Identification of immune- and oxidative stress-related signature genes as potential targets for mRNA vaccines for pancreatic cancer patients.

Adenocarcinoma of the pancreas (PAAD) is one of the deadliest malignant tumors, and messenger ribonucleic acid vaccines, which constitute the latest generation of vaccine technology, are expected to lead to new ideas for the treatment of pancreatic cancer. The Cancer Genome Atlas-PAAD and Genotype-Tissue Expression data were merged and analyzed. Weighted gene coexpression network analysis was used to identify gene modules associated with tumor mutational burden among the genes related to both immunity and oxidative stress. Differentially expressed immune-related oxidative stress genes were screened via univariate Cox regression analysis, and these genes were analyzed via nonnegative matrix factorization. After immune infiltration analysis, least absolute shrinkage and selection operator regression combined with Cox regression was used to construct the model, and the usefulness of the model was predicted based on the receiver operating characteristic curve and decision curve analysis curves after model construction. Finally, metabolic pathway enrichment was analyzed using gene set enrichment analysis combined with Kyoto Encyclopedia of Genes and Genomes and gene ontology biological process analyses. This model consisting of the ERAP2, mesenchymal-epithelial transition factor (MET), CXCL9, and angiotensinogen (AGT) genes can be used to help predict the prognosis of pancreatic cancer patients more accurately than existing models. ERAP2 is involved in immune activation and is important in cancer immune evasion. MET binds to hepatocyte growth factor, leading to the dimerization and phosphorylation of c-MET. This activates various signaling pathways, including MAPK and PI3K, to regulate the proliferation, invasion, and migration of cancer cells. CXCL9 overexpression is associated with a poor patient prognosis and reduces the number of CD8 + cytotoxic T lymphocytes in the PAAD tumor microenvironment. AGT is cleaved by the renin enzyme to produce angiotensin 1, and AGT-converting enzyme cleaves angiotensin 1 to produce angiotensin 2. Exposure to AGT-converting enzyme inhibitors after pancreatic cancer diagnosis is associated with improved survival. The 4 genes identified in the present study - ERAP2, MET, CXCL9, and AGT - are expected to serve as targets for messenger ribonucleic acid vaccine development and need to be further investigated in depth.

Two Cytochrome P450s, CYP709B1 and CYP704C1, Play Essential Roles in Metabolism-Based Multiple Herbicide Resistance in American Sloughgrass (Beckmannia syzigachne (Steud.) Fernald).

This study confirmed a field population of American sloughgrass (Beckmannia syzigachne (Steud.) Fernald) that developed simultaneously high levels of resistance (resistance index >10) to three divergent modes of action herbicides: fenoxaprop-P-ethyl, mesosulfuron-methyl, and isoproturon. The resistance phenotype observed in this population was not attributed to target-site alterations; rather, the resistant plants exhibited a significant increase in the activity of cytochrome P450s (P450s) and enhanced metabolism rates for all three herbicides. RNA sequencing revealed significant upregulation of two P450s, CYP709B1 and CYP704C1, in the resistant plants both before and after herbicide treatments. Molecular docking predicted that the homology models of these P450s should exhibit a binding affinity for a range of herbicides. The heterologous expression of the identified P450s in yeast cells indicated improved growth in the presence of all three of the aforementioned herbicides. Collectively, the increased expression of CYP709B1 and CYP704C1 likely contributed to the P450s-mediated enhanced metabolism, thereby conferring multiple herbicide resistance in B. syzigachne.

Therapeutic effects of flavonoids on pulmonary fibrosis: A preclinical meta-analysis.

