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Melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) is a rare systemic autoimmune disease associated with a high rate of mortality attributable to rapidly progressive interstitial lung disease. MDA5-positive DM is often complicated by a typical rash and muscle weakness. Herein, we describe a 50-year-old woman who presented with worsening pulmonary symptoms with an absence of typical clinical characteristics. We also review the treatments and prognosis made in similar cases, highlighting that closer attention should be paid to patients presenting with atypical DM, particularly when clinical manifestations such as rash and muscle weakness are not apparent.

We report a case of an advanced non-small cell lung cancer (NSCLC) patient with brain metastasis, RET fusion, and high expression of programmed death ligand 1 (PD-L1) at initial treatment. After receiving radiotherapy for the brain metastasis, the patient started with anlotinib and added immunotherapy with sintilimab. The patient had a good response to anlotinib and sintilimab treatment, tolerated the adverse reactions, and had a progression-free survival (PFS) of over 17 months. To the best of our knowledge, this is the first clinical case report in the literature describing the benefit of anlotinib and sintilimab treatment for non-small cell lung cancer with RET fusion and high PD-L1 expression. This study explores the biomarker selection for targeted therapy and combined immunotherapy in NSCLC patients.

The imbalanced fertilization and the consequential deterioration on the rhizosphere microbial community (RMC) were two potential reasons for the quick yielding degradation of Phyllostachys violascens (Lei-bamboo), a high-value shoot-oriented bamboo. However, most research only focused on nitrogen, phosphorus, and potassium; the studies on the dynamics of other nutrients, such as calcium and magnesium; and their driving mechanisms, lags far behind. Thus, Lei-bamboo fields of different mulching and recovery ages were selected to investigate the dynamics of calcium and magnesium in both soil and bamboo tissue, and to explore their relationship to RMC composition and network patterns. The results showed that mulching increased the content of soil acidification, total organic carbon, alkali-hydrolysable nitrogen, available phosphorus, and available potassium but reduced soil exchangeable magnesium and calcium in soil as well as the magnesium and calcium content in rhizome, stem, and leaf of Lei-bamboo, which indicated an increased relative limitation on magnesium and calcium. Mulching also enhanced the α-diversity and reshaped the composition of RMC, which had a close link to Mg rather than nitrogen, phosphorus, and potassium. As the mulching years increased, the RMC network became bigger and more complex, and the magnesium and calcium gradually appeared in the network center, which further support the magnesium and calcium deficiency to RMC. Nearly all the variation mentioned above could be revered after the removing of mulching. Structural equation modeling showed two main pathways that mulching leads to magnesium and calcium deficiency in Lei-bamboo, one is directly by lowering soil magnesium and calcium content, the other one is indirectly by improving RMC network interactions, a sign of weakened mutualism between RMC and plant roots that hampering the uptake of nutrients. This research highlights the quick magnesium and calcium deficiency caused by mulching in Lei-bamboo forest and the contribution of RMC in amplify the effects of soil magnesium and calcium deficiency, which offers valuable information on balancing fertilization pattern for future sustainable Lei-bamboo cultivation.

BackgroundInflammation plays a crucial role in the pathophysiology of dry eye (DE). This study aims to provide a comprehensive overview of the current status, hotspots and trends in DE anti-inflammatory research through bibliometric analysis.MethodAll publications were searched using the Web of Science Core Collection (WoSCC) database from 2004 to 2024. Bibliometric analyses were performed using VOSviewer, R-bibliometrix, and CiteSpace, and data were managed using Microsoft Office Excel 2019.ResultsThere were 603 papers published between 2004 and 2024 included in this study, with the number of papers increasing each year. The United States was the major contributor, with the largest number of publications and the greatest impact. Baylor College of Medicine was the most influential research institution. Pflugfelder, Stephen C. and Tsubota, Kazuo were the most prolific authors in this area of research, while Dana, Reza was the most cited author in the field with the highest impact. The Journal with the highest number of publications was Investigative Ophthalmology & Visual Science, while the highest impact journal was Ocular Surface. Research hotspots were focused on the mechanisms of inflammation in DE and interventions for anti-inflammatory therapy. Future studies would favor more inflammation-related targeted therapies and physical therapies.ConclusionThis study is the first bibliometric analysis to comprehensively summarize research trends and developments in DE anti-inflammatory treatments, pointing out recent research frontiers and hot directions for scholars studying DE anti-inflammatory treatments.

IntroductionLong COVID (LC) poses a persistent challenge in clinical practice due to limited understanding of its etiology. LC is hypothesized to stem from aberrant immune responses in COVID-19. Vaccinations, which boost immune cells to restore function, could help ease LC symptoms.MethodsTo exclude the impact of vaccination, we examined the immune cell profiles of recovering COVID-19 patients before vaccines were available. White blood cell differentials were monitored in ninety-twohealthy unvaccinated controls. Seventy-six unvaccinated COVID-19 patients were monitored upon admission and on the 50th day post-symptom onset (DPSO50). Peripheral lymphocyte subsets were analyzed using flow cytometry.ResultsMild cases showed no significant changes in lymphocyte counts or subsets from admission to DPSO50. By DPSO50, severe and critical cases showed almost complete recovery from lymphopenia, with critical cases having CD19+ B-cell counts approximately 45% lower than the mild group. Severe and critical cases exhibited reduced B-cell frequencies, with critical cases displaying around 48% higher natural killer (NK) cell counts. In mild cases, NK cell counts negatively correlated with B-cell counts (r=-0.528, p=0.02). Additionally, critical cases showed positive correlations between NK cell counts and CD4+ T-cell counts (r=0.83, p

IntroductionPlatelets are hyperactived during acute COVID-19, promoting clotting and modulating immune-cell responses. Immune thrombocytopenia in adults can manifest as an uncommon complication resulting from various viral infections or as a rare adverse event associated with vaccination. However, their role in convalescent COVID-19 patients remains underexplored. This study examines platelet dynamics early in the pandemic, 48 days post-symptom onset, in unvaccinated patients.MethodsThis longitudinal study included 298 unvaccinated COVID-19 patients (17 mild, 281 moderate) from multiple centers. Clinical evaluations and peripheral lymphocyte subset analyses via flow cytometry were conducted upon admission and on day 48 post-symptom onset (DPSO 48).ResultsAt DPSO 48, 5.3% of moderate COVID-19 patients exhibited high platelet counts (>300×109/L), associated with elevated total T-cells (26.4%), CD4 T-cells (24.4%), CD8 T-cells (36.9%), and Tregs (33.9%) compared to patients with normal platelet counts. However, the CD4/CD8 T-cell ratio and T-cell subset frequencies remained unaffected, indicating ongoing T-cell homeostasis restoration. Additionally, a significant positive correlation (r=0.636, p=0.03) was found between platelet counts and B cells in patients with elevated platelet counts.DiscussionPlatelets may play a pivotal role in immune regulation during the recovery phase of COVID-19. Targeting platelets and their secreted mediators could improve immune balance in patients with immune disorders, highlighting a potential therapeutic approach for enhancing recovery in post-COVID-19 patients.

With the growth of the global population and the increasing scarcity of resources, the sustainability and efficiency improvement of agricultural production have become urgent needs. The rapid development of nanotechnology provides new solutions to this challenge, especially the application of nanoparticles in agriculture, which is gradually demonstrating its unique advantages and broad prospects. Nonetheless, various nanoparticles can influence plant growth in diverse manners, often through distinct mechanisms of action. Beyond their direct effects on the plant itself, they frequently alter the physicochemical properties of the soil and modulate the structure of microbial communities in the rhizosphere. This review focuses intently on the diverse methods through which nanoparticles can modulate plant growth, delving deeply into the interactions between nanoparticles and plants, as well as nanoparticles with soil and microbial communities. The aim is to offer a comprehensive reference for the utilization of functionalized nanoparticles in the agricultural sector.

