Lactobacillus salivarius Ameliorates AFB1-induced hepatotoxicity via PINK1/Parkin-mediated mitophagy in Geese.

Aflatoxin B1 (AFB1) is commonly found in feed ingredients and foods all over the world, posing a significant threat to food safety and public health in animals and humans. Lactobacillus salivarius (L. salivarius) was recorded to improve the intestinal health and performance of chickens. However, whether L. salivarius can alleviate AFB1-induced hepatotoxicity in geese was unknown. A total of 300 Lande geese were randomly assigned to five groups: control group, AFB1 low-dose group (L), L. salivarius+AFB1 low-dose group (LL), AFB1 high dosage groups (H), L. salivarius+AFB1 high dosage groups (LH), respectively. The results showed that the concentrations of ALT, AST, and GGT significantly increased after exposure to AFB1. Similarly, severe damage of hepatic morphology was observed including the hepatic structure injury and inflammatory cell infiltration. The oxidative stress was evidenced by the elevated concentrations of MDA, and decreased activities of GSH-Px, GSH and SOD. The observation of immunofluorescence, real-time PCR, and western blotting showed that the expression of PINK1 and the value of LC3II/LC3I were increased, but that of p62 significantly decreased after AFB1 exposure. Moreover, the supplementation of L. salivarius effectively improved the geese performance, ameliorated AFB1-induced oxidative stress, inhibited mitochondrial mitophagy and enhanced the liver restoration to normal level. The present study demonstrated that L. salivarius ameliorated AFB1-induced the hepatotoxicity by decreasing the oxidative stress, and regulating the expression of PINK1/Parkin-mediated mitophagy in the mitochondria of the geese liver. Furthermore, this investigation suggested that L. salivarius might serve as a novel and safe additive for preventing AFB1 contamination in poultry feed.

The protective effects of Lactobacillus SNK-6 on growth, organ health, and intestinal function in geese exposed to low concentration Aflatoxin B1.

Aflatoxin B1 (AFB1) is a prevalent mycotoxin present in feed ingredients. In this study, we investigated the effects of Lactobacillus salivarius (L. salivarius) on the Landes geese exposed to AFB1. The 300 one-day-old Landes geese were randomly divided into five groups: The control group received a basic diet, while the other groups were fed a basic diet supplemented with 10 µg/kg AFB1, 10 µg/kg AFB1+ 4*108 cfu/g L. salivarius, 50 µg/kg AFB1, and 50 µg/kg AFB1 + 4*108 cfu/g L. salivarius for 63 d. Results showed that high level AFB1 exposure significantly decreased final BW and ADG, increased feed/gain ratio (F/G) and liver index (P < 0.05). L. salivarius improved levels of IL-1, IL-6, and IL-12 under low level of AFB1 exposure (P < 0.05), along with similar trends observed in serum IgA, IgG, IgM, T3, T4, TNF-ɑ, and EDT (P < 0.05). AFB1 exposure reduced jejunum villus high and villus high/crypt depth ratio, and suppressed expression of ZO-1, Occludin, and Claudin-1 mRNA, and significant improved with L. salivarius supplementation under low level AFB1 exposure (P < 0.05). AFB1 significantly increased expression levels of TLR3 and NF-kB1, with supplementation of L. salivarius showing significant improvement under low AFB1 exposure (P < 0.05). Cecal microbiota sequencing revealed that under low level AFB1 exposure, supplementation with L. salivarius increased the abundance of Bacteroidetes and Lactococcus. In summary, supplementation with 4*108 cfu/g L. salivarius under 10 µg/kg AFB1 exposure improved growth performance and immune capacity, enhanced jejunum morphology, reduced liver inflammation, altered the cecal microbial structure, and positively affected the growth and development of geese.

Bone marrow mesenchymal stem cell-derived exosomal miR-221-3p promotes angiogenesis and wound healing in diabetes via the downregulation of forkhead box P1.

