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IntroductionThe identification of peptides eluted from HLA complexes by mass spectrometry (MS) can provide critical data for deep learning models of antigen presentation prediction and promote neoantigen vaccine design. A major challenge remains in determining which HLA allele eluted peptides correspond to.MethodsTo address this, we present a tool for prediction of multiple allele (MA) presentation called LRMAHpan, which integrates LSTM network and ResNet_CA network for antigen processing and presentation prediction. We trained and tested the LRMAHpan BA (binding affinity) and the LRMAHpan AP (antigen processing) models using mass spectrometry data, subsequently combined them into the LRMAHpan PS (presentation score) model. Our approach is based on a novel pHLA encoding method that enables the integration of neoantigen prediction tasks into computer vision methods. This method aggregates MA data into a multichannel matrix and incorporates peptide sequences to efficiently capture binding signals.ResultsLRMAHpan outperforms standard predictors such as NetMHCpan 4.1, MHCflurry 2.0, and TransPHLA in terms of positive predictive value (PPV) when applied to MA data. Additionally, it can accommodate peptides of variable lengths and predict HLA class I and II presentation. We also predicted neoantigens in a cohort of metastatic melanoma patients, identifying several shared neoantigens.DiscussionOur results demonstrate that LRMAHpan significantly improves the accuracy of antigen presentation predictions.

IntroductionAs one of the most common complications of diabetes, diabetic cardiomyopathy (DCM) is the main cause of heart failure in patients with diabetes. However, the lack of effective treatments for DCM remains a clinical challenge. (Pro) renin receptor (PRR) is a member of renin angiotensin aldosterone system (RAAS). Here, we aim to determine whether PRR is involved in myocardial pyroptosis in diabetic cardiomyopathy.MethodsWe established diabetic rats model by intraperitoneal injection of streptozotocin (STZ). PRR overexpression adenovirus or PRR knockdown adenovirus was injected into the tail vein. Western blot, histopathology and immunohistochemistry staining, ELISA and Echocardiography were used to detect cardiac function changes and myocardial injury levels of DCM rats. Primary cardiomyocytes were stimulated with high glucose and PRR overexpression or PRR knockdown was achieved by adenovirus transfection, we also used the inhibitor of AMPK to decrease the activity of AMPK. Western blot, Real-time PCR, Immunofluorescence and ELISA were used to detect the level of PRR and pyroptosis in cardiomyocyte.ResultsWe found that high glucose increased the expression of PRR in heart. After overexpression of PRR, the expression of the pyroptosis related proteins such as Caspase-1, IL-1β, IL-18, and NLRP3 was significantly increased, the phosphorylation level of AMPK was significantly decreased, and the fibrosis level was significantly increased, thus aggravating the cardiac function injury of DCM. On the contrary, PRR knockdown can alleviate the level of myocardial pyroptosis in DCM and improve cardiac function. The related mechanism was that PRR could inhibit AMPK phosphorylation and promote the activation of NLRP3 inflammasome.DiscussionPRR aggravated pyroptosis of cardiomyocyte, increased the dysfunction of cardiomyocyte, and may be related to the decrease of AMPK phosphorylation and the overactivation of NLRP3. This may provide new ideas and targets for the treatment of DCM.

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.

IntroductionThis study explores the effectiveness of music therapy in repairing psychological trauma in bereaved families, aiming to provide a comprehensive understanding of its potential therapeutic impact. It begins with an analysis of the current situation faced by bereaved families, identifying the psychological challenges they experience.MethodsThe research design included the recruitment of participants from bereaved families, who were then divided into an experimental group and a control group. An optimized Long Short-Term Memory (LSTM) network model was constructed to analyze music therapy data, tailored specifically to capture the nuances of this therapeutic process. The experimental procedure detailed the specific operations involved in the music therapy sessions and established a clear comparison framework between the two groups.ResultsThe performance of the proposed LSTM model demonstrated high accuracy (0.85), precision (0.86), recall (0.84), and F1-score (0.85), indicating its effectiveness in predicting treatment outcomes. When compared to the Self-Reporting Inventory-90 (SCL-90) scale, the model captured the trend of treatment effects with a high level of accuracy and reliability. Notably, participants numbered 2, 6, and 8 in the experimental group showed substantial improvement rates of 67.21%, 71.45%, and 75.67%, respectively, in their psychological health issues.DiscussionThe comparative analysis between the experimental and control groups confirmed that the music therapy approach, as guided by the proposed LSTM model, led to a more significant improvement in psychological health issues for bereaved families. This suggests that the model offers a promising avenue for enhancing the effectiveness of music therapy in this context.

ObjectiveTo explore the association between representative insulin resistance (IR) indices and the risk of kidney stone disease in an American adult population. The representative IR indices referred to metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride glucose-body mass index (TyG-BMI), visceral adiposity index (VAI), and homeostatic model assessment of IR (HOMA-IR).MethodsWe investigated adult participants who joined the 2015–2018 National Health and Nutrition Examination Survey (NHANES) and reported kidney stone histories. Weighted proportions, multivariable regression analysis, and restricted cubic splines were used to evaluate the associations between IR indices and kidney stones after their adjustment for gender, age, race, education, smoking status, alcohol drinking frequency, hypertension and diabetes status, physical activity level, water intake, and levels of calcium, cholesterol, and uric acid.ResultsA total of 19,225 participants were included. The weighted prevalence of kidney stone was 11.1%. A multivariable logistic regression model showed a dose–response relationship between the METS-IR and kidney stone [odds ratio (OR) = 1.02, 95% confidence interval (CI) (1.01, 1.04), p

IntroductionPlant carbon black (PCB) is a new feed additive for zearalenone adsorption in China. However, information regarding whether PCB can effectively absorb deoxynivalenol (DON) is limited.MethodsTo explore this research gap, the present study examined the adsorption effectiveness of DON by PCB using a phosphate buffer, artificial gastric juice, and artificial intestinal juice. In a 21-day in vivo trial, 48 male piglets were randomly assigned to four treatment groups: (1) uncontaminated basal diet (CTR), (2) basal diet supplemented with 1 mg/kg PCB(PCB), (3) 2.3 mg/kg DON-contaminated diet (DON), and (4) 2.3 mg/kg DON-contaminated diet supplemented with 0.1% PCB (DON+PCB).ResultsWhen DON concentration was 1 µg/mL, the adsorption rate of PCB on DON in phosphate buffer systems (pH 2.0 and 6.0) and the artificial gastric and intestinal juices were 100%, 100%, 71.46%, and 77.20%, respectively. In the in vivo trial, the DON group significantly increased the DON+deepoxy-deoxynivalenol (DOM-1) content in serum as well as the inflammation cytokine proteins (interleukin-6, interleukin-8, and tumor necrosis factor-α) and mRNA expression of interleukin-6 and longchain acyl-CoA synthetase 4 in the jejunum and ileum. It decreased the villus height, goblet cells, mucosal thickness, and mRNA expression of Claudin-1 compared to the CTR group. In addition, DON decreased the Shannon and Simpson indices; reduced the relative abundances of Firmicutes, Lactobacillus, Candidatus_Saccharimonas, and Ruminococcus; and increased the relative abundances of Terrisporobacter and Clostridium_sensu_stricto_1 in the cecal content.DiscussionIn conclusion, these results suggest that PCB showed high adsorption efficacy on DON in vitro, and exhibit the protective effects against various intestinal toxicity manifestations in DON-challenged piglets.

IntroductionIt is well known that there are significant differences in the prevalence of chronic pain between males and females. Human and animal imaging studies have shown that chronic pain profoundly alters the structure and function of brain regions. However, there is limited research on the sex-specific mechanisms underlying the brain plasticity and adaptive changes associated with chronic pain. In this article, we conducted a multimodal study to evaluate how nerve injury-induced chronic pain affects the brain.MethodsMale and female Sprague-Dawley (SD) rats with spared nerve injury (SNI) model underwent resting-state functional magnetic resonance imaging (rs-fMRI) (male sham group: n = 18; male SNI group: n = 18; female sham group: n = 20; female SNI group: n = 18) and magnetic resonance diffusion tensor imaging (DTI) (male sham group: n = 23; male SNI group: n = 21; female sham group: n = 20; female SNI group: n = 21) scanning. ICA method, Fractional amplitude of low-frequency fluctuations (fALFF), immunofluorescence staining, and graph theory analysis was utilized to extract the rs-fMRI changes of brain regions of each group.ResultsUsing SNI model, which promotes long-lasting mechanical allodynia, we found that neuropathic pain deeply modified the intrinsic organization of the brain functional network in male and female rats (main effect of operation: F = 298.449, P < 0.001). 64 independent components (ICs) in the brain were divided and assigned to 16 systems. In male rats, we observed significant alterations in the microstructure of the hippocampal cornu ammonis 1 and cornu ammonis 2 (CA1/CA2) region, as indicated by increased mean diffusivity (MD) (CA1_L: P = 0.02; CA1_R: P = 0.031; CA2_L: P = 0.035; CA2_R: P = 0.015) and radial diffusivity (RD) (CA1_L: P = 0.028; CA1_R: P = 0.033; CA2_L: P = 0.037; CA2_R: P = 0.038) values, along with enhanced activating transcription factor 3 (ATF3) expression. Conversely, in female rats, we found significant increases in the fractional amplitude of low frequency fluctuations (fALFF) value within the hippocampal dentate gyrus (DG) (F = 5.419, P = 0.023), accompanied by elevated c-Fos signal (F = 6.269, P = 0.031). Furthermore, graph theory analysis revealed notable differences in the small-world network of the hippocampal system in female rats, characterized by reduced small-world attributes and increased inter-nodal transmission efficiency.DiscussionOur study indicates sex differences in structural and functional alterations in the hippocampal system in rats under chronic pain conditions. The results suggest that the hippocampus system plays an important role in the different mechanisms of chronic pain in different sexes. These findings provide reliable insights to explore the complex mechanisms underlying sex differences in chronic pain.

