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BackgroundThe treatment of vitiligo is complex, and providing guidance based on lifestyle habits is a good option that has not been summarized or analyzed.ObjectiveTo elucidate the relationship between vitiligo and lifestyle factors.MethodsFour databases (PubMed, Embase, Cochrane, and China National Knowledge Internet) were searched for articles published between 1980 and December 2022. Keywords such as smoking, drinking, exercise, diet, and sleep were used.ResultsBased on the search strategy, 875 relevant studies were retrieved, and 73 were included in this study, of which 41 studies with 8,542 patients with vitiligo were included in the meta-analysis. Vitamin C [mean difference (MD), −0.342; 95% confidence interval (CI), −1.090–0.407; p >0.05), folic acid (MD, −1.463; 95% CI, −7.133–4.208; p >0.05), and selenium (MD, 0.350; 95% CI, −0.687–1.387; p >0.05) levels did not differ between the groups. Vitamin E (MD, −1.408; 95% CI, −2.611–−0.206; p

ObjectiveTo establish a predictive model for distinguishing testicular benign or yolk sac tumors in children.MethodsWe retrospectively analyzed data for 119 consecutive patients with unilateral testicular tumors treated at a single institution from June 2014 to July 2020. The patients were divided into the benign (n = 90) and yolk sac (n = 29) tumor groups based on the pathological diagnosis. We recorded patient age, serum markers [serum alpha-fetoprotein (AFP), human chorionic gonadotropin], and tumor ultrasonic findings (maximum diameter, ultrasonic echo, blood flow signal). Predictive factors were identified using descriptive statistical methods. A nomogram was established for preoperative prediction. An additional 46 patients were used as a validation cohort to verify the model.ResultsPatients with testicular yolk sac tumors were younger (median age: 14.0 vs. 34.0 months, P = 0.001) and had a higher incidence of elevated AFP levels (93.1% vs. 2.2%, P

IntroductionAdamantinomatous craniopharyngioma (ACP) is difficult to cure completely and prone to recurrence after surgery. Ferroptosis as an iron-dependent programmed cell death, may be a critical process in ACP. The study aimed to screen diagnostic markers related to ferroptosis in ACP to improve diagnostic accuracy.MethodsGene expression profiles of ACP were obtained from the gene expression omnibus (GEO) database. Limma package was used to analyze the differently expressed genes (DEGs). The intersection of DEGs and ferroptosis-related factors was obtained as differently expressed ferroptosis-related genes (DEFRGs). Enrichment analysis was processed, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), disease ontology (DO), gene set enrichment analysis (GSEA), and Gene Set Variation Analysis (GSVA) analysis. Machine learning algorithms were undertaken for screening diagnostic markers associated with ferroptosis in ACP. The levels of DEFRGs were verified in ACP patients. A nomogram was drawn to predict the relationship between key DEFRG expression and risk of disease. The disease groups were then clustered by consensus clustering analysis.ResultsDEGs were screened between ACP and normal samples. Ferroptosis-related factors were obtained from the FerrDb V2 and GeneCard databases. The correlation between DEFRGs and ferroptosis markers was also confirmed. A total of 6 overlapped DEFRGs were obtained. Based on the results of the nomogram, CASP8, KRT16, KRT19, and TP63 were the protective factors of the risk of disease, while GOT1 and TFAP2C were the risk factors. According to screened DEFRGs, the consensus clustering matrix was differentiated, and the number of clusters was stable. CASP8, KRT16, KRT19, and TP63, were upregulated in ACP patients, while GOT1 was downregulated. CASP8, KRT16, KRT19, TP63, CASP8, and GOT1 affect multiple ferroptosis marker genes. The combination of these genes might be the biomarker for ACP diagnosis via participating ferroptosis process.DiscussionFerroptosis-related genes, including CASP8, KRT16, KRT19, TP63, and GOT1 were the potential markers for ACP, which lays the theoretical foundation for ACP diagnosis.

Infection is one of the leading causes of death in patients with hematologic cancers. Hematologic cancer patients with compromised immune systems are already susceptible to infections, which come on even more rapidly and are difficult to control after they develop neutrophil deficiencies from high-dose chemotherapy. After patients have developed an infection, the determination of the type of infection becomes a priority for clinicians. In this review, we summarize the biomarkers currently used for the prediction of infections in patients with hematologic cancers; procalcitonin, CD64, cytokines, and CD14 et al. can be used to determine bacterial infections, and (1-3)-β-D-glucan and galactomannan et al. can be used as a determination of fungal infections. We have also focused on the use of metagenomic next-generation sequencing in infections in patients with hematologic cancers, which has excellent clinical value in infection prediction and can detect microorganisms that cannot be detected by conventional testing methods such as blood cultures. Of course, we also focused on infection biomarkers that are not yet used in blood cancer patients but could be used as a future research direction, e.g., human neutrophil lipocalin, serum amyloid A, and heparin-binding protein et al. Finally, clinicians need to combine multiple infection biomarkers, the patient’s clinical condition, local susceptibility to the type of infection, and many other factors to make a determination of the type of infection.

IntroductionNadofaragene firadenovec (Ad-IFNα/Syn3) is now approved for BCG-unresponsive bladder cancer (BLCA). IFNα is a pleiotropic cytokine that causes direct tumor cell killing via TRAIL-mediated apoptosis, angiogenesis inhibition, and activation of the innate and adaptive immune system. We established an immunocompetent murine BLCA model to study the effects of murine adenoviral IFNα (muAd-Ifnα) gene therapy on cancer cells and the tumor microenvironment using a novel murine equivalent of Nadofaragene firadenovec (muAd-Ifnα).MethodsTumors were induced by instilling MB49 cells into the bladders of mice; luciferase imaging confirmed tumor development. Mice were treated with adenovirus control (Ad-Ctrl; empty vector), or muAd-Ifnα (3x1011 VP/mL), and survival analysis was performed. For single-cell sequencing (scRNAseq) analysis (72h), bladders were harvested and treated with collagenase/hyaluronidase and TrypLE for cell dissociation. Single cells were suspended in PBS/1% FBS buffer; viability was assessed with Vicell cell counter. scRNAseq analysis was performed using 10X genomics 3’ sequencing. Raw RNAseq data were pre-processed using Cell Ranger single-cell software. Seurat (R package) was used to normalize and cluster the scRNA data. Pooled differential gene expression analysis in specific cell clusters was performed with DESeq2.ResultsWe identified 16 cell clusters based on marker expression which were grouped into epithelial (tumor), uroplakin-enriched, endothelial, T-cells, neutrophils, and macrophage clusters. Top differentially expressed genes between muAd-Ifnα and Ad-Ctrl were identified. Within the specific cell clusters, IPA analysis revealed significant differences between muAd-Ifnα and control. IFNα signaling and hypercytokinemia/chemokinemia were upregulated in all clusters. Cell death pathways were upregulated in tumor and endothelial clusters. T-cells demonstrated upregulation of the immunogenic cell death signaling pathway and a decrease in the Th2 pathway genes. Macrophages showed upregulation of PD1/PD-L1 pathways along with downregulation of macrophage activation pathways (alternate and classical). Multiplex immunofluorescence confirmed increased infiltration with macrophages in muAd-Ifnα treated tumors compared to controls. PD1/PD-L1 expression was reduced at 72h.DiscussionThis single-cell analysis builds upon our understanding of the impact of Ad-IFNα on tumor cells and other compartments of the microenvironment. These data will help identify mechanisms to improve patient selection and therapeutic efficacy of Nadofaragene firadenovec.

IntroductionProlonged mechanical ventilation in intensive care units (ICUs) leads to increased morbidity, higher mortality rates, and elevated healthcare costs. Predicting successful weaning from mechanical ventilation with accuracy is essential for optimizing resource use and improving patient outcomes. The International Classification of Functioning, Disability and Health (ICF) framework offers a holistic perspective on health conditions and can be adapted to identify key predictors of weaning readiness. This study aims to develop a Delphi-based core predictor set for weaning in critically ill patients, utilizing the ICF model.Methods and analysisThe core predictor set development comprises three steps: (1) Literature review and expert consultation to gather weaning predictors, (2) Predictor alignment with ICF categories per established rules, and (3) Three-round Delphi survey with a multidisciplinary team. A systematic review across major databases will be conducted to identify predictors related to weaning predictors in critically ill adults from cohort studies, trials, and reviews. Predictors will then be categorized within ICF domains. A multidisciplinary expert panel will evaluate the relevance of each predictor using a 9-point Likert scale to achieve consensus.DiscussionThis study will contribute to the development of a standardized, evidence-based predictor set for weaning readiness in critically ill patients. Using the ICF framework, this study aims to encompass the complex factors that influence weaning, thereby enabling personalized care plans and improving weaning outcomes. The Delphi methodology guarantees a thorough, iterative process for building consensus by integrating diverse clinical perspectives.ConclusionThe proposed Delphi-based study protocol aims to establish a core set of predictors for weaning in the ICU setting, guided by the ICF model. Successful implementation of this predictor set could enhance decision-making around weaning trials, reduce unnecessary ventilation days, and ultimately improve patient outcomes and healthcare efficiency. Future validation and implementation studies will be essential to confirm the utility and generalizability of this predictor set in clinical practice.