AIM: Impaired wound healing in patients with diabetes can develop into nonhealing ulcerations. Because bone marrow mesenchymal stem cells (BMSCs) exosomes can promote wound healing, this study aims to investigate the mechanism of BMSCs-isolated exosomal miR-221-3p in angiogenesis and diabetic wound healing. METHODS: To mimic diabetes in vitro, human umbilical vein endothelial cells (HUVECs) were subjected to high glucose (HG). Exosomes were derived from BMSCs and identified by transmission electron microscopy (TEM), western blot analysis and dynamic light scattering (DLS). The ability to differentiate BMSCs was assessed via Oil red O staining, alkaline phosphatase (ALP) staining and alizarin red staining. The ability to internalise PKH26-labelled exosomes was assessed using confocal microscopy. Migration, cell viability and angiogenesis were tested by scratch, MTT and tube formation assays separately. The miRNA and protein levels were analysed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) or western blotting. The relationship among miR-221-3p, FOXP1 and SPRY1 was determined using the dual-luciferase reporter, ChIP and RIP assays. RESULTS: Exosomal miR-221-3p was successfully isolated from BMSCs and delivered into HUVECs. HG was found to suppress the angiogenesis, cell viability and migration of HUVECs and exosomal miR-221-3p separated from BMSCs inhibited the above phenomenon. FOXP1 could transcriptionally upregulate SPRY1, and the silencing of FOXP1 reversed the HG-stimulated angiogenesis inhibition, cell viability and migration in HUVECs via the downregulation of SPRY1. Meanwhile, miR-221-3p directly targeted FOXP1 and the overexpression of FOXP1 reversed the positive effect of exosomal miR-221-3p on HUVEC angiogenesis. CONCLUSION: Exosomal miR-221-3p isolated from BMSCs promoted angiogenesis in diabetic wounds through the mediation of the FOXP1/SPRY1 axis. Furthermore, the findings of this study can provide new insights into probing strategies against diabetes.

The prognostic value of preoperative systemic inflammatory response index in predicting outcomes of acute type A aortic dissection patients underwent surgical treatment.

Background: The systemic inflammatory response index (SIRI) is a novel inflammatory-immune biological marker that has prognostic value in various cardiovascular diseases. This study aims to investigate the relationship between SIRI and short-term and long-term prognosis in patients with acute type A aortic dissection (AAAD) underwent surgical treatment. Methods: We conducted a retrospective analysis of patients with AAAD who underwent emergency surgical treatment at our center. Through multifactorial logistics regression analysis and cox proportional hazards regression analysis, we identified SIRI as an independent risk factor for major adverse events (MAEs) and long-term aorta-related adverse events (ARAEs) post-surgery. The optimal cutoff value of preoperative SIRI was determined using receiver operating characteristic (ROC) curve analysis, and patients were divided into low SIRI group and high SIRI group. The prognostic outcomes at different time points post-surgery for the two groups of patients were analyzed using Kaplan-Meier survival analysis, and the significance was determined by log-rank test. Results: A total of 691 AAAD patients were included in this study. Among them, 50 patients (7.2%) died within 30 days post-surgery, and 175 patients (25.3%) experienced MAEs. A total of 641 patients were followed up, with an average follow-up time of 33.5 ± 17.5 months, during which 113 patients (17.6%) experienced ARAEs. The results of multifactorial logistics regression analysis and cox proportional hazards regression analysis showed that SIRI was an independent risk factor for postoperative MAEs (OR=3.148, 95%CI[1.650-6.006], p<0.001) and ARAEs (HR=2.248, 95%CI[1.050-4.809], p<0.037). Kaplan-Meier analysis demonstrated that the MAEs-free survival in the high SIRI group was significantly lower than that in the low SIRI group, and a similar trend was observed in the ARAEs-free survival during follow-up (log-rank test, p<0.001). Conclusion: Preoperative SIRI is significantly associated with the short-term and long-term prognosis of AAAD patients underwent emergency open surgery, demonstrating its valuable prognostic value. Therefore, preoperative SIRI is a reliable biological marker that can serve as a valuable tool for preoperative risk stratification and decision management.

Surgical management of the aortic root in acute type A aortic dissection: A comparative analysis.