Low-temperature and low-salt fermented Chinese kohlrabi (LSCK) represents a novel approach to producing low-salt kohlrabi without the need for desalination during processing, as compared to traditional techniques. However, the profile of its non-volatile metabolites remains unclear. In order to investigate the non-volatile metabolites and their changes in LSCK during fermentation, the LSCKs fermented for 0 day (0D), 45 days (45D) and 90 days (90D) were analyzed using LC-MS/MS non-targeted metabolomics coupled with multivariate statistical analysis. The results showed that 60, 74, and 68 differential metabolites were identified in the three groups A1 (0D and 45D), A2 (0D and 90D), and A3 (45D and 90D) (VIP >1, p 1), respectively. The differential metabolites were mainly amino acids, peptides, and analogues, fatty acyls, organic acids and derivatives, and carbohydrates and carbohydrate conjugates. Seventeen common differential metabolites were identified in A1, A2, and A3 groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that the alanine, aspartate and glutamate metabolism, butanoate metabolism, α-linolenic acid metabolism, arginine biosynthesis, and phenylalanine metabolism were significantly correlated with the differential metabolites. The present study elucidates for the first time the changes in non-volatile differential metabolites and their associated metabolic pathways in the novel Chinese low-salt kohlrabi, providing a theoretical basis for improving the industrial fermentation process of this innovative product.

BackgroundNatural infection or vaccination have provided robust immune defense against SARS-CoV-2 invasion, nevertheless, Omicron variants still successfully cause breakthrough infection, and the underlying mechanisms are poorly understood.MethodsSequential blood samples were continuously collected at different time points from 252 volunteers who were received the CanSino Ad5-nCoV (n= 183) vaccine or the Sinovac CoronaVac inactivated vaccine (n= 69). The anti-SARS-CoV-2 prototype and Omicron BA.5.2 as well as XBB.1.16 variant neutralizing antibodies (Nab) in sera were detected by ELISA. Sera were also used to measure pseudo and live virus neutralization assay. The associations between the anti-prototype Nab levels and different HLA-ABC alleles were analyzed using artificial intelligence (AI)-deep learning techniques. The frequency of B cells in PBMCs was investigated by flow cytometry assay (FACs).ResultsIndividuals carrying the HLA-B*15 allele manifested the highest concentrations of anti-SARS-CoV-2 prototype Nab after vax administration. Unfortunately, these volunteers are more susceptible to Omicron BA.5.2 breakthrough infection due to their sera have poorer anti-BA.5.2 Nab and lower levels of viral neutralization efficacy. FACs confirmed that a significant decrease in CD19+CD27+RBD+ memory B cells in these HLA-B*15 population compared to other cohorts. Importantly, generating lower concentrations of cross-reactive anti-XBB.1.16 Nab post-BA.5.2 infection caused HLA-B*15 individuals to be further infected by XBB.1.16 variant.ConclusionsIndividuals carrying the HLA-B*15 allele respond better to COVID-19 vax including the CanSino Ad5-nCoV and the Sinovac CoronaVac inactivated vaccines, but are more susceptible to Omicron variant infection, thus, a novel vaccine against this population is necessary for COVID-19 pandemic control in the future.

Percutaneous coronary intervention (PCI), as a relatively rapid and effective minimally invasive treatment for coronary heart disease (CHD), can effectively relieve coronary artery stenosis and restore myocardial perfusion. However, the occurrence of major adverse cardiovascular events (MACE) is a significant challenge for post PCI care. To better understand risk/benefit indicators and provide post PCI MACE prediction, 408 patients with CHD who had undergone PCI treatment from 2018 to 2021 in Tianjin Chest hospital were retrospectively studied for their clinical characteristics in relation with the MACE occurrence during a 12-month follow-up. In the study, 194 patients had MACE and 214 patients remained MACE-free. Using uni- and multivariate regression analyses, we have shown that smoking history, elevated serum C-reactive protein levels (hs-CRP), and high haemoglobin levels A1c (HbA1c) are all independent risk factors for MACE after PCI. Furthermore, we have discovered that the serum level of IL-38, one of the latest members identified in the IL-1 cytokine family, is another predictive factor and is reversely related to the occurrence of MACE. The serum level of IL-38 alone is capable of predicting non-MACE occurrence in subcategorized patients with abnormal levels of hs-CRP and/or HbA1c.

BackgroundPostoperative delirium (POD) is a usual neurological complication, often leading to poor prognoses. Early identification of high-risk patients is crucial for preventing POD. Sarcopenia is an age-related geriatric syndrome characterized by the loss of skeletal muscle mass and function, and previous studies indicated that preoperative low muscle mass might be a predictor for POD. However, the association between preoperative sarcopenia and POD remains to be fully elucidated. This study was to explore the correlation between preoperative sarcopenia and POD following gastrointestinal cancer surgery in older patients.MethodsOlder patients (≥60 years) undergoing gastrointestinal cancer surgery were enrolled. Sarcopenia was defined based on the Special Interest Group on sarcopenia of the International Society of Physical and Rehabilitation Medicine (ISarcoPRM), which combined the loss of muscle mass (evaluated by ultrasound) and function (assessed by chair stand test and handgrip strength) before surgery. POD assessment was performed using the Confusion Assessment Method (CAM) or CAM for the intensive care unit (CAM-ICU) during the first 7 days after surgery or before discharge. Multivariate logistic regression analysis examined the correlation between preoperative sarcopenia and POD. Moreover, the receiver operator characteristic (ROC) curve was applied to analyze the predictive effect of the preoperative sarcopenia in POD.ResultsOne hundred and thirty patients were finally included, of which 43 patients presented with sarcopenia before surgery. Twenty-four patients ultimately developed POD, and the incidence was 18.5%. The results of the multivariate analyses demonstrated that preoperative sarcopenia was still independently associated with POD after adjusting for age ≥70 years, preoperative Mini-Mental State Examination score, and intraoperative blood transfusion. The area under the ROC curve of preoperative sarcopenia in predicting POD was 0.680 (95% confidence interval 0.557–0.804).ConclusionPreoperative sarcopenia defined by ISarcoPRM criteria was independently associated with POD in geriatric patients after gastrointestinal cancer surgery.

IntroductionGranulocytic myeloid-derived suppressor cells (G-MDSCs) show fast recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) constituting the major part of peripheral blood in the early phase. Although G-MDSCs mediate immune suppression through multiple mechanisms, they may also promote inflammation under specific conditions. MethodsG-MDSCs were isolated from 82 patients following allo-HSCT within 90 days after allo-HSCT, and their interactions with autologous CD3+ T-cells were examined. T-cell proliferation was assessed by flow cytometry following CFSE staining, while differentiation and interferon-γ secretion were characterized using chemokine receptor profiling and ELISpot assays, respectively. NK cell cytotoxicity was evaluated through co-culture with K562 cells. An aGVHD xenogeneic model in humanized mice was employed to study the in vivo effects of human leukocytes. Furthermore, transcriptional alterations in G-MDSCs were analyzed via RNA sequencing to investigate functional transitions.ResultsG-MDSCs promoted inflammation in the early-stage, by facilitating cytokine secretion and proliferation of T cells, as well as their differentiation into pro-inflammatory T helper subsets. At day 28, patients with a higher number of G-MDSCs exhibited an increased risk of developing grades II-IV aGvHD. Besides, adoptive transfer of G-MDSCs from patients at day 28 into humanized mice exacerbated aGvHD. However, at day 90, G-MDSCs led to immunosuppression, characterized by upregulated expression of indoleamine 2,3-dioxygenase gene and interleukin-10 secretion, coupled with the inhibition of T cell proliferation. Furthermore, transcriptional analysis of G-MDSCs at day 28 and day 90 revealed that 1445 genes were differentially expressed. These genes were associated with various pathways, revealing the molecular signatures of early post-transplant differentiation in G-MDSCs. In addition, genes linked to the endoplasmic reticulum stress were upregulated in patients without aGvHD. The acquisition of immunosuppressive function by G-MDSCs may depend on the activation of CXCL2 and DERL1 genes. ConclusionOur findings revealed the alteration in the immune characteristics of G-MDSCs within the first 90 days post-allo-HSCT. Moreover, the quantity of G-MDSCs at day 28 may serve as a predictive indicator for the development of aGvHD.