BACKGROUND: The efficacy of flavonoid supplementation in animal models of pulmonary fibrosis has been demonstrated. PURPOSE: We conducted a systematic review and meta-analysis to evaluate the efficacy and underlying mechanisms of flavonoids in animal models of bleomycin-induced pulmonary fibrosis. STUDY DESIGN: Relevant studies (n = 45) were identified from English- and Chinese-language databases from the inception of the database until October 2023. METHODS: Methodological quality was evaluated using the SYRCLE risk of bias tool. Statistical analyses were conducted using RevMan 5.3 and Stata 17.0. Lung inflammation and fibrosis score were the primary outcome indicators. RESULTS: Flavonoids can alleviate pathological changes in the lungs. The beneficial effects of flavonoids on pulmonary fibrosis likely relate to their inhibition of inflammatory responses, restoration of oxidative and antioxidant homeostasis, and regulation of fibroblast proliferation, migration, and activation by transforming growth factor ß1/mothers against the decapentaplegic homologue/AMP-activated protein kinase (TGF-ß1/Smad3/AMPK), inhibitor kappa B alpha/nuclear factor-kappa B (IκBα/NF-κB), phosphatidylinositol 3-kinase (PI3K)/AKT, interleukin 6/signal transducer/activator of transcription 3 (IL6/STAT3), and nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2-Keap1) pathways. CONCLUSION: Flavonoids are potential candidate compounds for the prevention and treatment of pulmonary fibrosis. However, extensive preclinical research is necessary to confirm the antifibrotic properties of natural flavonoids.

Contrast­associated acute kidney injury in myocardial infarction patients undergoing elective percutaneous coronary intervention: insight from the Iodixanol-AKI Registry.

Previous studies have reported a high occurrence of contrast-associated acute kidney injury (CA-AKI) in myocardial infarction (MI) patients undergoing primary percutaneous coronary intervention (PCI). However, the data on CA-AKI in MI patients who underwent elective PCI are limited. To evaluate the incidence of CA-AKI in MI patients undergoing elective PCI. The data were sourced from the Iodixanol-AKI Registry of MI patients scheduled to undergo elective PCI in 8 medical centers from May 2020 to November 2021. The participants were divided into three groups: acute, prior, and multiple MI. The outcomes measured were CA-AKI and the composite endpoint of major adverse renal and cardiovascular events (MARCE). The incidence of CA-AKI was 4.46% (37/830) in the MI patients, 4.40% (7/159) in the acute MI patients, 4.41% (22/499) in the prior MI patients, and 4.65% (8/172) in the multiple MI patients. Of note, 36 patients (97.30%) at AKI stage 1, and only 1 patient at AKI stage 2. There was no difference in the incidence of CA-AKI (P = 0.991) among the three groups. Multivariate regression analysis revealed that the independent risk factors for CA-AKI were diabetes and an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. MARCE occurred in 3.4% (28/830) of the total patients and was not associated with either any subgroup of patients with MI or AKI. The incidence of CA-AKI was low and mainly limited to mildly impaired renal function in MI patients undergoing elective PCI.

P2X7 receptor deficiency attenuates cisplatin-induced kidney injury via inhibiting NLRP3 inflammasome activation.

Nephrotoxicity is a major constraint of cisplatin application in many solid tumors. Since the lack of preventive strategies, the necessity exists to identify critical molecular targets involved in cisplatin nephrotoxicity. The Purinergic ligand-gcotedion channel 7 receptor (P2X7R) is a ligand-gated ion channel that is predominantly implicated in inflammation and cell death. Our aim is to investigate the role P2X7R in cisplatin-induced acute and chronic kidney injury, as well as the underlying mechanism. In this study, we found that cisplatin can cause an increase in the expression of P2X7R in mouse kidney tissue, and P2X7R knockout can alleviate acute renal function damage caused by cisplatin, as well as the expression of kidney injury molecule 1 (KIM-1) and interleukin-18 (IL-18). Cisplatin can cause an increase in the expression of nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in mouse kidney tissue. Compared with wild-type mice, P2X7R -/- mice showed decreased expression of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved Caspase-1, and cleaved IL-1ß in kidney tissue after cisplatin administration, and the apoptosis of renal tubular epithelial cells were also decreased. In addition, we also found that NLRP3 knockout can improve cisplatin induced degeneration, detachment, and necrosis of renal tubular epithelial cells. Furthermore, P2X7R -/- mice also showed reduced renal fibrosis and better long-term renal prognosis. In conclusion, our study identified that P2X7R knockout can improve cisplatin induced acute renal injury and chronic renal fibrosis by inhibiting the activation of NLRP3 inflammasome.