Implant surface designs have advanced to address challenges in oral rehabilitation for healthy and compromised bone. Several studies have analyzed the effects of altering material surfaces on osteogenic differentiation. However, the crucial role of osteoclasts in osseointegration has often been overlooked. Overactive osteoclasts can compromise implant stability. In this study, we employed a silanization method to alter pure titanium to produce a surface loaded with the antimicrobial peptide GL13K that enhanced biocompatibility. Pure titanium (Ti), silanization-modified titanium, and GL13K-modified titanium (GL13K-Ti) were co-cultured with macrophages. Our findings indicated that GL13K-Ti partially inhibited osteoclastogenesis and expression of osteoclast-related genes and proteins by limiting the formation of the actin ring, an important structure for osteoclast bone resorption. Our subsequent experiments confirmed the epigenetic role in regulating this process. GL13K-Ti was found to impact the degree of methylation modifications of H3K27 in the NFATc1 promoter region following RANKL-induced osteoclastic differentiation. In conclusion, our study unveils the potential mechanism of methylation modifications, a type of epigenetic regulatory modality, on osteoclastogenesis and activity on the surface of a material. This presents novel concepts and ideas for further broadening the clinical indications of oral implants and targeting the design of implant surfaces.

With the increasing variation of the network topology and the high complexity of the processing measurement data, the transient voltage stability assessment of the new power system is facing significant challenges in low accuracy and high time costs. To address the shortcomings of the existing method and apply it to online assessment, this paper proposes an assessment method based on feature learning for disturbance signal energy (DSE) from bus voltages. Firstly, the relationship between DSE and system transient voltage stability is established, and the calculation of DSE from bus voltage time series is detailed. Subsequently, a transient voltage stability assessment method based on the ID3 Decision Tree algorithm and DSE is proposed. Finally, by employing the Support Vector Machine (SVM) to construct the optimal boundary in the feature space formed by the key buses, the transient voltage stability margin (TVSM) for specific scenarios is proposed. Simulation results on the IEEE 39-bus system demonstrate that the proposed method can rapidly and accurately assess the transient voltage stability of the system and calculate the stability margin, providing intuitive and interpretable results with high engineering application value.

BackgroundThe global status of chronic kidney disease (CKD) is underestimated, particularly the burden on adolescents and young adults (early-onset, aged 15–39).ObjectiveWe aim to investigate the pattern and trend of early-onset CKD from 1990 to 2019.MethodsWe analyzed age-specific rates of early-onset CKD incidence, death, and disability-adjusted life years (DALY) using Global Burden of Disease Study 2019 data. We examined the global, regional, national, gender-based, age group-based, and temporal changes of early-onset CKD burden from 1990 to 2019, as well as proportional DALY attributions of various risk factors.ResultsFrom 1990 to 2019, the global age-specific incidence rate (per 100,000 population) significantly increased from 25.04 (95% confidence interval 18.51, 31.65) to 32.21 (23.73, 40.81) for early-onset CKD. However, the global age-specific death rate significantly decreased from 2.96 (2.76, 3.15) to 2.86 (2.61, 3.11), and the age-specific DALY rate remained stable. Regarding sociodemographic indexes (SDI), countries with middle SDI had the highest incidence rates and the fastest increasing trends, while those with low and low-middle SDI experienced the highest death and DALY rates. Women had a generally higher age-specific incidence rate than men, whereas men showed higher age-specific death and DALY rates. In addition, the burdens of CKD increased with age among adolescents and young adults. Moreover, the main attributable risk factors for DALY of early-onset CKD were high systolic blood pressure (SBP), fasting plasma glucose (FPG), and body mass index (BMI).ConclusionThe age-specific incidence rate of early-onset CKD increased significantly from 1990 to 2019, and the age-specific DALY rate remained stable. High SBP, high FPG, and high BMI were the primary risk factors. Targeted prevention and healthcare measures should be developed considering age, gender, and region.

In this study, the storm surge processes and characteristics of Tide-Surge Interactions (TSI) induced by the sequential tropical cyclones (TCs) BARIJAT and MANGKHUT (2018) in the Northern South China Sea (NSCS) are investigated using the numerical model. By comparing the impacts of the two TCs, we find that storm surges are significantly influenced by multiple factors. Notably, bays situated on the western side of the cyclone’s landfall point exhibit a double peak pattern in storm surge. In addition, TSI exhibits a pronounced impact across bays affected by the two TCs, with amplitude fluctuations ranging from -0.3 to 0.3 meters and contributing approximately -5% to -20% to the peaks of storm surge. Comparative analysis of TSI variations reveals that tides act as the primary determinant, significantly influencing both the magnitude and period of TSI. Dynamic analysis further highlights that variations in TSI are dominated by barotropic pressure gradient and bottom friction stress. Moreover, TSI affects the frequency of storm surges, introducing high-frequency tidal signals to storm surges and reducing the frequency of storm surges.

ObjectiveCopy number changes at Chromosomal 16p13.11 have been implicated in a variety of human diseases including congenital cardiac abnormalities. The clinical correlation of copy number variants (CNVs) in this region with developmental abnormalities remains controversial as most of the patients inherit the duplication from an unaffected parent.MethodsWe performed CNV analysis on 164 patients with defective left-right (LR) patterning based on whole genome-exome sequencing (WG-ES) followed by multiplex ligation-dependent probe amplification (MLPA) validation. Most cases were accompanied with complex congenital heart disease (CHD).ResultsCNVs at 16p13.11 were identified in a total of 21 cases, accounting for 12.80% (21/164) evaluated cases. We observed a marked overrepresentation of chromosome 16p13.11 duplications in cases when compared with healthy controls according to literature reports (15/164, 9.14% versus 0.09% in controls). Notably, in two independent family trios, de novo 16p13.11 micro-duplications were identified in two patients with laterality defects and CHD. Moreover, 16p13.11 micro-duplication was segregated with the disease in a family trio containing 2 affected individuals. Notably, five coding genes, NOMO1, PKD1P3, NPIPA1, PDXDC1, and NTAN1, were potentially affected by micro-CNV at 16p13.11 in these patients.ConclusionOur study provides new family-trio based evidences to support 16p13.11 micro-duplications predispose individuals to defective cardiac left-right patterning and laterality disorder.

ObjectiveThis systematic review and meta-analysis aimed to investigate the association between circulating irisin levels and osteoporosis in women, exploring irisin’s potential role in the pathophysiology and management of osteoporosis.MethodWe searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, WanFang, and VIP databases up to January 2023. The inclusion criteria were observational studies reporting on circulating irisin levels in women. The standardized mean difference (SMD) and correlation coefficients with a 95% confidence interval (CI) were used as the main effect measures under a random-effects model. Heterogeneity was evaluated using the Cochrane Q statistic and the I2 statistics. Subgroup analysis and univariate meta-regression analysis were performed to identify the sources of heterogeneity. The quality of the included study was assessed by the Newcastle-Ottawa Score. The quality of evidence was evaluated using the GRADE system. Publication bias was assessed using Begg’s and Egger’s test, and the trim-and-fill method. Sensitivity analysis was performed to assess the stability of the results.ResultsFifteen studies with a total of 2856 participants met the criteria. The analysis showed significantly lower irisin levels in postmenopausal osteoporotic women compared to non-osteoporotic controls (SMD = -1.66, 95% CI: -2.43 to -0.89, P < 0.0001; I2 = 98%, P < 0.00001) and in postmenopausal individuals with osteoporotic fractures than in non-fractures controls (SMD = -1.25, 95% CI: -2.15 to -0.34, P = 0.007; I2 = 97%, P < 0.00001). Correlation analysis revealed that irisin levels positively correlated with lumbar spine BMD (r = 0.37, 95% CI: 0.18 to 0.54), femoral BMD (r = 0.30, 95% CI: 0.18 to 0.42), and femoral neck BMD (r = 0.31, 95% CI: 0.14 to 0.47) in women. Despite significant heterogeneity, the robustness of the results was supported by using the random effects model and sensitivity analysis.ConclusionThe current evidence suggests that lower irisin levels are significantly associated with osteoporosis and fracture in postmenopausal women, suggesting its utility as a potential biomarker for early detection of osteoporosis and therapeutic target. However, further high-quality prospective research controlling for confounding factors is needed to clarify the relationship between irisin levels and osteoporotic outcomes.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023410264.