Adipose tissue, an indispensable organ, fulfils the pivotal role of energy storage and metabolism and is instrumental in maintaining the dynamic equilibrium of energy and health of the organism. Adipocyte hypertrophy and adipocyte hyperplasia (adipogenesis) are the two primary mechanisms of fat deposition. Mature adipocytes are obtained by differentiating mesenchymal stem cells into preadipocytes and redifferentiation. However, the mechanisms orchestrating adipogenesis remain unclear. Autophagy, an alternative cell death pathway that sustains intracellular energy homeostasis through the degradation of cellular components, is implicated in regulating adipogenesis. Furthermore, adipose tissue functions as an endocrine organ, producing various cytokines, and certain inflammatory factors, in turn, modulate autophagy and adipogenesis. Additionally, autophagy influences intracellular redox homeostasis by regulating reactive oxygen species, which play pivotal roles in adipogenesis. There is a growing interest in exploring the involvement of autophagy, inflammation, and oxidative stress in adipogenesis. The present manuscript reviews the impact of autophagy, oxidative stress, and inflammation on the regulation of adipogenesis and, for the first time, discusses their interactions during adipogenesis. An integrated analysis of the role of autophagy, inflammation and oxidative stress will contribute to elucidating the mechanisms of adipogenesis and expediting the exploration of molecular targets for treating obesity-related metabolic disorders.

We describe the case of a 10-year-old boy with asthma (AS), accompanied by allergic rhinitis (AR), food allergy (FA), and combined attention-deficit/hyperactivity disorder (ADHD), who was treated at Shanghai Renji Hospital on 11 July 2020. The efficiency of the previous treatment with salmeterol/ticlosone was poor. Treatment with montelukast sodium resulted in development of neurological symptoms. Treatment with omalizumab in combination with subcutaneous immunotherapy (SCIT) was then initiated in our department based on anti-asthmatic therapy. Symptoms of asthma were completely controlled, and FA and AR symptoms improved. The treatment regimen led to a significant improvement in ADHD symptoms and the overall quality of life of the patient. The literature search was done in the PubMed database using “attention deficit/hyperactivity disorder/ADHD” and “asthma” as keywords, and we identified 47 relevant articles. In conclusion, our results show that treating asthma with omalizumab in combination with salmeterol/ticlosone and SCIT is efficient in controlling symptoms of multiple allergies and may lead to the improvement in ADHD symptoms and the overall quality of life of pediatric patients with ADHD. While current studies suggest that allergic diseases are closely related to ADHD, there is still a lack of studies or case reports of complete treatment protocols to provide clinical clues for management of the disease.

OTULIN deficiency is a complex disease characterized by a wide range of clinical manifestations, including skin rash, joint welling, lipodystrophy to pulmonary abscess, and sepsis shock. This disease is mechanistically linked to mutations in the OTULIN gene, resulting in an immune disorder that compromises the body’s ability to effectively combat pathogens and foreign stimuli. The OTULIN gene is responsible for encoding a deubiquitinating enzyme crucial for hydrolyzing Met1-poly Ub chains, and its dysfunction leads to dysregulated immune responses. Patients with OTULIN deficiency often exhibit an increase in monocytes, including neutrophils and macrophages, along with inflammatory clinical features. The onset of symptoms typically occurs at an early age. However, individuals with OTULIN haploinsufficiency are particularly susceptible to life-threatening staphylococcal infections. Currently, the most effective treatment for patients with OTULIN biallelic mutations involves the use of TNF-blocking agents, which target the dysregulated immune response. In conclusion, OTULIN deficiency presents a complex clinical picture with diverse manifestations, attributed to mutations in the OTULIN gene. Understanding the underlying mechanisms is crucial for developing targeted therapeutic interventions to address this challenging condition. Further research into the pathophysiology of OTULIN deficiency is essential for improving clinical management and outcomes for affected individuals.

AimTo evaluate the efficacy and safety of URLi (ultra rapid lispro insulin) compared to insulin lispro as bolus insulin with basal insulin using CGM in the individuals with type 2 diabetes(T2D) in China.MethodsThis was a double-blind, randomized, parallel, prospective, phase 3 study. Subjects with uncontrolled T2D were recruited and randomized 1:2 into the insulin lispro and URLi groups. Subjects received a consistent basal insulin regimen during the study and self-administered insulin lispro or URLi before each meal throughout the treatment period. Subjects underwent a 3-day continuous glucose monitoring (CGM) at the baseline and endpoint respectively, and then CGM data were analyzed. The primary endpoint was to compare the difference in postprandial glucose (PPG) control using CGM between the two groups.ResultsA total of 57 subjects with T2D completed the study. Our CGM data showed that postprandial glucose excursions after breakfast (BPPGE) in the URLi group was lower than that in the insulin lispro group (1.59 ± 1.57 mmol/L vs 2.51 ± 1.73 mmol/L, p = 0.046). 1-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.37 ± 3.28 mmol/L vs 0.24 ± 2.58 mmol/L, p = 0.047). 2-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.12 ± 4.00 mmol/L vs 1.22 ± 2.90 mmol/L, p = 0.021). The mean HbA1c level decreased by 1.1% in the URLi group and 0.99% in the insulin lispro group, with no treatment difference (p = 0.642). In the CGM profile, TBR was not significantly different between the two groups (p = 0.743). The weight gain also did not differ between the two groups (p = 0.303).ConclusionURLi can control breakfast PPG better than insulin lispro in adults with T2D in China, while it is non-inferior in improving HbA1c. The incidence of hypoglycemic and weight gain were similar between the two groups.

Lumen formation, as a key process of biological tube construction, is essential in various physiological processes such as nutrient and waste transporting, gas exchanging, and structural supporting. However, the mechanisms underlying tubular lumen development are still not fully understood. In the present study, we identified a matrix metalloproteinase, Nas15, which is enriched in the apical domain of the Ciona embryonic notochord. The expression level of the Nas15 gene significantly increased during notochord lumen formation and expansion. Nas15 loss-of-function resulted in abnormal notochord lumen expansion in Ciona embryos. Besides, yeast two-hybrid screening and CO-IP results indicated a Phosphatase 2 Catalytic Subunit Alpha (PPP2CA) physically interacted with Nas15. PPP2CA also involved in notochord lumen formation via localizing Nas15. Furthermore, we investigated the distribution of laminin in Nas15 disrupted embryos. In conclusion, our results revealed a mechanisms of how notochord cells regulating lumen expansion via metalloproteinase-mediated ECM localization. This findings provide insight into the mechanisms of tubular organ lumen formation and serve as a reference for research on human abnormal lumenogenesis diseases.

The worldwide incidence of cognitive impairment is escalating, yet no effective solutions for these afflictions have been discovered. Consequently, the importance of early identification and immediate intervention is heightened. Advanced eye movements—a form of voluntary eye movements that includes anti-saccades, memory-guided saccades, predictive saccades, pro-saccades and gap/overlap saccades, mediated by the cerebral cortex and subcortical pathways reflect cognitive levels and functions across different domains. In view of their objectivity, reproducibility, and non-invasive characteristics, advanced eye movement examination possesses significant prospective utility across a wide range of cognitive impairment. This paper extensively reviews various models associated with advanced eye movement examinations and their current applications in cognitive impairment such as Alzheimer’s disease, Lewy body dementia and frontotemporal dementia. Advanced eye movement examination can serve as a biomarker for early screening diagnosis and research on cognitive impairment. In the future, combining advanced eye movement examination with neuropsychological scale assessment and other diagnostic methods may contribute to further early identification of these types of diseases.

This paper is devoted to investigating a class of stochastic neutral-type neural networks with delays. By using the fixed point theorem and the properties of neutral-type operator, we obtain the existence conditions for periodic solutions of stochastic neutral-type neural networks. Furthermore, we obtain the conditions for the exponential stability of periodic solutions using Gronwall-Bellman inequality and stochastic analysis technique. Finally, a numerical example is given to show the effectiveness and merits of the present results. Our results can be used to obtain the existence and exponential stability of periodic solution to the corresponding deterministic systems.

