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Pancreatic cancer (PC) is an aggressive and metastatic gastrointestinal tumor with a poor prognosis. Persistent activation of the TGF-β/Smad signaling induces PC cell (PCC) invasion and infiltration via epithelial-to-mesenchymal transition (EMT). Hedgehog signaling is a crucial pathway for the development of PC via the transcription factors Gli1/2/3. This study aimed to investigate the underlying molecular mechanisms of action of hedgehog activation in TGF-β1-triggered EMT in PCCs (PANC-1 and BxPc-3). In addition, overexpression and shRNA techniques were used to evaluate the role of Smad4 in TGF-β1-treated PCCs. Our data showed that TGF-β1 promoted PCC invasion and infiltration via Smad2/3-dependent EMT. Hedgehog-Gli signaling axis in PCCs was activated upon TGF-β1 stimulation. Inhibition of hedgehog with cyclopamine effectively antagonized TGF-β1-induced EMT, thereby suggesting that the hedgehog signaling may act as a downstream cascade signaling of TGF-β1. As a key protein that assists the nuclear translocation of Smad2/3, Smad4 was highly expressed in PANC-1 cells, but not in BxPc-3 cells. Conversely, Gli1 expression was low in PANC-1 cells, but high in BxPc-3 cells. Furthermore, knockdown of Smad4 in PANC-1 cells by shRNA inhibited TGF-β1-mediated EMT and collagen deposition. Overexpression of Smad4 did not affect TGF-β1-mediated EMT due to the lack of significant increase in nuclear expression of Smad4. Importantly, Gli1 activity was upregulated by Smad4 knockdown in PANC-1 cells and downregulated by Smad4 overexpression in BxPc-3 cells, indicating that Gli1 may be a negative target protein downstream of Smad4. Thus, Smad4 regulates TGF-β1-mediated hedgehog activation to promote EMT in PCCs by suppressing Gli1 activity.

Abstract Objectives To explore whether monitored anesthesia care is more beneficial to the outcome of transcatheter aortic valve implantation. Methods The research methodology involved comprehensive searches across major databases, including the Cochrane Library, PubMed, Scopus, and Web of Science, covering the period from January 1, 2010, to March 1, 2024. The aim was to identify trials comparing different anesthetic methods for transcatheter aortic valve implantation. The primary outcomes assessed were mortality and length of hospital stay, while secondary outcomes included common complications such as bleeding, stroke, paravalvular leakage, renal failure, and others. Data synthesis was conducted using risk ratios or standardized mean differences, along with 95% confidence intervals. The study protocol was prospectively registered with PROSPERO (CRD42024507749). Results A total of 35 trials and 45,616 patients were included in this study. The results showed that monitored anesthesia care significantly reduced the patient's risk of death, shortened the patient's length of hospital stay, and also reduced the risk of common complications such as paravalvular leakage (RR, 0.80; 95% CI: 0.72 to 0.88; p

Abstract Background The estimated pulse wave velocity (ePWV) is a recently developed, simple and useful tool to measure arterial stiffness and to predict long-term cardiovascular mortality. However, the association of ePWV with mortality risk in patients with subarachnoid hemorrhage (SAH) is unclear. Herein, this study aims to assess the potential prediction value of ePWV on short- and long-term mortality of SAH patients. Methods Data of adult patients with no traumatic SAH were extracted from the Medical Information Mart for Intensive Care (MIMIC) III and IV database in this retrospective cohort study. Weighted univariate and multivariable Cox regression analyses were used to explore the associations of ePWV levels with 30-day mortality and 1-year mortality in SAH patients. The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). In addition, subgroup analyses of age, the sequential organ failure assessment (SOFA) score, surgery, atrial fibrillation (AF), renal failure (RF), hepatic diseases, chronic obstructive pulmonary disease (COPD), sepsis, hypertension, and diabetes mellitus (DM) were also performed. Results Among 1,481 eligible patients, 339 died within 30 days and 435 died within 1 year. After adjusting for covariates, ePWV ≥ 12.10 was associated with higher risk of both 30-day mortality (HR = 1.77, 95%CI: 1.17–2.67) and 1-year mortality (HR = 1.97, 95%CI: 1.36–2.85), compared to ePWV