Hippophae tibetana, belonging to the Elaeagnaceae family, is an endemic plant species of the Qinghai–Tibet Plateau, valued for its remarkable ecological restoration capabilities, as well as medicinal and edible properties. Despite being acknowledged as a useful species, its mitochondrial genome data and those of other species of the Elaeagnaceae family are lacking to date. In this study, we, for the first time, successfully assembled the mitochondrial genome of H. tibetana, which is 464,208 bp long and comprises 31 tRNA genes, 3 rRNA genes, 37 protein-coding genes, and 3 pseudogenes. Analysis of the genome revealed a high copy number of the trnM-CAT gene and a high prevalence of repetitive sequences, both of which likely contribute to genome rearrangement and adaptive evolution. Through nucleotide diversity and codon usage bias analyses, we identified specific genes that are crucial for adaptation to high-altitude conditions. Notably, genes such as atp6, ccmB, nad4L, and nad7 exhibited signs of positive selection, indicating the presence of unique adaptive traits for survival in extreme environments. Phylogenetic analysis confirmed the close relationship between the Elaeagnaceae family and other related families, whereas intergenomic sequence transfer analysis revealed a substantial presence of homologous fragments among the mitochondrial, chloroplast, and whole genomes, which may be linked to the high-altitude adaptation mechanisms of H. tibetana. The findings of this study not only enrich our knowledge of H. tibetana molecular biology but also advance our understanding of the adaptive evolution of plants on the Qinghai–Tibet Plateau. This study provides a solid scientific foundation for the molecular breeding, conservation, and utilization of H. tibetana genetic resources.

ObjectiveTo investigate the difference in the effectiveness and refraction of the foldable capsular buckle (FCB) in rhegmatogenous retinal detachment (RRD).MethodsSix patients with simple RRD were treated for FCB scleral buckling at Xiamen Eye Center of Xiamen University from October 2023 to February 2024. The parameters assessed included demographic data, clinical data such as preoperative ocular axis, corneal endothelial count, macular foveal thickness, operative time, preoperative and final follow-up intro ocular pressure (IOP), retinal attachment status, and postoperative complications. Refractive change before and after surgery, including sphere, cylinder degree, spherical equivalent, and absolute spherical equivalent difference were compared.ResultsAll six patients with sound retinal reattachment after FCB scleral buckling, including two men and four women, mean age 41.33 ± 12.40 years old, duration before surgery onset to 7.17 ± 7.16 days, FCB mean operation time 36.67 ± 13.07 min, Preoperative IOP mean 13.35 ± 2.64 mmHg and mean 21.12 ± 8.09 mmHg of final follow-up IOP; there was no significant difference between preoperative IOP and follow-up IOP (p = 0.050). The preoperative sphere range was −6.25 to +2.50 D, and the cylinder range was −2.50 to +1.00 D; the absolute spherical equivalent difference before and after was 1.60 ± 1.69 degrees.ConclusionFCB can achieve retinal reattachment and restore visual function in cases of RRD. The shorter duration of external scleral buckle compression with FCB suggests that FCB scleral buckling holds greater promise in the clinical treatment of RRD caused by retinal tears.

IntroductionScreening excellent bacterial strains for fermentation is the key to improving the nutritional value and bioavailability of soybean meal (SBM). This study investigated the application of Bacillus subtilis-fermented soybean meal (FSBM) on the feed of Pacific white shrimp (Litopenaeus vannamei).MethodsFSBM was used to replace 0%, 25%, 50%, 75%, and 100% fish meal, and the feeding trial was lasted for 8 weeks (initial weight: 0.9 g). Results and discussionThe amino acid profile in the whole shrimp body was tested. FSBM substitution only significantly reduced the content lysine in whole shrimp body, but increased the content of arginine. Fatty acid data showed that the content of n-6 PUFAs in whole shrimp was significantly increased by FSBM substitution. In muscle, FSBM substitution significantly reduced the content of MUFAs, but increased the content of PUFAs including C18:3n-3, C18:2n-6 and C20:4n-6. No hepatopancreas structure modifications appeared in the 25% group compared with the control group. Subsequently, we investigated the response patterns of different organs to FSBM substitution from antioxidant, endoplasmic reticulum stress and immunity. A high proportion of FSBM significantly reduced the content of GSH in hemolymph and hepatopancreas, while increased the mRNA expression of cat. FSBM substitution did not affect the activities of antioxidant enzymes in the intestine. However, the mRNA expression level of hsp70 in the intestine was significantly reduced by FSBM. In terms of immunity, the mRNA expression levels of lgbp and penaeidin in the hepatopancreas showed a significant linear increase trend. In muscle, high proportion of FSBM significantly increased the mRNA expression of imd. FSBM substitution did not significantly affect the expression of immune genes in the intestine. In terms of endoplasmic reticulum stress, FSBM substitution significantly increased the mRNA expression of eif2α in the hepatopancreas. In muscle, FSBM substitution inhibited the mRNA expression of bip. In the intestine, FSBM replacing 75% of fish meal significantly increased the mRNA expression of bip and ire1. In summary, this study indicated that when the fish meal content account for 40% in diets (dry weight), the screened Bacillus subtilis-FSBM can replace 25% of fish meal protein without reducing the antioxidant and immune abilities of shrimp.

Intestinal microbiota community is an important factor affecting the nutritional and health status of poultry, and its balance is crucial for improving the overall health of poultry. The study aimed to investigate the effect of dietary supplementation with Glycyrrhiza uralensis extract (GUE), Lactobacillus acidophilus (Lac) and their combination (GL) on growth performance and intestinal health in broilers in an 84-day feeding experiment. Supplementary 0.1% GUE and 4.5×107 CFU/g Lac significantly increased average daily gain (ADG), and GL (0.1% GUE and 4.5×107 CFU/g Lac) increased ADG and average daily feed intake (ADFI), and decreased feed conversion rate (FCR) in broilers aged 29 to 84 d and 1 to 84 d. Dietary GUE, Lac and GL increased the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity and decreased Malondialdehyde (MDA) content in the jejunum mucosa of broilers, and increased secretory IgA (sIgA) content in broilers at 84 d. Moreover, GUE, Lac and GL increased cecal microbial richness and diversity, and modulated microbial community composition. Both GUE and Lac reduced the harmful bacteria Epsilonbacteraeota, Helicobacter, and H. pullorum at 28 d and Proteobacteria, Escherichia, and E. coli at 84 d, while Lac and GL increased beneficial bacteria Lactobacillus and L. gallinarum at 28 d. Compared with individual supplementation, GL markedly increased the SOD activity and the sIgA content, and reduced Helicobacter and Helicobacter pullorum. In conclusion, GUE and Lactobacillus acidophilus as feed additives benefit growth performance and intestinal health, and their combined use shows an even more positive effect in broilers.

IntroductionA multitude of variables influence the healing of tooth extraction wounds, and delayed or non-healing extraction wounds might complicate later prosthodontic therapy. In this research, we analyzed the effects of systemic clopidogrel and aspirin alone or in combination on the healing of tooth extraction wounds in mice in order to provide experimental evidence for the healing of extraction wounds in patients who are clinically treated with the two medicines.Methods7-week-old ICR mice were randomly divided into four groups: control group (CON), clopidogrel group (CLOP), aspirin group (ASP), and clopidogrel combined with aspirin group (CLOP + ASP); left upper first molar was extracted, after which mice in 1 week of adaptive feeding, CLOP/ASP/CLOP + ASP groups were respectively administered with clopidogrel (10 mg/kg/d), aspirin (15 mg/kg/d), clopidogrel (10 mg/kg/d)+aspirin (15 mg/kg/d), and the control group was given an equal amount of 0.9% saline by gavage. Mice in each group were euthanized at 14 and 28 days postoperatively, and the maxilla was extracted. The tissues in the extraction sockets were examined using MicroCT and sectioned for HE staining, Masson staining, and TRAP staining, and immunohistochemistry staining (for TRAP, RANKL and osteoprotegerin).ResultsMicroCT analysis showed that at day 14, BS/BV was significantly lower in CLOP and CLOP + ASP groups compared to control and ASP groups, while BV/TV, Tb.Th was significantly higher. At day 28, BV/TV was significantly higher in the CLOP + ASP group compared to the CLOP group, with p < 0.05 for all results. HE staining and Masson trichrome staining findings revealed that at day 28, the mesenchyme in the bone was further decreased compared to that at day 14, accompanied with tightly arranged and interconnected bone trabeculae. In the quantitative analysis of Masson, the fraction of newly formed collagen was significantly higher in the CLOP group in comparison with that in the CON group (p < 0.05). At day 14, the ASP group had substantially more TRAP-positive cells than the CLOP and CLOP + ASP groups (p < 0.05). In immunohistochemical staining, RANKL expression was found to be significantly higher in the ASP group than those in the other three groups at day 28 (p < 0.05); OPG expression was significantly higher in the CLOP group and the CLOP + ASP group compared with that at day 14, and was higher than that in the ASP group at day 14 and day 28. OPG/RANKL was significantly higher in the CLOP and the CLOP + ASP groups than in the ASP group (p < 0.05).ConclusionClopidogrel alone promotes osteogenesis in the extraction wound, whereas aspirin alone inhibits alveolar bone healing. When the two drugs were combined, the healing effect of the extraction wound was more similar to that of the clopidogrel alone group. These results indicated that clopidogrel could promote the healing of the tooth extraction wound, and neutralize the adverse effect of ASP on osteogenesis when the two drugs were used in combination.