The brown planthopper (BPH) is the most destructive insect pest that threatens rice production globally. Developing rice varieties incorporating BPH-resistant genes has proven to be an effective control measure against BPH. In this study, we assessed the resistance of a core collection consisting of 502 rice germplasms by evaluating resistance scores, weight gain rates and honeydew excretions. A total of 117 rice varieties (23.31%) exhibited resistance to BPH. Genome-wide association studies (GWAS) were performed on both the entire panel of 502 rice varieties and its subspecies, and 6 loci were significantly associated with resistance scores (P value < 1.0e-8). Within these loci, we identified eight candidate genes encoding receptor-like protein kinase (RLK), nucleotide-binding and leucine-rich repeat (NB-LRR), or LRR proteins. Two loci had not been detected in previous study and were entirely novel. Furthermore, we evaluated the predictive ability of genomic selection for resistance to BPH. The results revealed that the highest prediction accuracy for BPH resistance reached 0.633. As expected, the prediction accuracy increased progressively with an increasing number of SNPs, and a total of 6.7K SNPs displayed comparable accuracy to 268K SNPs. Among various statistical models tested, the random forest model exhibited superior predictive accuracy. Moreover, increasing the size of training population improved prediction accuracy; however, there was no significant difference in prediction accuracy between a training population size of 737 and 1179. Additionally, when there existed close genetic relatedness between the training and validation populations, higher prediction accuracies were observed compared to scenarios when they were genetically distant. These findings provide valuable resistance candidate genes and germplasm resources and are crucial for the application of genomic selection for breeding durable BPH-resistant rice varieties.

AimThe purpose of this study is to examine the design and implementation of a high-fidelity simulation training course for medical and nursing collaboration, based on the Fink integrated course design model. Additionally, the study aims to validate the teaching effectiveness of the course.BackgroundPrevious empirical studies have highlighted the effectiveness of collaborative healthcare education in institutional teaching and hospital training. However, the development of healthcare collaborative education in China has been slow to develop in China. In recent years, Chinese nursing educators and researchers have shown interest in utilizing high-fidelity simulators for healthcare collaborative education. These simulators help address the limitations of traditional nursing teaching and healthcare separation simulation. Nevertheless, a standardized simulation interprofessional education curriculum is still lacking. Therefore, nursing educators need to develop a standardized high-fidelity simulation training curriculum for healthcare collaboration, guided by established science curriculum development theories.MethodsA high-fidelity simulation training course on healthcare collaboration was designed based on the Fink integrated curriculum design model. The course was taught to 14 nursing students and 8 clinical medicine students from March to July 2022. To comprehensively evaluate the effectiveness of the healthcare collaboration high-fidelity simulation training course, several assessment tools were used. These included course grades, satisfaction and self-confidence scales, simulation teaching practice scales, healthcare collaboration attitude scales, critical thinking skills scales, and semi-structured interviews.ResultsAfter the course was implemented, students demonstrated high overall scores (79.19 ± 5.12) and reported high satisfaction ratings (4.44 ± 0.37). They also exhibited increased self-confidence (4.16 ± 0.33). Additionally, students evaluated all four dimensions of the course teaching practice scale positively. Furthermore, the study demonstrated significant improvements in various aspects, such as attitudes toward medical and nursing collaboration (t = −7.135, P < 0.01), shared education and teamwork (t = −3.247, P = 0.002), job autonomy for nurses (t = −1.782, P = 0.000), and reduced physician dominance (t = −6.768, P = 0.000). The critical thinking skills of the students showed significant improvement, with higher scores in truth-seeking (t = −3.052, P = 0.004), analytical ability (t = −2.561, P = 0.014), systematic ability (t = −3.491, P = 0.001), self-confidence in critical thinking (t = −4.024, P = 0.000), and curiosity (t = −5.318, P = 0.000) compared to their scores before the course (all P < 0.05). The interviews showed that the course’s student-centered approach enabled active learning. Students suggested enhancing teaching cases and allocating more time for reflection and summarization.ConclusionThe study successfully designed a high-fidelity simulation training course for healthcare collaboration by utilizing the Fink integrated curriculum design model. The findings provide valuable insights for the development of standardized curricula and healthcare collaboration education in China. Moreover, the course adheres to best practice principles, fostering improved attitudes toward healthcare collaboration and enhancing students’ healthcare collaboration and clinical thinking skills.

The host defence responses play vital roles in viral infection and are regulated by complex interactive networks. The host immune system recognizes viral pathogens through the interaction of pattern-recognition receptors (PRRs) with pathogen-associated molecular patterns (PAMPs). As a PRR mainly in the cytoplasm, cyclic GMP-AMP synthase (cGAS) senses and binds virus DNA and subsequently activates stimulator of interferon genes (STING) to trigger a series of intracellular signalling cascades to defend against invading pathogenic microorganisms. Integrated omic and functional analyses identify the cGAS-STING pathway regulating various host cellular responses and controlling viral infections. Aside from its most common function in regulating inflammation and type I interferon, a growing body of evidence suggests that the cGAS-STING signalling axis is closely associated with a series of cellular responses, such as oxidative stress, autophagy, and endoplasmic reticulum stress, which have major impacts on physiological homeostasis. Interestingly, these host cellular responses play dual roles in the regulation of the cGAS-STING signalling axis and the clearance of viruses. Here, we outline recent insights into cGAS-STING in regulating type I interferon, inflammation, oxidative stress, autophagy and endoplasmic reticulum stress and discuss their interactions with viral infections. A detailed understanding of the cGAS-STING-mediated potential antiviral effects contributes to revealing the pathogenesis of certain viruses and sheds light on effective solutions for antiviral therapy.

BackgroundChina has the world’s largest mobile population. As mobility increases, ensuring the health protection of this population is receiving more attention. Strengthening public health education is a crucial measure to improve their health and achieve equal access to basic public health services in China. Previous research has demonstrated that public health education has an impact on the health of mobile populations. However, there has been limited investigation into the mediating pathways through which health education influences the health of mobile populations, and few studies have examined the heterogeneity of this effect.ObjectivesThe aim of this study was to analyze the impact of public health education on the health of the mobile population and its mechanism of action. Additionally, we aimed to explore the differences in this impact among different subdivided groups.MethodsThis paper analyses the impact of public health education on the health of the mobile population using the 2018 China Migrant Dynamic Survey (CMDS) Data,. The data was cleaned and 4,034 people were included in the analysis. The study employed ordered logistic regression modeling to analyze the mediating pathways through which health education affects health. Additionally, binary logistic regression model, probit model, propensity score matching method and instrumental variables were used to verify the robustness of the results.ResultsThe self-assessed health status of the mobile population was good, and 82.10% of them accepted public health education. However, 17.89% of the mobile population did not receive any health education. Acceptance of health education can help improve the health status of the mobile population (OR = 1.178, 95% CI = 0.979–1.418). The study found that public health education can positively impact the health of mobile populations by influencing their health and hospitalization behaviors, as well as their social support. The analysis of heterogeneity revealed that the impact of public health education is more significant among rural, middle-aged, low-education, and low-income groups of the mobile population.ConclusionPublic health education can have a positive impact on the health of the migrant populations. To further improve health education for this group, it is necessary to actively promote the establishment of health records for the migrant population, to facilitate the contracting of family doctors by the migrant population, to improve the accessibility to hospitalization services, reduce the burden of hospitalization costs, and enhance social support. Simultaneously, it is essential to offer precise and varied health education to the migrant population based on their characteristics, to promote equity among diverse groups of individuals. These findings not only help to enrich theoretical research on health education for migrant populations and the health of migrant populations but also help to improve the level of public health education for migrant populations and improve the health protection of migrant populations.

ObjectivesIt is a pivotal element of China’s health system reform to improve the health security of health insurance for the mobile population. Achieving this objective is integral to the success of the reform. The aim of this study was to analyze the impact of different enrollment characteristics of basic health insurance on the health of the mobile population and to investigate the mediating role of health service utilization behavior.MethodsThis cross-sectional study included 135,372 migrants who participated in the 2018 China Migrants Dynamic Survey (CMDS). Two indicators were employed in this study to assess the characteristics of the mobile population’s involvement in basic health insurance–namely, whether or not they participated in local health insurance and the type of health insurance in which they participated. The health status of the mobile population was measured using self-assessed health. Health service utilization behavior was divided into public health service utilization and medical service utilization. Multivariate ordered logistic regression was employed to examine the effect of health insurance on the health of the mobile population. Subsequently, the Bootstrap method was applied to analyze the mediating effect of health service utilization behavior in the relationship between health insurance and the health of the mobile population.ResultsHealth insurance had a positive impact on health, public health services, and health service utilization among the mobile population. However, enrollment in local health insurance (OR = 1.088, 95% CI = 1.043–1.134) and enrollment in Basic Medical Insurance for Urban Employees (OR = 1.178, 95% CI = 1.090–1.273) were more likely to be associated with higher levels of health and a greater likelihood of receiving health service utilization. The results of the mediating mechanism analysis indicated that health education, health records, family doctor contracting, receiving inpatient services, and being hospitalized locally all played a partially mediating role in the impact of the place of enrollment on health. Regarding the effect of the type of enrollment on health, three types of services–namely, health education, health records, and contracting with a family doctor–played a partially mediating role, while receiving inpatient services and being hospitalized locally did not exhibit a mediating effect. The effect of the type of participation on health is partially mediated.ConclusionBased on the impact of the different enrolment characteristics of basic health insurance on the health of the mobile population and the mediating role of health service utilization in this impact, furthermore, improvement of health insurance coverage for the mobile population should focus on improving the accessibility of health services, increasing the level of health insurance coverage, mitigating differences in treatment between the different insurance systems, and simplifying the process of transferring the health insurance relationships.