IntroductionThe endometrium plays a crucial role in early human pregnancy, particularly in embryo implantation, survival, and growth. However, invasion and infection by pathogens can lead to endometritis, infertility, and poor reproductive outcomes. Understanding the mechanisms of endometritis and its impact on fertility remains limited. An infection model using patient-derived endometrial epithelial gland organoids (EEGOs) was established to advance in vitro studies on endometritis and related infertility.MethodsAn EEGOs infection model was constructed and characterized from human endometrium, treating the organoids with estrogen and progesterone to observe changes in the proliferative and secretory phases. The organoids were infected with E. coli, and the release of inflammatory cytokines in the supernatant was detected using ELISA. RNA-seq was employed to analyze the differences before and after E. coli treatment, and differential gene mRNA expression was validated using real-time quantitative PCR. Additionally, the effect of E2 in alleviating inflammation was assessed through markers of receptivity (PAEP, LIF, ITGβ), proliferation (Ki67), and barrier repair (ZO-1).ResultsThe constructed human EEGOs exhibited long-term expansion capability, genetic stability, and characteristic hormonal responses, strongly expressing epithelial markers (MUC1, E-Cadherin). After E. coli infection, the expression levels of inflammatory cytokines TNF-α, IL-8, and IFN-γ increased significantly (P

BackgroundOptimizing the diagnosis and treatment of hematological diseases is a challenging yet crucial research area. Effective treatment plans typically require the comprehensive integration of cell morphology, immunology, cytogenetics, and molecular biology. These plans also consider patient-specific factors such as disease stage, age, and genetic mutation status. With the advancement of artificial intelligence (AI), more “AI + medical” application models are emerging. In clinical practice, many AI-assisted systems have been successfully applied to the diagnosis and treatment of hematological diseases, enhancing precision and efficiency and offering valuable solutions for clinical practice.ObjectiveThis study summarizes the research progress of various AI-assisted systems applied in the clinical diagnosis and treatment of hematological diseases, with a focus on their application in morphology, immunology, cytogenetics, and molecular biology diagnosis, as well as prognosis prediction and treatment.MethodsUsing PubMed, Web of Science, and other network search engines, we conducted a literature search on studies from the past 5 years using the main keywords “artificial intelligence” and “hematological diseases.” We classified the clinical applications of AI systems according to the diagnosis and treatment. We outline and summarize the current advancements in AI for optimizing the diagnosis and treatment of hematological diseases, as well as the difficulties and challenges in promoting the standardization of clinical diagnosis and treatment in this field.ResultsAI can significantly shorten turnaround times, reduce diagnostic costs, and accurately predict disease outcomes through applications in image-recognition technology, genomic data analysis, data mining, pattern recognition, and personalized medicine. However, several challenges remain, including the lack of AI product standards, standardized data, medical–industrial collaboration, and the complexity and non-interpretability of AI systems. In addition, regulatory gaps can lead to data privacy issues. Therefore, more research and improvements are needed to fully leverage the potential of AI to promote standardization of the clinical diagnosis and treatment of hematological diseases.ConclusionOur results serve as a reference point for the clinical diagnosis and treatment of hematological diseases and the development of AI-assisted clinical diagnosis and treatment systems. We offer suggestions for further development of AI in hematology and standardization of clinical diagnosis and treatment.

Taste quality is one of the most important indicators for assessing the quality of rice. However, there has been a lack of systematic studies investigating the impact factors of taste quality. In this study, chromosomal segment substitution lines (CSSLs) with notable differences in physicochemical properties were obtained by screening the CSSL population. A correlation analysis between the physicochemical properties and the taste qualities of rice revealed that amylose and protein content are significantly negatively correlated with the taste value of both freshly cooked and rehydrated instant rice. The alkali spreading value (ASV) had limited impact on the taste value of rice, but low-ASV rice is more resistant to cooking. Grain chalkiness played a critical role in maintaining the integrity of freshly cooked rice and instant rice grains after rehydration. In summary, our study provides crucial insights and guidance for rice breeding, with the goal of developing excellent quality and enhancing the processing of instant rice.

IntroductionBacterial spot, caused by diverse xanthomonads classified into four lineages within three species, poses a significant threat to global pepper and tomato production. In Taiwan, tomato bacterial spot xanthomonads phylogenetically related to an atypical Xanthomonas euvesicatoria pv. perforans (Xep) strain NI1 from Nigeria were found.MethodsTo investigate the genetic structure of Taiwanese Xep strains and determine the phylogenetic position of the atypical strains, we completed high-quality, gap-free, circularized genomes of seven Taiwanese Xep strains and performed comparative genomic analyses with genomes of X. euvesicatoria pathovars. Average nucleotide identity, core genome analysis, and phylogenomic analysis were conducted.ResultsThree sequenced strains were identified as typical Xep, while four clustered with the atypical strain NI1, forming a distinct genomovar within X. euvesicatoria, proposed as X. euvesicatoria genomovar taiwanensis (Xet). This new lineage likely originated in Taiwan and spread to Nigeria through global seed trade. At the genomovar level, chromosomes remained conserved among Taiwanese strains, while plasmids likely contributed to bacterial virulence, avirulence, and field fitness. Gap-free genomes revealed associations between the evolution of type III effectors, horizontal gene transfer events, plasmid diversity, and recombination.DiscussionThis study highlights the critical roles of horizontal gene transfer and plasmids in shaping the genetic makeup, evolution, and environmental adaptation of plant pathogenic xanthomonads. The identification of a new genomovar, X. euvesicatoria genomovar taiwanensis, provides insights into the diversity and global spread of bacterial spot pathogens through seed trade.

ObjectiveThis study aims to explore the influence of combining autologous platelet-rich gel (APG) with continuous vacuum-sealed drainage (CVSD) and the exogenous recombinant human acidic fibroblast growth factor (rh-aFGF) on the healing processes of diabetic foot ulcers (DFU). The primary objective is to elucidate the complex molecular mechanisms associated with DFU, providing innovative perspectives for its treatment.MethodsNinety patients diagnosed with DFU were randomly allocated into three distinct groups. Group A underwent CVSD following wound cleansing to facilitate healing. In Group B, in addition to conventional treatment, negative pressure wound therapy was applied, and rh-aFGF was introduced into normal saline for lavage, building upon the procedures of Group A. Group C received APG along with the interventions applied in Group B. The clinical efficacy of each group was systematically observed and analyzed. Additionally, changes in plasma oxidative stress, inflammatory markers, vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) were assessed both before treatment and 14 days post-treatment.ResultsFollowing treatment, all groups exhibited commendable clinical efficacy. Group C demonstrated a superior wound healing rate, reduced frequency of dressing changes, and shorter wound healing duration (P< 0.05). Compared to baseline measurements, the levels of superoxide dismutase and PEDF increased, while malondialdehyde, VEGF, interleukin-6, interleukin-8, and monocyte chemotactic factor MCP-1 decreased in the wound tissue across all groups. Notably, Group C showed the most significant improvement in clinical efficacy and fortification of molecular mechanisms against oxidative stress (all P< 0.05).ConclusionsThe integrative therapeutic approach combining APG with CVSD and rh-aFGF demonstrates notable efficacy in advancing wound healing. This effectiveness is evident through the reduced frequency of dressing changes and alleviation of wound-related pain. Additionally, the treatment regimen improves the cure rate for challenging, refractory wounds. These favorable outcomes can be attributed to the reduction of oxidative stress levels, attenuation of the local inflammatory response, and the enhancement of the balance between PEDF and VEGF.