Case Report: Isolated Vertigo as the Sole Manifestation of Left Lateral Medullary Infarction Following Contralateral Varicella-Zoster Virus Infection.

Background: Cerebral infarct associated with varicella-zoster virus (VZV) has been reported in the literature, while isolated central dizziness due to lateral medullary infarct (LMI) following VZV infection is rarely reported. Case report: We report the case of a 65-year-old man who presented to the neurology department because of herpes zoster on the right trigeminal nerve distribution. At 12 hours after admission, he developed transient vertigo along with nausea and unsteady walking and left-sided spontaneous horizontal nystagmus, gaze-evoked nystagmus, and upbeat nystagmus. The other usual signs of LMI including Horner syndrome, dysarthria, swallowing difficulty, and hemibody sensory change were absent. Video head impulse indicated decreased head impulse gain of the vestibulo-ocular reflex for the bilateral horizontal, anterior, and posterior semicircular canals with abnormal saccade waves. Suppression head impulse paradigm showed few downward saccades reflecting anti-compensatory saccades after the end of the head impulse back to the head-fixed target and decreased vestibulo-ocular reflex gain values of bilateral semicircular canals. Brain magnetic resonance imaging (MRI) showed a small infarct in the far dorsolateral portion of the left rostral medulla. The cerebrospinal fluid was positive for VZV DNA. Conclusions: In patients with VZV infection who develop dizziness, the possibility of cerebral infarct should be considered. Patients with facial herpes zoster and neurological symptoms always be screened for stroke using MRI and lumbar puncture should be performed and acyclovir administered empirically.

S-scheme heterojunction phthalocyanine/TiO2 photoelectrochemical sensor for innovative glutathione detection.

A novel photoelectrochemical sensor, employing an S-scheme heterojunction of phthalocyanine and TiO2 nanoparticles, has been developed to enable highly sensitive determination of glutathione. By integrating the favorable stability, environmental benignity, and electronic properties of the TiO2 matrix with the unique photoactivity of phthalocyanine species, the designed sensor presents a substantial linear dynamic range and a low detection limit for the quantification of glutathione. The sensitivity is attributed to efficient charge transfer and separation across the staggered heterojunction energy levels, which generates measurable photocurrent signals. Systematic variation of phthalocyanine content reveals an optimal composition that balances light harvesting capacity and electron-hole recombination rates. The incorporation of phosphotungstic acid (PTA) in sample preparation effectively minimizes interference from compounds like L-cysteine and others. Consequently, this leads to an improvement in accuracy through the reduction of impurity levels. Appreciable photocurrent enhancements are observed upon introduction of both oxidized and reduced glutathione at the optimized composite photoanode. Coupled with advantageous features of photoelectrochemical transduction such as simplicity, cost-effectiveness, and resistance to fouling, this sensor holds great promise for practical applications in complex biological media.

Elevating Discharge Voltage of Li2CO3-routine Li-CO2 Battery over 2.9 V at an Ultra-wide Temperature Window.

The Li-CO2 batteries utilizing greenhouse gas CO2 possess advantages of high energy density and environmental friendliness. However, these batteries following Li2CO3-product route typically exhibit low work voltage (<2.5 V) and energy efficiency. Herein, we have demonstrated for the first time that cobalt phthalocyanine (CoPc) as homogeneous catalyst can elevate the work plateau towards 2.98 V, which is higher than its theoretical discharge voltage without changing the Li2CO3-product route. This unprecedented discharge voltage is illustrated by mass spectrum and electrochemical analyses that CoPc has powerful adsorption capability with CO2 (-7.484 kJ/mol) and forms discharge intermediate of C33H16CoN8O2. Besides high discharge capacity of 18724 mAh/g and robust cyclability over 1600 hours (1000 mAh/g cut-off) at a current density of 100 mA/g , the batteries show high temperature adaptability (-30~80 °C). Our work is paving a promising avenue for the progress of high-efficiency Li-CO2 batteries.