BackgroundThe effect of robotic surgery (RS) for rectal cancer after neoadjuvant therapy is still controversial, and a comprehensive search and analysis of the current relevant evidence is necessary. Our study aimed to evaluate the efficacy of RS for rectal cancer after neoadjuvant therapy compared with conventional laparoscopic surgery (LS).MethodsUp to August 23, 2023, Embase, PubMed, Web of Science, and Cochrane databases were searched for studies of RS for rectal cancer after neoadjuvant therapy. Odds ratio (OR) or mean difference (MD) was used to calculate the effect sizes using RevMan 5.3.ResultsA total of 12 studies reporting on 11,686 participants were included. Compared with LS, RS increased the operative time (MD 35.16 min; 95% CI: 16.24, 54.07), but it did significantly reduce the risk of the conversion to open surgery (OR 0.46, 95% CI 0.40, 0.53) and improved the TME incomplete rate (OR 0.40, 95% CI 0.17, 0.93). Moreover, there were no difference in total postoperative complications (OR 1.13, 95% CI 0.84, 1.52), circumferential resection margin positivity (OR 0.90, 95% CI 0.63, 1.27), distal margin positive (OR 0.60, 95% CI 0.29, 1.22), blood loss (MD −11.57 ml; 95% CI: −39.09, 15.94), length of hospital stay (MD −0.08 days; 95% CI: −1.26, 1.10), mortality (OR 0.59, 95% CI 0.29, 1.21), lymph node harvested (MD 0.69.; 95% CI: −0.43, 1.82), and the time of first flatus (MD −0.47 days; 95% CI: −1.19, 0.25) between the two groups.ConclusionsRS was associated with superiority over LS in reducing the risk of the conversion to open surgery and improving TME incomplete rate, which suggested that RS could be an effective method for treating rectal cancer after neoadjuvant therapy.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=460084, PROSPERO (CRD42023460084).

Previous studies have found that negative parental rearing styles can negatively predict the acquisition of ego identity, while it has not been discussed whether the overcompetitive attitudes, a stable personality, will further hinder their ego identity development under the model of educational involutionary. The study used the Overcompetitive Attitude Scale, the Brief Parental Rearing Styles Questionnaire, and the Ego Identity Status Scale to investigate 550 young students in a school in Suzhou in order to explore the influence of parental rearing styles on adolescents’ ego identity development and the role of involutional attitudes. The results showed that: (1) Adolescents’ overcompetitive attitude was positively predicted by parental rejection and overprotection, while it was negatively predicted by parental emotional warmth. (2) Parental emotional warmth significantly predicted adolescents’ ego identity status more favorably than parental rejection, overprotection, and overcompetitive attitude. (3) Overcompetitive attitude plays a partial intermediary role between parental rearing style and ego identity.

Previous research has indicated that natural landscapes exhibit a greater capacity for ameliorating negative emotional states in individuals when compared to urban landscapes. Nevertheless, significant scientific inquiries, such as the uniformity of the rejuvenating effect across distinct categories of natural landscapes on college students and the choice of the optimal plant community for achieving the most potent restorative effect, remain unexplored. This study aimed to address these questions by selecting four plant communities (single-layer grassland, single-layer woodland, tree-grass composite woodland, tree-shrub-grass composite woodland) and using an electroencephalography method to capture the neuroelectric activity of the participants in combination with the Positive and Negative Affect Schedule score to explore the effects of plant community types on emotional recovery. The results showed that all four plant communities significantly increased positive emotions and significantly reduced negative emotions. There was no significant difference in the recovery effect of positive emotions among the four plant community types, but there was a significant difference in the recovery effect of negative emotions. The effect of tree-shrub-grass composite woodland on the negative emotion recovery effect is the best; the EEG results found that the alpha wave amplitude induced by the tree-shrub-grass composite woodland was significantly higher than that of the other three groups of plant communities, and the EEG and behavioral results were consistent. The results show that the tree-shrub-grass composite woodland has the best restoration effect and has stronger planning and design significance.

Obesity and asthma are global public health problems. Obesity-related asthma is a special phenotype of asthma with a complex pathogenesis. Its occurrence and development are related to mechanical compression, inflammatory response, metabolic regulation, gene regulation, and vitamin D deficiency. Different treatment strategies used in the process of weight loss have a beneficial impact on asthma. Alterations in gut and airway microbial community structure and their metabolites may also contribute to obesity-related asthma. The role of the Th17/Treg balance in the gut microbiota regulating the immune responses and host metabolism is important. Therapeutic measures associated with the gut microbiota variety may contribute to improving chronic inflammation associated with obesity by regulating the Th17/Treg balance. An early reduction in microbial diversity can predict the development of asthma and lead to allergy through an imbalance of Th2/Th1 responses. Short-chain fatty acids (SCFAs) regulate the differentiation and activation of regulatory T cells, thereby regulating immune homeostasis in the lung to suppress allergic inflammation and weight gain. Therefore, clarifying the microbial mechanism of obesity-related asthma has important guiding significance for clinical treatment. In this review, we used the following terms: “asthma and obesity” and “obesity-related asthma”, combining “phenotype”, “airway inflammation” and “lung function”, and reviewed the characteristics and pathogenesis of obesity-related asthma, the relationship between the gut and airway microbiota and obesity-related asthma, and the current treatment measures for the disease.

Objective: Pancreatic sinistral portal hypertension (PSPH) is a common complication of acute pancreatitis (AP) and can cause massive gastrointestinal bleeding, which is one of the causes of AP-related mortality. However, there is currently no predictive model for AP concurrent with PSPH. This study aimed to identify the risk factors for AP concurrent with PSPH and use these factors to build a related predictive model.Materials and methods: We collected clinical data from 282 patients with AP. 192 patients were used as a training group and 90 patients as a validation group. Univariate and multivariate analyses were used to identify independent risk factors for AP complicated with PSPH, and then a nomogram was established. The models are cross verification and Internal verification. The predictive ability and accuracy of the model were evaluated based on the working curve of the subjects and the calibration curve, respectively. The clinical value of the model was evaluated using decision curve analysis (DCA).Results: The univariate analysis revealed significant differences in the occurrence of PSPH with respect to sex, recurrent AP, history of hypertension, smoking history, patency of the splenic vein, pancreatic necrosis or pancreatic pseudocyst formation, the most significant site of pancreatic swelling, presence of a Dmure D polymer, MCTSI, and involvement of lipase and amylase. The logistic multivariate regression analysis showed that male sex, splenic-vein stenosis or occlusion and swelling were located in the body-tail, and MCTSI was an independent risk factor for PSPH. The nomogram and ROC curve were constructed. The area under the working curve of the subjects was 0.91, and the sensitivity and specificity were 82.5% and 89.1%, respectively. In the validation group, the C-index is 0.826. The nomogram was internally validated using 1,000 bootstrap samples, and the c-index was 0.898. The calibration curve demonstrated that the predicted probability was concordant with the observed probability, and the DCA confirmed that the model had robust clinical utility.Conclusion: Male sex, splenic-vein stenosis or occlusion, recurrent AP, and swelling are located in the body-tail, and MCTSI is an independent risk factor for the occurrence of PSPH. The predictive model developed for AP complicated with PSPH may serve toward developing preventive and therapeutic approaches for PSPH.