BackgroundThe gut microbiota plays a pivotal role in the development of diabetes and kidney disease. However, it is not clear how the intestinal microecological imbalance is involved in the context of diabetic kidney disease (DKD), the leading cause of renal failure.ObjectivesTo elucidate the gut microbial signatures associated with DKD progression towards end-stage renal disease (ESRD) and explore whether they could reflect renal dysfunction and psychological distress.MethodsA cross-sectional study was conducted to explore the gut microbial signatures of 29 DKD non-ESRD patients and 19 DKD ESRD patients compared to 20 healthy controls. Differential analysis was performed to detect distinct gut microbial alterations in diversities and taxon abundance of DKD with and without ESRD. Renal dysfunction was estimated by urea, creatinine, and estimated glomerular filtration rate. Psychological distress was assessed using the Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale.ResultsAlpha diversity indexes were reduced in DKD patients, particularly those with ESRD. Beta diversity analysis revealed that the gut microbial compositions of DKD patients were different with healthy individuals whereas similar compositions were observed in DKD patients. Taxon differential analysis showed that when compared with the controls, DKD patients exhibit distinct microbial profiles including reduced abundances of butyrate-produced, anti-inflammatory bacteria Faecalibacterium, Lachnospira, Roseburia Lachnoclostridium, and increased abundances of pro-inflammatory bacteria Collinsella, Streptococcus etc. These distinctive genera presented consistent associations with renal dysfunction, as well as psychological distress, especially in DKD patients.ConclusionsDKD patients, especially those who have progressed to ESRD, exhibit unique characteristics in their gut microbiota that are associated with both renal dysfunction and psychological distress. The gut microbiota may be a significant factor in the deterioration of DKD and its eventual progression to ESRD.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours, arising mainly from the interstitial cells of Cajal (ICCs) of the gastrointestinal tract. As radiotherapy and chemotherapy are generally ineffective for GISTs, the current primary treatment is surgical resection. However, surgical resection is not choice for most patients. Therefore, new therapeutic strategies are urgently needed. Targeted therapy, represented by tyrosine kinase inhibitors (TKIs), and immunotherapy, represented by immune checkpoint inhibitor therapies and chimeric antigen receptor T-cell immunotherapy (CAR-T), offer new therapeutic options in GISTs and have shown promising treatment responses. In this review, we summarize the molecular classification and immune microenvironment of GISTs and discuss the corresponding targeted therapy and immunotherapy options. This updated knowledge may provide more options for future therapeutic strategies and applications in GISTs.

All-trans retinoic acid (ATRA) plays a role in tissue development, neural function, reproduction, vision, cell growth and differentiation, tumor immunity, and apoptosis. ATRA can act by inducing autophagic signaling, angiogenesis, cell differentiation, apoptosis, and immune function. In the blood system ATRA was first used with great success in acute promyelocytic leukemia (APL), where ATRA differentiated leukemia cells into mature granulocytes. ATRA can play a role not only in APL, but may also play a role in other hematologic diseases such as immune thrombocytopenia (ITP), myelodysplastic syndromes (MDS), non-APL acute myeloid leukemia (AML), aplastic anemia (AA), multiple myeloma (MM), etc., especially by regulating mesenchymal stem cells and regulatory T cells for the treatment of ITP. ATRA can also increase the expression of CD38 expressed by tumor cells, thus improving the efficacy of daratumumab and CD38-CART. In this review, we focus on the mechanism of action of ATRA, its role in various hematologic diseases, drug combinations, and ongoing clinical trials.

BackgroundInflammatory scores are known to reflect the systemic inflammatory burden. Despite this, the association between the inflammatory score and the risk of all-cause and cardiovascular mortality in patients with metabolic syndrome (MetS) remains poorly understood. To address this gap in the literature, this study investigated this potential association between these two factors.MethodsA total of 3401 patients with MetS from the National Health and Nutrition Examination Survey (1999–2010) were enrolled. Survival status and cause of death were obtained by linking data from the National Death Index (NDI). The inflammatory score was calculated based on the sum of the Z-scores for white blood cell (WBC) count and C-reactive protein (CRP) at baseline. The patients were divided into inflammatory score quartiles. Cox proportional hazards regression was used to determine the association between inflammatory score and mortality. Restricted cubic splines (RCS) were used to explore the dose-response relationship between inflammatory score and mortality. Stratified analyses and interaction tests were conducted according to sex, age, body mass index (BMI), alcohol consumption, smoking status, hypertension, diabetes, and stroke status.ResultsAfter a mean follow-up of 145.9 months, 1039 all-cause deaths and 295 cardiovascular deaths were recorded. The results of multivariate Cox regression analysis showed that compared to the lowest quartile (Q1), patients in the highest quartile (Q4) had a 1.74-fold increased risk of all-cause mortality (Model 3: HR = 1.74, 95%CI 1.30–2.32, P < 0.001) and a 1.87-fold increased risk of cardiovascular mortality (Model 3: HR = 1.87, 95%CI 1.12–3.13, P = 0.020). There was a ‘J’-shaped nonlinear relationship between the inflammatory score and all-cause mortality (P for nonlinearity = 0.001), and a marginally significant ‘J’-shaped relationship with cardiovascular mortality (P for nonlinearity = 0.057). The threshold points of the inflammatory score for adverse outcomes were - 0.643 and - 0.621, respectively.ConclusionThe inflammatory score is independently associated with increased all-cause and cardiovascular mortality in patients with MetS, and risk stratification of these patients using inflammatory scores may provide specific therapeutic strategies to improve their prognosis.

IntroductionPromoting enterprises’ digital transformation is fundamental to implementing the digital China strategy and realizing high-quality development.MethodsTaking China’s A-share listed companies from 2007 to 2021 as a research sample, this study examines the impact of sharing auditors with customers on the digital transformation of suppliers.ResultsThe results show that sharing auditors with customers can promote suppliers’ digital transformation, and this promotion effect is stronger among suppliers with weaker bargaining power, lower media attention, and higher auditor industry expertise. In terms of the mechanism of action, sharing auditors with customers can help strengthen the supplier’s supervision, alleviate suppliers’ financing constraints, and thus facilitate their digital transformation. Further research finds that when suppliers share auditors with their customers, suppliers’ digital transformation helps promote innovation.DiscussionThe research conclusion provides effective empirical evidence for alleviating the dilemma of digital transformation of enterprises.

Plant-parasitic nematodes (PPNs) are among the most damaging pathogens to host plants. Plants can modulate their associated bacteria to cope with nematode infections. The tritrophic plant–nematode–microbe interactions are highly taxa-dependent, resulting in the effectiveness of nematode agents being variable among different host plants. Ficus tikoua is a versatile plant with high application potential for fruits or medicines. In recent years, a few farmers have attempted to cultivate this species in Sichuan, China, where parasitic nematodes are present. We used 16S rRNA genes to explore the effects of nematode parasitism on root-associated bacteria in this species. Our results revealed that nematode infection had effects on both endophytic bacterial communities and rhizosphere communities in F. tikoua roots, but on different levels. The species richness increased in the rhizosphere bacterial communities of infected individuals, but the community composition remained similar as compared with that of healthy individuals. Nematode infection induces a deterministic assembly process in the endophytic bacterial communities of parasitized organs. Significant taxonomic and functional changes were observed in the endophytic communities of root knots. These changes were characterized by the enrichment of nitrogen-fixing bacteria, including Bradyrhizobium, Allorhizobium–Neorhizobium–Pararhizobium–Rhizobium, and nematode-antagonistic bacteria, such as Pseudonocardia, Pseudomonas, Steroidobacter, Rhizobacter, and Ferrovibrio. Our results would help the understanding of the tritrophic plant–nematode–bacterium interactions in host plants other than dominant crops and vegetables and would provide essential information for successful nematode management when F. tikoua were cultivated on large scales.

Choroid plexus papilloma (CPP) is a rare benign intracranial tumor origin that predominantly manifests in the lateral ventricle in children, accounting for 0.3%–0.6% of all primary intracranial tumors. It is extremely rare to have the CPP in the trigone of the lateral ventricle through the contralateral posterior interhemispheric transfalcine transprecuneus approach (PITTA). Herein, we report this rare case. A 7-year-old girl presented with headache. Magnetic resonance imaging of the brain showed periatrial lesions, and histopathological examination confirmed CPP (WHO grade I). The contralateral PITTA is a safe, effective, reasonable, and appropriate for some lesions in the trigone of the lateral ventricle. It provides a wider surgical angle (especially for the lateral extension) and reduces the risk of disturbance of the optic radiation compared with the conventional approaches. The use of multiple modern neurosurgical techniques, including interventional embolization, intraoperative navigation, microscope, and electrophysiological monitoring, make the procedure much easier and more accurate, and the neuroendoscope adds to the visualization of the microscope and can reduce surgical complications.