The landscape of programmed cell death-related lncRNAs in Alzheimer's disease and Parkinson's disease.

This study delivers a thorough analysis of long non-coding RNAs (lncRNAs) in regulating programmed cell death (PCD), vital for neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD). We propose a new framework PCDLnc, and identified 20 significant lncRNAs, including HEIH, SNHG15, and SNHG5, associated with PCD gene sets, which were known for roles in proliferation and apoptosis in neurodegenerative diseases. By using GREAT software, we identified regulatory functions of top lncRNAs in different neurodegenerative diseases. Moreover, lncRNAs cis-regulated mRNAs linked to neurodegeneration, including JAK2, AKT1, EGFR, CDC42, SNCA, and ADIPOQ, highlighting their therapeutic potential in neurodegenerative diseases. A further exploration into the differential expression of mRNA identified by PCDLnc revealed a role in apoptosis, ferroptosis and autophagy. Additionally, protein-protein interaction (PPI) network analysis exposed abnormal interactions among key genes, despite their consistent expression levels between disease and normal samples. The randomforest model effectively distinguished between disease samples, indicating a high level of accuracy. Shared gene subsets in AD and PD might serve as potential biomarkers, along with disease-specific gene sets. Besides, we also found the strong relationship between AD and immune infiltration. This research highlights the role of lncRNAs and their associated genes in PCD in neurodegenerative diseases, offering potential therapeutic targets and diagnostic markers for future study and clinical application.

Robust distributed fixed-time cooperative hunting control for multi-quadrotor with obstacles avoidance.

This paper addressed the robust distributed fixed-time cooperative hunting problem of multiple quadrotors subject to disturbances in obstacles environment. To handle the underactuated issue inherent in quadrotor dynamics, an inner-outer (attitude-position) loop cascade control configuration is proposed to achieve the cooperative flight control of quadrotors. For position subsystem, as the information of target cannot be accessible to all quadrotors, a distributed fixed-time observer is devised to estimate the target's information. To improve the system's robustness, a fixed-time extended state observer is designed to reject disturbances actively. Based on two observers, the sliding mode position encirclement control protocol with repulsive force is presented to avoid obstacles and encircle the target within a fixed time. For attitude subsystem, a sliding mode attitude tracking control protocol is proposed such that tracking errors can converge to zero even under disturbances. The stability analysis is performed to show the stabilization of the whole closed-loop system with fixed-time convergence. Finally, two sets of comparison simulation are provided to show the superiority of the developed control strategy.

Efficacy of submental island flap closing advanced mandibular MRONJ lesion in malignancy patients.

OBJECTIVE: This study evaluated the effectiveness of a submental island flap in closing advanced mandibular medication-related osteonecrosis of the jaw (MRONJ) wounds in patients with malignant tumors. SUBJECTS AND METHODS: A total of 85 patients with stage II and III MRONJ of mandible with malignant tumor as their primary disease were retrospectively analyzed. All patients underwent surgical treatment, and the soft tissue wound closure was performed either with a submental island flap (SIF) or mucoperiosteal flap (MF). Univariate and multifactorial models were applied to analyze the factors influencing patients' prognosis. RESULTS: Univariate analysis (p = 0.004, OR 0.075-0.575, 95% CI) and binary logistic regression (p = 0.017, OR 0.032-0.713, 95% CI) suggested that the surgical prognosis of SIF wound closure was significantly better than that of MF. CONCLUSION: Closure of wound after resection of mandibular MRONJ lesions in patients with malignant tumors using SIF had a better clinical prognosis compared with MF.