BackgroundHeart failure (HF) is a complex and life-threatening syndrome associated with significant morbidity and mortality. While TikTok has gained popularity as a social media platform for sharing HF-related information, the quality of such content on TikTok remains unexplored.MethodsA cross-sectional analysis was conducted on TikTok videos related to HF in China. The sources of the videos were identified and analyzed. The content comprehensiveness of the videos was evaluated using six questions that covered definition, signs and symptoms, risk factors, evaluation, management, and outcomes. The reliability and quality of the videos were assessed using three standardized evaluation instruments: DISCERN, JAMA benchmarks, and the Global Quality Scale. Additionally, the correlation between video quality and video characteristics was further investigated.ResultsAmong the video sources, 92.2% were attributed to health professionals, while news agencies and non-profit organizations accounted for 5.7% and 2.1%, respectively. The content comprehensiveness score for the videos was 3.36 (SD 3.56), with news agencies receiving the highest scores of 4.06 (SD 3.31). The median DISCERN, JAMA, and GQS scores for all 141 videos were 26.50 (IQR 25.00–28.750), 2.00 (IQR 2.00–2.00), and 2.00 (IQR 2.00–2.00), respectively. Videos from health professionals had significantly higher JAMA scores compared to those from non-profit organizations (P

The Bph15 gene, known for its ability to confer resistance to the brown planthopper (BPH; Nilaparvata lugens Stål), has been extensively employed in rice breeding. However, the molecular mechanism by which Bph15 provides resistance against BPH in rice remains poorly understood. In this study, we reported that the transcription factor OsWRKY71 was highly responsive to BPH infestation and exhibited early-induced expression in Bph15-NIL (near-isogenic line) plants, and OsWRKY71 was localized in the nucleus of rice protoplasts. The knockout of OsWRKY71 in the Bph15-NIL background by CRISPR-Cas9 technology resulted in an impaired Bph15-mediated resistance against BPH. Transcriptome analysis revealed that the transcript profiles responsive to BPH differed between the wrky71 mutant and Bph15-NIL, and the knockout of OsWRKY71 altered the expression of defense genes. Subsequent quantitative RT-PCR analysis identified three genes, namely sesquiterpene synthase OsSTPS2, EXO70 family gene OsEXO70J1, and disease resistance gene RGA2, which might participate in BPH resistance conferred by OsWRKY71 in Bph15-NIL plants. Our investigation demonstrated the pivotal involvement of OsWRKY71 in Bph15-mediated resistance and provided new insights into the rice defense mechanisms against BPH.

BackgroundLiver metastasis is one of the primary causes of death for the patients with pancreatic neuroendocrine tumors (PNETs). However, no curative therapy has been developed so far.MethodsThe anti-tumor efficacy of a genetically engineered tumor-targeting Salmonella typhimurium YB1 was evaluated on a non-functional INR1G9 liver metastasis model. Differential inflammatory factors were screened by Cytometric Bead Array. Antibody depletion assay and liver-targeted AAV2/8 expression vector were used for functional evaluation of the differential inflammatory factors.ResultsWe demonstrated that YB1 showed significant anti-tumor efficacy as a monotherapy. Since YB1 cannot infect INR1G9 cells, its anti-tumor effect was possibly due to the modulation of the tumor immune microenvironment. Two inflammatory factors IFNγ and CCL2 were elevated in the liver after YB1 administration, but only IFNγ was found to be responsible for the anti-tumor effect. Liver-targeted expression of IFNγ caused the activation of macrophages and NK cells, and reproduced the therapeutic effect of YB1 on liver metastasis.ConclusionWe demonstrated that YB1 may exhibit anti-tumor effect mainly based on IFNγ induction. Targeted IFNγ therapy can replace YB1 for treating liver metastasis of PNETs.

The effect of probiotics on postoperative infectious complications and nutritional status in patients with gastric cancer is still controversial, and a comprehensive search and analysis of the current relevant evidence is necessary. Our study aimed to define the effects of probiotics on surgical outcomes in gastric cancer patients undergoing surgery. Up to June 20, 2023, Embase, PubMed, Web of Science, and Cochrane databases were searched for randomized controlled trials of probiotics in gastric cancer patients undergoing surgery. Relative risk (RR) or mean difference (MD) was used to calculate the effect sizes using RevMan 5.3. A total of nine studies reporting on 861 participants were included. Perioperative supplementation with probiotics did not improve weight loss (MD 0.73 kg; 95% CI: −0.56, 2.02) or serum prealbumin levels (MD 9.48 mg/L 95% CI: −3.43, 22.40), but did reduce the incidence of postoperative infectious complications (RR 0.46, 95% CI 0.28, 0.77), shorten the time to first exhaust (MD −11.27 h; 95% CI: −16.83, −5.70), the time to first defecation (MD −15.71 h; 95% CI: −25.62, −5.79), and the length of hospital stay (MD −0.94 days; 95% CI: −1.33, −0.55), and increase serum albumin levels (MD 0.73 g/L; 95% CI: 0.01, 1.46) in gastric cancer patients undergoing surgery. Probiotics are effective in preventing postoperative infectious complications, promoting postoperative recovery, and improving nutritional status in gastric cancer patients undergoing surgery. Our study highlights the importance of probiotics for healthcare systems and offers a potential strategy to improve the prognosis and reduce the medical burden of gastric cancer patients undergoing surgery.

BackgroundMalignant bone tumors are a type of cancer with varying malignancy and prognosis. Accurate diagnosis and classification are crucial for treatment and prognosis assessment. Machine learning has been introduced for early differential diagnosis of malignant bone tumors, but its performance is controversial. This systematic review and meta-analysis aims to explore the diagnostic value of machine learning for malignant bone tumors.MethodsPubMed, Embase, Cochrane Library, and Web of Science were searched for literature on machine learning in the differential diagnosis of malignant bone tumors up to October 31, 2022. The risk of bias assessment was conducted using QUADAS-2. A bivariate mixed-effects model was used for meta-analysis, with subgroup analyses by machine learning methods and modeling approaches.ResultsThe inclusion comprised 31 publications with 382,371 patients, including 141,315 with malignant bone tumors. Meta-analysis results showed machine learning sensitivity and specificity of 0.87 [95% CI: 0.81,0.91] and 0.91 [95% CI: 0.86,0.94] in the training set, and 0.83 [95% CI: 0.74,0.89] and 0.87 [95% CI: 0.79,0.92] in the validation set. Subgroup analysis revealed MRI-based radiomics was the most common approach, with sensitivity and specificity of 0.85 [95% CI: 0.74,0.91] and 0.87 [95% CI: 0.81,0.91] in the training set, and 0.79 [95% CI: 0.70,0.86] and 0.79 [95% CI: 0.70,0.86] in the validation set. Convolutional neural networks were the most common model type, with sensitivity and specificity of 0.86 [95% CI: 0.72,0.94] and 0.92 [95% CI: 0.82,0.97] in the training set, and 0.87 [95% CI: 0.51,0.98] and 0.87 [95% CI: 0.69,0.96] in the validation set.ConclusionMachine learning is mainly applied in radiomics for diagnosing malignant bone tumors, showing desirable diagnostic performance. Machine learning can be an early adjunctive diagnostic method but requires further research and validation to determine its practical efficiency and clinical application prospects.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023387057.

Brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most destructive pests of rice. Non-coding RNA plays an important regulatory role in various biological processes. However, comprehensive identification and characterization of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in BPH-infested rice have not been performed. Here, we performed a genome-wide analysis of lncRNAs and circRNAs in BPH6-transgenic (resistant, BPH6G) and Nipponbare (susceptible, NIP) rice plants before and after BPH feeding (early and late stage) via deep RNA-sequencing. A total of 310 lncRNAs and 129 circRNAs were found to be differentially expressed. To reveal the different responses of resistant and susceptible rice to BPH herbivory, the potential functions of these lncRNAs and circRNAs as competitive endogenous RNAs (ceRNAs) were predicted and investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Dual-luciferase reporter assays revealed that miR1846c and miR530 were targeted by the lncRNAs XLOC_042442 and XLOC_028297, respectively. In responsive to BPH infestation, 39 lncRNAs and 21 circRNAs were predicted to combine with 133 common miRNAs and compete for miRNA binding sites with 834 mRNAs. These mRNAs predictably participated in cell wall organization or biogenesis, developmental growth, single-organism cellular process, and the response to stress. This study comprehensively identified and characterized lncRNAs and circRNAs, and integrated their potential ceRNA functions, to reveal the rice BPH-resistance network. These results lay a foundation for further study on the functions of lncRNAs and circRNAs in the rice-BPH interaction, and enriched our understanding of the BPH-resistance response in rice.