BACKGROUND: This study aimed to assess the early- and mid-term outcomes of aortic root repair and replacement, and to provide evidence to improve root management in acute type A aortic dissection (AAAD). METHODS: This study enrolled 455 patients who underwent AAAD root repair (n = 307) or replacement (n = 148) between January 2016 and December 2017. Inverse probability of treatment weighting (IPTW) method was used to control for treatment selection bias. The primary outcomes were in-hospital mortality, mid-term survival, and proximal aortic reintervention. RESULTS: The success rate of root repair was 99.7%. The in-hospital mortality in the conservative root repair (CRR) and aggressive root replacement (ARR) were 8.1% and 10.8%. The median follow-up time was 67.76 months (IQR, 67-72 months). After adjusting for baseline factors, there was no significant differences in mid-term survival (p = .750) or the proximal aortic reintervention rate (p = .550) between the two groups. According to Cox analysis, age, hypertension, severe aortic regurgitation, CPB time, and concomitant CABG were all factors associated with mid-term mortality. Regarding reintervention, multivariate analysis identified renal insufficiency, bicuspid aortic valve, root diameter ≥ 45 mm, and severe aortic regurgitation as risk factors, while CRR did not increase the risk of reintervention. The subgroup analysis revealed heterogeneity in the effects of surgical treatment across diverse populations based on a variety of risk factors. CONCLUSIONS: For patients with AAAD, both CRR and ARR are appropriate operations with promising early and mid-term outcomes. The effects of treatment show heterogeneity across diverse populations based on various risk factors.

10× single-cell sequencing revealed cellular composition heterogeneity in cardiac myxoma with malignant glandular properties.

Cardiac myxoma is the most common primary cardiac tumor in adults. The histogenesis and cellular composition of myxoma are still unclear. This study aims to reveal the role of myxoma cell components and their gene expression in tumor development. We obtained single living cells by enzymatic digestion of tissues from 4 cases of surgically resected cardiac myxoma. Of course, there was 1 case of glandular myxoma and 3 cases of nonglandular myxoma. Then, 10× single-cell sequencing was performed. We identified 12 types and 11 types of cell populations in glandular myxoma and nonglandular myxoma, respectively. Heterogeneous epithelial cells are the main components of glandular myxoma. The similarities and differences in T cells in both glandular and nonglandular myxoma were analyzed by KEGG and GO. The most important finding was that there was active communication between T cells and epithelial cells. These results clarify the possible tissue occurrence and heterogeneity of cardiac myxoma and provide a theoretical basis and guidance for clinical diagnosis and treatment.

Maternal choline supplementation mitigates premature foetal weight gain induced by an obesogenic diet, potentially linked to increased amniotic fluid leptin levels in rats.

Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas choline, an essential nutrient for foetal development, has shown promise in mitigating some negative impacts of maternal obesity. Here, we investigate whether a maternal obesogenic diet alters foetal growth and leptin levels in the foetal stomach, amniotic fluid (AF), and placenta in late gestation and explore the potential modulating effects of maternal choline supplementation. Female rats were fed a control (CD) or a western diet (WD) four weeks before mating and during gestation, half of them supplemented with choline (pregnancy days 11-17). Leptin levels (in foetal stomach, AF, and placenta) and leptin gene expression (in placenta) were assessed on gestation days 20 and 21. At day 20, maternal WD feeding resulted in greater leptin levels in foetal stomach, placenta, and AF. The increased AF leptin levels were associated with a premature increase in foetal weight in both sexes. Maternal choline supplementation partially prevented these alterations, but effects differed in CD dams, causing increased AF leptin levels and greater weight in male foetuses at day 20. Maternal choline supplementation effectively mitigates premature foetal overgrowth induced by an obesogenic diet, potentially linked to increased AF leptin levels. Further research is needed to explore the sex-specific effects.

Advancing Integration of Direct C-H Arylation-Derived Star-Shaped Oligomers as Second Acceptors for Ternary Organic Solar Cells.

Organic solar cells (OSCs) could benefit from the ternary bulk heterojunction (BHJ), a method that allows for fine-tuning of light capture, cascade energy levels, and film shape, in order to increase their power conversion efficiency (PCE). In this work, the third components of PM6:Y6 and PM6:BTP-eC9 BHJs are a set of four star-shaped unfused ring electron acceptors (SSUFREAs), i.e., BD-IC, BFD-IC, BD-2FIC, and BFD-2FIC, that are facilely synthesized by direct C-H arylation. The four SSUFREAs all show complete complementary absorption with PM6, Y6, and BTP-eC9, which facilitates light harvesting and exciton collection. When BFD-2FIC is added as a third component, the PCEs of PM6:Y6 and PM6:BTP-eC9 binary BHJs are able to be improved from 15.31% to 16.85%, and from 16.23% to 17.23%, respectively, showing that BFD-2FIC is useful for most effective ternary OSCs in general, and increasing short circuit current (JSC) and better film morphology are two additional benefits. The ternary PM6:Y6:BFD-2FIC exhibits a 9.7% percentage of increase in PCE compared to the PM6:Y6 binary BHJ, which is one of the highest percentage increases among the reported ternary BHJs, showing the huge potential of BFD-2FIC for ternary BHJ OSCs.