Transcriptome analysis of Kunming mice responses to the bite of Xenopsylla cheopis.

BACKGROUND: Flea bites could trigger a series of complex molecular responses in the host. However, our understanding of the responses at the molecular level is still relatively limited. This study quantifies the changes in gene expression in mice after flea bites by RNA sequencing (RNA-seq) from their spleens, revealing the potential biological effects of host response to flea bites. METHODS: RNA-seq was used for transcriptome analysis to screen for differentially expressed genes (DEGs) between the control mice group and the flea bite mice group. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on DEGs. Protein-protein interaction (PPI) network analysis on DEGs related to immune processes was performed. Finally, we randomly selected several genes from the screened DEGs to validate the results from the transcriptome data by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: A total of 521 DEGs were identified, including 277 upregulated and 244 downregulated. There were 258 GO terms significantly enriched by upregulated DEGs and 419 GO terms significantly enriched by downregulated DEGs. Among the upregulated DEGs, 22 GO terms were associated with immune cells (e.g., B cells and T cells) and immune regulatory processes, while among the downregulated DEGs, 58 GO terms were associated with immune cells and immune regulatory processes. Through PPI analysis, we found that CD40 molecules with significantly downregulated expression levels after flea bites may play an important role in host immune regulation. Through KEGG pathway enrichment analysis, a total of 26 significantly enriched KEGG pathways were identified. The RT-qPCR analysis results indicated that the transcriptome sequencing results were reliable. CONCLUSIONS: Through in-depth analysis of transcriptome changes in mice caused by flea bites, we revealed that flea bites could stimulate a series of biological and immunological responses in mice. These findings not only provided a deeper understanding of the impact of flea bites on the host but also provided a basis for further research on the interaction between ectoparasites and the host. We believe that digging deeper into the significance of these transcriptome changes will help reveal more about the adaptive response of the host to ectoparasites.

Relationships Between Meteorological Factors and Mongolian Gerbils and Its Flea Burdens - Xilingol League, Inner Mongolia Autonomous Region, China, 2012-2021.

Introduction: Plague is a significant global infectious disease, its spread is linked to host and flea populations. Meteorological conditions can impact flea populations and host densities, hence influencing plague outbreaks. Investigating the connection between meteorological factors, flea populations, and rodent densities in Inner Mongolia's natural plague foci can aid in predicting and managing plague outbreaks. Methods: Monthly data on flea index, rodent density, meteorological factors, and normalized difference vegetation index (NDVI) were collected for the study area. Generalized additive modeling (GAM) was used to analyze the non-linear and lag effects of meteorological factors on flea index and rodent density. Structural equation modeling (SEM) was employed to investigate the relationships among meteorological factors, NDVI, flea index, and rodent density. Results: GAM analysis revealed that temperature, precipitation, relative humidity, and NDVI had significant linear, non-linear, and time-lagged impacts on the density of Mongolian gerbils and the flea index. SEM analysis indicated that meteorological factors could directly influence the density and flea index of Mongolian gerbils, or indirectly impact NDVI, subsequently influencing gerbil density and the flea index. Conclusions: Meteorological factors primarily influence gerbil density and flea index indirectly by affecting NDVI and the relationship between flea index and gerbil density. This study offers additional support for the significance of meteorological factors and NDVI in influencing the vector-rodent system, offering valuable insights for predicting and managing plague outbreaks.

Evaluating the clinical efficacy and safety of concurrent chemoradiotherapy with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer.