Introduction: Seasonal—interannual variations in surface water storage revealed by the Gravity Recovery and Climate Experiment (GRACE) satellites have received less attention than storage trends in the literature. We focus on six large endorheic basins and develop variability attribution diagnostics against independent precipitation and evapotranspiration (hereafter P and E) datasets.Methods: We generate a flux-inferred storage (FIS), representing the integral of the component flux anomalies into and out of a region, enabling a comparison between the P and E contributions to GRACE water storage anomalies on seasonal to interannual timescales. Additionally, a monthly budget closure approach is applied, giving self-consistent coupled water and energy exchanges from 2002 to 2020.Results: On seasonal timescales, P and E data show insufficient cancellation, implying over-large seasonal variations in surface storage. In most basins, P drives the seasonal storage cycle with E dampening storage amplitudes, although in the Caspian Basin, seasonal storage is driven by E, with P remaining seasonally constant when integrated over the whole drainage basin. Budget closure mostly adjusts E, which has larger uncertainties, in fitting the GRACE data. On year-to-year and multi-year timescales, there is a strong correlation between P-driven storage and the observed GRACE variability, which ranges between 0.55 and 0.88 across all basins, and this is maintained after budget closure. However, storage changes driven by P alone from GPCP are too large compared to GRACE, with E data from FLUXCOM generally having only very weakly compensating interannual variations. After budget closure, interannual E variability is substantially increased. Closed energy budgets often show interannual amplitudes, partly driven by radiation and partly by water budget variation through shared latent heat losses, although these have not been independently verified.Discussion: Although water flux trends cannot be detected with significance due to the large interannual variability, the strong agreement between multi-annual GRACE storage and precipitation variations, especially over the Caspian basin, lends no support to the suggestion that E changes driven by climate change are responsible for water storage trends seen by GRACE.

BackgroundGlioblastoma (GBM) is adults’ most common and fatally malignant brain tumor. The heterogeneity is the leading cause of treatment failure. However, the relationship between cellular heterogeneity, tumor microenvironment, and GBM progression is still elusive.MethodsIntegrated analysis of single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (stRNA-seq) of GBM were conducted to analyze the spatial tumor microenvironment. We investigated the subpopulation heterogeneity of malignant cells through gene set enrichment analyses, cell communications analyses, and pseudotime analyses. Significantly changed genes of the pseudotime analysis were screened to create a tumor progress-related gene risk score (TPRGRS) using Cox regression algorithms in the bulkRNA-sequencing(bulkRNA-seq) dataset. We combined the TPRGRS and clinical characteristics to predict the prognosis of patients with GBM. Furthermore, functional analysis was applied to uncover the underlying mechanisms of the TPRGRS.ResultsGBM cells were accurately charted to their spatial locations and uncovered their spatial colocalization. The malignant cells were divided into five clusters with transcriptional and functional heterogeneity, including unclassified malignant cells and astrocyte-like, mesenchymal-like, oligodendrocytes-progenitor-like, and neural-progenitor-like malignant cells. Cell-cell communications analysis in scRNA-seq and stRNA-seq identified ligand-receptor pairs of the CXCL, EGF, FGF, and MIF signaling pathways as bridges implying that tumor microenvironment may cause malignant cells’ transcriptomic adaptability and disease progression. Pseudotime analysis showed the differentiation trajectory of GBM cells from proneural to mesenchymal transition and identified genes or pathways that affect cell differentiation. TPRGRS could successfully divide patients with GBM in three datasets into high- and low-risk groups, which was proved to be a prognostic factor independent of routine clinicopathological characteristics. Functional analysis revealed the TPRGRS associated with growth factor binding, cytokine activity, signaling receptor activator activity functions, and oncogenic pathways. Further analysis revealed the association of the TPRGRS with gene mutations and immunity in GBM. Finally, the external datasets and qRT-PCR verified high expressions of the TPRGRS mRNAs in GBM cells.ConclusionOur study provides novel insights into heterogeneity in GBM based on scRNA-seq and stRNA-seq data. Moreover, our study proposed a malignant cell transition-based TPRGRS through integrated analysis of bulkRNA-seq and scRNA-seq data, combined with the routine clinicopathological evaluation of tumors, which may provide more personalized drug regimens for GBM patients.

We present the China Ocean ReAnalysis version 2 (CORA2) in this paper. We compare CORA2 with its predecessor, CORA1, and with other ocean reanalysis products created between 2004 and 2019 [GLORYS12v1 (Global Ocean reanalysis and Simulation), HYCOM (HYbrid Coordinate Ocean Model), GREP (Global ocean Reanalysis Ensemble Product), SODA3 (Simple Ocean Data Assimilation, version 3), and ECCO4 (Estimating the Circulation and Climate of the Ocean, version 4)], to demonstrate its improvements and reliability. In addition to providing tide and sea ice signals, the accuracy and eddy kinetic energy (EKE) of CORA2 are also improved owing to an enhanced resolution of 9 km and updated data assimilation scheme compared with CORA1. Error analysis shows that the root-mean-square error (RMSE) of CORA2 sea-surface temperature (SST) remains around 0.3°C, which is comparable to that of GREP and smaller than those of the other products studied. The subsurface temperature (salinity) RMSE of CORA2, at 0.87°C (0.15 psu), is comparable to that of SODA3, smaller than that of ECCO4, and larger than those of GLORYS12v1, HYCOM, and GREP. CORA2 and GLORYS12v1 can better represent sub-monthly-scale variations in subsurface temperature and salinity than the other products. Although the correlation coefficient of sea-level anomaly (SLA) in CORA2 does not exceed 0.8 in the whole region, as those of GREP and GLORYS12v1 do, it is more effective than ECCO4 and SODA3 in the Indian Ocean and Pacific Ocean. CORA2 can reproduce the variations in steric sea level and ocean heat content (OHC) on the multiple timescales as the other products. The linear trend of the steric sea level of CORA2 is closer to that of GREP than that of the other products, and the long-term warming trends of global OHC in the high-resolution CORA2 and GLORYS12v1 are greater than those in the low-resolution EN4 and GREP. Although CORA2 shows overall poorer performance in the Atlantic Ocean, it still achieves good results from 2009 onward. We plan to further improve CORA2 by assimilating the best available observation data using the incremental analysis update (IAU) procedure and improving the SLA assimilation method.

IntroductionResveratrol (RES) is a polyphenol organic compound with antioxidant and anti-inflammatory properties. This study aimed to determine whether and how RES can alleviate liver injury in lipopolysaccharide (LPS)-induced gibel carp.MethodsGibel carp were fed a diet with or without RES and were cultured for 8 weeks, followed by LPS injection.Results and discussionThe results suggested that RES attenuated the resulting oxidative stress and inflammation by activating the Nrf2/Keap1 pathway and inhibiting the NF-κB pathway, as confirmed by changes in oxidative stress, inflammation-related gene expression, and antioxidant enzyme activity. Furthermore, RES cleared damaged mitochondria and enhanced mitochondrial biogenesis to mitigate reactive oxygen species (ROS) accumulation by upregulating the SIRT1/PGC-1α and PINK1/Parkin pathways and reducing p62 expression. Overall, RES alleviated LPS-induced oxidative stress and inflammation in gibel carp through mitochondria-related mechanisms.

Objective: To analyze the cranial computed tomography (CT) imaging features of patients with primary ciliary dyskinesia (PCD) who have exudative otitis media (OME) and sinusitis using a deep learning model for early intervention in PCD.Methods: Thirty-two children with PCD diagnosed at the Children’s Hospital of Fudan University, Shanghai, China, between January 2010 and January 2021 who had undergone cranial CT were retrospectively analyzed. Thirty-two children with OME and sinusitis diagnosed using cranial CT formed the control group. Multiple deep learning neural network training models based on PyTorch were built, and the optimal model was trained and selected to observe the differences between the cranial CT images of patients with PCD and those of general patients and to screen patients with PCD.Results: The Swin-Transformer, ConvNeXt, and GoogLeNet training models had optimal results, with an accuracy of approximately 0.94; VGG11, VGG16, VGG19, ResNet 34, and ResNet 50, which are neural network models with fewer layers, achieved relatively strong results; and Transformer and other neural networks with more layers or neural network models with larger receptive fields exhibited a relatively weak performance. A heat map revealed the differences in the sinus, middle ear mastoid, and fourth ventricle between the patients with PCD and the control group. Transfer learning can improve the modeling effect of neural networks.Conclusion: Deep learning-based CT imaging models can accurately screen for PCD and identify differences between the cranial CT images.

ObjectiveFor respiratory failure patients, mechanical ventilation (MV) is a life-saving therapy to maintain respiratory function. However, MV could also cause damage to pulmonary structures, result in ventilator-induced lung injury (VILI) and eventually progress to mechanical ventilation-induced pulmonary fibrosis (MVPF). Mechanically ventilated patients with MVPF are closely related to increased mortality and poor quality of life in long-term survival. Thus, a thorough understanding of the involved mechanism is necessary.MethodsWe used next-generation sequencing to identify differentially expressed non-coding RNAs (ncRNAs) in BALF EVs which were isolated from Sham and MV mice. Bioinformatics analysis was conducted to identify the engaged ncRNAs and related signaling pathways in the process of MVPF.ResultsWe found 1801 messenger RNAs (mRNA), 53 micro RNAs (miRNA), 273 circular RNAs (circRNA) and 552 long non-coding RNAs (lncRNA) in mice BALF EVs of two groups, which showed significant differential expression. TargetScan predicted that 53 differentially expressed miRNAs targeted 3105 mRNAs. MiRanda revealed that 273 differentially expressed circRNAs were associated with 241 mRNAs while 552 differentially expressed lncRNAs were predicated to target 20528 mRNAs. GO, KEGG pathway analysis and KOG classification showed that these differentially expressed ncRNA-targeted mRNAs were enriched in fibrosis related signaling pathways and biological processes. By taking the intersection of miRNAs target genes, circRNAs target genes and lncRNAs target genes, we found 24 common key genes and 6 downregulated genes were confirmed by qRT-PCR.ConclusionsChanges in BALF-EV ncRNAs may contribute to MVPF. Identification of key target genes involved in the pathogenesis of MVPF could lead to interventions that slow or reverse fibrosis progression.