Abstract Background Thromboelastography (TEG) is a widely utilized clinical testing method for real‐time monitoring of platelet function and the thrombosis process. Lipid metabolism disorders are crucial risk factors for thrombosis. The lipid metabolism characteristics of hamsters resemble those of humans more closely than mice and rats, and their relatively large blood volume makes them suitable for studying the mechanisms of thrombosis related to plasma lipid mechanisms. Whole blood samples from golden Syrian hamsters and healthy humans were obtained following standard clinical procedures. TEG was employed to evaluate coagulation factor function, fibrinogen (Fib) function, platelet function, and the fibrinolytic system. Methods The whole blood from hamster or healthy human was isolated following the clinical procedure, and TEG was employed to evaluate the coagulation factor function, Fib function, platelet function, and fibrinolytic system. Coagulation analysis used ACLTOP750 automatic coagulation analysis pipeline. Blood routine testing used XN‐2000 automatic blood analyzer. Results TEG parameters revealed that hamsters exhibited stronger coagulation factor function than humans (reaction time [R], p = 0.0117), with stronger Fib function (alpha angle, p

Background: Neuromyelitis optica spectrum disorders (NMOSD) is characterized by inflammatory demyelinating events in the central nervous system (CNS), primarily affecting the spinal cord and optic nerve, with a significant influence of astrocytes. Longitudinal extensive transverse myelitis (LETM) is a distinct and relatively rare spinal cord syndrome, commonly associated with NMOSD. Case presentation: This report describes a unique case of myelitis in a patient diagnosed with NMOSD. The patient exhibited an uncommon manifestation of ultra- LETM (u-LETM), coexisting with connective tissue disorders including Sjögren's syndrome and autoimmune hepatitis-primary cholestatic cirrhosis. In the acute phase, high-dose methylprednisolone pulse therapy was administered in combination with intravenous human immunoglobulin, while prednisone was gradually tapered and discontinued upon stabilization of the patient's condition. Simultaneously, sequential disease-modifying therapy was initiated, starting with long-term oral administration of mycophenolate mofetil, followed by cyclophosphamide, telitacicept, and Inebilizumab. During follow-up visits conducted every three months, the patient showed gradual improvement, eventually achieving the ability to stand and walk independently. Conclusions: Early and comprehensive evaluation of autoimmune diseases is crucial in patients with NMOSD presenting with u-LETM as the initial symptom. Prompt treatment initiation, followed by disease-modifying therapy, is essential for improving patient prognosis.

BackgroundBreast cancer (BRCA) represents a substantial global health challenge marked by inadequate early detection rates. The complex interplay between the tumor immune microenvironment and fatty acid metabolism in BRCA requires further investigation to elucidate the specific role of lipid metabolism in this disease.MethodsWe systematically integrated nine machine learning algorithms into 184 unique combinations to develop a consensus model for lipid metabolism-related prognostic genes (LMPGS). Additionally, transcriptomics analysis provided a comprehensive understanding of this prognostic signature. Using the ESTIMATE method, we evaluated immune infiltration among different risk subgroups and assessed their responsiveness to immunotherapy. Tailored treatments were screened for specific risk subgroups. Finally, we verified the expression of key genes through in vitro experiments.ResultsWe identified 259 differentially expressed genes (DEGs) related to lipid metabolism through analysis of the cancer genome atlas program (TCGA) database. Subsequently, via univariate Cox regression analysis and C-index analysis, we developed an optimal machine learning algorithm to construct a 21-gene LMPGS model. We used optimal cutoff values to divide the lipid metabolism prognostic gene scores into two groups according to high and low scores. Our study revealed distinct biological functions and mutation landscapes between high-scoring and low-scoring patients. The low-scoring group presented a greater immune score, whereas the high-scoring group presented enhanced responses to both immunotherapy and chemotherapy drugs. Single-cell analysis highlighted significant upregulation of CPNE3 in epithelial cells. Moreover, by employing molecular docking, we identified niclosamide as a potential targeted therapeutic drug. Finally, our experiments demonstrated high expression of MTMR9 and CPNE3 in BRCA and their significant correlation with prognosis.ConclusionBy employing bioinformatics and diverse machine learning algorithms, we successfully identified genes associated with lipid metabolism in BRCA and uncovered potential therapeutic agents, thereby offering novel insights into the mechanisms and treatment strategies for BRCA.