OBJECTIVE: A preclinical study showed that nab-paclitaxel acted as a radiosensitizer and improved tumor radiotherapy in a supra-additive manner. In this study, we aimed to evaluate the clinical efficacy and safety of concurrent chemoradiotherapy (CCRT) with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer with an unfavorable prognosis. METHODS: Eligible patients with stage IB1-IIA2 (FIGO 2009) cervical carcinoma were recruited retrospectively between August 2018 to May 2021. Patients in both the cisplatin and nab-paclitaxel groups received postoperative radiotherapy and weekly intravenous cisplatin 40 mg/m2 or nab-paclitaxel 100 mg concurrently. An analysis of overall survival, progression-free survival, and adverse reactions was conducted. RESULTS: A total of 105 early-stage cervical cancer patients were included into our study. The median follow-up time was 38.7 months. The 3-year overall survival and progression-free survival in both group was similar. The cycles of chemotherapy in the cisplatin group were less than those in the nab-paclitaxel group (4.5 vs. 5.0; p = 0.001). Patients in the cisplatin group had a significantly higher frequency of hematological adverse events than patients in the nab-paclitaxel group (P < 0.05). Patients in the cisplatin group had a significantly higher frequency of grade 3-4 leukopenia (46.1% vs. 18.9%; P = 0.03), grade 1-2 thrombocytopenia (32.7% vs. 9.5%; P = 0.014) than patients in the nab-paclitaxel group. Gastrointestinal reactions, such as vomiting, nausea, and anorexia were significantly reduced in the nab-paclitaxel group compared with those in the cisplatin group. Regarding the effects on alopecia, the incidence rate of the nab-paclitaxel group was higher than that of the cisplatin group (P = 0.001). There were no differences between the groups in terms of other adverse reactions. CONCLUSION: The results of this study indicate that nab-paclitaxel-based concurrent radiotherapy is tolerable and effective, and can be considered an alternative to cisplatin chemotherapy.

How public environmental appeals affect the collaborative governance in pollution and carbon reduction: Evidence from spatial effects across Chinese cities.

China has always adhered to the strategy of sustainable development. It is prevalent the public want a good living environment, which requires local governments and businesses to enhance their environmental governance capabilities. Using the panel data from Chinese cities from 2012 to 2019 and econometrics models, we examine the impact mechanisms of public environmental appeals (PEA) on efficiency of collaborative governance in pollution reduction and carbon mitigation (GPC). Results indicate that there is a positive spatial clustering of GPC across cities, with high-high clustering is notably concentrated in the southern regions of China and low-low clustering is prevalent in the northern regions. Spatial econometrics model results reveal that the stronger PEA, the higher GPC. The result of mechanism analysis shows the mediation of environmentally friendly technological innovation is crucial. Subsequent inquiry uncovers that the digital economy positively moderates the impact of PEA on GPC. The Belt and Road policy region exhibits heightened sensitivity to PEA, thereby enhancing the positive impact of PEA on GPC.

Ecoclimate drivers shape virome diversity in a globally invasive tick species.

Spillovers of viruses from animals to humans occur more frequently under warmer conditions, particularly arboviruses. The invasive tick species Haemaphysalis longicornis, the Asian longhorned tick, poses a significant public health threat due to its global expansion and its potential to carry a wide range of pathogens. We analyzed meta-transcriptomic data from 3595 adult H. longicornis ticks collected between 2016 and 2019 in 22 provinces across China encompassing diverse ecological conditions. Generalized additive modeling revealed that climate factors exerted a stronger influence on the virome of H. longicornis than other ecological factors, such as ecotypes, distance to coastline, animal host, tick gender, and antiviral immunity. To understand how climate changes drive the tick virome, we performed a mechanistic investigation using causality inference with emphasis on the significance of this process for public health. Our findings demonstrated that higher temperatures and lower relative humidity/precipitation contribute to variations in animal host diversity, leading to increased diversity of the tick virome, particularly the evenness of vertebrate-associated viruses. These findings may explain the evolution of tick-borne viruses into generalists across multiple hosts, thereby increasing the probability of spillover events involving tick-borne pathogens. Deep learning projections have indicated that the diversity of the H. longicornis virome is expected to increase in 81.9% of regions under the SSP8.5 scenario from 2019 to 2030. Extension of surveillance should be implemented to avert the spread of tick-borne diseases.

Discriminative diagnosis of ovarian endometriosis cysts and benign mucinous cystadenomas based on the ConvNeXt algorithm.