IntroductionMacranthoidin B (MB) is a primary active component of Flos Lonicerae. In Chinese veterinary clinics, Flos Lonicerae is frequently used in combination with florfenicol to prevent and treat infections in livestock and poultry. However, potential interactions between Flos Lonicerae and florfenicol remain unclear. To systematically study these interactions, it is crucial to investigate the individual phytochemicals within Flos Lonicerae. Therefore, MB was selected for this study to assess its effect on the pharmacokinetics of florfenicol in vivo and to explore the underlying mechanisms involved.MethodsMale Sprague-Dawley rats were administered MB (60 mg/kg BW) or sterile water orally for 7 consecutive days. On the 8th day, a single oral dose of florfenicol (25 mg/kg BW) was given. Florfenicol pharmacokinetics were analyzed using ultra-high performance liquid chromatography. The hepatic expression levels of cytochrome P450 (CYP1A2, CYP2C11, CYP3A1), UDP-glucuronosyltransferase (UGT1A1), P-glycoprotein (P-gp), and nuclear receptors, including constitutive androstane receptor (CAR), pregnane X receptor (PXR), and retinoid X receptor alpha (RXRα), were quantified via reverse transcription-quantitative polymerase chain reaction and Western blotting (WB). Hepatic CYP1A2 and CYP2C11 activities were measured using a cocktail method. Additionally, the subcellular expression and localization of CAR, PXR, and RXRαin hepatocytes was assessed using WB and immunofluorescence staining.ResultsMB significantly reduces the AUC(0-∞) and MRT(0-∞) of florfenicol. MB also markedly upregulates the mRNA and protein expression of hepatic CYP1A2 and CYP2C11, along with their catalytic activities. Substantial upregulation of CAR and PXR proteins occurs in the hepatocyte nucleus, along with significant nuclear colocalization of the transcriptionally active CAR/RXRα and PXR/RXRαheterodimers, indicating MB-induced nuclear translocation of both CAR and PXR.DiscussionThese findings suggest that MB-induced alterations in florfenicol pharmacokinetics, particularly its accelerated elimination, may be due to increased expression and activities of CYP1A2 and CYP2C11, with CAR and PXR potentially involved in these regulatory effects. Further investigation is yet needed to fully elucidate the clinical implications of these interactions concerning the efficacy of florfenicol in veterinary medicine.

ObjectiveThis study analyzed the prevalence, epidemiological characteristics and risk factors of birth defects among livebirths in central China, aiming to provide evidences for the prevention of birth defects and government Decision-makings.MethodsBirth data from China’s Hubei Province between 2015 and 2022 were collected, including basic information of the livebirths, the mothers and the fathers, as well as information about delivery and each prenatal examination. The livebirths prevalence of birth defects was calculated and the trends were mapped. The basic characteristics of birth defects were evaluated by the difference analysis between case and health groups. Univariate and multivariate Poisson regression was performed to examine the independent risk factors for birth defects.ResultsAmong 43,568 livebirths, 166 livebirths were born with birth defects, resulted in a total prevalence rate of 3.81 per 1,000 livebirths, showing a remarkable uptrend from 0.41per 1,000 livebirths in 2015 to 9.23 per 1,000 livebirths in 2022. The peak of the prevalence was in January and February. Congenital malformation of the musculoskeletal system was the main type of birth defect in central China livebirths, followed by cleft lip and cleft palate. Overall, newborns with birth defect had significantly earlier delivery gestational age, poorer health and higher proportion of infants with low birth weight than healthy births. The gender of livebirths, excess weight at delivery (≥80 kg) of mothers, more than 2 times of gravidity or parity of mothers, and advanced paternal age (≥40 years) were independent risk factors for birth defects (or specific birth defects).ConclusionThe livebirths prevalence of birth defects shows increasing trend in central China, which deserves the attention of the government and would-be parents. Elevated paternal age, excess maternal weight, gravidity and parity should be considered when planning their families.

The interplay between immune components and the epithelium plays a crucial role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Natural killer (NK) cells, one of the main tumor-killing immune cell populations, have received increasing attention in HNSCC immunotherapy. In this review, we explore the mechanism underlying the interplay between NK cells and HNSCC. A series of immune evasion strategies utilized by cancer cells restrict HNSCC infiltration of NK cells. Overcoming these limitations can fully exploit the antineoplastic potential of NK cells. We also investigated the tumor-killing efficacy of NK cell-based immunotherapies, immunotherapeutic strategies, and new results from clinical trials. Notably, cetuximab, the most essential component of NK cell-based immunotherapy, inhibits the epidermal growth factor receptor (EGFR) signaling pathway and activates the immune system in conjunction with NK cells, inducing innate effector functions and improving patient prognosis. In addition, we compiled information on other areas for the improvement of patient prognosis using anti-EGFR receptor-based monoclonal antibody drugs and the underlying mechanisms and prognoses of new immunotherapeutic strategies for the treatment of HNSCC.

Recent advances in immunotherapy represent a breakthrough in solid tumor treatment but the existing data indicate that immunotherapy is not effective in improving the survival time of patients with glioblastoma. The tumor microenvironment (TME) exerts a series of inhibitory effects on immune effector cells, which limits the clinical application of immunotherapy. Growing evidence shows that phosphate and tension homology deleted on chromosome ten (PTEN) plays an essential role in TME immunosuppression of glioblastoma. Emerging evidence also indicates that targeting PTEN can improve the anti-tumor immunity in TME and enhance the immunotherapy effect, highlighting the potential of PTEN as a promising therapeutic target. This review summarizes the function and specific upstream and downstream targets of PTEN-associated immune cells in glioblastoma TME, providing potential drug targets and therapeutic options for glioblastoma.

Reducing carbon emissions from agricultural soils contributes to global greenhouse mitigation. Although the integration of no-tillage practices into maize/pea intercropping systems can achieve this reduction, the specific microbial mechanisms involved remain unclear. This study aimed to explore the effects of integrating maize/pea intercropping and no-tillage technologies on soil carbon emissions and microbial communities. The results indicated that intercropping no-till maize with peas reduced the average soil respiration rates by 19%. In 2021 and 2022, intercropping no-till maize with peas decreased soil carbon emissions by 25.1 and 30.4%, respectively. This practice resulted in a reduction of soil microbiota carbon and nitrogen by 26.9 and 19.7%, respectively, while simultaneously increasing the soil microbial gene beta diversity. Proteobacteria, Actinobacteria, Planctomycetes, Firmicutes, Bacteroidetes, and Acidobacteria collectively represented over 95% of the population and were predominant across all treatments. Intercropping no-till maize with peas decreased the abundance of carbohydrate-active enzymes in the soil. The structural equation modeling indicated that combined no-tillage and intercropping practices effectively decreased soil carbon emissions by modulating the community structure of soil microorganisms. This affected the abundance of carbohydrate-active enzymes and carbon-metabolizing genes in the soil. This study indicated that no-tillage and intercropping methods contributed to carbon reduction by influencing soil microbes. This study can provide microbial-level insights for refining agronomic practices to mitigate soil carbon emissions.

Coix seed is a good product for both medicinal and food use, which is highly susceptible to aflatoxin B1 (AFB1) contamination during field transport, storage, and processing. The aim of this study is to find microbial strains that can solve the problem of contamination of coix seed. In this study, the AFB1-degrading microorganism SX1-1 was isolated and identified as a Bacillus megaterium based on morphology, microscopy, and 16S rDNA sequencing. The optimum culture conditions for SX1-1 to degrade AFB1 were determined to be 12 h. The optimum degradation conditions were 72 h, 57°C, and an initial pH of 8.0. The highest degradation of AFB1 was observed in the fermentation supernatant of the SX1-1 strain, with a degradation rate of 97.45%. In addition, whole-genome sequencing analysis of this strain revealed the presence of a number of enzymes that could potentially degrade AFB1. Importantly, SX1-1 was able to degrade AFB1-contaminated coix seed in situ by 50.06% after co-culture. In conclusion, this strain had a high AFB1 degradation ability, and has great potential and great application as a biocontrol agent for AFB1 degradation of coix seed.