ObjectiveTo investigate the association between dietary and some other environmental factors and the risk of inflammatory bowel diseases (IBD) in Chinese population.Materials and methodsA multicenter case-control study was conducted involving 11 hospitals across China. A total of 1,230 subjects were enrolled consecutively, and diet and environmental factor questionnaires were collected. IBD patients were matched with healthy controls (HC) using propensity-score matching (PSM) at a 1:1 ratio with a caliper value of 0.02. Multivariate conditional logistic regression analyses were performed to evaluate the associations between diet, environmental factors, and IBD.ResultsModerate alcohol and milk consumption, as well as daily intake of fresh fruit, were protective factors for both Crohn's disease (CD) and ulcerative colitis (UC). Conversely, the consumption of eggs and chocolate increased the risk of IBD. Outdoor time for more than 25% of the day was a protective factor only for CD. In eastern regions of China, CD patients had higher egg consumption and less outdoor time, while UC patients consumed more chocolate. IBD patients from urban areas or with higher per capita monthly income consumed more fruit, eggs, and chocolate.ConclusionsThis study reveals an association between specific foods, outdoor time, and the emergence of IBD in the Chinese population. The findings emphasize the importance of a balanced diet, sufficient outdoor time and activities, and tailored prevention strategies considering regional variations.

This report describes a case of concomitant diabetic ketoacidosis (DKA) and thyroid storm (TS) in a 20-year-old male patient that presented both diagnostic and management challenges owing to their intricate interrelationship in endocrine-metabolic disorders. The patient, previously diagnosed with type 1 diabetes mellitus (T1DM) and hyperthyroidism, was admitted to the emergency department with symptoms of DKA and progressive exacerbation of TS. Initial treatment focused on correcting DKA; as the disease progressed to TS, it was promptly recognized and treated. This case emphasizes the rarity of simultaneous occurrence of DKA and TS, as well as the challenges in clinical diagnosis posed by the interacting pathophysiological processes and overlapping clinical manifestations of DKA and TS. The patient’s treatment process involved multiple disciplines, and after treatment, the patient’s critical condition of both endocrine metabolic diseases was alleviated, after which he recovered and was eventually discharged from the hospital. This case report aims to emphasize the need for heightened awareness in patients with complex clinical presentations, stress the possibility of concurrent complications, and underscore the importance of prompt and collaborative treatment strategies.

BackgroundThe aim of this study is to develop a predictive model utilizing deep learning and machine learning techniques that will inform clinical decision-making by predicting the 1-year postoperative recovery of patients with lumbar disk herniation.MethodsThe clinical data of 470 inpatients who underwent tubular microdiscectomy (TMD) between January 2018 and January 2021 were retrospectively analyzed as variables. The dataset was randomly divided into a training set (n = 329) and a test set (n = 141) using a 10-fold cross-validation technique. Various deep learning and machine learning algorithms including Random Forests, Extreme Gradient Boosting, Support Vector Machines, Extra Trees, K-Nearest Neighbors, Logistic Regression, Light Gradient Boosting Machine, and MLP (Artificial Neural Networks) were employed to develop predictive models for the recovery of patients with lumbar disk herniation 1 year after surgery. The cure rate score of lumbar JOA score 1 year after TMD was used as an outcome indicator. The primary evaluation metric was the area under the receiver operating characteristic curve (AUC), with additional measures including decision curve analysis (DCA), accuracy, sensitivity, specificity, and others.ResultsThe heat map of the correlation matrix revealed low inter-feature correlation. The predictive model employing both machine learning and deep learning algorithms was constructed using 15 variables after feature engineering. Among the eight algorithms utilized, the MLP algorithm demonstrated the best performance.ConclusionOur study findings demonstrate that the MLP algorithm provides superior predictive performance for the recovery of patients with lumbar disk herniation 1 year after surgery.

IntroductionTriple-negative breast cancer (TNBC) is linked to a poorer outlook, heightened aggressiveness relative to other breast cancer variants, and limited treatment choices. The absence of conventional treatment methods makes TNBC patients susceptible to metastasis. The objective of this research was to assess the clinical and pathological traits of TNBC patients, predict the influence of risk elements on their outlook, and create a prediction model to assist doctors in treating TNBC patients and enhancing their prognosis.MethodsWe included 23,394 individuals with complete baseline clinical data and survival information who were diagnosed with primary TNBC between 2010 and 2015 based on the SEER database. External validation utilised a group from The Affiliated Lihuili Hospital of Ningbo University. Independent risk factors linked to TNBC prognosis were identified through univariate, multivariate, and least absolute shrinkage and selection operator regression methods. These characteristics were chosen as parameters to develop 3- and 5-year overall survival (OS) and breast cancer-specific survival (BCSS) nomogram models. Model accuracy was assessed using calibration curves, consistency indices (C-indices), receiver operating characteristic curves (ROCs), and decision curve analyses (DCAs). Finally, TNBC patients were divided into groups of high, medium, and low risk, employing the nomogram model for conducting a Kaplan-Meier survival analysis.ResultsIn the training cohort, variables such as age at diagnosis, marital status, grade, T stage, N stage, M stage, surgery, radiation, and chemotherapy were linked to OS and BCSS. For the nomogram, the C-indices stood at 0.762, 0.747, and 0.764 in forecasting OS across the training, internal validation, and external validation groups, respectively. Additionally, the C-index values for the training, internal validation, and external validation groups in BCSS prediction stood at 0.793, 0.755, and 0.811, in that order. The findings revealed that the calibration of our nomogram model was successful, and the time-variant ROC curves highlighted its effectiveness in clinical settings. Ultimately, the clinical DCA showcased the prospective clinical advantages of the suggested model. Furthermore, the online version was simple to use, and nomogram classification may enhance the differentiation of TNBC prognosis and distinguish risk groups more accurately.ConclusionThese nomograms are precise tools for assessing risk in patients with TNBC and forecasting survival. They can help doctors identify prognostic markers and create more effective treatment plans for patients with TNBC, providing more accurate assessments of their 3- and 5-year OS and BCSS.

BackgroundNurse turnover has become a salient issue in healthcare system worldwide and seriously compromises patient outcomes. Social support is considered an effective contributor to alleviate nurse turnover intention (TI). However, the degree of correlation between social support and nurse TI remains elusive.AimsThis study aims to evaluate the strength of the effectiveness of social support on TI among nurses as well as its potential moderators.DesignThis systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.MethodsTo obtained qualified studies, two researchers searched Embase, PubMed, Web of science, CINAHL, CNKI, WanFang, and Chinese Medical Journal Full Text Database from inception to January 6, 2024. Meta-analysis, publication bias, and sensitivity analysis were carried out on the included studies using CMA 3.0 software, and the moderating effect was verified through meta-analysis of variance (ANOVA).ResultsA total of 38 studies were obtained, involving 63,989 clinical nurses. The comprehensive effect size of the random effect model showed a significant medium negative correlation between social support and TI among nurses (p

This study examined the applicability of indocyanine green (ICG) fluorescence imaging to assist the laparoscopic resection of retroperitoneal tumors in pediatric patients via an abdominal approach. Conducted prospectively at the Guangzhou Women and Children's Medical Center from May to September 2023, the research included three pediatric cases, for whom laparoscopic retroperitoneal tumor resections were performed utilizing ICG fluorescence imaging. In each case, ICG was intravenously administered (0.3 mg/kg) prior to surgery, enabling the visualization of vital vascular structures through real-time fluorescence imaging. The trocar's placement was guided by a “four-hole” technique from the healthy side in a 70-degree lateral decubitus position. The operations were accomplished successfully without any complications. Pathological analysis of the patients identified one case of Wilms tumor of the embryonal type, one ganglioneuroblastoma of the mature type without N-MYC gene amplification, and one mature cystic teratoma. The findings suggest that with careful patient selection and skilled surgical execution, the utilization of ICG fluorescence imaging in the laparoscopic resection of retroperitoneal tumors is both safe and effective in children. This approach significantly improves the visualization of critical blood vessels, thus enhancing surgical safety.

Social media has profoundly changed our modes of self-expression, communication, and participation in public discourse, generating volumes of conversations and content that cover every aspect of our social lives. Social media platforms have thus become increasingly important as data sources to identify social trends and phenomena. In recent years, academics have steadily lost ground on access to social media data as technology companies have set more restrictions on Application Programming Interfaces (APIs) or entirely closed public APIs. This circumstance halts the work of many social scientists who have used such data to study issues of public good. We considered the viability of eight approaches for image-based social media data collection: data philanthropy organizations, data repositories, data donation, third-party data companies, homegrown tools, and various web scraping tools and scripts. This paper discusses the advantages and challenges of these approaches from literature and from the authors' experience. We conclude the paper by discussing mechanisms for improving social media data collection that will enable this future frontier of social science research.

IntroductionFolliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity.MethodsMice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400μg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC–MS).ResultsIn this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4).ConclusionThese results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.

Early diagenetic nodules with low permeable and weather-resistant structures are considered to be favorable for biosignature preservation. Numerous nodular structures forming in neutral-to-alkaline and saline diagenetic fluids were previously identified at Gale Crater on Mars, yet their astrobiological significance remains poorly understood. In the Mars-like western Qaidam Basin, China, there are a multitude of carbonate nodules which can be analogous to those found at Gale Crater on Mars in terms of their formation backgrounds and post-depositional processes. In this study, we combine microscopic, spectroscopic, and geochemical methods to characterize the biosignature preservation of the Qaidam nodules. Carbonaceous materials, including an organic annulus inferred to be a fossil spore or algal filament microfossil, are observed in the Qaidam nodules. The total organic carbon contents of the Qaidam nodules are slightly higher than those of the surrounding fluvio-lacustrine deposits, suggesting that early diagenesis of the Qaidam nodules might facilitate the rapid entombment of biomass within magnesium carbonate or aragonite matrixes before complete degradation. The carbonate matrix showing alternating micritic and sparry layers as well as enrichment of 13C could have a physicochemical origin though the possibilities of biomineralization and organomineralization cannot be entirely ruled out. The I-1350/1,600 distribution of carbonaceous materials implies the existence of carbon precursors of various subcellular components or coexisting organisms in pore waters. Organic carbon isotopes indicate the carbon fixation pathways such as the Calvin cycle or the Wood-Ljungdahl pathway utilized by organisms in pore waters. The findings of this study shed light into the taphonomy and detection of biosignatures in terrestrial playa nodules, with potential applications for biosignature exploration on Mars.

BackgroundAcute promyelocytic leukemia (APL) is rarely caused by the PLZF::RARα fusion gene. While APL patients with PLZF::RARα fusion commonly exhibit diverse hematologic symptoms, the presentation of myeloid sarcoma (MS) as an initial manifestation is infrequent.Case presentationA 61-year-old patient was referred to our hospital with 6-month history of low back pain and difficulty walking. Before this admission, spine magnetic resonance imaging (MRI) conducted at another hospital revealed multiple abnormal signals in the left iliac bone and vertebral bodies spanning the thoracic (T11-T12), lumbar (L1-L4), and sacral (S1/S3) regions. This led to a provisional diagnosis of bone tumors with an unknown cause. On admission, complete blood count (CBC) test and peripheral blood smear revealed a slightly increased counts of monocytes. Immunohistochemical staining of both spinal and bone marrow (BM) biopsy revealed positive expression for CD117, myeloperoxidase (MPO), and lysozyme. BM aspirate showed a significant elevation in the percentage of promyelocytes (21%), which were morphologically characterized by round nuclei and hypergranular cytoplasm. Multiparameter flow cytometry of BM aspirate revealed that blasts were positive for CD13, CD33, CD117, and MPO. Through the integrated application of chromosome analysis, fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), and Sanger sequencing, it was determined that the patient possessed a normal karyotype and a rare cryptic PLZF::RARα fusion gene, confirming the diagnosis of APL.ConclusionIn the present study, we report the clinical features and outcome of a rare APL patient characterized by a cryptic PLZF::RARα fusion and spinal myeloid sarcoma (MS) as the initial presenting symptom. Our study not only offers valuable insights into the heterogeneity of APL clinical manifestations but also emphasizes the crucial need to promptly consider the potential link between APL and MS for ensuring a timely diagnosis and personalized treatments.

BackgroundAtherogenic Index of plasma (AIP) is closely related to metabolic abnormalities. But as of now, there is no definitive conclusion on the dose-response relationship pattern between AIP and metabolic associated fatty liver disease (MAFLD).ObjectiveThe objective of this study was to provide a fresh insight for understanding the intrinsic link between AIP and the prevalence of MAFLD by exploring the dose-response pattern between AIP and MAFLD.MethodsA total of 9254 participants received the survey and 1090 participants were finally included according to the screening criteria. To evaluate the association between AIP and the prevalence of MAFLD based on weighted multivariate logistic regression. Sensitivity analysis of the association between AIP and MAFLD was performed using propensity score matching (PSM). Restrictive cubic splines (RCS) were used to identify patterns of dose-response relationships between AIP and MAFLD, and receiver operator characteristic (ROC) curves were used to evaluate the predictive ability of AIP and traditional lipid parameters for MAFLD.ResultsIn this study, a total of 563 participants were found to have MAFLD. The results of weighted multivariate logistic regression analysis demonstrated that, after adjusting for sex and age, participants in the highest quartile (Q4) of AIP had a significantly increased risk of developing MAFLD compared to those in the lowest quartile (Q1) (Model 2: OR = 9.03, 95% CI 4.75–17.17). A similar trend was observed in the fully adjusted model (Model 3: OR = 3.85, 95% CI 1.55–9.52). The RCS analysis revealed a linear dose-response association between AIP and MAFLD(P for crude non-linearity = 0.087). This association remained significant after accounting for potential confounding variables(P for adjusted non-linearity = 0.663). The ROC curve results suggest that AIP performs better than traditional lipid indicators in predicting MAFLD (AUC = 0.732, 95%CI 0.705–0.758).ConclusionA linear dose-response relationship exists between AIP and MAFLD, suggesting that as AIP increases, so does the risk of developing MAFLD.

Numerous studies have demonstrated that polysaccharides derived from chicory possess the ability to regulate host signaling and modify mucosal damage. Yet, the effect and mechanism of short-chain fructo-oligosaccharides (scFOS) on gastric mucosa remain unclear. Hence, the protective effect of three scFOS (1-Kestose, Nystose, and 1F-Fructofuranosylnystose) against ethanol-induced injury in gastric epithelial (GES-1) cells, and the underlying molecular mechanism involved was investigated in this study. Treatment with 7% ethanol decreased the cell viability of GES-1 cells, resulting in oxidative stress and inflammation. However, pretreatment with scFOS exhibited significant improvements in cell viability, and mitigated oxidative stress and inflammation. scFOS markedly elevated the protein expression of Nrf2, HO-1, SOD1 and SOD2, while suppressing the expression of Keap1. scFOS pretreatment could also maintain mitochondrial membrane potential balance and reduce apoptosis. In addition, scFOS was observed to reduce the protein level of NLRP3, Caspase-1 and ASC. In conclusion, scFOS served a preventive function in mitigating oxidative stress and inflammation in ethanol-exposed GES-1 cells through modulation of the Keap1/Nrf2 and NLRP3 inflammasome signaling pathways. Collectively, the results indicated that scFOS could significantly mitigate ethanol-induced gastric cell damage, suggesting its potential for safeguarding gastrointestinal health.

ObjectiveThe established link between posttranslational modifications of histone and non-histone lysine (K) residues in cell metabolism, and their role in cancer progression, is well-documented. However, the lactylation expression signature in triple-negative breast cancer (TNBC) remains underexplored.MethodsWe conducted a comprehensive lactylproteome profiling of eight pairs of TNBC samples and their matched adjacent tissues. This was achieved through 4-Dimensional label-free quantitative proteomics combined with lactylation analysis (4D-LFQP-LA). The expression of identified lactylated proteins in TNBC was detected using immunoblotting and immunohistochemistry (IHC) with specific primary antibodies, and their clinicopathological and prognostic significance was evaluated.ResultsOur analysis identified 58 lactylation sites on 48 proteins, delineating the protein lactylation alteration signature in TNBC. Bioinformatic and functional analyses indicated that these lactylated proteins play crucial roles in regulating key biological processes in TNBC. Notably, lactylation of lysine at position 12 (H4K12lac) in the histone H4 domain was found to be upregulated in TNBC. Further investigations showed a high prevalence of H4K12lac upregulation in TNBC, with positive rates of 93.19% (137/147) and 92.93% (92/99) in TNBC tissue chip and validation cohorts, respectively. H4K12lac expression correlated positively with Ki-67 and inversely with overall survival (OS) in TNBC (HR [hazard ratio] =2.813, 95%CI [credibility interval]: 1.242-6.371, P=0.0164), suggesting its potential as an independent prognostic marker (HR=3.477, 95%CI: 1.324-9.130, P=0.011).ConclusionsLactylation is a significant post-translational modification in TNBC proteins. H4K12lac emerges as a promising biomarker for TNBC, offering insights into the lactylation profiles of TNBC proteins and linking histone modifications to clinical implications in TNBC.