PURPOSE: The objective of this study was to develop a deep learning model, using the ConvNeXt algorithm, that can effectively differentiate between ovarian endometriosis cysts (OEC) and benign mucinous cystadenomas (MC) by analyzing ultrasound images. The performance of the model in the diagnostic differentiation of these two conditions was also evaluated. METHODS: A retrospective analysis was conducted on OEC and MC patients who had sought medical attention at the Fourth Affiliated Hospital of Harbin Medical University between August 2018 and May 2023. The diagnosis was established based on postoperative pathology or the characteristics of aspirated fluid guided by ultrasound, serving as the gold standard. Ultrasound images were collected and subjected to screening and preprocessing procedures. The data set was randomly divided into training, validation, and testing sets in a ratio of 5:3:2. Transfer learning was utilized to determine the initial weights of the ConvNeXt deep learning algorithm, which were further adjusted by retraining the algorithm using the training and validation ultrasound images to establish a new deep learning model. The weights that yielded the highest accuracy were selected to evaluate the diagnostic performance of the model using the validation set. Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) was calculated. Additionally, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and odds ratio were calculated. Decision curve analysis (DCA) curves were plotted. RESULTS: The study included 786 ultrasound images from 184 patients diagnosed with either OEC or MC. The deep learning model achieved an AUC of 0.90 (95 % CI: 0.85-0.95) in accurately distinguishing between the two conditions, with a sensitivity of 90 % (95 % CI: 84 %-95 %), specificity of 90 % (95 % CI: 77 %-97 %), a positive predictive value of 96 % (95 % CI: 91 %-99 %), a negative predictive value of 77 % (95 % CI: 63 %-88 %), a positive likelihood ratio of 9.27 (95 % CI: 3.65-23.56), and a negative likelihood ratio of 0.11 (95 % CI: 0.06-0.19). The DCA curve demonstrated the practical clinical utility of the model. CONCLUSIONS: The deep learning model developed using the ConvNeXt algorithm exhibits high accuracy (90 %) in distinguishing between OEC and MC. This model demonstrates excellent diagnostic performance and clinical utility, providing a novel approach for the clinical differentiation of these two conditions.

4-Octyl Itaconate Attenuates Neuroinflammation in Experimental Autoimmune Encephalomyelitis Via Regulating Microglia.

Abnormal activation of microglia, the resident macrophages in the central nervous system, plays an important role in the pathogenesis of multiple sclerosis (MS). The immune responsive gene 1(IRG1)/itaconate axis is involved in regulating microglia-mediated neuroinflammation. 4-Octyl itaconate (4-OI), a derivative of itaconate, plays a crucial immunomodulatory role in macrophages. This study investigated the effects and mechanisms of action of 4-OI on experimental autoimmune encephalomyelitis (EAE) and inflammatory BV2 microglia. In an EAE mouse model, clinical evaluation was conducted during the disease course. Hematoxylin and eosin staining was performed to assess inflammatory infiltration and Luxol Fast Blue was used to visualize pathological damage. Quantitative real-time polymerase chain reaction, western blotting and immunofluorescence were used to evaluate inflammatory response and microglial function status in EAE mice. BV2 microglia were used to further investigate the effects and mechanisms of action of 4-OI in vitro. 4-OI significantly alleviated the clinical symptoms of EAE, the inflammatory infiltration, and demyelination; reduced the levels of inflammatory factors; and inhibited the classical activation of microglia in the spinal cord. 4-OI successfully suppressed the classical activation of BV2 microglia and decreased the levels of inflammatory factors by activating the Nrf2/HO-1 signaling pathway. Furthermore, 4-OI downregulated IRG1 expression in both EAE mice and inflammatory BV2 microglia. 4-OI attenuates the microglia-mediated neuroinflammation and has promising therapeutic effects in MS.

A "twelve-section ultrasonic screening and diagnosis method" and management system for screening and treating neonatal congenital heart disease at the grassroots level in Tang County, Hebei Province, China.