IntroductionSnakebites are acute systemic toxic diseases caused by snake venom entering the body through wounds. Failure to use antivenom immediately and difficulty in obtaining antivenoms are frequently responsible for worsening disease. Traditional Chinese medicine is commonly used to supplement and replace antivenom in treating snakebites. The Jidesheng snake pill (JDS) is a widely used traditional Chinese medicine that has achieved good clinical therapeutic effects; however, its mechanism remains unclear. Therefore, metabolomics techniques were employed to explore the pathophysiological mechanisms of JDS treatment of Agkistrodon halys (Ah) snake venom-poisoned mice.MethodsThe Ah group mouse model was established by intramuscular injection of Ah venom into the hind legs of the mice. The Ah venom + JDS group model was established using JDS after the affected area was treated with Ah venom. Hematoxylin and eosin (HE) staining was used to evaluate the severity of gastrocnemius injury. Quantitative polymerase chain reaction (qPCR) was utilized to detect the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1), muscle-specific creatine kinase (CKM), thrombin antithrombin complex (TAT), and tumor necrosis factor-alpha (TNF-α). Gas chromatography-mass spectrometry (GC-MS) was performed with multivariate statistical analysis to provide new insights into the global metabolic profile of Ah venom-poisoned mice.ResultsHE staining revealed increased red cell necrosis, local hemorrhage, and neutrophil infiltration in the Ah venom group than in the control group. Several compounds were identified, including lipids, amino acids, peptides, and organooxygen. Eighty differential metabolites were screened between the control group and the Ah venom group, and 24 were screened between the Ah venom and JDS groups. The mechanism of Ah venom poisoning in mice may involve aminoacyl-tRNA biosynthesis, various amino acid metabolism disorders, tricarboxylic acid circulation disorders, and abnormal fatty acid metabolism. JDS may reduce symptoms by affecting long-chain fatty acid and amino acid metabolism and promoting nicotinamide-nicotinamide metabolism.ConclusionOur results suggest that metabolomics has huge prospects for elucidating the pathophysiology of Agkistrodon haly venom poisoning and therapeutic mechanisms of JDS.

Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumor is a highly aggressive malignant tumor that typically presents in bone and soft tissue. Primary ES of the intestine is relatively rare, which poses a challenge in distinguishing it from other primary tumors of the small intestine through imaging. This article details a case study of ES originating in the intestine. Computed tomography (CT) imaging suggested a small intestinal stromal tumor, and so the patient underwent resection of the small bowel and omental tumor. Pathology results confirmed the diagnosis of ES of the small intestine. Following surgery, the patient underwent six cycles of chemotherapy, and a follow-up positron emission tomography–CT revealed widespread dissemination of the disease with intraperitoneal metastasis, ultimately resulting in the death of the patient.

Brain metastatic cancer poses a significant clinical challenge, with limited treatment options and poor prognosis for patients. In recent years, immunotherapy has emerged as a promising strategy for addressing brain metastases, offering distinct advantages over conventional treatments. This review explores the evolving landscape of tumor immunotherapy in the context of brain metastatic cancer, focusing on the intricate interplay between the tumor microenvironment (TME) and immunotherapeutic approaches. By elucidating the complex interactions within the TME, including the role of immune cells, cytokines, and extracellular matrix components, this review highlights the potential of immunotherapy to reshape the treatment paradigm for brain metastases. Leveraging immune checkpoint inhibitors, cellular immunotherapies, and personalized treatment strategies, immunotherapy holds promise in overcoming the challenges posed by the blood-brain barrier and immunosuppressive microenvironment of brain metastases. Through a comprehensive analysis of current research findings and future directions, this review underscores the transformative impact of immunotherapy on the management of brain metastatic cancer, offering new insights and opportunities for personalized and precise therapeutic interventions.

Pharmacovigilance plays a crucial role in ensuring the safety of pharmaceutical products. It involves the systematic monitoring of adverse events and the detection of potential safety concerns related to drugs. Manual literature screening for pharmacovigilance related articles is a labor-intensive and time-consuming task, requiring streamlined solutions to cope with the continuous growth of literature. The primary objective of this study is to assess the performance of Large Language Models (LLMs) in automating literature screening for pharmacovigilance, aiming to enhance the process by identifying relevant articles more effectively. This study represents a novel application of LLMs including OpenAI’s GPT-3.5, GPT-4, and Anthropic’s Claude2, in the field of pharmacovigilance, evaluating their ability to categorize medical publications as relevant or irrelevant for safety signal reviews. Our analysis encompassed N-shot learning, chain-of-thought reasoning, and evaluating metrics, with a focus on factors impacting accuracy. The findings highlight the promising potential of LLMs in literature screening, achieving a reproducibility of 93%, sensitivity of 97%, and specificity of 67% showcasing notable strengths in terms of reproducibility and sensitivity, although with moderate specificity. Notably, performance improved when models were provided examples consisting of abstracts, labels, and corresponding reasoning explanations. Moreover, our exploration identified several potential contributing factors influencing prediction outcomes. These factors encompassed the choice of key words and prompts, the balance of the examples, and variations in reasoning explanations. By configuring advanced LLMs for efficient screening of extensive literature databases, this study underscores the transformative potential of these models in drug safety monitoring. Furthermore, these insights gained from this study can inform the development of automated systems for pharmacovigilance, contributing to the ongoing efforts to ensure the safety and efficacy of pharmacovigilance products.

IntroductionSchizophrenia (SCZ) is a severe psychiatric disorder whose pathophysiology remains elusive. Recent investigations have underscored the significance of systemic inflammation, particularly the impact of circulating inflammatory proteins, in SCZ.MethodsThis study explores the potential causal association between certain inflammatory proteins and SCZ. Bidirectional Mendelian randomization (MR) analyses were conducted utilizing data from expansive genome-wide association studies (GWAS). Data regarding circulating inflammatory proteins were sourced from the GWAS Catalog database, encompassing 91 inflammatory cytokines. SCZ-related data were derived from the Finngen database, incorporating 47,696 cases and 359,290 controls. Analytical methods such as inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode were employed to evaluate the association between inflammatory cytokines and SCZ. Sensitivity analyses were also performed to affirm the robustness of the results.ResultsFollowing FDR adjustment, significant associations were observed between levels of inflammatory cytokines, including Fibroblast Growth Factor 5 (OR = 1.140, 95%CI = 1.045, 1.243, p = 0.003, FDR=0.015), C-C Motif Chemokine 4 (OR = 0.888, 95%CI = 0.816, 0.967, p = 0.006, FDR = 0.015), C-X-C Motif Chemokine 1 (OR = 0.833, 95%CI = 0.721, 0.962, p = 0.013, FDR = 0.064), and C-X-C Motif Chemokine 5 (OR = 0.870, 95%CI = 0.778, 0.973, p = 0.015, FDR = 0.074), and the risk of SCZ.ConclusionOur results from MR analysis suggest a potential causal link between circulating inflammatory cytokines and SCZ, thereby enriching our understanding of the interactions between inflammation and SCZ. Furthermore, these insights provide a valuable foundation for devising therapeutic strategies targeting inflammation.