IntroductionChronic Ankle Instability (CAI) is a musculoskeletal condition that evolves from acute ankle sprains, and its underlying mechanisms have yet to reach a consensus. Mounting evidence suggests that neuroplastic changes in the brain following ankle injuries play a pivotal role in the development of CAI. Balance deficits are a significant risk factor associated with CAI, yet there is a scarcity of evidence regarding the sensorimotor cortical plasticity related to balance control in affected individuals. This study aims to evaluate the differences in cortical activity and balance abilities between patients with CAI and uninjured individuals during a single-leg stance, as well as the correlation between these factors, in order to elucidate the neurophysiological alterations in balance control among patients with CAI.MethodsThe study enrolled 24 patients with CAI and 24 uninjured participants. During single-leg stance, cortical activity was measured using a functional near-infrared spectroscopy (fNIRS) system, which included assessments of the pre-motor cortex (PMC), supplementary motor area (SMA), primary motor cortex (M1), and primary somatosensory cortex (S1). Concurrently, balance parameters were tested utilizing a three-dimensional force platform.ResultsIndependent sample t-tests revealed that, compared with the uninjured individuals, the patients with CAI exhibited a significant increase in the changes of oxyhemoglobin concentration (ΔHbO) during single-leg stance within the left S1 at Channel 5 (t = 2.101, p = 0.041, Cohen’s d = 0.607), left M1 at Channel 6 (t = 2.363, p = 0.022, Cohen’s d = 0.682), right M1 at Channel 15 (t = 2.273, p = 0.029, Cohen’s d = 0.656), and right PMC/SMA at Channel 11 (t = 2.467, p = 0.018, Cohen’s d = 0.712). Additionally, the center of pressure root mean square (COP-RMS) in the mediolateral (ML) direction was significantly greater (t = 2.630, p = 0.012, Cohen’s d = 0.759) in the patients with CAI. Furthermore, a moderate positive correlation was found between ML direction COP-RMS and ΔHbO2 in the M1 (r = 0.436; p = 0.033) and PMC/SMA (r = 0.488, p = 0.016), as well as between anteroposterior (AP) direction COP-RMS and ΔHbO in the M1 (r = 0.483, p = 0.017).ConclusionPatients with CAI demonstrate increased cortical activation in the bilateral M1, ipsilateral PMC/SMA, and contralateral S1. This suggests that patients with CAI may require additional brain resources to maintain balance during single-leg stance, representing a compensatory mechanism to uphold task performance amidst diminished lateral balance ability in the ankle joint.

BackgroundThe consumption of cheese and fish has been linked to the onset of depression. However, the connection between consuming cheese, consuming fish, experiencing depression, and the pathways that mediate this relationship remains unclear. The purpose of this research was to investigate the potential association between the consumption of cheese and fish and the occurrence of depression. Moreover, it is important to identify any metabolites that might be involved and understand their respective roles and functions.MethodsA two-step, two-sample Mendelian randomization (MR) study was conducted using genome-wide association study (GWAS) data on cheese, non-oily fish, and oily fish consumption and depression, along with 12 alternate mediators. The study included a total of 451,486 participants in the cheese consumption group, 460,880 in the non-oily fish consumption group, 460,443 in the oily fish consumption group, and 322,580 with a diagnosis of depression. The single nucleotide polymorphism (SNP) estimates were pooled using inverse-variance weighted, weighted median, MR-Egger, simple mode, and weighted mode.ResultsThe data we collected suggested that consuming more cheese correlated with a lower likelihood of experiencing depression (OR: 0.95; 95% CI: 0.92 to 0.98). Neither non-oily fish nor oily fish consumption was directly linked to depression onset (p = 0.08, p = 0.78, respectively). Although there was a direct causal relationship with depression, the mediating relationship of triglycerides (TG), total cholesterol in large HDL, cholesterol to total lipids ratio in large HDL, free cholesterol to total lipids ratio in large HDL, glycine, and phospholipids to total lipids ratio in very large HDL of cheese intake on depression risk were − 0.002 (95% CI: −0.023 - 0.020), −0.002 (95% CI: −0.049 - 0.045), −0.001 (95% CI: −0.033 - 0.031), −0.001 (95% CI: −0.018 - 0.015), 0.001 (95% CI: −0.035 - 0.037), and − 0.001 (95% CI: −0.024 - 0.021), respectively. The mediating relationship of uridine, free cholesterol to total lipids ratio in large HDL, total cholesterol in large HDL, acetoacetate, and 3-hydroxybutyrate (3-HB) between non-oily fish consumption and depression risk were 0.016 (95% CI: −0.008 - 0.040), 0.011 (95% CI: −1.269 - 1.290), 0.010 (95% CI: −1.316 - 1.335), 0.011 (95% CI: −0.089 - 0.110), and 0.008 (95% CI: −0.051 - 0.068), respectively. The mediation effect of uridine and free cholesterol to total lipids ratio in large HDL between intake of oily fish and the risk of depression was found to be 0.006 (95% CI: −0.015 - 0.028) and − 0.002 (95% CI: −0.020 - 0.017), respectively. The correlation between eating cheese and experiencing depression persisted even when adjusting for other variables like Indian snacks, mango consumption, sushi consumption, and unsalted peanuts using multivariable MR.ConclusionThe consumption of cheese and fish influenced the likelihood of experiencing depression, and this may be mediated by certain metabolites in the body. Our study provided a new perspective on the clinical treatment of depression.

IntroductionPhysical and mental health problems among pilots affect their working state and impact flight safety. Although pilots’ physical and mental health problems have become increasingly prominent, their health has not been taken seriously. This study aimed to clarify challenges and support needs related to psychological and physical health among pilots to inform development of a more scientific and comprehensive physical and mental health system for civil aviation pilots.MethodsThis qualitative study recruited pilots from nine civil aviation companies. Focus group interviews via an online conference platform were conducted in August 2022. Colaizzi analysis was used to derive themes from the data and explore pilots’ experiences, challenges, and support needs.ResultsThe main sub-themes capturing pilots’ psychological and physical health challenges were: (1) imbalance between family life and work; (2) pressure from assessment and physical examination eligibility requirements; (3) pressure from worries about being infected with COVID-19; (4) nutrition deficiency during working hours; (5) changes in eating habits because of the COVID-19 pandemic; (6) sleep deprivation; (7) occupational diseases; (8) lack of support from the company in coping with stress; (9) pilots’ yearly examination standards; (10) support with sports equipment; (11) respecting planned rest time; and (12) isolation periods.DiscussionThe interviewed pilots experienced major psychological pressure from various sources, and their physical health condition was concerning. We offer several suggestions that could be addressed to improve pilots’ physical and mental health. However, more research is needed to compare standard health measures for pilots around the world in order to improve their physical and mental health and contribute to overall aviation safety.

Gastrointestinal cancers account for approximately one-third of the total global cancer incidence and mortality with a poor prognosis. It is one of the leading causes of cancer-related deaths worldwide. Most of these diseases lack effective treatment, occurring as a result of inappropriate models to develop safe and potent therapies. As a novel preclinical model, tumor patient-derived organoids (PDOs), can be established from patients’ tumor tissue and cultured in the laboratory in 3D architectures. This 3D model can not only highly simulate and preserve key biological characteristics of the source tumor tissue in vitro but also reproduce the in vivo tumor microenvironment through co-culture. Our review provided an overview of the different in vitro models in current tumor research, the derivation of cells in PDO models, and the application of PDO model technology in gastrointestinal cancers, particularly the applications in combination with CRISPR/Cas9 gene editing technology, tumor microenvironment simulation, drug screening, drug development, and personalized medicine. It also elucidates the ethical status quo of organoid research and the current challenges encountered in clinical research, and offers a forward-looking assessment of the potential paths for clinical organoid research advancement.

IntroductionIn light of the public health burden of the COVID-19 pandemic, boosting the safety and immunogenicity of COVID-19 vaccines is of great concern. Numerous Traditional Chinese medicine (TCM) preparations have shown to beneficially modulate immunity. Based on pilot experiments in mice that showed that supplementation with Huoxiang Suling Shuanghua Decoction (HSSD) significantly enhances serum anti-RBD IgG titers after inoculation with recombinant SARS-CoV-2 S-RBD protein, we conducted this randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the potential immunogenicity boosting effect of oral HSSD after a third homologous immunization with Sinovac’s CoronaVac SARS-CoV-2 (CVS) inactivated vaccine.MethodsA total of 70 participants were randomly assigned (1:1 ratio) to receive a third dose of CVS vaccination and either oral placebo or oral HSSD for 7 days. Safety aspects were assessed by recording local and systemic adverse events, and by blood and urine biochemistry and liver and kidney function tests. Main outcomes evaluated included serum anti-RBD IgG titer, T lymphocyte subsets, serum IgG and IgM levels, complement components (C3 and C4), and serum cytokines (IL-6 and IFN-γ). In addition, metabolomics technology was used to analyze differential metabolite expression after supplementation with HSSD.ResultsFollowing a third CVS vaccination, significantly increased serum anti-RBD IgG titer, reduced serum IL-6 levels, increased serum IgG, IgM, and C3 and C4 levels, and improved cellular immunity, evidenced by reduce balance deviations in the distribution of lymphocyte subsets, was observed in the HSSD group compared with the placebo group. No serious adverse events were recorded in either group. Serum metabolomics results suggested that the mechanisms by which HSSD boosted the immunogenicity of the CVS vaccine are related to differential regulation of purine metabolism, vitamin B6 metabolism, folate biosynthesis, arginine and proline metabolism, and steroid hormone biosynthesis.ConclusionOral HSSD boosts the immunogenicity of the CVS vaccine in young and adult individuals. This trial provides clinical reference for evaluation of TCM immunomodulators to improve the immune response to COVID-19 vaccines.