Clinical predictive value of the age, creatinine, and ejection fraction score in patients in acute type A aortic dissection after total arch replacement.

The age, creatinine, and ejection fraction (ACEF) score has been accepted as a predictor of poor outcome in elective operations. This study aimed to investigate the predictive value of ACEF score in acute type A aortic dissection (AAAD) patients after total arch replacement. A total of 227 AAAD patients from July 2021 and June 2022 were enrolled and divided into Tertiles 1 (ACEF ≤ 0.73), Tertiles 2 (0.73 < ACEF ≤ 0.95), and Tertiles 3 (ACEF > 0.95). Using inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Cox logistic regression was used to further evaluate the survival prediction ability of ACEF score. The in-hospital mortality was 9.8%. After IPTW, in the baseline characteristics reached an equilibrium, a higher ACEF score before operation still associated with higher in-hospital mortality. After 1 year follow-up, 184 patients (90.6%) survival. Multivariable analysis revealed that ACEF score (adjusted hazard ratio 1.68; 95% confidence interval 1.34-4.91; p = 0.036) and binary ACEF score (adjusted HR 2.26; 95% CI 1.82-6.20; p < 0.001) was independently associated with 1-year survival. In addition, net reclassification improvement (NRI) and integrated differentiation improvement (IDI) verified that the ACEF score and binary ACEF score is an accurate predictive tool in clinical settings. In conclusions, ACEF score could be considered as a useful tool to risk stratification in patients with AAAD before operation in daily clinical work.

Effect of Cymbopogon martini (Roxb.) Will.Watson essential oil on antioxidant activity, immune and intestinal barrier-related function, and gut microbiota in pigeons infected by Candida albicans.

Essential oils are potential alternatives to antibiotics for preventing Candida albicans (C. albicans) infection which is responsible for economic losses in the pigeon industry. Cymbopogon martini essential oil (EO) can inhibit pathogens, particularly fungal pathogens but its potential beneficial effects on C. albicans-infected pigeons remain unclear. Therefore, we investigated the impact of C. martini EO on antioxidant activity, immune response, intestinal barrier function, and intestinal microbiota in C. albicans-infected pigeons. The pigeons were divided into four groups as follows: (1) NC group: C. albicans uninfected/C. martini EO untreated group; (2) PC group: C. albicans infected/C. martini EO untreated group; (3) LPA group: C. albicans infected/1% C. martini EO treated group; and (4) HPA group: C. albicans infected/2% C. martini EO treated group. The pigeons were infected with C. albicans from day of age 35 to 41 and treated with C. martini EO from day of age 42 to 44, with samples collected on day of age 45 for analysis. The results demonstrated that C. martini EO prevented the reduction in the antioxidant enzymes SOD and GSH-Px causes by C. albicans challenge in pigeons. Furthermore, C. martini EO could decrease the relative expression of IL-1ß, TGF-ß, and IL-8 in the ileum, as well as IL-1ß and IL-8 in the crop, while increasing the relative expression of Claudin-1 in the ileum and the crop and Occludin in the ileum in infected pigeons. Although the gut microbiota composition was not significantly affected by C. martini EO, 2% C. martini EO increased the abundance of Alistipes and Pedobacter. In conclusion, the application of 2% C. martini EO not only enhanced the level of antioxidant activity and the expression of genes related to intestinal barrier function but also inhibited inflammatory genes in C. albicans-infected pigeons and increased the abundance of gut bacteria that are resistant to C. albicans.

High-Performance Contact-Doped WSe2 Transistors Using TaSe2 Electrodes.