Abstract Background Unintended (unwanted) pregnancy is a sexual and reproductive health issue with psychosocial consequences for the individual, their family, and society. However, the relationship between social support and related mental health issues, like depression and the effects of childhood adversity, is poorly studied. This study aims to explore the connections between childhood adversity, perceived social support, and depressive symptoms in pre-abortion women (women who have decided to have an abortion) in a clinical setting, based on the common risk factor approach and social support theory. Methods A total of 299 pre-abortion Chinese women 18–45 years were recruited in a hospital in Shantou, China. Hierarchical linear regression analyses were employed to examine the relative effects of childhood adversity and sources of social support on depressive symptoms, controlling for sociodemographic influences. Results The results show that 37.2 percent of participants reported at least one adverse experience in childhood. More than half of the respondents were at risk for depression. Results of regression analysis showed that childhood adversities were negatively associated with depressive symptoms before sources of social support were entered into the model. However, when the sources of perceived social support were added, the effect of childhood adversity was not significant. Perceived social support explained the additional 15 percent variance in depressive symptoms. Additionally, being married (β = -.12, p

Background This study aims to identify a novel gene signature for coronary artery disease (CAD), explore the role of immune cell infiltration in CAD pathogenesis, and assess the cell function of mast cell-expressed membrane protein 1 (MCEMP1) in human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL). Methods To identify differentially expressed genes (DEGs) of CAD, datasets GSE24519 and GSE61145 were downloaded from the Gene Expression Omnibus (GEO) database using the R “limma” package with p < 0.05 and |log2 FC| > 1. Gene ontology (GO) and pathway analyses were conducted to determine the biological functions of DEGs. Hub genes were identified using support vector machine-recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO). The expression levels of these hub genes in CAD were validated using the GSE113079 dataset. CIBERSORT program was used to quantify the proportion of immune cell infiltration. Western blot assay and qRT‐PCR were used to detect the expression of hub genes in ox-LDL-treated HUVECs to validate the bioinformatics results. Knockdown interference sequences for MCEMP1 were synthesized, and cell proliferation and apoptosis were examined using a CCK8 kit and Muse® Cell Analyzer, respectively. The concentrations of IL-1β, IL-6, and TNF-α were measured with respective enzyme-linked immunosorbent assay (ELISA) kits. Results A total of 73 DEGs (four down-regulated genes and 69 up-regulated genes) were identified in the metadata (GSE24519 and GSE61145) cohort. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results indicated that these DEGs might be associated with the regulation of platelet aggregation, defense response or response to bacterium, NF-kappa B signaling pathway, and lipid and atherosclerosis. Using SVM-RFE and LASSO, seven hub genes were obtained from the metadata. The upregulated expression of DIRC2 and MCEMP1 in CAD was confirmed in the GSE113079 dataset and in ox-LDL-treated HUVECs. The associations between the two hub genes (DIRC2 and MCEMP1) and the 22 types of immune cell infiltrates in CAD were found. MCEMP1 knockdown accelerated cell proliferation and suppressed cell apoptosis for ox-LDL-treated HUVECs. Additionally, MCEMP1 knockdown appeared to decrease the expression of inflammatory factors IL-1β, IL-6, and TNF-α. Conclusions The results of this study indicate that MCEMP1 may play an important role in CAD pathophysiology.

Terrestrial dissolved organic matter (tDOM) holds great promise for controlling cyanobacteria blooms through watershed management. To identify tDOM that could inhibit the growth, photosynthesis and colony formation, unicellular Microcystis aeruginosa Kützing (FACHB-469) was cultivated and treated with varying concentrations of gallic acid, proline and tea polyphenols at different levels of iron. The results indicated that gallic acid and tea polyphenols could inhibit Microcystis growth by suppressing photosynthesis and colony formation by reducing extracellular polysaccharides (EPS) secretion. However, proline had no significant effect on the growth, photosynthesis, colony size and EPS content of Microcystis. Transcriptome analysis showed Microcystis may optimize the internal energy transfer mode of photosynthesis through the change of phycobilisome at different levels of iron. In addition, Microcystis adapted to different iron concentration environments by regulating the expression of genes associated with iron uptake and transport. These findings suggest that the effects of plant species on algal blooms should be considered in reforestation of watershed. This consideration necessitates finding a balance between the costs and benefits of controlling cyanobacteria blooms using tDOM.