The renin-angiotensin system (RAS) is a major classic therapeutic target for cardiovascular diseases. In addition to the circulating RAS, local tissue RAS has been identified in various tissues and plays roles in tissue inflammation and tissue fibrosis. (Pro)renin receptor (PRR) was identified as a new member of RAS in 2002. Studies have demonstrated the effects of PRR and its soluble form in local tissue RAS. Moreover, as an important part of vacuolar H+-ATPase, it also contributes to normal lysosome function and cell survival. Evidently, PRR participates in the pathogenesis of cardiovascular diseases and may be a potential therapeutic target of cardiovascular diseases. This review focuses on the effects of PRR and its soluble form on the physiological state, hypertension, myocardial ischemia reperfusion injury, heart failure, metabolic cardiomyopathy, and atherosclerosis. We aimed to investigate the possibilities and challenges of PRR and its soluble form as a new therapeutic target in cardiovascular diseases.

Egocentric distance perception has been widely concerned by researchers in the field of spatial perception due to its significance in daily life. The frame of perception involves the perceived distance from an observer to an object. Over the years, researchers have been searching for an optimal way to measure the perceived distance and their contribution constitutes a critical aspect of the field. This paper summarizes the methodological findings and divides the measurement methods for egocentric distance perception into three categories according to the behavior types. The first is Perceptional Method, including successive equal-appearing intervals of distance judgment measurement, verbal report, and perceptual distance matching task. The second is Directed Action Method, including blind walking, blind-walking gesturing, blindfolded throwing, and blind rope pulling. The last one is Indirect Action Method, including triangulation-by-pointing and triangulation-by-walking. In the meantime, we summarize each method’s procedure, core logic, scope of application, advantages, and disadvantages. In the end, we discuss the future concerns of egocentric distance perception.

Frizzled (FZD) proteins are receptors for the WNT family ligands. Inherited human diseases and genetic experiments using knockout mice have revealed a central role of FZDs in multiple aspects of embryonic development and tissue homeostasis. Misregulated FZD signaling has also been found in many cancers. Recent studies on three out of the ten mammalian FZDs in melanoma have shown that they promote tumor cell proliferation and invasion, via the activation of the canonical WNT/β-catenin or non-canonical PCP signaling pathway. In this concise review, we summarize our current knowledge of individual FZDs in melanoma, discuss the involvement of both the canonical and non-canonical pathways, and describe ongoing efforts to target the FZD receptors for melanoma treatment.

Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of bone metabolic disorders and bone fracture due to disease progression and clinical treatment. The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors, now greatly prescribed for the treatment of T2DM, on bone metabolism is not clear. This study aimed to explore the possible influence of bone metabolic disorder and the underlying mechanism through a comparison of three different SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) in the treatment of type 2 diabetic mice. For the in vivo experiments, four groups (DM, DM+Cana, DM+Dapa, and DM+Empa) were established using micro-CT to detect the bone microarchitecture and bone-related parameters. The study results indicated that canagliflozin, but not dapagliflozin or empagliflozin, increased bone mineral density (p

BackgroundProgrammed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors displayed considerable advantages in neoadjuvant therapy of non-small cell lung cancer (NSCLC), but the specific application of neoadjuvant immunotherapy has not been well determined, and the long-term prognostic data of neoadjuvant immunochemotherapy combined with surgical resection of NSCLC remains limited. In this study, we intended to assess the efficacy of the neoadjuvant therapy of the PD-1 inhibitor and long-term prognosis in patients with resectable NSCLC.MethodsWe retrospectively analyzed NSCLC surgical patients treated with neoadjuvant therapy in our hospital, and divided them into a neoadjuvant chemotherapy group and a neoadjuvant immunotherapy combined with chemotherapy group. The propensity score matching method was used to evaluate the effectiveness of immunotherapy combined with chemotherapy in the treatment of resectable lung cancer, and the long-term prognosis of these two groups was compared.ResultsA total of 62 cases were enrolled, including 20 patients (20/62, 32.26%) in the immunotherapy group and 42 patients (42/62, 67.74%) in the chemotherapy group. The clinical baseline data of these two groups were balanced. In the immunotherapy group, all patients had tumor regression in imaging finding (tumor regression ratio: 11.88% - 75.00%). In the chemotherapy group, 30 patients had tumor regression (tumor regression ratio: 2.70% - 58.97%). The R0 removal rates of cancers were comparable between the immunotherapy group and chemotherapy group (19/20, 95.00% vs. 39/42, 92.86%, P=1.000). The two groups were balanced in complete minimally invasive surgery, pneumonectomy, operative duration, blood loss, postoperative complications, and hospital stay. The immunotherapy group had more sleeve resection (36.84% vs. 10.26%, p=0.039) including bronchial sleeve and vascular sleeve, higher pathological complete response (pCR) rate (57.89% vs. 5.13%, P

BackgroundIndocyanine green (ICG) imaging-guided lymphadenectomy has been introduced in gastric cancer (GC) surgery and its clinical value remains controversial. The aim of this study is to evaluate the efficacy of ICG fluorescence imaging-guided lymphadenectomy in radical gastrectomy for GC.MethodsStudies comparing lymphadenectomy in radical gastrectomy between use and non-use of ICG fluorescence imaging up to July 2022 were systematically searched from PubMed, Web of Science, Embase and Cochrane Library. A pooled analysis was performed for the available data regarding the baseline features, the number of retrieved lymph nodes (LNs), the number of metastatic LNs and surgical outcomes as well as oncological outcomes. RevMan 5.3 software was used to perform the statistical analysis. Quality evaluation and publication bias were also conducted.Results17 studies with a total of 2274 patients (1186 in the ICG group and 1088 in the control group) undergoing radical gastrectomy and lymphadenectomy were included. In the pooled analysis, the baseline features were basically comparable. However, the number of retrieved LNs in the ICG group was significantly more than that in the control group (MD = 7.41, 95% CI = 5.44 to 9.37, P < 0.00001). No significant difference was found between the ICG and control groups in terms of metastatic LNs (MD = -0.05, 95% CI = -0.25 to 0.16, P = 0.65). In addition, the use of ICG could reduce intraoperative blood loss (MD = -17.96, 95% CI = -27.89 to -8.04, P = 0.0004) without increasing operative time (P = 0.14) and overall complications (P = 0.10). In terms of oncological outcomes, the use of ICG could reduce the overall recurrence rate (OR = 0.50; 95% CI 0.28-0.89; P = 0.02) but could not increase the 2-year overall survival rate (OR = 1.25; 95% CI 0.72-2.18; P = 0.43).ConclusionsICG imaging-guided lymphadenectomy is valuable for complete LNs dissection in radical gastrectomy for GC. However, more high-quality randomized controlled trials are needed to confirm this benefit.

The frequency of chronic cutaneous wounds are sharply increasing in aging populations. Patients with age-related diseases, such as diabetes, tumors, renal failure and stroke are prone to soft tissue and skin injury, compounded by slowed healing in aging. Imbalance of wound inflammation, loss of growth factor secretion, and impairment of tissue repair abilities are all possible reasons for failed healing. Therefore, it is vital to explore novel approaches to accelerate wound healing. Platelet-rich plasma (PRP) as a cell therapy has been widely applied for tissue repair and regeneration. PRP promotes wound healing by releasing antimicrobial peptides, growth factors and micro-RNAs. Medical evidence indicates that autologous platelet-rich plasma (au-PRP) can promote wound healing effectively, safely and rapidly. However, its clinical application is usually restricted to patients with chronic cutaneous wounds, generally because of other severe complications and poor clinical comorbidities. Allogeneic platelet-rich plasma (al-PRP), with abundant sources, has demonstrated its superiority in the field of chronic wound treatment. Al-PRP could overcome the limitations of au-PRP and has promising prospects in clinical applications. The aim of this review is to summarize the current status and future challenges of al-PRP in chronic cutaneous wound management. We also summarized clinical cases to further describe the application of al-PRP for chronic wounds in clinical practice.