BACKGROUND: To explore a method for screening and diagnosing neonatal congenital heart disease (CHD) applicable to grassroots level, evaluate the prevalence of CHD, and establish a hierarchical management system for CHD screening and treatment at the grassroots level. METHODS: A total of 24,253 newborns born in Tang County between January 2016 and December 2020 were consecutively enrolled and screened by trained primary physicians via the "twelve-section ultrasonic screening and diagnosis method" (referred to as the "twelve-section method"). Specialized staff from the CHD Screening and Diagnosis Center of Hebei Children's Hospital regularly visited the local area for definite diagnosis of CHD in newborns who screened positive. Newborns with CHD were managed according to the hierarchical management system. RESULTS: The centre confirmed that, except for 2 newborns with patent ductus arteriosus missed in the diagnosis of ventricular septal defect combined with severe pulmonary hypertension, newborns with other isolated or concomitant simple CHDs were identified at the grassroots level. The sensitivity, specificity and diagnostic coincidence rate of the twelve-section method for screening complex CHD were 92%, 99.6% and 84%, respectively. A total of 301 children with CHD were identified. The overall CHD prevalence was 12.4‰. According to the hierarchical management system, 113 patients with simple CHD recovered spontaneously during local follow-up, 48 patients continued local follow-up, 106 patients were referred to the centre for surgery (including 17 patients with severe CHD and 89 patients with progressive CHD), 1 patient died without surgery, and 8 patients were lost to follow-up. Eighteen patients with complex CHD were directly referred to the centre for surgery, 3 patients died without surgery, and 4 patients were lost to follow-up. Most patients who received early intervention achieved satisfactory results. The mortality rate of CHD was approximately 28.86 per 100,000 children. CONCLUSIONS: The "twelve-section method" is suitable for screening neonatal CHD at the grassroots level. The establishment of a hierarchical management system for CHD screening and treatment is conducive to the scientific management of CHD, which has important clinical and social significance for early detection, early intervention, reduction in mortality and improvement of the prognosis of complex and severe CHDs.

Design of health information management model for elderly care using an advanced higher-order hybrid clustering algorithm from the perspective of sports and medicine integration.

In the context of integrating sports and medicine domains, the urgent resolution of elderly health supervision requires effective data clustering algorithms. This paper introduces a novel higher-order hybrid clustering algorithm that combines density values and the particle swarm optimization (PSO) algorithm. Initially, the traditional PSO algorithm is enhanced by integrating the Global Evolution Dynamic Model (GEDM) into the Distribution Estimation Algorithm (EDA), constructing a weighted covariance matrix-based GEDM. This adapted PSO algorithm dynamically selects between the Global Evolution Dynamic Model and the standard PSO algorithm to update population information, significantly enhancing convergence speed while mitigating the risk of local optima entrapment. Subsequently, the higher-order hybrid clustering algorithm is formulated based on the density value and the refined PSO algorithm. The PSO clustering algorithm is adopted in the initial clustering phase, culminating in class clusters after a finite number of iterations. These clusters then undergo the application of the density peak search algorithm to identify candidate centroids. The final centroids are determined through a fusion of the initial class clusters and the identified candidate centroids. Results showcase remarkable improvements: achieving 99.13%, 82.22%, and 99.22% for F-measure, recall, and precision on dataset S1, and 75.22%, 64.0%, and 64.4% on dataset CMC. Notably, the proposed algorithm yields a 75.22%, 64.4%, and 64.6% rate on dataset S, significantly surpassing the comparative schemes' performance. Moreover, employing the text vector representation of the LDA topic vector model underscores the efficacy of the higher-order hybrid clustering algorithm in efficiently clustering text information. This innovative approach facilitates swift and accurate clustering of elderly health data from the perspective of sports and medicine integration. It enables the identification of patterns and regularities within the data, facilitating the formulation of personalized health management strategies and addressing latent health concerns among the elderly population.