IntroductionSpent mushroom substrate (SMS) is a solid waste in agricultural production that contains abundant lignocellulosic fibers. The indiscriminate disposal of SMS will lead to significant resource waste and pollution of the surrounding environment.The isolation and screening of microorganisms with high cellulase degradation capacity is the key to improving SMS utilization.MethodsThe cellulose-degrading microbial consortiums were constructed through antagonism and enzyme activity test. The effect of microbial consortiums on lignocellulose degradation was systematically evaluated by SMS liquid fermentation experiments.ResultsIn this study, four strains of cellulose-degrading bacteria were screened, and F16, F, and F7 were identified as B. amyloliquefaciens, PX1 identified as B. velezensis. At the same time, two groups of cellulose efficient degrading microbial consortiums (PX1 + F7 and F16 + F) were successfully constructed. When SMS was used as the sole carbon source, their carboxymethyl cellulase (CMCase) activities were 225.16 and 156.63 U/mL, respectively, and the filter paper enzyme (FPase) activities were 1.91 and 1.64 U/mL, respectively. PX1 + F7 had the highest degradation rate of hemicellulose and lignin, reaching 52.96% and 52.13%, respectively, and the degradation rate of F16 + F was as high as 56.30%. Field emission scanning electron microscopy (FESEM) analysis showed that the surface microstructure of SMS changed significantly after microbial consortiums treatment, and the change of absorption peak in Fourier transform infrared spectroscopy (FTIR) and the increase of crystallinity in X-ray diffraction (XRD) confirmed that the microbial consortiums had an actual degradation effect on SMS. The results showed that PX1 + F7 and F16 + F could effectively secrete cellulase and degrade cellulose, which had practical significance for the degradation of SMS.DiscussionIn this study, the constructed PX1 + F7 and F16 + F strains can effectively secrete cellulase and degrade cellulose, which holds practical significance in the degradation of SMS. The results can provide technical support for treating high-cellulose solid waste and for the comprehensive utilization of biomass resources.

BackgroundVisual field defect (VFD) refers to the phenomenon that the eye is unable to see a certain area within the normal range of vision, which may be caused by eye diseases, neurological diseases and other reasons. Transcranial direct current stimulation (tDCS) is expected to be an effective treatment for the recovery or partial recovery of VFD. This paper describes the potential for tDCS in combination with visual retraining strategies to have a positive impact on vision recovery, and the potential for neuroplasticity to play a key role in vision recovery.MethodsThis case report includes two patients. Patient 1 was diagnosed with a right occipital hemorrhage and homonymous hemianopia. Patient 2 had multiple facial fractures, a contusion of the right eye, and damage to the optic nerve of the right eye, which was diagnosed as a peripheral nerve injury (optic nerve injury). We administered a series of treatments to two patients, including transcranial direct current stimulation; visual field restoration rehabilitation: paracentric gaze training, upper and lower visual field training, VR rehabilitation, and perceptual training. One time per day, 5 days per week, total 6 weeks.ResultsAfter 6 weeks of visual rehabilitation and tDCS treatment, Patient 1 Humphrey visual field examination showed a significant improvement compared to the initial visit, with a reduction in the extent of visual field defects, increased visual acuity, and improvement in most visual functions. Patient 2 had an expanded visual field, improved visual sensitivity, and substantial improvement in visual function.ConclusionOur case reports support the feasibility and effectiveness of tDCS combined with visual rehabilitation training in the treatment of occipital stroke and optic nerve injury settings.

Objective To investigate the factors involved in the development of thyroid nodules and the correlation between homocysteine (Hcy) and albumin-globulin ratio (AGR) and thyroid autoantibodies in adults. Methods As a retrospective study, a total of 1 427 people who received physical examination at the Second Hospital Affiliated to Hebei North College from October 2019 to August 2020 and the clinical data of the subjects who fulfilled the criteria of NAR were selected for analysis by simple random sampling. All of subjects underwent thyroid color ultrasound scanning and were divided into a control group (without thyroid nodules, n=52) and an observation group (with thyroid nodules, n=48). The general clinical data of the two study groups were compared, and the correlation between Hcy and AGR and thyroid autoantibodies was analyzed.Confunding factors affecting the incidence of thyroid nodules were screened using multifactorial unconditional logistic regression analysis. Results The observation group showed statistically significant differences in gender, age, diastolic blood pressure, systolic blood pressure, Hcy, AGR, TGAb, and TPOAb as compared to the control group (P＜0.05); Using adult Hcy as the dependent variable and Spearman′s correlation analysis of AGR, TGAb and TPOAb, adult Hcy was negatively correlated with AGR (r=-0.384, P＜0.05) and TGAb and TPOAb were positively correlated (r=0.218, 0.224, P＜0.05); Using age, sex, diastolic blood pressure, systolic blood pressure, Hcy, AGR TGAb and TPOAb as independent variables and thyroid nodules as dependent variables, a multifactor logistic regression analysis was performed in 100 subjects who experienced physical check. The analysis showed that age ≥40 years and female were relevant factors for the development of thyroid nodules factors (P＜0.05), Hcy, AGR, TGAb and TPOAb were correlated with thyroid nodules (P＜0.05). Conclusions Thyroid nodules are more common in middle-aged women, and there is a correlation between Hcy, AGR, TGAb, and TPOAb levels and thyroid nodules. Regular thyroid screening examination should be carried out based on the above indicators.