcoholic liver disease (ALD) has a complex pathogenesis. Although early-stage ALD can be reversed by ceasing alcohol consumption, early symptoms are difficult to detect, and several factors contribute to making alcohol difficult to quit. Continued alcohol abuse worsens the condition, meaning it may gradually progress into alcoholic hepatitis and cirrhosis, ultimately, resulting in irreversible consequences. Therefore, effective treatments are urgently needed for early-stage ALD. Current research mainly focuses on preventing the progression of alcoholic fatty liver to alcoholic hepatitis and cirrhosis. However, challenges remain in identifying key therapeutic targets and understanding the molecular mechanisms that underlie the treatment of alcoholic hepatitis and cirrhosis, such as the limited discovery of effective therapeutic targets and treatments. Here, we downloaded ALD microarray data from Gene Expression Omnibus and used bioinformatics to compare and identify the hub genes involved in the progression of alcoholic fatty liver to alcoholic hepatitis and cirrhosis. We also predicted target miRNAs and long non-coding RNAs (lncRNAs) to elucidate the regulatory mechanisms (the mRNA-miRNA-lncRNA axis) underlying this progression, thereby building a competitive endogenous RNA (ceRNA) mechanism for lncRNA, miRNA, and mRNA. This study provides a theoretical basis for the early treatment of alcoholic hepatitis and cirrhosis and identifies potential therapeutic targets.

Aspirin versus metformin in pregnancies at high risk of preterm pre-eclampsia in China (AVERT): protocol for a multicentre, double-blind, 3-arm randomised controlled trial.

INTRODUCTION: Pre-eclampsia (PE) affects about 5% of Chinese pregnant women and is a major cause of maternal and perinatal morbidity and mortality. The first trimester screening model developed by the Fetal Medicine Foundation, which uses the Bayes theorem to combine maternal characteristics and medical history together with measurements of biomarkers, has been proven to be effective and has superior screening performance to that of the traditional risk factor-based approach for the prediction of PE. Prophylactic use of low-dose aspirin in women at risk for PE has resulted in a lower incidence of preterm-PE. However, there is no consensus on the preferred aspirin dosage for the prevention of preterm-PE. Evidence has also suggested that metformin has the potential benefit in preventing PE in pregnant women who are at high risk of the disorder. METHOD AND ANALYSIS: We present a protocol (V.2.0, date 17 March 2022) for the AVERT trial, which is a multicentre, double-blinded, 3-arm randomised controlled trial (RCT) that uses an effective PE screening programme to explore the optimal dosage of aspirin and the role of metformin for the prevention of PE among high-risk pregnant women in China. We intend to recruit 66 000 singleton pregnancies without treatment of low-dose aspirin and metformin at 11-13 weeks' gestation and all eligible women attending for their first trimester routine scan will be invited to undergo screening for preterm-PE by the combination of maternal factors, mean arterial pressure and placental growth factor. Women found to be at high risk of developing preterm-PE will be invited to take part in the RCT. This study will compare the incidence of preterm-PE with delivery at <37 weeks' gestation, as the primary outcome, of three different interventional groups: (1) aspirin 75 mg daily, (2) aspirin 150 mg daily and (3) aspirin 75 mg with metformin 1.5 g daily. 957 participants per treatment group are required to detect a significant difference of 59% in the reduction of the incidence of preterm-PE with 80% power and type I error of 5%. Pregnancy and neonatal outcomes will be collected and analysed. ETHICS AND DISSEMINATION: Ethical approval for the study was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No. 2021.406) in Hong Kong and the Ethics Committee of each participating hospital in Mainland China. The study is registered at ClinicalTrials.gov. The results of the AVERT trial will be disseminated at international academic conferences and published in high-impact factor journals. TRIAL REGISTRATION NUMBER: NCT05580523.