Two-dimensional (2D) transitional metal dichalcogenides (TMDs) have garnered significant attention due to their potential for next-generation electronics, which require device scaling. However, the performance of TMD-based field-effect transistors (FETs) is greatly limited by the contact resistance. This study develops an effective strategy to optimize the contact resistance of WSe2 FETs by combining contact doping and 2D metallic electrode materials. The contact regions were doped using a laser, and the metallic TaSe2 flakes were stacked on doped WSe2 as electrodes. Doping the contact areas decreases the depletion width, while introducing the TaSe2 contact results in a lower Schottky barrier. This method significantly improves the electrical performance of the WSe2 FETs. The doped WSe2/TaSe2 contact exhibits an ultralow Schottky barrier height of 65 meV and a contact resistance of 11 kΩ·µm, which is a 50-fold reduction compared to the conventional Cr/Au contact. Our method offers a way on fabricating high-performance 2D FETs.

Exploring the molecular biology of ischemic cardiomyopathy based on ferroptosis­related genes.

Ischemic cardiomyopathy (ICM) is a serious cardiac disease with a very high mortality rate worldwide, which causes myocardial ischemia and hypoxia as the main damage. Further understanding of the underlying pathological processes of cardiomyocyte injury is key to the development of cardioprotective strategies. Ferroptosis is an iron-dependent form of regulated cell death characterized by the accumulation of lipid hydroperoxides to lethal levels, resulting in oxidative damage to the cell membrane. The current understanding of the role and regulation of ferroptosis in ICM is still limited, especially in the absence of evidence from large-scale transcriptomic data. Through comprehensive bioinformatics analysis of human ICM transcriptome data obtained from the Gene Expression Omnibus database, the present study identified differentially expressed ferroptosis-related genes (DEFRGs) in ICM. Subsequently, their potential biological mechanisms and cross-talk were analyzed, and hub genes were identified by constructing protein-protein interaction networks. Ferroptosis features such as reactive oxygen species generation, changes in ferroptosis marker proteins, iron ion aggregation and lipid oxidation, were identified in the H9c2 anoxic reoxygenation injury model. Finally, the diagnostic ability of Gap junction alpha-1 (GJA1), Solute carrier family 40 member 1 (SLC40A1), Alpha-synuclein (SNCA) were identified through receiver operating characteristic curves and the expression of DEFRGs was verified in an in vitro model. Furthermore, potential drugs (retinoic acid) that could regulate ICM ferroptosis were predicted based on key DEFRGs. The present article presents new insights into the role of ferroptosis in ICM, investigating the regulatory role of ferroptosis in the pathological process of ICM and advocating for ferroptosis as a potential novel therapeutic target for ICM based on evidence from the ICM transcriptome.

A sterol analog inhibits hedgehog pathway by blocking cholesterylation of smoothened.

The hedgehog (Hh) signaling pathway has long been a hotspot for anti-cancer drug development due to its important role in cell proliferation and tumorigenesis. However, most clinically available Hh pathway inhibitors target the seven-transmembrane region (7TM) of smoothened (SMO), and the acquired drug resistance is an urgent problem in SMO inhibitory therapy. Here, we identify a sterol analog Q29 and show that it can inhibit the Hh pathway through binding to the cysteine-rich domain (CRD) of SMO and blocking its cholesterylation. Q29 suppresses Hh signaling-dependent cell proliferation and arrests Hh-dependent medulloblastoma growth. Q29 exhibits an additive inhibitory effect on medulloblastoma with vismodegib, a clinically used SMO-7TM inhibitor for treating basal cell carcinoma (BCC). Importantly, Q29 overcomes resistance caused by SMO mutants against SMO-7TM inhibitors and inhibits the activity of SMO oncogenic variants. Our work demonstrates that the SMO-CRD inhibitor can be a new way to treat Hh pathway-driven cancers.

miR-200a-3p inhibits the PDGF-BB-induced proliferation of VSMCs by affecting their phenotype-associated proteins.