Alzheimer’s disease (AD) is one of the most common chronic neurodegenerative diseases. Hyperphosphorylated tau plays an indispensable role in neuronal dysfunction and synaptic damage in AD. Proteolysis-targeting chimeras (PROTACs) are a novel type of chimeric molecule that can degrade target proteins by inducing their polyubiquitination. This approach has shown promise for reducing tau protein levels, which is a potential therapeutic target for AD. Compared with traditional drug therapies, the use of PROTACs to reduce tau levels may offer a more specific and efficient strategy for treating AD, with fewer side effects. In the present study, we designed and synthesized a series of small-molecule PROTACs to knock down tau protein. Of these, compound C8 was able to lower both total and phosphorylated tau levels in HEK293 cells with stable expression of wild-type full-length human tau (termed HEK293-htau) and htau-overexpressed mice. Western blot findings indicated that C8 degraded tau protein through the ubiquitin–proteasome system in a time-dependent manner. In htau-overexpressed mice, the results of both the novel object recognition and Morris water maze tests revealed that C8 markedly improved cognitive function. Together, our findings suggest that the use of the small-molecule PROTAC C8 to degrade phosphorylated tau may be a promising therapeutic strategy for AD.

BackgroundThis study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH).MethodsPre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters.ResultsSignificantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05).ConclusionSerum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.

BackgroundQuercetin, a widespread polyphenolic flavonoid, is known for its extensive health benefits and is commonly found in the plant kingdom. The natural occurrence and extraction methods of quercetin are crucial due to its bioactive potential.PurposeThis review aims to comprehensively cover the natural sources of quercetin, its extraction methods, bioavailability, pharmacokinetics, and its role in various cell death pathways and liver fibrosis.MethodsA comprehensive literature search was performed across several electronic databases, including PubMed, Embase, CNKI, Wanfang database, and ClinicalTrials.gov, up to 10 February 2024. The search terms employed were “quercetin”, “natural sources of quercetin”, “quercetin extraction methods”, “bioavailability of quercetin”, “pharmacokinetics of quercetin”, “cell death pathways”, “apoptosis”, “autophagy”, “pyroptosis”, “necroptosis”, “ferroptosis”, “cuproptosis”, “liver fibrosis”, and “hepatic stellate cells”. These keywords were interconnected using AND/OR as necessary. The search focused on studies that detailed the bioavailability and pharmacokinetics of quercetin, its role in different cell death pathways, and its effects on liver fibrosis.ResultsThis review details quercetin’s involvement in various cell death pathways, including apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis, with particular attention to its regulatory influence on apoptosis and autophagy. It dissects the mechanisms through which quercetin affects these pathways across different cell types and dosages. Moreover, the paper delves into quercetin’s effects on liver fibrosis, its interactions with hepatic stellate cells, and its modulation of pertinent signaling cascades. Additionally, it articulates from a physical organic chemistry standpoint the uniqueness of quercetin’s structure and its potential for specific actions in the liver.ConclusionThe paper provides a detailed analysis of quercetin, suggesting its significant role in modulating cell death mechanisms and mitigating liver fibrosis, underscoring its therapeutic potential.

BackgroundPatients with nasopharyngeal carcinoma are notably susceptible to high nutritional risks. If not addressed, this susceptibility can lead to malnutrition, resulting in numerous adverse clinical outcomes. Despite the significance of this issue, there is limited comprehensive research on the topic.ObjectiveThe objective of our study was to identify nutritional risk factors in patients with nasopharyngeal carcinoma.MethodsFor this cross-sectional study, we recruited a total of 377 patients with nasopharyngeal carcinoma. The Nutritional Risk Screening 2002 tool was used to assess their nutritional risk. These patients were divided into a well-nourished group (n = 222) and a nutritional risk group (n = 155). Potential risk factors were screened out using univariate analysis (p

BackgroundPerivascular adipose tissue (PVAT) dysfunction impairs vascular homeostasis. Impaired inflammation and bone morphogenetic protein-4 (BMP4) signaling are involved in thoracic PVAT dysfunction by regulating adipokine secretion and adipocyte phenotype transformation. We investigated whether aerobic exercise training could ameliorate high-fat diet (HFD)-induced PVAT dysfunction via improved inflammatory response and BMP4-mediated signaling pathways.MethodsSprague-Dawley rats (n = 24) were divided into three groups, namely control, high-fat diet (HFD), and HFD plus exercise (HEx). After a 6-week intervention, PVAT functional efficiency and changes in inflammatory biomarkers (circulating concentrations in blood and mRNA expressions in thoracic PVAT) were assessed.ResultsChronic HFD feeding caused obesity and dyslipidemia in rats. HFD decreased the relaxation response of PVAT-containing vascular rings and impaired PVAT-regulated vasodilatation. However, exercise training effectively reversed these diet-induced pathological changes to PVAT. This was accompanied by significantly (p < 0.05) restoring the morphological structure and the decreased lipid droplet size in PVAT. Furthermore, HFD-induced impaired inflammatory response (both in circulation and PVAT) was notably ameliorated by exercise training (p < 0.05). Specifically, exercise training substantially reversed HFD-induced WAT-like characteristics to BAT-like characteristics as evidenced by increased UCP1 and decreased FABP4 protein levels in PVAT against HFD. Exercise training promoted transcriptional activation of BMP4 and associated signaling molecules (p38/MAPK, ATF2, PGC1α, and Smad5) that are involved in browning of adipose tissue. In conjunction with gene expressions, exercise training increased BMP4 protein content and activated downstream cascades, represented by upregulated p38/MAPK and PGC1α proteins in PVAT.ConclusionRegular exercise training can reverse HFD-induced obesity, dyslipidemia, and thoracic PVAT dysfunction in rats. The browning of adipose tissue through exercise appears to be modulated through improved inflammatory response and/or BMP4-mediated signaling cascades in obese rats.

Atopic dermatitis (AD) is a common inflammatory skin disease that significantly affects patients’ quality of life. This study aimed to evaluate the therapeutic potential of cell-free fat extract (FE) in AD. In this study, the therapeutic effect of DNCB-induced AD mouse models was investigated. Dermatitis scores and transepidermal water loss (TEWL) were recorded to evaluate the severity of dermatitis. Histological analysis and cytokines measurement were conducted to assess the therapeutic effect. Additionally, the ability of FE to protect cells from ROS-induced damage and its ROS scavenging capacity both in vitro and in vivo were investigated. Furthermore, we performed Th1/2 cell differentiation with and without FE to elucidate the underlying therapeutic mechanism. FE reduced apoptosis and cell death of HaCat cells exposed to oxidative stress. Moreover, FE exhibited concentration-dependent antioxidant activity and scavenged ROS both in vitro and vivo. Treatment with FE alleviated AD symptoms in mice, as evidenced by improved TEWL, restored epidermis thickness, reduced mast cell infiltration, decreased DNA oxidative damage and lower inflammatory cytokines like IFN-γ, IL-4, and IL-13. FE also inhibited the differentiation of Th2 cells in vitro. Our findings indicate that FE regulates oxidative stress and mitigates Th2-mediated inflammation in atopic dermatitis by inhibiting Th2 cell differentiation, suggesting that FE has the potential as a future treatment option for AD.

Background: Acute rejection (AR) is the predominant form of rejection observed in liver transplantation and plays a crucial role in transplant immunology. This study aims to utilize bibliometric analysis to understand the status quo, hotspots, and future trends of research on AR after liver transplantation.Methods: We searched the Web of Science Core Collection (WoSCC) for studies on AR after liver transplantation published from 1988 to 2022. The Bibliometric Online Analysis Platform, VOSviewer, and CiteSpace were used for analysis of all extracted publications.Results: This study included 2,398 articles published in 456 journals by 12,568 authors from 1,965 institutions in 55 countries/regions. The United States and its affiliated institution, the University of Pittsburgh, were the most productive contributors. Transplantation (n = 12,435) was the most frequently cited journal. Neuhaus P (n = 38) was the highest output author, and Demetris AJ (n = 670) was the most co-cited author. The research hotspots of AR after liver transplantation include pathogenesis, immunosuppressive therapy, and prognosis. Emerging research directions include regulatory T cells, immunosuppression minimization, intra-patient variability (IPV) of tacrolimus, and novel non-invasive diagnostic markers.Conclusion: Our study utilized bibliometric methods to analyze the study of AR after liver transplantation over the past 35 years. With the prolonged survival of liver transplant recipients, the most active areas currently focus on individualized treatment and improving patient prognosis. Minimizing adverse reactions to immunosuppressive therapy while simultaneously avoiding an increase in the risk of AR remains a future research focus.