In the field of medical image segmentation, achieving fast and accurate semantic segmentation of tumor cell nuclei and skin lesions is of significant importance. However, the considerable variations in skin lesion forms and cell types pose challenges to attaining high network accuracy and robustness. Additionally, as network depth increases, the growing parameter size and computational complexity make practical implementation difficult. To address these issues, this paper proposes MD-UNet, a fast cell nucleus segmentation network that integrates Tokenized Multi-Layer Perceptron modules, attention mechanisms, and Inception structures. Firstly, tokenized MLP modules are employed to label and project convolutional features, reducing computational complexity. Secondly, the paper introduces Depthwise Attention blocks and Multi-layer Feature Extraction modules. The Depthwise Attention blocks eliminate irrelevant and noisy responses from coarse-scale extracted information, serving as alternatives to skip connections in the UNet architecture. The Multi-layer Feature Extraction modules capture a wider range of high-level and low-level semantic features during decoding and facilitate feature fusion. The proposed MD-UNet approach is evaluated on two datasets: the International Skin Imaging Collaboration (ISIC2018) dataset and the PanNuke dataset. The experimental results demonstrate that MD-UNet achieves the best performance on both datasets.

ObjectiveThe aim of this study was to investigate the clinical traits and consequences of systemic lupus erythematosus (SLE) complicated by active cytomegalovirus (CMV) infection.MethodsThis retrospective review involved the examination of medical records for patients diagnosed with SLE who had an active CMV infection at the time of their discharge from Peking Union Medical College Hospital between June 2016 and December 2022. The consistency between plasma CMV deoxyribonucleic acid (DNA) viral load and pp65 antigenemia was analyzed using the chi-square test. Related factors for CMV disease in SLE complicated by active CMV infection patients were analyzed by univariate analysis and multivariable stepwise logistic regression. Cox hazards regression analysis was used to determine predictors for all-cause mortality and CMV recurrence within 3 months.ResultsA total of 206 patients were enrolled in this study. Of the 123 patients who were detected with both plasma CMV DNA viral load and pp65 antigenemia within an interval not exceeding 72 h, the consistency between plasma CMV DNA viral load and pp65 antigenemia was not good (Kappa = −0.304, p < 0.001). Plasma CMV DNA viral load ≥ 1,600 copies/mL [odds ratio (OR) 4.411, 95% CI 1.871–10.402, p = 0.001], current glucocorticoids dose (equivalent to prednisolone) ≥60 mg/d (OR 2.155, 95% CI 1.071–4.334, p = 0.031), and elevated alanine transaminase (OR 3.409, 95% CI 1.563–7.435, p = 0.002) were significant clinical clues indicating CMV disease in SLE. Multivariable Cox hazards regression analysis showed that CMV organ involvement [hazard ratio (HR) 47.222, 95% CI 5.621–396.689, p < 0.001], SLE multi-system involvement (HR 1.794, 95% CI 1.029–3.128, p = 0.039), and elevated hypersensitive C-reactive protein (hsCRP) (HR 5.767, 95% CI 1.190–27.943, p = 0.030) were independent risk factors for 3-month all-cause mortality. CMV organ involvement (HR 3.404, 95% CI 1.074–10.793, p = 0.037) was an independent risk factor for CMV recurrence within 3 months.ConclusionIn SLE patients, plasma CMV DNA viral load seemed to have a higher value in the diagnosis of CMV disease; patients with CMV organ involvement, SLE multi-system involvement, and elevated hsCRP might have a higher risk of 3-month all-cause mortality; and patients with CMV organ involvement might have a higher risk of CMV recurrence within 3 months.

The Banqiao area in the Bohai Bay Basin has experienced three stages of extensional deformation, leading to the formation of numerous fault-bound traps. Faults, acting as boundary conditions for these traps, play a crucial role in hydrocarbon accumulation. In this study, we conducted a 3D structural modeling of the area using high-resolution 3D seismic data and established a fault-reservoir database based on previous research. Our findings reveal four levels of faults in the Banqiao area: basin-controlling faults, boundary faults, derivative master faults, and secondary adjusting faults. The structural units can be categorized into subsag areas, slope areas, stress tran-sition zones, bifurcation and main incised fault zones, and southern block areas. The segmented growth of the main boundary faults controls the evolution of the subsags, with the subsidence center gradually shifting eastward from Rift Phase I to Rift Phase II, aligning with the distribution of source rocks. Fault-bound traps in the Banqiao area include single faults, intersecting faults, and side faults. Faults primarily act as barriers to lateral hydrocarbon migration during the process of hydrocarbon accumulation, while also providing pathways to a lesser extent. By integrating the fault-reservoir database with the fault system classification, we identified four types of fault-controlled hydro-carbon accumulation models: like-dipping fault barrier model, oppositely-dipping fault barrier model, intersecting fault barrier model, and reactivation-controlled secondary hydrocarbon ac-cumulation model. This structural geological model effectively demonstrates the spatial configura-tion of faults and their role in hydrocarbon accumulation in the Banqiao area. The fault control mechanisms presented in the model can also be applied to other blocks in the Bohai Bay Basin, laying a foundation for future petroleum exploration in continental rifted basins and facilitating the ap-plication of big data algorithms in various geoscientific research fields.

ObjectiveTo investigate the effect and clinical significance of Delphian lymph nodes (DLN) on the factors influencing papillary thyroid cancer (PTC) to provide individualized guidance for the surgical treatment of thyroid cancer.MethodsRelevant studies from PubMed, Web of Science, the Cochrane Library, Embase, and China National Knowledge Infrastructure databases were searched until February 13, 2023. Stringent selection parameters were used to obtain included data and homogeneous articles. Analyses were performed using Revman 5.4 and SPSS software. A P-value of < 0.05 was considered statistically significant.ResultsFive studies were finally included in this study. The results revealed a higher risk of DLN metastasis (DLNM) in patients with tumor size >1cm, multifocality, and extrathyroidal extension (ETE) of the thyroid. The risk of central lymph node metastasis (CLNM) was 11.25 times higher in DLN-positive patients with PTC than in DLN-negative (OR = 11.25, 95% CI: 8.64–14.64, P < 0.05) patients. The risk of LLNM was 5.57 times higher in DLN-positive patients with PTC than in DLN-negative (OR = 5.57, 95% CI: 4.57–6.78, P < 0.001) patients. The risk of postoperative recurrence in DLN-positive patients with PTC was 3.49 times higher (OR = 3.49, 95% CI: 1.91–6.38, P < 0.001) than in DLN-negative patients with PTC.ConclusionPatients with tumor size >1 cm in diameter, multifocality, and ETE have an increased risk for DLN development. DLN-positive patients with central and lateral cervical lymph node metastasis and postoperative recurrence are at higher risk than DLN-negative patients.

ObjectiveUsing data from NHANES 2007–2018, to examine the association between WWI (weight-adjusted waist index) index and prevalence of kidney stones.MethodsUsing multiple logistic regression analysis of the National Health and Nutrition Examination Survey (NHANES) 2007–2018, we evaluated the association between WWI index and the prevalence of kidney stones, followed by subgroup analysis of sensitive populations. Smooth curve fitting was used to determine whether there was a non-linear relationship between the WWI index and kidney stone prevalence, and threshold effect analysis was used to test this relationship.ResultsAmong 29,280 participants, 2,760 self-reported renal calculi. After adjustment for all confounders, there was a positive association between WWI and kidney stone prevalence (OR = 1.20, 95% CI: 1.12, 1.28), and this positive association was stronger with increasing WWI (and P = 0.01 for trend). Our results indicate a non-linear positive correlation between WWI index and kidney stones, with the saturation threshold effect analysis and the most important threshold value at 11.02. According to subgroup analysis, WWI showed the strongest association with kidney stone prevalence in participants aged 20–39 years, males, other US ethnic groups, and participants without hypertension and diabetes.ConclusionIncreased WWI is positively associated with increased incidence of kidney stones, and increased WWI is a high risk for kidney stones that should be treated with caution. This association should be more pronounced in people between the ages of 20 and 39 years, in men, in other US ethnic populations, and in participants who do not have hypertension or diabetes.