Accumulating evidence shows that the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) can significantly affect the long-term prognosis of coronary artery bypass grafting. This study aimed to explore the factors affecting the proliferation, migration, and phenotypic transformation of VSMCs. First, we stimulated VSMCs with different platelet-derived growth factor-BB (PDGF-BB) concentrations, analyzed the expression of phenotype-associated proteins by Western blotting, and examined cell proliferation by scratch wound healing and the 5-ethynyl-2-deoxyuridine (EdU) assay. VSMC proliferation was induced most by PDGF-BB treatment at 20 ng/mL. miR-200a-3p decreased significantly in A7r5 cells stimulated with PDGF-BB. The overexpression of miR-200a-3p reversed the downregulation of α-SMA (p < 0.001) and the upregulation of vimentin (p < 0.001) caused by PDGF-BB. CCK8 and EdU analyses showed that miR-200a-3p overexpression could inhibit PDGF-BB-induced cell proliferation (p < 0.001). However, flow cytometric analysis showed that it did not significantly increase cell apoptosis. Collectively, the overexpression of miR-200a-3p inhibited the proliferation and migration of VSMCs induced by PDGF-BB, partly by affecting phenotypic transformation-related proteins, providing a new strategy for relieving the restenosis of vein grafts.

Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss.

BACKGROUND: Episodic memory loss is a prominent clinical manifestation of Alzheimer's disease (AD), which is closely related to tau pathology and hippocampal impairment. Due to the heterogeneity of brain neurons, the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain unclear. Therefore, further investigation is necessary. METHODS: We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis, social behavioural tests, hippocampal electrophysiology, immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and iGABASnFR. Additionally, we utilized optogenetics and administered ursolic acid (UA) via oral gavage to examine the effects of these agents on social memory in mice. RESULTS: The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1 (vCA1) under both physiological conditions and AD-like tau pathology. As tau progressively accumulated, vCA1, especially its excitatory and parvalbumin (PV) neurons, were fully filled with mislocated and phosphorylated tau (p-Tau). This finding was not observed for dorsal hippocampal CA1 (dCA1). The overexpression of human tau (hTau) in excitatory and PV neurons mimicked AD-like tau accumulation, significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within vCA1. Photoactivating excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social memory. Notably, 1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB (TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social memory. CONCLUSION: This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau accumulation. Notably, our novel findings regarding the efficacy of UA in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for treating AD in the future.

A predictive model for postoperative adverse outcomes following surgical treatment of acute type A aortic dissection based on machine learning.

Acute type A aortic dissection (AAAD) has a high probability of postoperative adverse outcomes (PAO) after emergency surgery, so exploring the risk factors for PAO during hospitalization is key to reducing postoperative mortality and improving prognosis. An artificial intelligence approach was used to build a predictive model of PAO by clinical data-driven machine learning to predict the incidence of PAO after total arch repair for AAAD. This study included 380 patients with AAAD. The clinical features that are associated with PAO were selected using the LASSO regression analysis. Six different machine learning algorithms were tried for modeling, and the performance of each model was analyzed comprehensively using receiver operating characteristic curves, calibration curve, precision recall curve, and decision analysis curves. Explain the optimal model through Shapley Additive Explanation (SHAP) and perform an individualized risk assessment. After comprehensive analysis, the authors believe that the extreme gradient boosting (XGBoost) model is the optimal model, with better performance than other models. The authors successfully built a prediction model for PAO in AAAD patients based on the XGBoost algorithm and interpreted the model with the SHAP method, which helps to identify high-risk AAAD patients at an early stage and to adjust individual patient-related clinical treatment plans in a timely manner.

GLI family zinc finger protein 2 promotes skin fibroblast proliferation and DNA damage repair by targeting the miR-200/ataxia telangiectasia mutated axis in diabetic wound healing.

Diabetic foot ulcer (DFU) is a serious complication of diabetic patients which negatively affects their foot health. This study aimed to estimate the role and mechanism of the miR-200 family in DNA damage of diabetic wound healing. Human foreskin fibroblasts (HFF-1 cells) were stimulated with high glucose (HG). Db/db mice were utilized to conduct the DFU in vivo model. Cell viability was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. Superoxide dismutase activity was determined using detection kits. Reactive oxygen species determination was conducted via dichlorodihydrofluorescein-diacetate assays. Enzyme-linked immunosorbent assay was used to evaluate 8-oxo-7,8-dihydro-2'deoxyguanosine levels. Genes and protein expression were analyzed by quantitative real-time polymerase chain reaction, western blotting, or immunohistochemical analyses. Luciferase reporter gene and RNA immunoprecipitation assays determined the interaction with miR-200a/b/c-3p and GLI family zinc finger protein 2 (GLI2) or ataxia telangiectasia mutated (ATM) kinase. HG repressed cell proliferation and DNA damage repair, promoted miR-200a/b/c-3p expression, and suppressed ATM and GLI2. MiR-200a/b/c-3p inhibition ameliorated HG-induced cell proliferation and DNA damage repair repression. MiR-200a/b/c-3p targeted ATM. Then, the silenced ATM reversed the miR-200a/b/c-3p inhibition-mediated alleviative effects under HG. Next, GLI2 overexpression alleviated the HG-induced cell proliferation and DNA damage repair inhibition via miR-200a/b/c-3p. MiR-200a/b/c-3p inhibition significantly promoted DNA damage repair and wound healing in DFU mice. GLI2 promoted cell proliferation and DNA damage repair by regulating the miR-200/ATM axis to enhance diabetic wound healing in DFU.