Fructose-1, 6-bisphosphate aldolase (FBA) plays vital roles in plant growth, development, and response to abiotic stress. However, genome-wide identification and structural characterization of the potato (Solanum tuberosum L.) FBA gene family has not been systematically analyzed. In this study, we identified nine StFBA gene members in potato, with six StFBA genes localized in the chloroplast and three in the cytoplasm. The analysis of gene structures, protein structures, and phylogenetic relationships indicated that StFBA genes were divided into Class I and II, which exhibited significant differences in structure and function. Synteny analysis revealed that segmental duplication events promoted the expansion of the StFBA gene family. Promoter analysis showed that most StFBA genes contained cis-regulatory elements associated with light and stress responses. Expression analysis showed that StFBA3, StFBA8, and StFBA9 showing significantly higher expression levels in leaf, stolon, and tuber under blue light, indicating that these genes may improve photosynthesis and play an important function in regulating the induction and expansion of microtubers. Expression levels of the StFBA genes were influenced by drought and salt stress, indicating that they played important roles in abiotic stress. This work offers a theoretical foundation for in-depth understanding of the evolution and function of StFBA genes, as well as providing the basis for the genetic improvement of potatoes.

Objective:Aloperine (ALO) is an effective quinolizidine alkaloid. Previous research has demonstrated its antiarrhythmic effect by inhibiting voltage-gated sodium currents in rat ventricular myocytes. This study explored its effect on transient outward potassium currents (Ito) in rat atrial myocytes to identify potential targets in the context of ion channel currents.Methods:The Ito characteristics in rat atrial myocytes were recorded using a whole-cell patch-clamp technique. Molecular docking was performed to validate ligand-protein binding interactions.Results:ALO at concentrations of 3 and 10 μM significantly reduced Ito current densities. Gating kinetics analysis revealed ALO’s ability to slow Ito activation, hasten inactivation, and prolong transition from inactive to resting state. Molecular docking revealed that ALO could stably bind to KCND2.Conclusion:ALO may inhibit Ito by slowing the activation process, accelerating inactivation, and delaying the recovery time after inactivation, potentially preventing acetylcholine-induced AF.

IntroductionPlant height (PH) and ear height (EH) are key plant architectural traits in maize, which will affect the photosynthetic efficiency, high plant density tolerance, suitability for mechanical harvestingMethodsQTL mapping were conducted for PH and EH using a recombinant inbred line (RIL) population and two corresponding immortalized backcross (IB) populations obtained from crosses between the RIL population and the two parental lines.ResultsA total of 17 and 15 QTL were detected in the RIL and IB populations, respectively. Two QTL, qPH1-1 (qEH1-1) and qPH1-2 (qEH1-4) in the RIL, were simultaneously identified for PH and EH. Combing reported genome-wide association and cloned PH-related genes, co-expression network analyses were constructed, then five candidate genes with high confidence in major QTL were identified including Zm00001d011117 and Zm00001d011108, whose homologs have been confirmed to play a role in determining PH in maize and soybean.DiscussionQTL mapping used a immortalized backcross population is a new strategy. These identified genes in this study can provide new insights for improving the plant architecture in maize.

BackgroundMultiple studies have confirmed the significant role of cathepsins in the development and progression of digestive system tumors. However, further investigation is needed to determine the causal relationships.MethodsWe conducted a two-sample bidirectional Mendelian randomization (MR) study using pooled data from a genome-wide association study (GWAS) to assess the causal associations between nine cathepsins (cathepsin B, E, F, G, H, L2, O, S, and Z) and six types of digestive system tumors, including hepatocellular carcinoma (HCC), pancreatic cancer (PCa), biliary tract cancer (BTC), colorectal cancer (CRC), gastric carcinoma (GC), and esophageal cancer (EC). We employed the following methods including inverse variance weighting (IVW), MR-Egger, weighted median (WM), Cochran’s Q, MR-PRESSO, MR-Egger intercept test and leave-one-out sensitivity analysis. The STROBE-MR checklist for the reporting of MR studies was used in this study.ResultsThe risk of HCC increased with high levels of cathepsin G (IVW: p = 0.029, odds ratio (OR) = 1.369, 95% confidence interval (CI) = 1.033-1.814). Similarly, BTC was associated with elevated cathepsin B levels (IVW: p = 0.025, OR = 1.693, 95% CI = 1.070-2.681). Conversely, a reduction in PCa risk was associated with increased cathepsin H levels (IVW: p = 0.027, OR = 0.896, 95% CI = 0.812-0.988). Lastly, high levels of cathepsin L2 were found to lower the risk of CRC (IVW: p = 0.034, OR = 0.814, 95% CI = 0.674-0.985).ConclusionOur findings confirm the causal relationship between cathepsins and digestive system tumors, which can offer valuable insights for the diagnosis and treatment of digestive system tumors.

BackgroundSarcoma is a highly heterogeneous malignancy with a poor prognosis. Although chemotherapy and targeted therapy have improved the prognosis to some extent, the efficacy remains unsatisfactory in some patients. The efficacy and safety of immunotherapy in sarcoma need further evaluation.MethodsWe conducted a two-center study of sarcoma patients receiving PD-1 immunotherapy at Tianjin Medical University Cancer Institute and Hospital and Henan Provincial Cancer Hospital. The treatment regimens included PD-1 inhibitor monotherapy and combination therapy based on PD-1 inhibitors. The observed primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). Survival curves were compared using the Kaplan−Meier method.ResultsA total of 43 patients were included from the two centers. The median follow-up time for all patients was 13 months (range, 1-48 months). In the group of 37 patients with advanced or unresectable sarcoma, the mPFS was 6 months (95%CI: 5-12 months), and the mOS was 16 months (95%CI: 10-28 months). The ORR was 10.8% (4/37), and the DCR was 18.9% (7/37). Subgroup analysis showed no significant differences in mPFS (p=0.11) and mOS (p=0.88) between patients with PD-L1 negative/positive expression. There were also no significant differences in mPFS (p=0.13) or mOS (p=0.72) between PD-1 inhibitor monotherapy and combination therapy. Additionally, there were no significant differences in mPFS (p=0.52) or mOS (p=0.49) between osteogenic sarcoma and soft tissue sarcoma. Furthermore, the results showed no significant differences in mPFS (p=0.66) or mOS (p=0.96) between PD-1 inhibitors combined with targeted therapy and PD-1 inhibitors combined with AI chemotherapy. Among the 6 patients receiving adjuvant therapy after surgery, the mPFS was 15 months (95%CI: 6-NA months), and the mOS was not reached. In terms of safety, most adverse events were mild (grade 1-2) and manageable. The most severe grade 4 adverse events were bone marrow suppression, which occurred in 4 patients but resolved after treatment. There was also one case of a grade 4 adverse event related to hypertension.ConclusionImmunotherapy is an effective treatment modality for sarcoma with manageable safety. Further inclusion of more patients or prospective clinical trials is needed to validate these findings.