A Predictive Model for Prolonged Mechanical Ventilation After Triple-Branched Stent Graft for Acute Type A Aortic Dissection.

INTRODUCTION: The aim of this study is to develop a model for predicting the risk of prolonged mechanical ventilation (PMV) following surgical repair of acute type A aortic dissection (AAAD). METHODS: We retrospectively collected clinical data from 381 patients with AAAD who underwent emergency surgery. Clinical features variables for predicting postoperative PMV were selected through univariate analysis, least absolute shrinkage and selection operator regression analysis, and multivariate logistic regression analysis. A risk prediction model was established using a nomogram. The model's accuracy and reliability were evaluated using the area under the curve of the receiver operating characteristic curve and the calibration curve. Internal validation of the model was performed using bootstrap resampling. The clinical applicability of the model was assessed using decision curve analysis and clinical impact curve. RESULTS: Among the 381 patients, 199 patients (52.2%) experienced postoperative PMV. The predictive model exhibited good discriminative ability (area under the curve = 0.827, 95% confidence interval: 0.786-0.868, P < 0.05). The calibration curve confirmed that the predicted outcomes of the model closely approximated the ideal curve, indicating agreement between the predicted and actual results (with an average absolute error of 0.01 based on 1000 bootstrap resampling). The decision curve analysis curve demonstrated that the model has significant clinical value. CONCLUSIONS: The nomogram model established in this study can be used to predict the risk of postoperative PMV in patients with AAAD. It serves as a practical tool to assist clinicians in adjusting treatment strategies promptly and implementing targeted therapeutic measures.

Risk model for predicting mortality in patients with necrotizing soft tissue infections in the intensive care unit.

BACKGROUND: The goal of this study is to look into the factors that lead to death in patients with necrotizing soft tissue infections（NSTIs） in the intensive care unit and create a mortality risk model. METHODS: The clinical data of 106 patients with necrotizing soft tissue infections admitted to intensive care unit(ICU) of the First Affiliated Hospital of Wenzhou Medical University between January 2008 and December 2021 were retrospectively analyzed. Univariate analysis and multivariate analysis were performed to evaluate the risk factors impacting patient mortality. The regression coefficient in binary logistic regression analysis was converted into the item score in the model, and then the model score of each patient was calculated. Finally, an ROC curve was constructed to evaluate the efficiency of the model for predicting mortality. Thirteen patients with NSTIs admitted to ICU between January 2022 and November 2022 were used to validate the model. RESULTS: The death group had 44 patients, while the survival group had 62 patients. The overall mortality was 41.5%. Binary logistic regression analysis showed that risk factors for mortality were age≥ 60 years(OR:4.419; 95%CI:1.093-17.862; P = 0.037), creatinine ≥ 132µmol/L(OR:11.166; 95%CI:2.234-55.816; P = 0.003), creatine kinase ≥ 1104 U/L(OR:4.019; 95%CI:1.134-14.250; P = 0.031), prothrombin time ≥ 24.4 s(OR:11.589; 95%CI:2.510-53.506; P = 0.002), and invasive mechanical ventilation (OR:17.404; 95%CI:4.586-66.052; P＜0.000). The AUC of the model for predicting mortality was 0.940 (95% CI:0.894-0.986). When the cut-off value for the model was 4 points, the sensitivity was 95.5% and the specificity was 83.9%. CONCLUSION: The death risk model in this study for NSTIs patients in the intensive care unit shows high sensitivity and specificity. Patients with a score of ≥ 4 points have a higher risk of mortality.