Relevant studies increasingly indicate that female reproductive health is confronted with substantial challenges. Emerging research has revealed that the microbiome interacts with the anatomy, histology, and immunity of the female reproductive tract, which are the cornerstone of maintaining female reproductive health and preventing adverse pregnancy outcomes. Currently, the precise mechanisms underlying their interaction and impact on physiological functions of the reproductive tract remain elusive, constituting a prominent area of investigation within the field of female reproductive tract microecology. From this new perspective, we explore the mechanisms of interactions between the microbiome and the anatomy, histology, and immunity of the female reproductive tract, factors that affect the composition of the microbiome in the female reproductive tract, as well as personalized medicine approaches in managing female reproductive tract health based on the microbiome. This study highlights the pivotal role of the female reproductive tract microbiome in maintaining reproductive health and influencing the occurrence of reproductive tract diseases. These findings support the exploration of innovative approaches for the prevention, monitoring and treatment of female reproductive tract diseases based on the microbiome.

BackgroundEnhanced recovery after surgery (ERAS) has been widely used in adult surgery. However, few studies have reported the efficacy of ERAS in paediatric patients with Meckel's diverticulum (MD), the aim of the study was to prospectively evaluate the safety and efficacy of ERAS in treating MD.MethodsA prospective randomised controlled study of children with MD admitted to our hospital from Jan 1, 2021 to Dec 31, 2023 were conducted, we developed and implemented an ERAS program for this patients. All cases were strictly selected according to the inclusion and exclusion criteria. Among these patients, they were randomly assigned to the ERAS group or the traditional (TRAD) group with random number table row randomization. The main observational indicators were operation time, intraoperative hemorrhage, FLACC pain scale results on 2 h, 6 h, 12 h, 24 h after surgery, length of postoperative stay (LOPS), time to first defecation, time to first eating after surgery, time to discontinuation of intravenous infusion, total treatment cost, incidence of postoperative complications, 30-day readmission rate and parental satisfaction rate.ResultsA total of 50 patients underwent Meckel's diverticulectomy during this period, 7 patients were excluded, 23 patients were assigned to the ERAS group and 20 patients were assigned to the TRAD group. There were no significant differences in demographic data and operation time, intraoperative hemorrhage. The FLACC pain scale results on 2 h, 6 h, 12 h, 24 h after surgery were significantly lower in the ERAS group. The LOPS was 6.17 ± 0.89 days in the ERAS group and 8.30 ± 1.26 days in the TRAD group, resulting in a significantly shorter LOPS in ERAS group. ERAS could also reduce the first postoperative defecation time, the time to first eating after surgery and the time to discontinuation of intravenous infusion. The treatment cost was decreased in the ERAS group. The rate of complications and 30-day readmission were not significantly different between the two groups.ConclusionsIn this single-center study, the ERAS protocol for patients with MD requiring surgery was safe and effective.

With the rapid advancement of genetic and protein engineering, proteins and peptides have emerged as promising drug molecules for therapeutic applications. Consequently, there has been a growing interest in the field of chemical modification technology to address challenges associated with their clinical use, including rapid clearance from circulation, immunogenicity, physical and chemical instabilities (such as aggregation, adsorption, deamination, clipping, oxidation, etc.), and enzymatic degradation. Polyethylene glycol (PEG) modification offers an effective solution to these issues due to its favorable properties. This review presents recent progress in the development and application of PEGylated therapeutic proteins and peptides (TPPs). For this purpose, firstly, the physical and chemical properties as well as classification of PEG and its derivatives are described. Subsequently, a detailed summary is provided on the main sites of PEGylated TPPs and the factors that influence their PEGylation. Furthermore, notable instances of PEG-modified TPPs (including antimicrobial peptides (AMPs), interferon, asparaginase and antibodies) are highlighted. Finally, we propose the chemical modification of TPPs with PEG, followed by an analysis of the current development status and future prospects of PEGylated TPPs. This work provides a comprehensive literature review in this promising field while facilitating researchers in utilizing PEG polymers to modify TPPs for disease treatment.

Brain network analysis provides essential insights into the diagnosis of brain disease. Integrating multiple neuroimaging modalities has been demonstrated to be more effective than using a single modality for brain network analysis. However, a majority of existing brain network analysis methods based on multiple modalities often overlook both complementary information and unique characteristics from various modalities. To tackle this issue, we propose the Beta-Informativeness-Diffusion Multilayer Graph Embedding (BID-MGE) method. The proposed method seamlessly integrates structural connectivity (SC) and functional connectivity (FC) to learn more comprehensive information for diagnosing neuropsychiatric disorders. Specifically, a novel beta distribution mapping function (beta mapping) is utilized to increase vital information and weaken insignificant connections. The refined information helps the diffusion process concentrate on crucial brain regions to capture more discriminative features. To maximize the preservation of the unique characteristics of each modality, we design an optimal scale multilayer brain network, the inter-layer connections of which depend on node informativeness. Then, a multilayer informativeness diffusion is proposed to capture complementary information and unique characteristics from various modalities and generate node representations by incorporating the features of each node with those of their connected nodes. Finally, the node representations are reconfigured using principal component analysis (PCA), and cosine distances are calculated with reference to multiple templates for statistical analysis and classification. We implement the proposed method for brain network analysis of neuropsychiatric disorders. The results indicate that our method effectively identifies crucial brain regions associated with diseases, providing valuable insights into the pathology of the disease, and surpasses other advanced methods in classification performance.

ObjectiveThe aim of this study was to assess the ability of a multiparametric magnetic resonance imaging (MRI)-based radiomics signature model to predict disease-free survival (DFS) in patients with rectal cancer treated by surgery.Materials and methodsWe evaluated data of 194 patients with rectal cancer who had undergone radical surgery between April 2016 and September 2021. The mean age of all patients was 62.6 ± 9.7 years (range: 37–86 years). The study endpoint was DFS and 1132 radiomic features were extracted from preoperative MRIs, including contrast-enhanced T1- and T2-weighted imaging and apparent diffusion coefficient values. The study patients were randomly allocated to training (n=97) and validation cohorts (n=97) in a ratio of 5:5. A multivariable Cox regression model was used to generate a radiomics signature (rad score). The associations of rad score with DFS were evaluated using Kaplan–Meier analysis. Three models, namely a radiomics nomogram, radiomics signature, and clinical model, were compared using the Akaike information criterion.ResultThe rad score, which was composed of four MRI features, stratified rectal cancer patients into low- and high-risk groups and was associated with DFS in both the training (p = 0.0026) and validation sets (p = 0.036). Moreover, a radiomics nomogram model that combined rad score and independent clinical risk factors performed better (Harrell concordance index [C-index] =0.77) than a purely radiomics signature (C-index=0.73) or clinical model (C-index=0.70).ConclusionAn MRI radiomics model that incorporates a radiomics signature and clinicopathological factors more accurately predicts DFS than does a clinical model in patients with rectal cancer.

IntroductionThe short-chain fatty acids (SCFAs) contained in breast milk play a key role in infant growth, affecting metabolism and enhancing intestinal immunity by regulating inflammation.MethodsIn order to examine the associations between the microbiota and SCFA levels in breast milk, and explore the roles of SCFAs in regulating the infant gut microbiota, we enrolled 50 paired mothers and infants and collected both breast milk and infant fecal samples. Breast milk SCFA contents were determined by UPLC-MS, and whole genome shotgun sequencing was applied to determine the microbial composition of breast milk and infant feces. The SCFA levels in breast milk were grouped into tertiles as high, medium, or low, and the differences of intestinal microbiota and KEGG pathways were compared among groups.ResultsThe results demonstrated that breast milk butyric acid (C4) is significantly associated with Clostridium leptum richness in breastmilk. Additionally, the specific Bifidobacterium may have an interactive symbiosis with the main species of C4-producing bacteria in human milk. Women with a low breast milk C4 tertile are associated with a high abundance of Salmonella and Salmonella enterica in their infants' feces. KEGG pathway analysis further showed that the content of C4 in breast milk is significantly correlated with the infants' metabolic pathways of lysine and arginine biosynthesis.DiscussionThis study suggests that interactive symbiosis of the microbiota exists in breast milk. Certain breast milk microbes could be beneficial by producing C4 and further influence the abundance of certain gut microbes in infants, playing an important role in early immune and metabolic development.

ObjectiveThis study aims to predict cervical lymph node metastasis in papillary thyroid carcinoma (PTC) patients with high accuracy. To achieve this, we introduce a novel deep learning model, DualSwinThyroid, leveraging multi-modal ultrasound imaging data for prediction.Materials and methodsWe assembled a substantial dataset consisting of 3652 multi-modal ultrasound images from 299 PTC patients in this retrospective study. The newly developed DualSwinThyroid model integrates various ultrasound modalities and clinical data. Following its creation, we rigorously assessed the model’s performance against a separate testing set, comparing it with established machine learning models and previous deep learning approaches.ResultsDemonstrating remarkable precision, DualSwinThyroid achieved an AUC of 0.924 and an 96.3% accuracy on the test set. The model efficiently processed multi-modal data, pinpointing features indicative of lymph node metastasis in thyroid nodule ultrasound images. It offers a three-tier classification that aligns each level with a specific surgical strategy for PTC treatment.ConclusionDualSwinThyroid, a deep learning model designed with multi-modal ultrasound radiomics, effectively estimates the degree of cervical lymph node metastasis in PTC patients. In addition, it also provides early, precise identification and facilitation of interventions for high-risk groups, thereby enhancing the strategic selection of surgical approaches in managing PTC patients.

African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2 weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC_HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5 days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV.

Allergic diseases in children are major public health concerns due to their widespread and rising prevalence. Food-specific immunoglobulin G4(FS-IgG4) has been detected in patients with allergic diseases, but its clinical significance is still debated. In the present study, 407 children with allergic diseases were recruited and categorized into three groups according to the different systems involved: the respiratory system group, the skin system group, and a multiple system group, with the collection of clinical symptoms and serum antibodies, including total immunoglobulin E (IgE), house dust mite (HDM) IgE, food-specific IgE (FS-IgE), and FS-IgG4. Part of these patients were followed up with the intervention of FS-IgG4-guided diet elimination with or without add-on probiotics supplement. The analysis at baseline revealed distinct serum levels of different antibodies. The positive rate of FS-IgG4 in all groups was more than 80%, and the proportion of total IgE and FS-IgG4 both positive in the multi-system group was the highest (p=0.039). Egg and milk were the foods with the highest positive rate of FS-IgG4 in all groups. After diet elimination for more than 3 months, serum FS-IgG4 in children significantly decreased (P

BackgroundSleep disturbances are an early indicator of cognitive impairment and exacerbate its progression. While pharmacological treatments for sleep disorders exist, their side-effect profile includes an increased risk of falls and the potential to exacerbate cognitive impairment. Non-pharmacological treatments such as physical exercise should be considered. However, uncertainties persist. We aimed to assess the potential benefits of exercise interventions on sleep in patients with cognitive impairment and determine the specific effects of various exercise modalities.Materials and methodsA systematic search was performed on seven databases for eligible studies published before Nov 2022. Randomized controlled trials of exercise for patients with cognitive impairment (mild cognitive impairment and Alzheimer’s disease) were included. All analyses were conducted using RevMan version 5.4. Meta-analysis and The Grading of Recommendations Assessment Development and Evaluations (GRADE) quality ratings were performed on sleep quality and objective sleep data.ResultsA total of 8 randomized controlled trials were included with a sample size of 486 subjects. For patients with cognitive impairment, physical exercise had a beneficial effect on sleep quality [MD = −3.55 (−5.57, −1.32), Z = 3.13, p = 0.002] and total sleep time [MD = 33.77 (23.92, 43.62), Z = 6.72, P

BackgroundThe relationship between the patterns of physical activity (PA) and frailty, including its various subdomains, remains poorly understood. Therefore, this study aims to investigate the correlations between the patterns of physical activity and frailty and its various subdomains in community-dwelling older women.MethodsA cross-sectional study investigated the association between physical activity and frailty in 1,099 women aged between 60 to 70 years. Triaxial accelerometers were used to measure bouted PA (a minimum duration of 10 min) and sporadic PA (a duration of

Introduction: Northeast Merino (NMS) is a breed developed in Northeast China during the 1960s for wool and meat production. It exhibits excellent traits such as high wool yield, superior meat quality, rapid growth rate, robust disease resistance, and adaptability to cold climates. However, no studies have used whole-genome sequencing data to investigate the superior traits of NMS.Methods: In this study, we investigated the population structure, genetic diversity, and selection signals of NMS using whole-genome sequencing data from 20 individuals. Two methods (integrated haplotype score and composite likelihood ratio) were used for selection signal analysis, and the Fixation Index was used to explore the selection signals of NMS and the other two breeds, Mongolian sheep and South African meat Merino.Results: The results showed that NMS had low inbreeding levels, high genomic diversity, and a pedigree of both Merino breeds and Chinese local breeds. A total length of 14.09 Mb genomic region containing 287 genes was detected using the two methods. Further exploration of the functions of these genes revealed that they are mainly concentrated in wool production performance (IRF2BP2, MAP3K7, and WNT3), meat production performance (NDUFA9, SETBP1, ZBTB38, and FTO), cold resistance (DNAJC13, LPGAT1, and PRDM16), and immune response (PRDM2, GALNT8, and HCAR2). The selection signals of NMS and the other two breeds annotated 87 and 23 genes, respectively. These genes were also mainly focused on wool and meat production performance.Conclusion: These results provide a basis for further breeding improvement, comprehensive use of this breed, and a reference for research on other breeds.

BackgroundSleep problems in preschoolers are becoming increasingly prominent, and the association between sleep status and anxiety symptoms has attracted growing attention. However, studies investigating the relationship between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms remain scant. We used the large sample data from the Longhua Cohort Study of Children in Shenzhen, China (LCCS) to analyze the association between bedtime and sleep in preschoolers and their anxiety symptoms.MethodsA cross-sectional study of 69,138 preschoolers in Longhua District, Shenzhen, China was conducted in 2022. Data on sociodemographic characteristics of families, bedtime, nighttime sleep duration of preschoolers, and their anxiety symptoms (measured by the Spence Preschool Children Anxiety Scale) were collected through a structured questionnaire completed by the parents. Using binary logistic regression models, the relationship between bedtime, nighttime sleep duration, and childhood anxiety symptoms was examined.ResultsThe bedtimes of preschoolers were concentrated between 21:01–22:00 (52.41%). Among the preschoolers, 38.70% had bedtimes later than 22:00, and 75.49% had insufficient nighttime sleep duration. The positive screening rate for anxiety symptoms among preschoolers was 3.50%. After adjusting for confounding factors using binary logistic regression models, compared with preschoolers with bedtime ≤21:00, The OR (95%CI) values of anxiety in preschoolers with bedtime ≥23:01, 22:01–23:00 and 21:01–22:00 were 2.86 (2.21–3.69), 1.51 (1.27–1.79) and 1.48 (1.26–1.76), respectively. Compared with those with sufficient nighttime sleep duration, the OR (95%CI) of children with nighttime sleep duration less than 9 h was 1.36 (1.23–1.51).ConclusionAn association exists between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms. Preschoolers with 21:00 for bedtime and a nighttime sleep duration of 10 h may have lower anxiety symptoms. These findings support the importance of adequate sleep for preventing anxiety symptoms in children.